Kate Rowland, MD, MS

PRACTICE CHANGER

Ask women who are at risk for sexually transmitted infections (STIs) to self-swab for chlamydia and gonorrhea testing; self-collection of vulvovaginal swabs with nucleic acid amplification testing (NAAT) has excellent sensitivity in women with and without symptoms.^1,2

STRENGTH OF RECOMMENDATION

B: Based on a prospective diagnostic cohort study.^1,2

ILLUSTRATIVE CASE

An 18-year-old patient requests testing for STIs. She has no symptoms. What is the best way to collect samples for chlamydia and gonorrhea testing?

Despite public health efforts, chlamydia and gonorrhea remain significant health problems, with more than 1.4 million cases of chlamydia and 321,849 cases of gonorrhea reported in the United States in 2011.³ Both can have devastating effects on reproduction, even in women who are ­asymptomatic.

Annual testing recommended for at-risk women

According to the CDC, most reported cases of chlamydia (70%) and gonorrhea (62%) occur in men and women between the ages of 15 and 24.³ Both the CDC and the US Preventive Services Task Force recommend annual chlamydia screening for all sexually active women younger than 25 and for older women who have certain risk factors (eg, having multiple sex partners or living in communities with a high burden of disease).^4,5 Annual gonorrhea screening is also recommended for sexually active women with risk factors.^4,5

How best to test? A number of unknowns

NAAT is the most sensitive test for detection of chlamydia and gonorrhea, but other questions about how best to screen for STIs remain.^1,6 It has not been clear whether self-collected vulvovaginal swabs are equivalent to clinician-collected urethral or endocervical swabs for the detection of gonorrhea, or whether NAAT testing of the self-collected swabs or culture of the clinician-collected swabs is a more sensitive test for gonorrhea.

While some studies have found self-collected vulvovaginal samples to be as sensitive as clinician-collected endocervical samples for the diagnosis of chlamydia and gonorrhea, samples are still often collected by clinicians.^7,8 Collecting endocervical swabs is uncomfortable for patients and time consuming for clinicians, and evidence suggests that patients prefer noninvasive sampling.⁹

STUDY SUMMARY
Self-collected samples are highly sensitive

This study was designed to compare the sensitivity and specificity of self-collected vulvovaginal swabs with that of clinician-collected swabs for chlamydia and gonorrhea, both in asymptomatic women and women with symptoms of an STI. Test methods were also assessed for gonorrhea, comparing detection rates of self-swabs tested with NAAT and the culture of clinician-collected urethral and endocervical samples.

The researchers evaluated a total of 3,973 women, ages 16 to 59, who sought care at a single sexual health center in the United Kingdom. The average age was 25; 37% of the participants reported a prior STI, and 42% had at least one symptom suggestive of an STI. Women were excluded from the study if they had taken an antibiotic in the preceding 28 days or were unable/unwilling to take a vulvovaginal swab or undergo clinician examination and sample collection.

The women performed vulvovaginal swabs for NAAT prior to a speculum exam; endocervical swab for both NAAT and culture and a urethral swab for culture were collected by the clinician. All the swabs sent for NAAT were tested for chlamydia and gonorrhea, and cultures were performed to detect gonorrhea.

Chlamydia: Vulvovaginal swabs have higher detection rates

Of the 3,867 participants with complete results, 10.2% were infected with chlamydia. Self-collected vulvovaginal swabs were significantly more sensitive than endocervical swabs (97% vs 88%) and had equal specificity (99.9% vs 100%). In women with symptoms of an STI, the sensitivity was 97% vs 88%; in those with no symptoms, the sensitivity was 97% vs 89%.

Gonorrhea: Self-collection, NAAT yield better results

Gonorrhea was found in 2.5% of the 3,859 women with complete results for testing of this STI. Self-collected swabs and clinician-collected swabs analyzed by NAAT both had excellent sensitivity (99% and 96%, respectively). But self-collected samples that underwent NAAT were significantly more sensitive than clinician-collected urethral and endocervical samples that were cultured (99% vs 81%). The number needed to test by self-collection for NAAT (compared with clinician-collected culture) to detect one additional case of gonorrhea was 5.

In women with symptoms suggestive of infection, the NAAT assays—both clinician- and self-collected—were equivalent and were more sensitive than gonorrhea culture. In asymptomatic women, 1.8% of whom had gonorrhea, the vulvovaginal swab sent for NAAT was more sensitive than culture (98% vs 78%) and was equivalent to the endocervical swab for NAAT (90%).

The bottom line: Self-collected vulvovaginal swabs are the sample of choice for both chlamydia and gonorrhea testing in women, regardless of whether they have symptoms. When a clinical examination is needed, either the clinician or the patient can collect a vulvovaginal swab.

WHAT’S NEW
Endocervical samples, ­cultures have lower ­detection rates

In this study, endocervical samples collected by the clinician rather than self-collected vulvovaginal samples would have missed 9% (one in 11) of chlamydial infections in women with symptoms of an STI. Vulvovaginal swabs and endocervical swabs have equal sensitivity for the diagnosis of gonorrhea when NAAT is used, but culture would have missed one in five gonorrhea infections (in women with and without symptoms).

CAVEATS
NAAT is costly and does not test for drug sensitivity

Although NAAT has replaced cell culture methodology as the gold standard for gonorrhea and chlamydia diagnosis, it is potentially costly if not readily available in your practice setting. What’s more, NAAT does not allow testing for antibiotic sensitivity, which is particularly relevant with increasing resistance of gonorrhea to multiple antibiotics. In addition, it’s unclear whether these results would apply to all NAAT assays or just the one used in this study.

These studies examine sensitivity and specificity of gonorrhea and chlamydia testing in a high-risk population: women who were seeking care in a sexual health center. Your patient population may be at lower risk, which will lower the prevalence of STIs and lower the positive predictive value of NAAT. A positive NAAT test for an STI should be followed by a confirmation NAAT in low-risk populations.

CHALLENGES TO IMPLEMENTATION
Reconsidering the way we practice

Most family practice providers are accustomed to performing a full examination on patients with a suspected STI, and changing the flow of the office visit may be difficult. And to implement this practice changer properly, it would be necessary to provide patient instruction in self-collection technique.

Also, making this change could be costly if you do not have this particular NAAT available. Once implemented, however, self-collection with NAAT will likely save time and be more comfortable for your patients. It will also provide a higher sensitivity in detecting chlamydia infections and equal sensitivity in detecting gonorrhea, compared with clinician-collected NAAT testing.

REFERENCES

1. Schoeman SA, Stewart CM, Booth RA, et al. Assessment of best single sample for finding chlamydia in women with and without symptoms: a diagnostic test study. BMJ. 2012;345:e8013.

2. Stewart CM, Schoeman SA, Booth RA, et al. Assessment of self taken swabs versus clinician taken swab for cultures for diagnosing gonorrhea in women: single centre, diagnostic accuracy study. BMJ. 2012;345: e8107.

3. CDC. Fact sheet: STD trends in the United States—2011 national data for chlamydia, gonorrhea, and syphilis (2012). www.cdc.gov/std/stats11/trends-2011.pdf. Accessed November 15, 2013.

4. CDC. Fact sheet: Incidence, prevalence, and cost of sexually transmitted infections in the United States (2013). www.cdc.gov/std/stats/STI-Estimates-Fact-Sheet-Feb-2013.pdf. Accessed November 15, 2013.

5. United States Preventive Services Task Force.  USPSTF Recommendations for STI screening (2008). www.uspreventiveservicestaskforce.org/uspstf08/methods/stinfections.htm. Accessed November 15, 2013.

6. CDC. 2010 STD treatment guidelines. www.cdc.gov/std/treatment/2010/default.htm. Accessed November 15, 2013.

7. Cook RL, Hutchison SL, Østergaard L, et al. Systematic review: non-invasive testing for Chlamydia trachomatis and Neisseria gonorrhoeae. Ann Intern Med. 2005;142:914-925.

8. Moss S, Mallinson H. The contribution of APTIMA Combo 2 assay to the diagnosis of gonorrhoea in genitourinary medicine setting. Int J STD AIDS. 2007;18:551-554.

9. Chernesky MA, Hook EW 3rd, Martin DH, et al. Women find it easy and prefer to collect their own vaginal swabs to diagnose ­Chlamydia trachomatis or Neisseria gonorrhaea infections. Sex Transm Dis. 2005;32: 729-733.

ACKNOWLEDGEMENT

The PURLs Surveillance System is supported in part by Grant Number UL 1RR 024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Copyright © 2013. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2013;62(11):651-653.

PRACTICE CHANGER

Ask women who are at risk for sexually transmitted infections (STIs) to self-swab for chlamydia and gonorrhea testing; self-collection of vulvovaginal swabs with nucleic acid amplification testing (NAAT) has excellent sensitivity in women with and without symptoms.^1,2

STRENGTH OF RECOMMENDATION

B: Based on a prospective diagnostic cohort study.^1,2

ILLUSTRATIVE CASE

An 18-year-old patient requests testing for STIs. She has no symptoms. What is the best way to collect samples for chlamydia and gonorrhea testing?

Despite public health efforts, chlamydia and gonorrhea remain significant health problems, with more than 1.4 million cases of chlamydia and 321,849 cases of gonorrhea reported in the United States in 2011.³ Both can have devastating effects on reproduction, even in women who are ­asymptomatic.

Annual testing recommended for at-risk women

According to the CDC, most reported cases of chlamydia (70%) and gonorrhea (62%) occur in men and women between the ages of 15 and 24.³ Both the CDC and the US Preventive Services Task Force recommend annual chlamydia screening for all sexually active women younger than 25 and for older women who have certain risk factors (eg, having multiple sex partners or living in communities with a high burden of disease).^4,5 Annual gonorrhea screening is also recommended for sexually active women with risk factors.^4,5

How best to test? A number of unknowns

NAAT is the most sensitive test for detection of chlamydia and gonorrhea, but other questions about how best to screen for STIs remain.^1,6 It has not been clear whether self-collected vulvovaginal swabs are equivalent to clinician-collected urethral or endocervical swabs for the detection of gonorrhea, or whether NAAT testing of the self-collected swabs or culture of the clinician-collected swabs is a more sensitive test for gonorrhea.

While some studies have found self-collected vulvovaginal samples to be as sensitive as clinician-collected endocervical samples for the diagnosis of chlamydia and gonorrhea, samples are still often collected by clinicians.^7,8 Collecting endocervical swabs is uncomfortable for patients and time consuming for clinicians, and evidence suggests that patients prefer noninvasive sampling.⁹

STUDY SUMMARY
Self-collected samples are highly sensitive

This study was designed to compare the sensitivity and specificity of self-collected vulvovaginal swabs with that of clinician-collected swabs for chlamydia and gonorrhea, both in asymptomatic women and women with symptoms of an STI. Test methods were also assessed for gonorrhea, comparing detection rates of self-swabs tested with NAAT and the culture of clinician-collected urethral and endocervical samples.

The researchers evaluated a total of 3,973 women, ages 16 to 59, who sought care at a single sexual health center in the United Kingdom. The average age was 25; 37% of the participants reported a prior STI, and 42% had at least one symptom suggestive of an STI. Women were excluded from the study if they had taken an antibiotic in the preceding 28 days or were unable/unwilling to take a vulvovaginal swab or undergo clinician examination and sample collection.

The women performed vulvovaginal swabs for NAAT prior to a speculum exam; endocervical swab for both NAAT and culture and a urethral swab for culture were collected by the clinician. All the swabs sent for NAAT were tested for chlamydia and gonorrhea, and cultures were performed to detect gonorrhea.

Chlamydia: Vulvovaginal swabs have higher detection rates

Of the 3,867 participants with complete results, 10.2% were infected with chlamydia. Self-collected vulvovaginal swabs were significantly more sensitive than endocervical swabs (97% vs 88%) and had equal specificity (99.9% vs 100%). In women with symptoms of an STI, the sensitivity was 97% vs 88%; in those with no symptoms, the sensitivity was 97% vs 89%.

Gonorrhea: Self-collection, NAAT yield better results

Gonorrhea was found in 2.5% of the 3,859 women with complete results for testing of this STI. Self-collected swabs and clinician-collected swabs analyzed by NAAT both had excellent sensitivity (99% and 96%, respectively). But self-collected samples that underwent NAAT were significantly more sensitive than clinician-collected urethral and endocervical samples that were cultured (99% vs 81%). The number needed to test by self-collection for NAAT (compared with clinician-collected culture) to detect one additional case of gonorrhea was 5.

In women with symptoms suggestive of infection, the NAAT assays—both clinician- and self-collected—were equivalent and were more sensitive than gonorrhea culture. In asymptomatic women, 1.8% of whom had gonorrhea, the vulvovaginal swab sent for NAAT was more sensitive than culture (98% vs 78%) and was equivalent to the endocervical swab for NAAT (90%).

The bottom line: Self-collected vulvovaginal swabs are the sample of choice for both chlamydia and gonorrhea testing in women, regardless of whether they have symptoms. When a clinical examination is needed, either the clinician or the patient can collect a vulvovaginal swab.

WHAT’S NEW
Endocervical samples, ­cultures have lower ­detection rates

In this study, endocervical samples collected by the clinician rather than self-collected vulvovaginal samples would have missed 9% (one in 11) of chlamydial infections in women with symptoms of an STI. Vulvovaginal swabs and endocervical swabs have equal sensitivity for the diagnosis of gonorrhea when NAAT is used, but culture would have missed one in five gonorrhea infections (in women with and without symptoms).

CAVEATS
NAAT is costly and does not test for drug sensitivity

Although NAAT has replaced cell culture methodology as the gold standard for gonorrhea and chlamydia diagnosis, it is potentially costly if not readily available in your practice setting. What’s more, NAAT does not allow testing for antibiotic sensitivity, which is particularly relevant with increasing resistance of gonorrhea to multiple antibiotics. In addition, it’s unclear whether these results would apply to all NAAT assays or just the one used in this study.

These studies examine sensitivity and specificity of gonorrhea and chlamydia testing in a high-risk population: women who were seeking care in a sexual health center. Your patient population may be at lower risk, which will lower the prevalence of STIs and lower the positive predictive value of NAAT. A positive NAAT test for an STI should be followed by a confirmation NAAT in low-risk populations.

CHALLENGES TO IMPLEMENTATION
Reconsidering the way we practice

Most family practice providers are accustomed to performing a full examination on patients with a suspected STI, and changing the flow of the office visit may be difficult. And to implement this practice changer properly, it would be necessary to provide patient instruction in self-collection technique.

Also, making this change could be costly if you do not have this particular NAAT available. Once implemented, however, self-collection with NAAT will likely save time and be more comfortable for your patients. It will also provide a higher sensitivity in detecting chlamydia infections and equal sensitivity in detecting gonorrhea, compared with clinician-collected NAAT testing.

REFERENCES

1. Schoeman SA, Stewart CM, Booth RA, et al. Assessment of best single sample for finding chlamydia in women with and without symptoms: a diagnostic test study. BMJ. 2012;345:e8013.

2. Stewart CM, Schoeman SA, Booth RA, et al. Assessment of self taken swabs versus clinician taken swab for cultures for diagnosing gonorrhea in women: single centre, diagnostic accuracy study. BMJ. 2012;345: e8107.

3. CDC. Fact sheet: STD trends in the United States—2011 national data for chlamydia, gonorrhea, and syphilis (2012). www.cdc.gov/std/stats11/trends-2011.pdf. Accessed November 15, 2013.

4. CDC. Fact sheet: Incidence, prevalence, and cost of sexually transmitted infections in the United States (2013). www.cdc.gov/std/stats/STI-Estimates-Fact-Sheet-Feb-2013.pdf. Accessed November 15, 2013.

5. United States Preventive Services Task Force.  USPSTF Recommendations for STI screening (2008). www.uspreventiveservicestaskforce.org/uspstf08/methods/stinfections.htm. Accessed November 15, 2013.

6. CDC. 2010 STD treatment guidelines. www.cdc.gov/std/treatment/2010/default.htm. Accessed November 15, 2013.

7. Cook RL, Hutchison SL, Østergaard L, et al. Systematic review: non-invasive testing for Chlamydia trachomatis and Neisseria gonorrhoeae. Ann Intern Med. 2005;142:914-925.

8. Moss S, Mallinson H. The contribution of APTIMA Combo 2 assay to the diagnosis of gonorrhoea in genitourinary medicine setting. Int J STD AIDS. 2007;18:551-554.

9. Chernesky MA, Hook EW 3rd, Martin DH, et al. Women find it easy and prefer to collect their own vaginal swabs to diagnose ­Chlamydia trachomatis or Neisseria gonorrhaea infections. Sex Transm Dis. 2005;32: 729-733.

ACKNOWLEDGEMENT

The PURLs Surveillance System is supported in part by Grant Number UL 1RR 024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Copyright © 2013. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2013;62(11):651-653.

PRACTICE CHANGER

Ask women who are at risk for sexually transmitted infections (STIs) to self-swab for chlamydia and gonorrhea testing; self-collection of vulvovaginal swabs with nucleic acid amplification testing (NAAT) has excellent sensitivity in women with and without symptoms.^1,2

STRENGTH OF RECOMMENDATION

B: Based on a prospective diagnostic cohort study.^1,2

ILLUSTRATIVE CASE

An 18-year-old patient requests testing for STIs. She has no symptoms. What is the best way to collect samples for chlamydia and gonorrhea testing?

Despite public health efforts, chlamydia and gonorrhea remain significant health problems, with more than 1.4 million cases of chlamydia and 321,849 cases of gonorrhea reported in the United States in 2011.³ Both can have devastating effects on reproduction, even in women who are ­asymptomatic.

Annual testing recommended for at-risk women

According to the CDC, most reported cases of chlamydia (70%) and gonorrhea (62%) occur in men and women between the ages of 15 and 24.³ Both the CDC and the US Preventive Services Task Force recommend annual chlamydia screening for all sexually active women younger than 25 and for older women who have certain risk factors (eg, having multiple sex partners or living in communities with a high burden of disease).^4,5 Annual gonorrhea screening is also recommended for sexually active women with risk factors.^4,5

How best to test? A number of unknowns

NAAT is the most sensitive test for detection of chlamydia and gonorrhea, but other questions about how best to screen for STIs remain.^1,6 It has not been clear whether self-collected vulvovaginal swabs are equivalent to clinician-collected urethral or endocervical swabs for the detection of gonorrhea, or whether NAAT testing of the self-collected swabs or culture of the clinician-collected swabs is a more sensitive test for gonorrhea.

While some studies have found self-collected vulvovaginal samples to be as sensitive as clinician-collected endocervical samples for the diagnosis of chlamydia and gonorrhea, samples are still often collected by clinicians.^7,8 Collecting endocervical swabs is uncomfortable for patients and time consuming for clinicians, and evidence suggests that patients prefer noninvasive sampling.⁹

STUDY SUMMARY
Self-collected samples are highly sensitive

This study was designed to compare the sensitivity and specificity of self-collected vulvovaginal swabs with that of clinician-collected swabs for chlamydia and gonorrhea, both in asymptomatic women and women with symptoms of an STI. Test methods were also assessed for gonorrhea, comparing detection rates of self-swabs tested with NAAT and the culture of clinician-collected urethral and endocervical samples.

The researchers evaluated a total of 3,973 women, ages 16 to 59, who sought care at a single sexual health center in the United Kingdom. The average age was 25; 37% of the participants reported a prior STI, and 42% had at least one symptom suggestive of an STI. Women were excluded from the study if they had taken an antibiotic in the preceding 28 days or were unable/unwilling to take a vulvovaginal swab or undergo clinician examination and sample collection.

The women performed vulvovaginal swabs for NAAT prior to a speculum exam; endocervical swab for both NAAT and culture and a urethral swab for culture were collected by the clinician. All the swabs sent for NAAT were tested for chlamydia and gonorrhea, and cultures were performed to detect gonorrhea.

Chlamydia: Vulvovaginal swabs have higher detection rates

Of the 3,867 participants with complete results, 10.2% were infected with chlamydia. Self-collected vulvovaginal swabs were significantly more sensitive than endocervical swabs (97% vs 88%) and had equal specificity (99.9% vs 100%). In women with symptoms of an STI, the sensitivity was 97% vs 88%; in those with no symptoms, the sensitivity was 97% vs 89%.

Gonorrhea: Self-collection, NAAT yield better results

Gonorrhea was found in 2.5% of the 3,859 women with complete results for testing of this STI. Self-collected swabs and clinician-collected swabs analyzed by NAAT both had excellent sensitivity (99% and 96%, respectively). But self-collected samples that underwent NAAT were significantly more sensitive than clinician-collected urethral and endocervical samples that were cultured (99% vs 81%). The number needed to test by self-collection for NAAT (compared with clinician-collected culture) to detect one additional case of gonorrhea was 5.

In women with symptoms suggestive of infection, the NAAT assays—both clinician- and self-collected—were equivalent and were more sensitive than gonorrhea culture. In asymptomatic women, 1.8% of whom had gonorrhea, the vulvovaginal swab sent for NAAT was more sensitive than culture (98% vs 78%) and was equivalent to the endocervical swab for NAAT (90%).

The bottom line: Self-collected vulvovaginal swabs are the sample of choice for both chlamydia and gonorrhea testing in women, regardless of whether they have symptoms. When a clinical examination is needed, either the clinician or the patient can collect a vulvovaginal swab.

WHAT’S NEW
Endocervical samples, ­cultures have lower ­detection rates

In this study, endocervical samples collected by the clinician rather than self-collected vulvovaginal samples would have missed 9% (one in 11) of chlamydial infections in women with symptoms of an STI. Vulvovaginal swabs and endocervical swabs have equal sensitivity for the diagnosis of gonorrhea when NAAT is used, but culture would have missed one in five gonorrhea infections (in women with and without symptoms).

CAVEATS
NAAT is costly and does not test for drug sensitivity

Although NAAT has replaced cell culture methodology as the gold standard for gonorrhea and chlamydia diagnosis, it is potentially costly if not readily available in your practice setting. What’s more, NAAT does not allow testing for antibiotic sensitivity, which is particularly relevant with increasing resistance of gonorrhea to multiple antibiotics. In addition, it’s unclear whether these results would apply to all NAAT assays or just the one used in this study.

These studies examine sensitivity and specificity of gonorrhea and chlamydia testing in a high-risk population: women who were seeking care in a sexual health center. Your patient population may be at lower risk, which will lower the prevalence of STIs and lower the positive predictive value of NAAT. A positive NAAT test for an STI should be followed by a confirmation NAAT in low-risk populations.

CHALLENGES TO IMPLEMENTATION
Reconsidering the way we practice

Most family practice providers are accustomed to performing a full examination on patients with a suspected STI, and changing the flow of the office visit may be difficult. And to implement this practice changer properly, it would be necessary to provide patient instruction in self-collection technique.

Also, making this change could be costly if you do not have this particular NAAT available. Once implemented, however, self-collection with NAAT will likely save time and be more comfortable for your patients. It will also provide a higher sensitivity in detecting chlamydia infections and equal sensitivity in detecting gonorrhea, compared with clinician-collected NAAT testing.

REFERENCES

1. Schoeman SA, Stewart CM, Booth RA, et al. Assessment of best single sample for finding chlamydia in women with and without symptoms: a diagnostic test study. BMJ. 2012;345:e8013.

2. Stewart CM, Schoeman SA, Booth RA, et al. Assessment of self taken swabs versus clinician taken swab for cultures for diagnosing gonorrhea in women: single centre, diagnostic accuracy study. BMJ. 2012;345: e8107.

3. CDC. Fact sheet: STD trends in the United States—2011 national data for chlamydia, gonorrhea, and syphilis (2012). www.cdc.gov/std/stats11/trends-2011.pdf. Accessed November 15, 2013.

4. CDC. Fact sheet: Incidence, prevalence, and cost of sexually transmitted infections in the United States (2013). www.cdc.gov/std/stats/STI-Estimates-Fact-Sheet-Feb-2013.pdf. Accessed November 15, 2013.

5. United States Preventive Services Task Force.  USPSTF Recommendations for STI screening (2008). www.uspreventiveservicestaskforce.org/uspstf08/methods/stinfections.htm. Accessed November 15, 2013.

6. CDC. 2010 STD treatment guidelines. www.cdc.gov/std/treatment/2010/default.htm. Accessed November 15, 2013.

7. Cook RL, Hutchison SL, Østergaard L, et al. Systematic review: non-invasive testing for Chlamydia trachomatis and Neisseria gonorrhoeae. Ann Intern Med. 2005;142:914-925.

8. Moss S, Mallinson H. The contribution of APTIMA Combo 2 assay to the diagnosis of gonorrhoea in genitourinary medicine setting. Int J STD AIDS. 2007;18:551-554.

9. Chernesky MA, Hook EW 3rd, Martin DH, et al. Women find it easy and prefer to collect their own vaginal swabs to diagnose ­Chlamydia trachomatis or Neisseria gonorrhaea infections. Sex Transm Dis. 2005;32: 729-733.

ACKNOWLEDGEMENT

The PURLs Surveillance System is supported in part by Grant Number UL 1RR 024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Copyright © 2013. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2013;62(11):651-653.

Illustrative case

An 18-year-old woman comes to your office requesting testing for STIs. She has no symptoms. What is the best way to collect samples for chlamydia and gonorrhea testing?

Despite public health efforts, chlamydia and gonorrhea remain significant health problems, with more than 1.4 million cases of chlamydia and 321,849 cases of gonorrhea reported in the United States in 2011.³ Both can have devastating effects on reproduction, even in women who are asymptomatic.

Annual testing is recommended for women at risk
According to the Centers for Disease Control and Prevention (CDC), most reported cases of chlamydia (70%) and gonorrhea (62%) occur in men and women between the ages of 15 and 24 years.³ Both the CDC and the US Preventive Services Task Force recommend annual chlamydia screening for all sexually active women younger than 25, and for older women with risk factors, including having multiple sex partners and living in communities with a high burden of disease.^4,5 Annual gonorrhea screening is recommended for sexually active women with risk factors, as well.^4,5

How best to test? A number of unknowns
NAAT is the most sensitive test for detection of chlamydia and gonorrhea, but other questions about how best to screen for STIs remain.^1,6 It has not been clear whether self-collected vulvovaginal swabs are equivalent to clinician-collected urethral or endocervical swabs for the detection of gonorrhea, or whether NAAT testing of the self-collected swabs or culture of the clinician-collected swabs is a more sensitive test for gonorrhea.

While some studies have found self-collected vulvovaginal samples to be as sensitive as clinician-collected endocervical samples for the diagnosis of chlamydia and gonorrhea, samples are still often collected by clinicians.^7,8 Collecting endocervical swabs is uncomfortable for patients and time consuming for clinicians, and evidence suggests that patients prefer noninvasive sampling.⁹

STUDY SUMMARY: Self-collected samples are highly sensitive

This study was designed to compare the sensitivity and specificity of self-collected vulvovaginal swabs vs clinician-collected swabs for chlamydia and gonorrhea, both in asymptomatic women and women with symptoms of an STI. Test methods were also assessed for gonorrhea, comparing detection rates of self-swabs tested with NAAT vs the culture of clinician-collected urethral and endocervical samples.

The researchers evaluated a total of 3973 women, ages 16 to 59 years, who sought care at a single sexual health center in the United Kingdom. The average age was 25 years; 37% of the participants reported a prior STI, and 42% had at least one symptom suggestive of an STI. Exclusion criteria included having taken an antibiotic in the preceding 28 days and being unable or unwilling to take a vulvovaginal swab or undergo clinician examination and sample collection.

Self-collected vulvovaginal swabs are the sample of choice for both chlamydia and gonorrhea testing in women, regardless of whether patients have symptoms.The women performed vulvovaginal swabs for NAAT (Aptima Combo-2, Hologic GenProbe, San Diego, Calif) prior to a speculum exam; endocervical swab for both NAAT and culture and a urethral swab for culture were collected by the clinician. All the swabs sent for NAAT were tested for chlamydia and gonorrhea, and cultures were performed to detect gonorrhea.

Chlamydia: Vulvovaginal swabs have higher detection rates

Of the 3867 participants with complete results, 10.2% were infected with chlamydia. Self-collected vulvovaginal swabs were significantly more sensitive than endocervical swabs (97% vs 88%; P<.00001) and had equal specificity (99.9% vs 100%). In women with symptoms of an STI, the sensitivity was 97% vs 88% (P<.0008); in those with no symptoms, the sensitivity was 97% vs 89% (P<.002).

Gonorrhea: Self-collection, NAAT yield better results

Gonorrhea was found in 2.5% of the 3859 women with complete results for testing of this STI. Self-collected swabs and physician-collected swabs analyzed by NAAT both had excellent sensitivity (99% vs 96%; P=.375). But self-collected samples that underwent NAAT were significantly more sensitive than clinician-collected urethral and endocervical samples that were cultured (99% vs 81%; P<.001). The number needed to test by self-collection for NAAT (compared with clinician-collected culture) to detect one additional case of gonorrhea was 5.

In women with symptoms suggestive of infection, the NAAT assays—both physician- and self-collected—were equivalent and were more sensitive than gonorrhea culture (P=.004). In asymptomatic women, 1.8% of whom had gonorrhea, the vulvovaginal swab sent for NAAT was more sensitive than culture (98% vs 78%; P=0.008) and equivalent to the endocervical swab for NAAT (90%).

The bottom line: Self-collected vulvovaginal swabs are the sample of choice for both chlamydia and gonorrhea testing in women, regardless of whether they have symptoms. When a clinical examination is needed, either the clinician or the patient can collect a vulvovaginal swab.

WHAT'S NEW: Endocervical samples, cultures have lower detection rates

In this study, endocervical samples collected by the physician rather than self-collected vulvovaginal samples would have missed 9% (one in 11) of chlamydial infections in women with symptoms of an STI. Vulvovaginal swabs and endocervical swabs have equal sensitivity for the diagnosis of gonorrhea when NAAT is used, but culture would have missed one in 5 gonorrhea infections (in women with and without symptoms).

CAVEATS: NAAT is costly, and does not test for drug sensitivity

Although NAAT has replaced cell culture methodology as the gold standard for gonorrhea and chlamydia diagnosis, it is potentially costly if not readily available in your practice setting. What’s more, NAAT does not allow testing for antibiotic sensitivity, which is particularly relevant with increasing resistance of gonorrhea to multiple antibiotics. In addition, it’s unclear whether these results would apply to all NAAT assays or just the one used in this study.

These studies examine sensitivity and specificity of gonorrhea and chlamydia testing in a high-risk population—women who were seeking care in a sexual health center. Your patient population may be lower risk, which will lower the prevalence of STIs and lower the positive predictive value of NAAT. A positive NAAT test for an STI should be followed by a confirmation NAAT in low-risk populations.

CHALLENGES TO IMPLEMENTATION: Reconsidering the way we practice

Most family physicians are accustomed to performing a full examination on patients with a suspected STI, and changing the flow of the office visit may be difficult. And, to implement this practice changer properly, it would be necessary to provide patient instruction in self-collection technique.

Also, making this change could be costly if you do not have this particular NAAT available. Once implemented, however, self-collection with NAAT will likely save time and be more comfortable for your patients. It will also provide a higher sensitivity in detecting chlamydia infections and equal sensitivity in detecting gonorrhea compared with physician-collected NAAT testing.

ACKNOWLEDGEMENT
The PURLs surveillance system was supported in part by Grant Number UL1RR024999 from the National center for Research Resources, a clinical Translational science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National center for Research Resources or the National Institutes of Health.

Click here to view PURL METHODOLOGY 1

Click here to view PURL METHODOLOGY 2

Illustrative case

An 18-year-old woman comes to your office requesting testing for STIs. She has no symptoms. What is the best way to collect samples for chlamydia and gonorrhea testing?

Despite public health efforts, chlamydia and gonorrhea remain significant health problems, with more than 1.4 million cases of chlamydia and 321,849 cases of gonorrhea reported in the United States in 2011.³ Both can have devastating effects on reproduction, even in women who are asymptomatic.

Annual testing is recommended for women at risk
According to the Centers for Disease Control and Prevention (CDC), most reported cases of chlamydia (70%) and gonorrhea (62%) occur in men and women between the ages of 15 and 24 years.³ Both the CDC and the US Preventive Services Task Force recommend annual chlamydia screening for all sexually active women younger than 25, and for older women with risk factors, including having multiple sex partners and living in communities with a high burden of disease.^4,5 Annual gonorrhea screening is recommended for sexually active women with risk factors, as well.^4,5

How best to test? A number of unknowns
NAAT is the most sensitive test for detection of chlamydia and gonorrhea, but other questions about how best to screen for STIs remain.^1,6 It has not been clear whether self-collected vulvovaginal swabs are equivalent to clinician-collected urethral or endocervical swabs for the detection of gonorrhea, or whether NAAT testing of the self-collected swabs or culture of the clinician-collected swabs is a more sensitive test for gonorrhea.

While some studies have found self-collected vulvovaginal samples to be as sensitive as clinician-collected endocervical samples for the diagnosis of chlamydia and gonorrhea, samples are still often collected by clinicians.^7,8 Collecting endocervical swabs is uncomfortable for patients and time consuming for clinicians, and evidence suggests that patients prefer noninvasive sampling.⁹

STUDY SUMMARY: Self-collected samples are highly sensitive

This study was designed to compare the sensitivity and specificity of self-collected vulvovaginal swabs vs clinician-collected swabs for chlamydia and gonorrhea, both in asymptomatic women and women with symptoms of an STI. Test methods were also assessed for gonorrhea, comparing detection rates of self-swabs tested with NAAT vs the culture of clinician-collected urethral and endocervical samples.

The researchers evaluated a total of 3973 women, ages 16 to 59 years, who sought care at a single sexual health center in the United Kingdom. The average age was 25 years; 37% of the participants reported a prior STI, and 42% had at least one symptom suggestive of an STI. Exclusion criteria included having taken an antibiotic in the preceding 28 days and being unable or unwilling to take a vulvovaginal swab or undergo clinician examination and sample collection.

Self-collected vulvovaginal swabs are the sample of choice for both chlamydia and gonorrhea testing in women, regardless of whether patients have symptoms.The women performed vulvovaginal swabs for NAAT (Aptima Combo-2, Hologic GenProbe, San Diego, Calif) prior to a speculum exam; endocervical swab for both NAAT and culture and a urethral swab for culture were collected by the clinician. All the swabs sent for NAAT were tested for chlamydia and gonorrhea, and cultures were performed to detect gonorrhea.

Chlamydia: Vulvovaginal swabs have higher detection rates

Of the 3867 participants with complete results, 10.2% were infected with chlamydia. Self-collected vulvovaginal swabs were significantly more sensitive than endocervical swabs (97% vs 88%; P<.00001) and had equal specificity (99.9% vs 100%). In women with symptoms of an STI, the sensitivity was 97% vs 88% (P<.0008); in those with no symptoms, the sensitivity was 97% vs 89% (P<.002).

Gonorrhea: Self-collection, NAAT yield better results

Gonorrhea was found in 2.5% of the 3859 women with complete results for testing of this STI. Self-collected swabs and physician-collected swabs analyzed by NAAT both had excellent sensitivity (99% vs 96%; P=.375). But self-collected samples that underwent NAAT were significantly more sensitive than clinician-collected urethral and endocervical samples that were cultured (99% vs 81%; P<.001). The number needed to test by self-collection for NAAT (compared with clinician-collected culture) to detect one additional case of gonorrhea was 5.

In women with symptoms suggestive of infection, the NAAT assays—both physician- and self-collected—were equivalent and were more sensitive than gonorrhea culture (P=.004). In asymptomatic women, 1.8% of whom had gonorrhea, the vulvovaginal swab sent for NAAT was more sensitive than culture (98% vs 78%; P=0.008) and equivalent to the endocervical swab for NAAT (90%).

The bottom line: Self-collected vulvovaginal swabs are the sample of choice for both chlamydia and gonorrhea testing in women, regardless of whether they have symptoms. When a clinical examination is needed, either the clinician or the patient can collect a vulvovaginal swab.

WHAT'S NEW: Endocervical samples, cultures have lower detection rates

In this study, endocervical samples collected by the physician rather than self-collected vulvovaginal samples would have missed 9% (one in 11) of chlamydial infections in women with symptoms of an STI. Vulvovaginal swabs and endocervical swabs have equal sensitivity for the diagnosis of gonorrhea when NAAT is used, but culture would have missed one in 5 gonorrhea infections (in women with and without symptoms).

CAVEATS: NAAT is costly, and does not test for drug sensitivity

Although NAAT has replaced cell culture methodology as the gold standard for gonorrhea and chlamydia diagnosis, it is potentially costly if not readily available in your practice setting. What’s more, NAAT does not allow testing for antibiotic sensitivity, which is particularly relevant with increasing resistance of gonorrhea to multiple antibiotics. In addition, it’s unclear whether these results would apply to all NAAT assays or just the one used in this study.

These studies examine sensitivity and specificity of gonorrhea and chlamydia testing in a high-risk population—women who were seeking care in a sexual health center. Your patient population may be lower risk, which will lower the prevalence of STIs and lower the positive predictive value of NAAT. A positive NAAT test for an STI should be followed by a confirmation NAAT in low-risk populations.

CHALLENGES TO IMPLEMENTATION: Reconsidering the way we practice

Most family physicians are accustomed to performing a full examination on patients with a suspected STI, and changing the flow of the office visit may be difficult. And, to implement this practice changer properly, it would be necessary to provide patient instruction in self-collection technique.

Also, making this change could be costly if you do not have this particular NAAT available. Once implemented, however, self-collection with NAAT will likely save time and be more comfortable for your patients. It will also provide a higher sensitivity in detecting chlamydia infections and equal sensitivity in detecting gonorrhea compared with physician-collected NAAT testing.

ACKNOWLEDGEMENT
The PURLs surveillance system was supported in part by Grant Number UL1RR024999 from the National center for Research Resources, a clinical Translational science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National center for Research Resources or the National Institutes of Health.

Click here to view PURL METHODOLOGY 1

Click here to view PURL METHODOLOGY 2

Illustrative case

An 18-year-old woman comes to your office requesting testing for STIs. She has no symptoms. What is the best way to collect samples for chlamydia and gonorrhea testing?

Despite public health efforts, chlamydia and gonorrhea remain significant health problems, with more than 1.4 million cases of chlamydia and 321,849 cases of gonorrhea reported in the United States in 2011.³ Both can have devastating effects on reproduction, even in women who are asymptomatic.

Annual testing is recommended for women at risk
According to the Centers for Disease Control and Prevention (CDC), most reported cases of chlamydia (70%) and gonorrhea (62%) occur in men and women between the ages of 15 and 24 years.³ Both the CDC and the US Preventive Services Task Force recommend annual chlamydia screening for all sexually active women younger than 25, and for older women with risk factors, including having multiple sex partners and living in communities with a high burden of disease.^4,5 Annual gonorrhea screening is recommended for sexually active women with risk factors, as well.^4,5

How best to test? A number of unknowns
NAAT is the most sensitive test for detection of chlamydia and gonorrhea, but other questions about how best to screen for STIs remain.^1,6 It has not been clear whether self-collected vulvovaginal swabs are equivalent to clinician-collected urethral or endocervical swabs for the detection of gonorrhea, or whether NAAT testing of the self-collected swabs or culture of the clinician-collected swabs is a more sensitive test for gonorrhea.

While some studies have found self-collected vulvovaginal samples to be as sensitive as clinician-collected endocervical samples for the diagnosis of chlamydia and gonorrhea, samples are still often collected by clinicians.^7,8 Collecting endocervical swabs is uncomfortable for patients and time consuming for clinicians, and evidence suggests that patients prefer noninvasive sampling.⁹

STUDY SUMMARY: Self-collected samples are highly sensitive

This study was designed to compare the sensitivity and specificity of self-collected vulvovaginal swabs vs clinician-collected swabs for chlamydia and gonorrhea, both in asymptomatic women and women with symptoms of an STI. Test methods were also assessed for gonorrhea, comparing detection rates of self-swabs tested with NAAT vs the culture of clinician-collected urethral and endocervical samples.

The researchers evaluated a total of 3973 women, ages 16 to 59 years, who sought care at a single sexual health center in the United Kingdom. The average age was 25 years; 37% of the participants reported a prior STI, and 42% had at least one symptom suggestive of an STI. Exclusion criteria included having taken an antibiotic in the preceding 28 days and being unable or unwilling to take a vulvovaginal swab or undergo clinician examination and sample collection.

Self-collected vulvovaginal swabs are the sample of choice for both chlamydia and gonorrhea testing in women, regardless of whether patients have symptoms.The women performed vulvovaginal swabs for NAAT (Aptima Combo-2, Hologic GenProbe, San Diego, Calif) prior to a speculum exam; endocervical swab for both NAAT and culture and a urethral swab for culture were collected by the clinician. All the swabs sent for NAAT were tested for chlamydia and gonorrhea, and cultures were performed to detect gonorrhea.

Chlamydia: Vulvovaginal swabs have higher detection rates

Of the 3867 participants with complete results, 10.2% were infected with chlamydia. Self-collected vulvovaginal swabs were significantly more sensitive than endocervical swabs (97% vs 88%; P<.00001) and had equal specificity (99.9% vs 100%). In women with symptoms of an STI, the sensitivity was 97% vs 88% (P<.0008); in those with no symptoms, the sensitivity was 97% vs 89% (P<.002).

Gonorrhea: Self-collection, NAAT yield better results

Gonorrhea was found in 2.5% of the 3859 women with complete results for testing of this STI. Self-collected swabs and physician-collected swabs analyzed by NAAT both had excellent sensitivity (99% vs 96%; P=.375). But self-collected samples that underwent NAAT were significantly more sensitive than clinician-collected urethral and endocervical samples that were cultured (99% vs 81%; P<.001). The number needed to test by self-collection for NAAT (compared with clinician-collected culture) to detect one additional case of gonorrhea was 5.

In women with symptoms suggestive of infection, the NAAT assays—both physician- and self-collected—were equivalent and were more sensitive than gonorrhea culture (P=.004). In asymptomatic women, 1.8% of whom had gonorrhea, the vulvovaginal swab sent for NAAT was more sensitive than culture (98% vs 78%; P=0.008) and equivalent to the endocervical swab for NAAT (90%).

The bottom line: Self-collected vulvovaginal swabs are the sample of choice for both chlamydia and gonorrhea testing in women, regardless of whether they have symptoms. When a clinical examination is needed, either the clinician or the patient can collect a vulvovaginal swab.

WHAT'S NEW: Endocervical samples, cultures have lower detection rates

In this study, endocervical samples collected by the physician rather than self-collected vulvovaginal samples would have missed 9% (one in 11) of chlamydial infections in women with symptoms of an STI. Vulvovaginal swabs and endocervical swabs have equal sensitivity for the diagnosis of gonorrhea when NAAT is used, but culture would have missed one in 5 gonorrhea infections (in women with and without symptoms).

CAVEATS: NAAT is costly, and does not test for drug sensitivity

Although NAAT has replaced cell culture methodology as the gold standard for gonorrhea and chlamydia diagnosis, it is potentially costly if not readily available in your practice setting. What’s more, NAAT does not allow testing for antibiotic sensitivity, which is particularly relevant with increasing resistance of gonorrhea to multiple antibiotics. In addition, it’s unclear whether these results would apply to all NAAT assays or just the one used in this study.

These studies examine sensitivity and specificity of gonorrhea and chlamydia testing in a high-risk population—women who were seeking care in a sexual health center. Your patient population may be lower risk, which will lower the prevalence of STIs and lower the positive predictive value of NAAT. A positive NAAT test for an STI should be followed by a confirmation NAAT in low-risk populations.

CHALLENGES TO IMPLEMENTATION: Reconsidering the way we practice

Most family physicians are accustomed to performing a full examination on patients with a suspected STI, and changing the flow of the office visit may be difficult. And, to implement this practice changer properly, it would be necessary to provide patient instruction in self-collection technique.

Also, making this change could be costly if you do not have this particular NAAT available. Once implemented, however, self-collection with NAAT will likely save time and be more comfortable for your patients. It will also provide a higher sensitivity in detecting chlamydia infections and equal sensitivity in detecting gonorrhea compared with physician-collected NAAT testing.

ACKNOWLEDGEMENT
The PURLs surveillance system was supported in part by Grant Number UL1RR024999 from the National center for Research Resources, a clinical Translational science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National center for Research Resources or the National Institutes of Health.

Click here to view PURL METHODOLOGY 1

Click here to view PURL METHODOLOGY 2

ILLUSTRATIVE CASE

On Day 4 of her hospitalization for a wound infection requiring IV antibiotics, a 45-year-old patient is told by her nurse that her IV catheter must be replaced. It’s hospital policy, the RN says, to replace the catheter every 96 hours. The patient is afraid of needles and is not eager to have her catheter replaced every few days. Is it really necessary to replace the IV, she wants to know.

Each year, nearly 200 million peripheral IV catheters are placed in patients in hospitals throughout the United States.² Many of the catheters need to be replaced due to phlebitis, infiltration, pain, or swelling at the IV site, but the rate of bloodstream infections associated with peripheral IVs is just 0.5 per 1000 catheter days.²

Timing of replacement is “unresolved”
The Centers for Disease Control and Prevention (CDC)’s 2011 guidelines state that it is not necessary to replace peripheral IV catheters in adults more than every 72 to 96 hours,³ but the CDC does not specify when the catheters should be replaced. For adult patients, the recommendation that a catheter be replaced only for clinical indications is an “unresolved issue,” according to the guidelines. For children, however, replacement only when clinically indicated is recommended by the CDC. Many hospitals have protocols that require replacement of IV catheters every 72 to 96 hours, regardless of clinical indication.

A 2008 study of 755 inpatients compared clinically indicated replacement of IV catheters with routine replacement and found no significant differences in phlebitis and infiltration rates between the 2 groups (38% vs 33%, respectively; relative risk [RR]=1.15; 95% confidence interval [CI], 0.95-1.40).⁴

A 2010 trial randomized 362 hospitalized patients to routine or clinically indicated replacement of peripheral IV lines, with median dwell times of 71 and 85 hours, respectively. There was no significant difference in rates of phlebitis between the routine replacement (7%) and clinically indicated (10%) groups (RR=1.44; 95% CI, 0.71-2.89; P=.34). No local infections or IV-related bloodstream infections occurred in either group.⁵

A 2010 Cochrane review included 5 randomized controlled trials (with a total of 3408 patients) that compared rates of suspected catheter-related phlebitis in patients whose catheters were routinely replaced with those in the clinically indicated group. The reviewers found no significant increase in phlebitis in the clinically indicated group (9%) vs the routine replacement group (7.2%) (odds ratio=1.24; 95% CI, 0.97-1.60; P=.09).⁶

Each of these studies had either a relatively small sample size or wide confidence intervals, raising the possibility of missing a real increase in infection due to inadequate statistical power. The study summarized here addressed these concerns.

STUDY SUMMARY: Forgoing routine replacement does not increase risk

Rickard et al¹ conducted a multicenter, nonblinded randomized equivalence trial to determine whether routine or clinically indicated removal reduced rates of infection. In the routine group, catheters were replaced every 72 to 96 hours. In the clinically indicated group, catheters were replaced in instances of phlebitis, infiltration, occlusion, accidental removal, or suspected infection related to the catheter.

Participants (N=3283) were inpatients on medical and surgical units who had IV catheters in place and were expected to need treatment for at least 4 days. Individuals whose IV catheters had been placed in an emergency were excluded, as were those who had a known bloodstream infection or who were not expected to have the IV in place for at least 24 hours. Follow-up data were available for all participants.

The primary outcome was phlebitis, with a prespecified equivalence margin of 3%. In both groups, phlebitis occurred in 7% of patients (RR=1.06; 95% CI, 0.83-1.36; P=.64). The absolute risk difference was 0.41% (95% CI, -1.33 to 2.15), which was within the equivalence margin.

The mean IV catheter dwell time was 70 hours in the routine replacement group and 99 hours in the clinically indicated group. Nine patients in the routine replacement group developed bloodstream infections, vs 4 patients in the clinically indicated group (hazard ratio=0.46; 95% CI, 0.14-1.48; P=.19). One patient in the routine placement group had a catheter-related bloodstream infection; no one in the clinically indicated group did. The mortality rate for each group was <1%.

WHAT’S NEW: We can order clinically indicated IV replacement with confidence

The findings of this equivalence trial support prior studies and add greater statistical power. The results suggest that we can recommend clinically indicated replacement of peripheral IV catheters without increasing the rate of phlebitis. Implementing clinically indicated replacement of IVs could decrease hospital costs and improve patient satisfaction.

CAVEATS: Findings do not apply to patients with bacteremia

Patients with known bacteremia were excluded from this study, and the results are therefore not generalizable to this population.

The nonblinded nature of this trial raises the possibility of observer and reporting bias. However, measures were taken to minimize the potential for bias. A structured outcome assessment was used to standardize reporting of signs of phlebitis. Both patients’ pain scores and nurses’ assessments of the IV sites were used to determine whether an infection was present, and the investigators and research nurses were not involved in the removal of the IV catheters.

This study did not report on the daily maintenance protocols the investigators used for the peripheral IVs. The study was conducted in hospitals in Australia, and we don’t know whether the protocols used in that country are similar to standard protocols in US hospitals.

CHALLENGES TO IMPLEMENTATION: Changing hospital protocols won’t be easy

Implementing the findings of this study will require that physicians work with the nursing staff and administrators to create and implement new protocols for assessing peripheral IV catheters in hospitals with routine IV replacement policies already in place. It would be necessary to ensure that all clinicians who place peripheral IV catheters are taught the clinical signs of phlebitis and are using a standardized protocol. That said, we think that this is a worthwhile change to achieve the long-term benefits of fewer unnecessary IV catheter replacements.

Acknowledgement

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

On Day 4 of her hospitalization for a wound infection requiring IV antibiotics, a 45-year-old patient is told by her nurse that her IV catheter must be replaced. It’s hospital policy, the RN says, to replace the catheter every 96 hours. The patient is afraid of needles and is not eager to have her catheter replaced every few days. Is it really necessary to replace the IV, she wants to know.

Each year, nearly 200 million peripheral IV catheters are placed in patients in hospitals throughout the United States.² Many of the catheters need to be replaced due to phlebitis, infiltration, pain, or swelling at the IV site, but the rate of bloodstream infections associated with peripheral IVs is just 0.5 per 1000 catheter days.²

Timing of replacement is “unresolved”
The Centers for Disease Control and Prevention (CDC)’s 2011 guidelines state that it is not necessary to replace peripheral IV catheters in adults more than every 72 to 96 hours,³ but the CDC does not specify when the catheters should be replaced. For adult patients, the recommendation that a catheter be replaced only for clinical indications is an “unresolved issue,” according to the guidelines. For children, however, replacement only when clinically indicated is recommended by the CDC. Many hospitals have protocols that require replacement of IV catheters every 72 to 96 hours, regardless of clinical indication.

A 2008 study of 755 inpatients compared clinically indicated replacement of IV catheters with routine replacement and found no significant differences in phlebitis and infiltration rates between the 2 groups (38% vs 33%, respectively; relative risk [RR]=1.15; 95% confidence interval [CI], 0.95-1.40).⁴

A 2010 trial randomized 362 hospitalized patients to routine or clinically indicated replacement of peripheral IV lines, with median dwell times of 71 and 85 hours, respectively. There was no significant difference in rates of phlebitis between the routine replacement (7%) and clinically indicated (10%) groups (RR=1.44; 95% CI, 0.71-2.89; P=.34). No local infections or IV-related bloodstream infections occurred in either group.⁵

A 2010 Cochrane review included 5 randomized controlled trials (with a total of 3408 patients) that compared rates of suspected catheter-related phlebitis in patients whose catheters were routinely replaced with those in the clinically indicated group. The reviewers found no significant increase in phlebitis in the clinically indicated group (9%) vs the routine replacement group (7.2%) (odds ratio=1.24; 95% CI, 0.97-1.60; P=.09).⁶

Each of these studies had either a relatively small sample size or wide confidence intervals, raising the possibility of missing a real increase in infection due to inadequate statistical power. The study summarized here addressed these concerns.

STUDY SUMMARY: Forgoing routine replacement does not increase risk

Rickard et al¹ conducted a multicenter, nonblinded randomized equivalence trial to determine whether routine or clinically indicated removal reduced rates of infection. In the routine group, catheters were replaced every 72 to 96 hours. In the clinically indicated group, catheters were replaced in instances of phlebitis, infiltration, occlusion, accidental removal, or suspected infection related to the catheter.

Participants (N=3283) were inpatients on medical and surgical units who had IV catheters in place and were expected to need treatment for at least 4 days. Individuals whose IV catheters had been placed in an emergency were excluded, as were those who had a known bloodstream infection or who were not expected to have the IV in place for at least 24 hours. Follow-up data were available for all participants.

The primary outcome was phlebitis, with a prespecified equivalence margin of 3%. In both groups, phlebitis occurred in 7% of patients (RR=1.06; 95% CI, 0.83-1.36; P=.64). The absolute risk difference was 0.41% (95% CI, -1.33 to 2.15), which was within the equivalence margin.

The mean IV catheter dwell time was 70 hours in the routine replacement group and 99 hours in the clinically indicated group. Nine patients in the routine replacement group developed bloodstream infections, vs 4 patients in the clinically indicated group (hazard ratio=0.46; 95% CI, 0.14-1.48; P=.19). One patient in the routine placement group had a catheter-related bloodstream infection; no one in the clinically indicated group did. The mortality rate for each group was <1%.

WHAT’S NEW: We can order clinically indicated IV replacement with confidence

The findings of this equivalence trial support prior studies and add greater statistical power. The results suggest that we can recommend clinically indicated replacement of peripheral IV catheters without increasing the rate of phlebitis. Implementing clinically indicated replacement of IVs could decrease hospital costs and improve patient satisfaction.

CAVEATS: Findings do not apply to patients with bacteremia

Patients with known bacteremia were excluded from this study, and the results are therefore not generalizable to this population.

The nonblinded nature of this trial raises the possibility of observer and reporting bias. However, measures were taken to minimize the potential for bias. A structured outcome assessment was used to standardize reporting of signs of phlebitis. Both patients’ pain scores and nurses’ assessments of the IV sites were used to determine whether an infection was present, and the investigators and research nurses were not involved in the removal of the IV catheters.

This study did not report on the daily maintenance protocols the investigators used for the peripheral IVs. The study was conducted in hospitals in Australia, and we don’t know whether the protocols used in that country are similar to standard protocols in US hospitals.

CHALLENGES TO IMPLEMENTATION: Changing hospital protocols won’t be easy

Implementing the findings of this study will require that physicians work with the nursing staff and administrators to create and implement new protocols for assessing peripheral IV catheters in hospitals with routine IV replacement policies already in place. It would be necessary to ensure that all clinicians who place peripheral IV catheters are taught the clinical signs of phlebitis and are using a standardized protocol. That said, we think that this is a worthwhile change to achieve the long-term benefits of fewer unnecessary IV catheter replacements.

Acknowledgement

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

On Day 4 of her hospitalization for a wound infection requiring IV antibiotics, a 45-year-old patient is told by her nurse that her IV catheter must be replaced. It’s hospital policy, the RN says, to replace the catheter every 96 hours. The patient is afraid of needles and is not eager to have her catheter replaced every few days. Is it really necessary to replace the IV, she wants to know.

Each year, nearly 200 million peripheral IV catheters are placed in patients in hospitals throughout the United States.² Many of the catheters need to be replaced due to phlebitis, infiltration, pain, or swelling at the IV site, but the rate of bloodstream infections associated with peripheral IVs is just 0.5 per 1000 catheter days.²

Timing of replacement is “unresolved”
The Centers for Disease Control and Prevention (CDC)’s 2011 guidelines state that it is not necessary to replace peripheral IV catheters in adults more than every 72 to 96 hours,³ but the CDC does not specify when the catheters should be replaced. For adult patients, the recommendation that a catheter be replaced only for clinical indications is an “unresolved issue,” according to the guidelines. For children, however, replacement only when clinically indicated is recommended by the CDC. Many hospitals have protocols that require replacement of IV catheters every 72 to 96 hours, regardless of clinical indication.

A 2008 study of 755 inpatients compared clinically indicated replacement of IV catheters with routine replacement and found no significant differences in phlebitis and infiltration rates between the 2 groups (38% vs 33%, respectively; relative risk [RR]=1.15; 95% confidence interval [CI], 0.95-1.40).⁴

A 2010 trial randomized 362 hospitalized patients to routine or clinically indicated replacement of peripheral IV lines, with median dwell times of 71 and 85 hours, respectively. There was no significant difference in rates of phlebitis between the routine replacement (7%) and clinically indicated (10%) groups (RR=1.44; 95% CI, 0.71-2.89; P=.34). No local infections or IV-related bloodstream infections occurred in either group.⁵

A 2010 Cochrane review included 5 randomized controlled trials (with a total of 3408 patients) that compared rates of suspected catheter-related phlebitis in patients whose catheters were routinely replaced with those in the clinically indicated group. The reviewers found no significant increase in phlebitis in the clinically indicated group (9%) vs the routine replacement group (7.2%) (odds ratio=1.24; 95% CI, 0.97-1.60; P=.09).⁶

Each of these studies had either a relatively small sample size or wide confidence intervals, raising the possibility of missing a real increase in infection due to inadequate statistical power. The study summarized here addressed these concerns.

STUDY SUMMARY: Forgoing routine replacement does not increase risk

Rickard et al¹ conducted a multicenter, nonblinded randomized equivalence trial to determine whether routine or clinically indicated removal reduced rates of infection. In the routine group, catheters were replaced every 72 to 96 hours. In the clinically indicated group, catheters were replaced in instances of phlebitis, infiltration, occlusion, accidental removal, or suspected infection related to the catheter.

Participants (N=3283) were inpatients on medical and surgical units who had IV catheters in place and were expected to need treatment for at least 4 days. Individuals whose IV catheters had been placed in an emergency were excluded, as were those who had a known bloodstream infection or who were not expected to have the IV in place for at least 24 hours. Follow-up data were available for all participants.

The primary outcome was phlebitis, with a prespecified equivalence margin of 3%. In both groups, phlebitis occurred in 7% of patients (RR=1.06; 95% CI, 0.83-1.36; P=.64). The absolute risk difference was 0.41% (95% CI, -1.33 to 2.15), which was within the equivalence margin.

The mean IV catheter dwell time was 70 hours in the routine replacement group and 99 hours in the clinically indicated group. Nine patients in the routine replacement group developed bloodstream infections, vs 4 patients in the clinically indicated group (hazard ratio=0.46; 95% CI, 0.14-1.48; P=.19). One patient in the routine placement group had a catheter-related bloodstream infection; no one in the clinically indicated group did. The mortality rate for each group was <1%.

WHAT’S NEW: We can order clinically indicated IV replacement with confidence

The findings of this equivalence trial support prior studies and add greater statistical power. The results suggest that we can recommend clinically indicated replacement of peripheral IV catheters without increasing the rate of phlebitis. Implementing clinically indicated replacement of IVs could decrease hospital costs and improve patient satisfaction.

CAVEATS: Findings do not apply to patients with bacteremia

Patients with known bacteremia were excluded from this study, and the results are therefore not generalizable to this population.

The nonblinded nature of this trial raises the possibility of observer and reporting bias. However, measures were taken to minimize the potential for bias. A structured outcome assessment was used to standardize reporting of signs of phlebitis. Both patients’ pain scores and nurses’ assessments of the IV sites were used to determine whether an infection was present, and the investigators and research nurses were not involved in the removal of the IV catheters.

This study did not report on the daily maintenance protocols the investigators used for the peripheral IVs. The study was conducted in hospitals in Australia, and we don’t know whether the protocols used in that country are similar to standard protocols in US hospitals.

CHALLENGES TO IMPLEMENTATION: Changing hospital protocols won’t be easy

Implementing the findings of this study will require that physicians work with the nursing staff and administrators to create and implement new protocols for assessing peripheral IV catheters in hospitals with routine IV replacement policies already in place. It would be necessary to ensure that all clinicians who place peripheral IV catheters are taught the clinical signs of phlebitis and are using a standardized protocol. That said, we think that this is a worthwhile change to achieve the long-term benefits of fewer unnecessary IV catheter replacements.

Acknowledgement

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Practice Changer
Treat low-risk patients with pulmonary embolism (PE) with low-molecular-weight heparin (LMWH) in an outpatient setting.¹

Strength of recommendation
B: Based on one good quality randomized controlled trial (RCT).

ILLUSTRATIVE CASE
Three months after undergoing surgical repair of an ankle fracture, a 50-year-old woman presents with acute-onset dyspnea at rest and pleuritic chest pain. Her left calf is tender and swollen. The patient has a history of hypertension and smokes about 10 cigarettes per day. Her temperature is 37ºC; ventricular rate, 98 beats/min; blood pressure, 135/85 mm Hg; respiratory rate, 25 breaths/min; and pulse oximetry, 92%. Spiral CT reveals a contrast filling defect indicative of a PE. Her score on the Pulmonary Embolism Severity Index (PESI) is 50, an indication of low risk. She wants to know if she can be treated at home. What should you tell her?

In the past, intravenous unfractionated heparin, administered in an inpatient setting, was the recommended initial anticoagulation therapy for patients with venous thromboembolism (VTE). LMWH, which can be administered subcutaneously and does not require laboratory monitoring, has made it possible to treat VTE without

hospitalization.

Outpatient PE care hindered

by lack of evidence
Guidelines from the American College of Physicians, the American Academy of Family Physicians, and the British Thoracic Society recommend outpatient treatment of deep vein thrombosis with LMWH, which they find to be safe and cost-effective for select patients.^2,3 Until recently, the safety and efficacy of outpatient management of PE has been less clear.

The lack of an accurate prediction tool to identify patients who could be treated safely outside the hospital was one barrier to the development of evidence-based recommendations for outpatient PE treatment. In 2005, the PESI,⁴ a validated tool that identifies patients with low risk for death from PE, was developed. Until recently, the absence of an RCT comparing inpatient and outpatient treatment for acute PE was another barrier.

STUDY SUMMARY
Outpatient treatment measures up
The Outpatient Treatment of Pulmonary Embolism (OTPE) study compared outpatient vs inpatient treatment of low-risk patients with acute PE. Participants had to be 18 or older, have acute symptomatic and objectively verified PE, and be at low risk for death based on the PESI score.4 In addition to excluding patients at moderate or high risk, the researchers identified 14 other exclusion criteria, including hypoxia, chest pain requiring opiates, and high risk for bleeding.

Patients were randomly assigned to the outpatient (n = 171) or inpatient (n = 168) group. Both groups received subcutaneous LMWH (enoxaparin, 1 mg/kg bid) for ≥ 5 days, followed by oral anticoagulation with a vitamin K antagonist for ≥ 90 days. Patients in the outpatient group were discharged from the emergency department (ED) within

24 hours of randomization, after being trained by a nurse to self-inject. Therapy after discharge was managed either by the patient's primary care physician or the hospital's anticoagulation staff.

The LMWH was discontinued in patients with an INR ≥ 2.0 for two consecutive days. All patients were followed for 90 days and contacted by the study team daily for the first week and then at 14, 30, 60, and 90 days. On each occasion, participants were asked about symptoms of recurrent VTE, bleeding, and the use of health care resources.

The primary outcome was the recurrence of symptomatic, objectively confirmed VTE within the study period. Secondary outcomes were major bleeding and all-cause mortality. Outcomes were confirmed by clinicians who were unaware of treatment

assignments.

Patients were also asked to rate their overall satisfaction with their care and their treatment preference 14 days after randomization, using a 5-point Likert questionnaire. Prior to the trial, the investigators decided that outpatient treatment would be considered noninferior to inpatient care if the difference between rates of recurrent VTE did not exceed 4%, a measure used in previous studies comparing treatment regimens for VTE and outpatient versus inpatient treatment of DVT.^5,6

Little difference in readmission rates, ED or office visits
One in 171 outpatients (0.6%) and none of the inpatients had recurrent VTE. Two outpatients (1.2%)—and no inpatients—developed major bleeding within 14 days, the result of intramuscular hematomas that occurred on days 3 and 13. There was one additional bleeding event (menometrorrhagia) in the outpatient group on day 50, but it was believed to be unrelated to the PE treatment. Per-protocol analysis, a more conservative measure used in noninferiority studies, found a difference in major bleeding rates of 3.8%. One person in each group died of non-VTE and nontreatment-related causes.

Almost all participants (99%) completed the satisfaction survey, which indicated that 92% of outpatients and 95% of inpatients were satisfied or very satisfied with their care. Hospital readmission rates, ED visits, and visits to primary care physicians were similar, with no significant differences between the

two groups. The mean time spent in the hospital was 0.5 days for outpatients and 3.9 days for inpatients. Fourteen percent of outpatients and 6% of inpatients received home nursing visits for enoxaparin injection. The total number of home visits was higher among outpatients (348 vs 105). Because both groups had extreme outliers, however, this difference was not statistically significant.

WHAT'S NEW
It's safe to keep

low-risk patients at home
This is the first RCT comparing the safety and effectiveness of outpatient and inpatient treatment of acute, symptomatic PE. Results were statistically comparable, and patients were satisfied being treated at home. Outpatient treatment was less expensive because of the shorter length of stay (0.5 vs 3.9 days) and was associated with the same rates of hospital readmission, ED visits, and visits to primary care physicians. There were more home nursing visits in the outpatient treatment group. But even if you assume a cost of $200 per home visit, the additional cost would be about $282 per individual in the outpatient group—significantly less than the cost of the additional 3.4 days in the hospital for each individual in the inpatient group.

The study also confirmed that the PESI accurately identifies low-risk patients with PE who can be treated in an outpatient setting. Thirty percent of patients who were screened for the OTPE trial met the low-risk eligibility requirement.

CAVEATS
Use of risk assessment tool is essential
The average age of patients in this study was 47 in the outpatient group and 49 in the inpatient group. In addition, only 1% to 3% of the patients were diagnosed with cancer. Older patients who have both cancer and PE would be unlikely to qualify for outpatient care.

Clinicians applying this practice changer should use the PESI to ensure that outpatient treatment for PE is used only for individuals at low risk.

CHALLENGES TO IMPLEMENTATION
ED coordination, training, and home care won't be easy
This practice changer may be difficult for primary care providers, who might not be included in emergency physicians' decisions regarding the appropriate treatment for acute PE. In this study, primary care physicians were notified of the randomized treatment plan for their patients, and 17 potential participants were excluded from the trial because of their doctors' opposition.

Outpatient management should be considered only if arrangements for adequate home nursing care can be made, if needed—and only for patients who are able to follow instructions and self-inject LMWH. Newer anticoagulation medications that are either injected once a day or taken orally might decrease the need for home nursing visits.  

REFERENCES
1. Aujesky D, Roy PM, Verschuren F, et al. Outpatient versus inpatient treatment for patients with acute pulmonary embolism: an international, open-label, randomised, non-inferiority trial. Lancet. 2011; 378:41-48.

2. Snow V, Qaseem A, Barry P, et al. Management of venous thromboembolism: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2007;146:204-210.

3. British Thoracic Society Standards of Care Committee Pulmonary Embolism Guideline Development Group. British Thoracic Society guidelines for the management of suspected acute pulmonary embolism. Thorax. 2003;58: 470-483.

4.  Aujesky D, Obrosky DS, Stone RA, et al. Derivation and validation of a prognostic model for pulmonary embolism. Am J Respir Crit Care Med. 2005;172:1041-1046.

5. Koopman MM, Prandoni P, Piovella F, et al. Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. The Tasman Study Group. N Engl J Med. 1996;334: 682-687.

6. Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009; 361:2342-2352.

ACKNOWLEDGEMENT
The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Copyright © 2012 The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2012;61(6):349-352.

Practice Changer
Treat low-risk patients with pulmonary embolism (PE) with low-molecular-weight heparin (LMWH) in an outpatient setting.¹

Strength of recommendation
B: Based on one good quality randomized controlled trial (RCT).

ILLUSTRATIVE CASE
Three months after undergoing surgical repair of an ankle fracture, a 50-year-old woman presents with acute-onset dyspnea at rest and pleuritic chest pain. Her left calf is tender and swollen. The patient has a history of hypertension and smokes about 10 cigarettes per day. Her temperature is 37ºC; ventricular rate, 98 beats/min; blood pressure, 135/85 mm Hg; respiratory rate, 25 breaths/min; and pulse oximetry, 92%. Spiral CT reveals a contrast filling defect indicative of a PE. Her score on the Pulmonary Embolism Severity Index (PESI) is 50, an indication of low risk. She wants to know if she can be treated at home. What should you tell her?

In the past, intravenous unfractionated heparin, administered in an inpatient setting, was the recommended initial anticoagulation therapy for patients with venous thromboembolism (VTE). LMWH, which can be administered subcutaneously and does not require laboratory monitoring, has made it possible to treat VTE without

hospitalization.

Outpatient PE care hindered

by lack of evidence
Guidelines from the American College of Physicians, the American Academy of Family Physicians, and the British Thoracic Society recommend outpatient treatment of deep vein thrombosis with LMWH, which they find to be safe and cost-effective for select patients.^2,3 Until recently, the safety and efficacy of outpatient management of PE has been less clear.

The lack of an accurate prediction tool to identify patients who could be treated safely outside the hospital was one barrier to the development of evidence-based recommendations for outpatient PE treatment. In 2005, the PESI,⁴ a validated tool that identifies patients with low risk for death from PE, was developed. Until recently, the absence of an RCT comparing inpatient and outpatient treatment for acute PE was another barrier.

STUDY SUMMARY
Outpatient treatment measures up
The Outpatient Treatment of Pulmonary Embolism (OTPE) study compared outpatient vs inpatient treatment of low-risk patients with acute PE. Participants had to be 18 or older, have acute symptomatic and objectively verified PE, and be at low risk for death based on the PESI score.4 In addition to excluding patients at moderate or high risk, the researchers identified 14 other exclusion criteria, including hypoxia, chest pain requiring opiates, and high risk for bleeding.

Patients were randomly assigned to the outpatient (n = 171) or inpatient (n = 168) group. Both groups received subcutaneous LMWH (enoxaparin, 1 mg/kg bid) for ≥ 5 days, followed by oral anticoagulation with a vitamin K antagonist for ≥ 90 days. Patients in the outpatient group were discharged from the emergency department (ED) within

24 hours of randomization, after being trained by a nurse to self-inject. Therapy after discharge was managed either by the patient's primary care physician or the hospital's anticoagulation staff.

The LMWH was discontinued in patients with an INR ≥ 2.0 for two consecutive days. All patients were followed for 90 days and contacted by the study team daily for the first week and then at 14, 30, 60, and 90 days. On each occasion, participants were asked about symptoms of recurrent VTE, bleeding, and the use of health care resources.

The primary outcome was the recurrence of symptomatic, objectively confirmed VTE within the study period. Secondary outcomes were major bleeding and all-cause mortality. Outcomes were confirmed by clinicians who were unaware of treatment

assignments.

Patients were also asked to rate their overall satisfaction with their care and their treatment preference 14 days after randomization, using a 5-point Likert questionnaire. Prior to the trial, the investigators decided that outpatient treatment would be considered noninferior to inpatient care if the difference between rates of recurrent VTE did not exceed 4%, a measure used in previous studies comparing treatment regimens for VTE and outpatient versus inpatient treatment of DVT.^5,6

Little difference in readmission rates, ED or office visits
One in 171 outpatients (0.6%) and none of the inpatients had recurrent VTE. Two outpatients (1.2%)—and no inpatients—developed major bleeding within 14 days, the result of intramuscular hematomas that occurred on days 3 and 13. There was one additional bleeding event (menometrorrhagia) in the outpatient group on day 50, but it was believed to be unrelated to the PE treatment. Per-protocol analysis, a more conservative measure used in noninferiority studies, found a difference in major bleeding rates of 3.8%. One person in each group died of non-VTE and nontreatment-related causes.

Almost all participants (99%) completed the satisfaction survey, which indicated that 92% of outpatients and 95% of inpatients were satisfied or very satisfied with their care. Hospital readmission rates, ED visits, and visits to primary care physicians were similar, with no significant differences between the

two groups. The mean time spent in the hospital was 0.5 days for outpatients and 3.9 days for inpatients. Fourteen percent of outpatients and 6% of inpatients received home nursing visits for enoxaparin injection. The total number of home visits was higher among outpatients (348 vs 105). Because both groups had extreme outliers, however, this difference was not statistically significant.

WHAT'S NEW
It's safe to keep

low-risk patients at home
This is the first RCT comparing the safety and effectiveness of outpatient and inpatient treatment of acute, symptomatic PE. Results were statistically comparable, and patients were satisfied being treated at home. Outpatient treatment was less expensive because of the shorter length of stay (0.5 vs 3.9 days) and was associated with the same rates of hospital readmission, ED visits, and visits to primary care physicians. There were more home nursing visits in the outpatient treatment group. But even if you assume a cost of $200 per home visit, the additional cost would be about $282 per individual in the outpatient group—significantly less than the cost of the additional 3.4 days in the hospital for each individual in the inpatient group.

The study also confirmed that the PESI accurately identifies low-risk patients with PE who can be treated in an outpatient setting. Thirty percent of patients who were screened for the OTPE trial met the low-risk eligibility requirement.

CAVEATS
Use of risk assessment tool is essential
The average age of patients in this study was 47 in the outpatient group and 49 in the inpatient group. In addition, only 1% to 3% of the patients were diagnosed with cancer. Older patients who have both cancer and PE would be unlikely to qualify for outpatient care.

Clinicians applying this practice changer should use the PESI to ensure that outpatient treatment for PE is used only for individuals at low risk.

CHALLENGES TO IMPLEMENTATION
ED coordination, training, and home care won't be easy
This practice changer may be difficult for primary care providers, who might not be included in emergency physicians' decisions regarding the appropriate treatment for acute PE. In this study, primary care physicians were notified of the randomized treatment plan for their patients, and 17 potential participants were excluded from the trial because of their doctors' opposition.

Outpatient management should be considered only if arrangements for adequate home nursing care can be made, if needed—and only for patients who are able to follow instructions and self-inject LMWH. Newer anticoagulation medications that are either injected once a day or taken orally might decrease the need for home nursing visits.  

REFERENCES
1. Aujesky D, Roy PM, Verschuren F, et al. Outpatient versus inpatient treatment for patients with acute pulmonary embolism: an international, open-label, randomised, non-inferiority trial. Lancet. 2011; 378:41-48.

2. Snow V, Qaseem A, Barry P, et al. Management of venous thromboembolism: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2007;146:204-210.

3. British Thoracic Society Standards of Care Committee Pulmonary Embolism Guideline Development Group. British Thoracic Society guidelines for the management of suspected acute pulmonary embolism. Thorax. 2003;58: 470-483.

4.  Aujesky D, Obrosky DS, Stone RA, et al. Derivation and validation of a prognostic model for pulmonary embolism. Am J Respir Crit Care Med. 2005;172:1041-1046.

5. Koopman MM, Prandoni P, Piovella F, et al. Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. The Tasman Study Group. N Engl J Med. 1996;334: 682-687.

6. Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009; 361:2342-2352.

ACKNOWLEDGEMENT
The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Copyright © 2012 The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2012;61(6):349-352.

Practice Changer
Treat low-risk patients with pulmonary embolism (PE) with low-molecular-weight heparin (LMWH) in an outpatient setting.¹

Strength of recommendation
B: Based on one good quality randomized controlled trial (RCT).

ILLUSTRATIVE CASE
Three months after undergoing surgical repair of an ankle fracture, a 50-year-old woman presents with acute-onset dyspnea at rest and pleuritic chest pain. Her left calf is tender and swollen. The patient has a history of hypertension and smokes about 10 cigarettes per day. Her temperature is 37ºC; ventricular rate, 98 beats/min; blood pressure, 135/85 mm Hg; respiratory rate, 25 breaths/min; and pulse oximetry, 92%. Spiral CT reveals a contrast filling defect indicative of a PE. Her score on the Pulmonary Embolism Severity Index (PESI) is 50, an indication of low risk. She wants to know if she can be treated at home. What should you tell her?

In the past, intravenous unfractionated heparin, administered in an inpatient setting, was the recommended initial anticoagulation therapy for patients with venous thromboembolism (VTE). LMWH, which can be administered subcutaneously and does not require laboratory monitoring, has made it possible to treat VTE without

hospitalization.

Outpatient PE care hindered

by lack of evidence
Guidelines from the American College of Physicians, the American Academy of Family Physicians, and the British Thoracic Society recommend outpatient treatment of deep vein thrombosis with LMWH, which they find to be safe and cost-effective for select patients.^2,3 Until recently, the safety and efficacy of outpatient management of PE has been less clear.

The lack of an accurate prediction tool to identify patients who could be treated safely outside the hospital was one barrier to the development of evidence-based recommendations for outpatient PE treatment. In 2005, the PESI,⁴ a validated tool that identifies patients with low risk for death from PE, was developed. Until recently, the absence of an RCT comparing inpatient and outpatient treatment for acute PE was another barrier.

STUDY SUMMARY
Outpatient treatment measures up
The Outpatient Treatment of Pulmonary Embolism (OTPE) study compared outpatient vs inpatient treatment of low-risk patients with acute PE. Participants had to be 18 or older, have acute symptomatic and objectively verified PE, and be at low risk for death based on the PESI score.4 In addition to excluding patients at moderate or high risk, the researchers identified 14 other exclusion criteria, including hypoxia, chest pain requiring opiates, and high risk for bleeding.

Patients were randomly assigned to the outpatient (n = 171) or inpatient (n = 168) group. Both groups received subcutaneous LMWH (enoxaparin, 1 mg/kg bid) for ≥ 5 days, followed by oral anticoagulation with a vitamin K antagonist for ≥ 90 days. Patients in the outpatient group were discharged from the emergency department (ED) within

24 hours of randomization, after being trained by a nurse to self-inject. Therapy after discharge was managed either by the patient's primary care physician or the hospital's anticoagulation staff.

The LMWH was discontinued in patients with an INR ≥ 2.0 for two consecutive days. All patients were followed for 90 days and contacted by the study team daily for the first week and then at 14, 30, 60, and 90 days. On each occasion, participants were asked about symptoms of recurrent VTE, bleeding, and the use of health care resources.

The primary outcome was the recurrence of symptomatic, objectively confirmed VTE within the study period. Secondary outcomes were major bleeding and all-cause mortality. Outcomes were confirmed by clinicians who were unaware of treatment

assignments.

Patients were also asked to rate their overall satisfaction with their care and their treatment preference 14 days after randomization, using a 5-point Likert questionnaire. Prior to the trial, the investigators decided that outpatient treatment would be considered noninferior to inpatient care if the difference between rates of recurrent VTE did not exceed 4%, a measure used in previous studies comparing treatment regimens for VTE and outpatient versus inpatient treatment of DVT.^5,6

Little difference in readmission rates, ED or office visits
One in 171 outpatients (0.6%) and none of the inpatients had recurrent VTE. Two outpatients (1.2%)—and no inpatients—developed major bleeding within 14 days, the result of intramuscular hematomas that occurred on days 3 and 13. There was one additional bleeding event (menometrorrhagia) in the outpatient group on day 50, but it was believed to be unrelated to the PE treatment. Per-protocol analysis, a more conservative measure used in noninferiority studies, found a difference in major bleeding rates of 3.8%. One person in each group died of non-VTE and nontreatment-related causes.

Almost all participants (99%) completed the satisfaction survey, which indicated that 92% of outpatients and 95% of inpatients were satisfied or very satisfied with their care. Hospital readmission rates, ED visits, and visits to primary care physicians were similar, with no significant differences between the

two groups. The mean time spent in the hospital was 0.5 days for outpatients and 3.9 days for inpatients. Fourteen percent of outpatients and 6% of inpatients received home nursing visits for enoxaparin injection. The total number of home visits was higher among outpatients (348 vs 105). Because both groups had extreme outliers, however, this difference was not statistically significant.

WHAT'S NEW
It's safe to keep

low-risk patients at home
This is the first RCT comparing the safety and effectiveness of outpatient and inpatient treatment of acute, symptomatic PE. Results were statistically comparable, and patients were satisfied being treated at home. Outpatient treatment was less expensive because of the shorter length of stay (0.5 vs 3.9 days) and was associated with the same rates of hospital readmission, ED visits, and visits to primary care physicians. There were more home nursing visits in the outpatient treatment group. But even if you assume a cost of $200 per home visit, the additional cost would be about $282 per individual in the outpatient group—significantly less than the cost of the additional 3.4 days in the hospital for each individual in the inpatient group.

The study also confirmed that the PESI accurately identifies low-risk patients with PE who can be treated in an outpatient setting. Thirty percent of patients who were screened for the OTPE trial met the low-risk eligibility requirement.

CAVEATS
Use of risk assessment tool is essential
The average age of patients in this study was 47 in the outpatient group and 49 in the inpatient group. In addition, only 1% to 3% of the patients were diagnosed with cancer. Older patients who have both cancer and PE would be unlikely to qualify for outpatient care.

Clinicians applying this practice changer should use the PESI to ensure that outpatient treatment for PE is used only for individuals at low risk.

CHALLENGES TO IMPLEMENTATION
ED coordination, training, and home care won't be easy
This practice changer may be difficult for primary care providers, who might not be included in emergency physicians' decisions regarding the appropriate treatment for acute PE. In this study, primary care physicians were notified of the randomized treatment plan for their patients, and 17 potential participants were excluded from the trial because of their doctors' opposition.

Outpatient management should be considered only if arrangements for adequate home nursing care can be made, if needed—and only for patients who are able to follow instructions and self-inject LMWH. Newer anticoagulation medications that are either injected once a day or taken orally might decrease the need for home nursing visits.  

REFERENCES
1. Aujesky D, Roy PM, Verschuren F, et al. Outpatient versus inpatient treatment for patients with acute pulmonary embolism: an international, open-label, randomised, non-inferiority trial. Lancet. 2011; 378:41-48.

2. Snow V, Qaseem A, Barry P, et al. Management of venous thromboembolism: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2007;146:204-210.

3. British Thoracic Society Standards of Care Committee Pulmonary Embolism Guideline Development Group. British Thoracic Society guidelines for the management of suspected acute pulmonary embolism. Thorax. 2003;58: 470-483.

4.  Aujesky D, Obrosky DS, Stone RA, et al. Derivation and validation of a prognostic model for pulmonary embolism. Am J Respir Crit Care Med. 2005;172:1041-1046.

5. Koopman MM, Prandoni P, Piovella F, et al. Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. The Tasman Study Group. N Engl J Med. 1996;334: 682-687.

6. Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009; 361:2342-2352.

ACKNOWLEDGEMENT
The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Copyright © 2012 The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2012;61(6):349-352.

Practice Changer
Stop prescribing amoxicillin for acute rhinosinusitis. It’s unlikely to provide a speedier recovery than OTC remedies alone.¹

Strength of recommendation
B: Based on a single high-quality randomized controlled trial.

ILLUSTRATIVE CASE
A 28-year-old man comes to your clinic after experiencing fatigue, purulent nasal discharge, and unilateral facial pain for nearly

10 days. Overall, he appears healthy, and you diagnose acute rhinosinusitis. You suggest OTC remedies for supportive care and wonder if a course of amoxicillin would speed his

recovery.

Each year, more than 30 million Americans—about one in seven adults—are diagnosed with sinusitis.² No more than 2% of these cases are thought to be bacterial.³

CDC guidelines for the diagnosis of acute bacterial rhinosinusitis include symptoms that last seven or more days, with maxillary pain or tenderness in the face or teeth and purulent nasal secretions.⁴ Patients with symptoms lasting less than seven days are unlikely to have a bacterial infection. But the nonspecific signs and symptoms included in the CDC guidelines limit their usefulness in determining whether the cause of the sinusitis is bacterial or viral on clinical grounds alone.

Most cases of sinusitis spontaneously resolve
In patients with acute bacterial sinusitis, the American Academy of Otolaryngology–Head and Neck Surgery (AAO–HNS) guidelines advocate watchful waiting and symptom relief with nasal oxymetazoline, pseudoephedrine, and saline nasal irrigation.³ The rate of spontaneous resolution is high: 80% of patients with clinically diagnosed sinusitis improve without treatment within two weeks.^1,5

Traditional decongestants and mucolytics have not demonstrated efficacy in resolving sinusitis, although rigorous evaluation is lacking. Other treatments, such as saline irrigation and intranasal corticosteroids, are of unclear benefit and need further study.^6-8

Lack of evidence has done little to curtail antibiotic use
A previous PURL that was based on a meta-analysis of antibiotic treatment trials for sinusitis recommended that we stop prescribing antibiotics for adults with acute sinusitis unless their symptoms are severe.^9,10 Yet antibiotics remain the mainstay of treatment.

Despite the AAO–HNS guidelines, evidence of spontaneous resolution, and accumulating data on the lack of efficacy of antimicrobials for sinusitis, 81% of patients diagnosed with acute sinusitis were given prescriptions for antibiotics, a study of primary care practices showed.¹¹ Frequent use of antibiotics contributes to high rates of drug resistance, and adverse events related to antibiotic use account for an estimated 142,500 emergency department visits annually.¹²

STUDY SUMMARY
Little benefit from amoxicillin, even for severe cases
Garbutt and colleagues revisited the issue, randomizing 166 patients from 10 primary care practices to receive amoxicillin plus symptomatic treatment or placebo plus symptomatic treatment for acute rhinosinusitis.¹

To be eligible for the study, patients had to be between the ages of 18 and 70, meet CDC diagnostic criteria for acute rhinosinusitis, and have moderate to very severe symptoms that were of seven- to-28-day duration and worsening or not improving, or of < 7-day duration but had worsened after an initial improvement. Exclusion criteria included complications from sinusitis, a history of allergy to penicillin or amoxicillin, antibiotic use in the past four weeks, comorbidities that impair immune function, cystic fibrosis, pregnancy, and mild symptoms.

Both groups had similar baseline characteristics, with participants who were predominantly white (79%) and female (64%). All the participants received a supply of symptomatic treatments: acetaminophen, guaifenesin, dextromethorphan, and sustained-release pseudoephedrine. The treatment group also received amoxicillin 1,500 mg/d, divided into three doses; the placebo group received identical-looking placebo pills.

Patients were assessed with the Sino-nasal Outcome Test-16 (SNOT-16), a validated measure that asks patients to assess both the severity and frequency of 16 sinus symptoms. SNOT-16 uses a 0-to-3 rating scale (0 = no problem; 3 = severe problem), with a clinically important difference of ≥ 0.5 on the mean score. The test was administered at enrollment and at days 3, 7, and 10. The disease-specific quality of life at day 3 was the primary outcome.

There was no statistically significantly difference in SNOT-16 scores between the amoxicillin and placebo groups on days 3 and 10. On day 7, there was a small statistically significant improvement in the amoxicillin group, but it did not reach the level of clinical importance (≥ 0.5) based on SNOT-16’s mean score.

The authors also asked participants to retrospectively assess symptom change since enrollment on a six-point scale. Those who reported that their symptoms were “a lot better” or “absent” were characterized as significantly improved. The results correlated with the data from the SNOT-16, showing no difference between the amoxicillin and control groups at days 3 and 10. On day 7, 74% of patients treated with amoxicillin self-

reported significant improvement in symptoms since the start of the study, versus 56% in the control group. The number needed to treat was 6 (95% confidence interval, 3 to 34; P = .02) for a reduction in symptoms at day 7.

Patients in both groups had similar rates of absenteeism, inability to perform usual activities, relapse and recurrence, and use of additional health care. Satisfaction with treatment was similar, as well.

No serious adverse effects occurred. Both groups reported similar frequencies (< 10%) of nausea, diarrhea, abdominal pain, or vaginitis.

WHAT’S NEW
Even severe sinusitis resolves without antibiotics
Previous studies recommended foregoing antibiotics for acute sinusitis, except when symptoms are severe. This study—in which more than half (52%) of patients in each group had symptoms rated severe or very severe—found no benefit to adding amoxicillin to supportive treatments.¹ Antibiotics did not shorten the duration of illness, prevent relapse and recurrence, or improve satisfaction with treatment. The researchers found a statistically significant difference between groups on day 7 of 0.19 points, but no clinically meaningful difference (≥ 0.5) based on the SNOT-16 mean score.

CAVEATS
Guidelines, risk of complications may give reason to pause
The 2012 Infectious Diseases Society of America guidelines recommend amoxicillin with clavulanic acid as empiric therapy for acute bacterial rhinosinusitis.⁷ The findings of the study by Garbutt et al—conducted at a time when the incidence of beta-lactamase-producing organisms was low and amoxicillin was the treatment of choice—suggest otherwise.

Serious complications of sinusitis, such as brain abscess, periorbital cellulitis, and meningitis, can occur, however. Patients who deteriorate clinically or develop high fever or severe headache require close follow-up, which may include further diagnostic evaluation or consultation with an otolaryngologist. Evidence is lacking as to whether antibiotics prevent such complications.⁵

CHALLENGES TO IMPLEMENTATION
Managing patient expectations
Many patients with symptoms of acute rhinosinusitis think they need an antibiotic. Managing their expectations and providing instructions about supportive treatments are time consuming and may be

difficult.

Nonetheless, we’re optimistic: We think that most patients today are aware of the problems associated with antibiotic resistance and wary of “superbugs,” and will therefore be receptive to this practice change. Clinicians can help by reminding patients of the adverse effects of antibiotics and the natural course of rhinosinusitis, as well as by offering symptomatic treatments.

REFERENCES
1. Garbutt J, Banister C, Spitznagel E, et al. Amoxicillin for acute rhinosinusitis: a randomized controlled trial. JAMA. 2012;307:685-692.

2. Centers for Disease Control and Prevention. Summary health statistics for US adults: National Health Interview Survey 2010. January 2012. www.cdc.gov/nchs/data/series/sr_10/sr10_252.pdf. Accessed July 9, 2012.

3. Rosenfeld RM, Andes D, Bhattacharyya N, et al. Clinical practice guideline: adult sinusitis. Otolaryngol Head Neck Surg. 2007:137(3 suppl):S1-S31.

4. Hickner JM, Bartlett JG, Besser RE, et al; American Academy of Family Physians; American College of Physicians; American Society of Internal Medicine; Centers for Disease Control; Infectious Disease Society of America. Principles of appropriate antibiotic use for acute rhinosinusitis in adults; background. Ann Intern Med. 2001;134:498-505.

5. Ahovuo-Saloranta A, Borisenk OV, Kovanen N, et al. Antibiotics for acute maxillary sinusitis. Cochrane Database Sys Rev. 2008(2):CD000243.

6. Allen G, Kelsberg G, Jankowski TA. Do nasal decongestants relieve symptoms? J Fam Pract. 2003;52:714-724.

7. Chow AW, Benninger MS, Brook I, et al. IDSA clinical practice guideline for acute bacterial rhinosinusitis in children and adults. Clin Infect Dis. 2012;54:e72-e112.

8. Zalmanovici A, Yaphe J. Intranasal steroids for acute sinusitis. Cochrane Database Syst Rev. 2009(4):CD005149.

9. Schumann A, Hickner, J. Patients insist on antibiotics for sinusitis? Here is a good reason to say “no.” J Fam Pract. 2008;57:464-468.

10. Young J, De Sutter A, Merenstein D, et al. Antibiotics for adults with clinically diagnosed acute rhinosinusitis: a meta-analysis of individual patient data. Lancet. 2008;371:908-914.

11. Gill JM, Fleischut P, Haas S. Use of antibiotics for adult upper respiratory infections in outpatient settings: a national ambulatory network study. Fam Med. 2006;38:349-354.

12. Shehab N, Patel PR, Srinivasan A, et al. Emergency department visits for antibiotic-associated adverse events. Clin Infect Dis. 2008; 47:735-743.

ACKNOWLEDGEMENT
The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Copyright © 2012 The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2012;61(10):610-612.

Practice Changer
Stop prescribing amoxicillin for acute rhinosinusitis. It’s unlikely to provide a speedier recovery than OTC remedies alone.¹

Strength of recommendation
B: Based on a single high-quality randomized controlled trial.

ILLUSTRATIVE CASE
A 28-year-old man comes to your clinic after experiencing fatigue, purulent nasal discharge, and unilateral facial pain for nearly

10 days. Overall, he appears healthy, and you diagnose acute rhinosinusitis. You suggest OTC remedies for supportive care and wonder if a course of amoxicillin would speed his

recovery.

Each year, more than 30 million Americans—about one in seven adults—are diagnosed with sinusitis.² No more than 2% of these cases are thought to be bacterial.³

CDC guidelines for the diagnosis of acute bacterial rhinosinusitis include symptoms that last seven or more days, with maxillary pain or tenderness in the face or teeth and purulent nasal secretions.⁴ Patients with symptoms lasting less than seven days are unlikely to have a bacterial infection. But the nonspecific signs and symptoms included in the CDC guidelines limit their usefulness in determining whether the cause of the sinusitis is bacterial or viral on clinical grounds alone.

Most cases of sinusitis spontaneously resolve
In patients with acute bacterial sinusitis, the American Academy of Otolaryngology–Head and Neck Surgery (AAO–HNS) guidelines advocate watchful waiting and symptom relief with nasal oxymetazoline, pseudoephedrine, and saline nasal irrigation.³ The rate of spontaneous resolution is high: 80% of patients with clinically diagnosed sinusitis improve without treatment within two weeks.^1,5

Traditional decongestants and mucolytics have not demonstrated efficacy in resolving sinusitis, although rigorous evaluation is lacking. Other treatments, such as saline irrigation and intranasal corticosteroids, are of unclear benefit and need further study.^6-8

Lack of evidence has done little to curtail antibiotic use
A previous PURL that was based on a meta-analysis of antibiotic treatment trials for sinusitis recommended that we stop prescribing antibiotics for adults with acute sinusitis unless their symptoms are severe.^9,10 Yet antibiotics remain the mainstay of treatment.

Despite the AAO–HNS guidelines, evidence of spontaneous resolution, and accumulating data on the lack of efficacy of antimicrobials for sinusitis, 81% of patients diagnosed with acute sinusitis were given prescriptions for antibiotics, a study of primary care practices showed.¹¹ Frequent use of antibiotics contributes to high rates of drug resistance, and adverse events related to antibiotic use account for an estimated 142,500 emergency department visits annually.¹²

STUDY SUMMARY
Little benefit from amoxicillin, even for severe cases
Garbutt and colleagues revisited the issue, randomizing 166 patients from 10 primary care practices to receive amoxicillin plus symptomatic treatment or placebo plus symptomatic treatment for acute rhinosinusitis.¹

To be eligible for the study, patients had to be between the ages of 18 and 70, meet CDC diagnostic criteria for acute rhinosinusitis, and have moderate to very severe symptoms that were of seven- to-28-day duration and worsening or not improving, or of < 7-day duration but had worsened after an initial improvement. Exclusion criteria included complications from sinusitis, a history of allergy to penicillin or amoxicillin, antibiotic use in the past four weeks, comorbidities that impair immune function, cystic fibrosis, pregnancy, and mild symptoms.

Both groups had similar baseline characteristics, with participants who were predominantly white (79%) and female (64%). All the participants received a supply of symptomatic treatments: acetaminophen, guaifenesin, dextromethorphan, and sustained-release pseudoephedrine. The treatment group also received amoxicillin 1,500 mg/d, divided into three doses; the placebo group received identical-looking placebo pills.

Patients were assessed with the Sino-nasal Outcome Test-16 (SNOT-16), a validated measure that asks patients to assess both the severity and frequency of 16 sinus symptoms. SNOT-16 uses a 0-to-3 rating scale (0 = no problem; 3 = severe problem), with a clinically important difference of ≥ 0.5 on the mean score. The test was administered at enrollment and at days 3, 7, and 10. The disease-specific quality of life at day 3 was the primary outcome.

There was no statistically significantly difference in SNOT-16 scores between the amoxicillin and placebo groups on days 3 and 10. On day 7, there was a small statistically significant improvement in the amoxicillin group, but it did not reach the level of clinical importance (≥ 0.5) based on SNOT-16’s mean score.

The authors also asked participants to retrospectively assess symptom change since enrollment on a six-point scale. Those who reported that their symptoms were “a lot better” or “absent” were characterized as significantly improved. The results correlated with the data from the SNOT-16, showing no difference between the amoxicillin and control groups at days 3 and 10. On day 7, 74% of patients treated with amoxicillin self-

reported significant improvement in symptoms since the start of the study, versus 56% in the control group. The number needed to treat was 6 (95% confidence interval, 3 to 34; P = .02) for a reduction in symptoms at day 7.

Patients in both groups had similar rates of absenteeism, inability to perform usual activities, relapse and recurrence, and use of additional health care. Satisfaction with treatment was similar, as well.

No serious adverse effects occurred. Both groups reported similar frequencies (< 10%) of nausea, diarrhea, abdominal pain, or vaginitis.

WHAT’S NEW
Even severe sinusitis resolves without antibiotics
Previous studies recommended foregoing antibiotics for acute sinusitis, except when symptoms are severe. This study—in which more than half (52%) of patients in each group had symptoms rated severe or very severe—found no benefit to adding amoxicillin to supportive treatments.¹ Antibiotics did not shorten the duration of illness, prevent relapse and recurrence, or improve satisfaction with treatment. The researchers found a statistically significant difference between groups on day 7 of 0.19 points, but no clinically meaningful difference (≥ 0.5) based on the SNOT-16 mean score.

CAVEATS
Guidelines, risk of complications may give reason to pause
The 2012 Infectious Diseases Society of America guidelines recommend amoxicillin with clavulanic acid as empiric therapy for acute bacterial rhinosinusitis.⁷ The findings of the study by Garbutt et al—conducted at a time when the incidence of beta-lactamase-producing organisms was low and amoxicillin was the treatment of choice—suggest otherwise.

Serious complications of sinusitis, such as brain abscess, periorbital cellulitis, and meningitis, can occur, however. Patients who deteriorate clinically or develop high fever or severe headache require close follow-up, which may include further diagnostic evaluation or consultation with an otolaryngologist. Evidence is lacking as to whether antibiotics prevent such complications.⁵

CHALLENGES TO IMPLEMENTATION
Managing patient expectations
Many patients with symptoms of acute rhinosinusitis think they need an antibiotic. Managing their expectations and providing instructions about supportive treatments are time consuming and may be

difficult.

Nonetheless, we’re optimistic: We think that most patients today are aware of the problems associated with antibiotic resistance and wary of “superbugs,” and will therefore be receptive to this practice change. Clinicians can help by reminding patients of the adverse effects of antibiotics and the natural course of rhinosinusitis, as well as by offering symptomatic treatments.

REFERENCES
1. Garbutt J, Banister C, Spitznagel E, et al. Amoxicillin for acute rhinosinusitis: a randomized controlled trial. JAMA. 2012;307:685-692.

2. Centers for Disease Control and Prevention. Summary health statistics for US adults: National Health Interview Survey 2010. January 2012. www.cdc.gov/nchs/data/series/sr_10/sr10_252.pdf. Accessed July 9, 2012.

3. Rosenfeld RM, Andes D, Bhattacharyya N, et al. Clinical practice guideline: adult sinusitis. Otolaryngol Head Neck Surg. 2007:137(3 suppl):S1-S31.

4. Hickner JM, Bartlett JG, Besser RE, et al; American Academy of Family Physians; American College of Physicians; American Society of Internal Medicine; Centers for Disease Control; Infectious Disease Society of America. Principles of appropriate antibiotic use for acute rhinosinusitis in adults; background. Ann Intern Med. 2001;134:498-505.

5. Ahovuo-Saloranta A, Borisenk OV, Kovanen N, et al. Antibiotics for acute maxillary sinusitis. Cochrane Database Sys Rev. 2008(2):CD000243.

6. Allen G, Kelsberg G, Jankowski TA. Do nasal decongestants relieve symptoms? J Fam Pract. 2003;52:714-724.

7. Chow AW, Benninger MS, Brook I, et al. IDSA clinical practice guideline for acute bacterial rhinosinusitis in children and adults. Clin Infect Dis. 2012;54:e72-e112.

8. Zalmanovici A, Yaphe J. Intranasal steroids for acute sinusitis. Cochrane Database Syst Rev. 2009(4):CD005149.

9. Schumann A, Hickner, J. Patients insist on antibiotics for sinusitis? Here is a good reason to say “no.” J Fam Pract. 2008;57:464-468.

10. Young J, De Sutter A, Merenstein D, et al. Antibiotics for adults with clinically diagnosed acute rhinosinusitis: a meta-analysis of individual patient data. Lancet. 2008;371:908-914.

11. Gill JM, Fleischut P, Haas S. Use of antibiotics for adult upper respiratory infections in outpatient settings: a national ambulatory network study. Fam Med. 2006;38:349-354.

12. Shehab N, Patel PR, Srinivasan A, et al. Emergency department visits for antibiotic-associated adverse events. Clin Infect Dis. 2008; 47:735-743.

ACKNOWLEDGEMENT
The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Copyright © 2012 The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2012;61(10):610-612.

Practice Changer
Stop prescribing amoxicillin for acute rhinosinusitis. It’s unlikely to provide a speedier recovery than OTC remedies alone.¹

Strength of recommendation
B: Based on a single high-quality randomized controlled trial.

ILLUSTRATIVE CASE
A 28-year-old man comes to your clinic after experiencing fatigue, purulent nasal discharge, and unilateral facial pain for nearly

10 days. Overall, he appears healthy, and you diagnose acute rhinosinusitis. You suggest OTC remedies for supportive care and wonder if a course of amoxicillin would speed his

recovery.

Each year, more than 30 million Americans—about one in seven adults—are diagnosed with sinusitis.² No more than 2% of these cases are thought to be bacterial.³

CDC guidelines for the diagnosis of acute bacterial rhinosinusitis include symptoms that last seven or more days, with maxillary pain or tenderness in the face or teeth and purulent nasal secretions.⁴ Patients with symptoms lasting less than seven days are unlikely to have a bacterial infection. But the nonspecific signs and symptoms included in the CDC guidelines limit their usefulness in determining whether the cause of the sinusitis is bacterial or viral on clinical grounds alone.

Most cases of sinusitis spontaneously resolve
In patients with acute bacterial sinusitis, the American Academy of Otolaryngology–Head and Neck Surgery (AAO–HNS) guidelines advocate watchful waiting and symptom relief with nasal oxymetazoline, pseudoephedrine, and saline nasal irrigation.³ The rate of spontaneous resolution is high: 80% of patients with clinically diagnosed sinusitis improve without treatment within two weeks.^1,5

Traditional decongestants and mucolytics have not demonstrated efficacy in resolving sinusitis, although rigorous evaluation is lacking. Other treatments, such as saline irrigation and intranasal corticosteroids, are of unclear benefit and need further study.^6-8

Lack of evidence has done little to curtail antibiotic use
A previous PURL that was based on a meta-analysis of antibiotic treatment trials for sinusitis recommended that we stop prescribing antibiotics for adults with acute sinusitis unless their symptoms are severe.^9,10 Yet antibiotics remain the mainstay of treatment.

Despite the AAO–HNS guidelines, evidence of spontaneous resolution, and accumulating data on the lack of efficacy of antimicrobials for sinusitis, 81% of patients diagnosed with acute sinusitis were given prescriptions for antibiotics, a study of primary care practices showed.¹¹ Frequent use of antibiotics contributes to high rates of drug resistance, and adverse events related to antibiotic use account for an estimated 142,500 emergency department visits annually.¹²

STUDY SUMMARY
Little benefit from amoxicillin, even for severe cases
Garbutt and colleagues revisited the issue, randomizing 166 patients from 10 primary care practices to receive amoxicillin plus symptomatic treatment or placebo plus symptomatic treatment for acute rhinosinusitis.¹

To be eligible for the study, patients had to be between the ages of 18 and 70, meet CDC diagnostic criteria for acute rhinosinusitis, and have moderate to very severe symptoms that were of seven- to-28-day duration and worsening or not improving, or of < 7-day duration but had worsened after an initial improvement. Exclusion criteria included complications from sinusitis, a history of allergy to penicillin or amoxicillin, antibiotic use in the past four weeks, comorbidities that impair immune function, cystic fibrosis, pregnancy, and mild symptoms.

Both groups had similar baseline characteristics, with participants who were predominantly white (79%) and female (64%). All the participants received a supply of symptomatic treatments: acetaminophen, guaifenesin, dextromethorphan, and sustained-release pseudoephedrine. The treatment group also received amoxicillin 1,500 mg/d, divided into three doses; the placebo group received identical-looking placebo pills.

Patients were assessed with the Sino-nasal Outcome Test-16 (SNOT-16), a validated measure that asks patients to assess both the severity and frequency of 16 sinus symptoms. SNOT-16 uses a 0-to-3 rating scale (0 = no problem; 3 = severe problem), with a clinically important difference of ≥ 0.5 on the mean score. The test was administered at enrollment and at days 3, 7, and 10. The disease-specific quality of life at day 3 was the primary outcome.

There was no statistically significantly difference in SNOT-16 scores between the amoxicillin and placebo groups on days 3 and 10. On day 7, there was a small statistically significant improvement in the amoxicillin group, but it did not reach the level of clinical importance (≥ 0.5) based on SNOT-16’s mean score.

The authors also asked participants to retrospectively assess symptom change since enrollment on a six-point scale. Those who reported that their symptoms were “a lot better” or “absent” were characterized as significantly improved. The results correlated with the data from the SNOT-16, showing no difference between the amoxicillin and control groups at days 3 and 10. On day 7, 74% of patients treated with amoxicillin self-

reported significant improvement in symptoms since the start of the study, versus 56% in the control group. The number needed to treat was 6 (95% confidence interval, 3 to 34; P = .02) for a reduction in symptoms at day 7.

Patients in both groups had similar rates of absenteeism, inability to perform usual activities, relapse and recurrence, and use of additional health care. Satisfaction with treatment was similar, as well.

No serious adverse effects occurred. Both groups reported similar frequencies (< 10%) of nausea, diarrhea, abdominal pain, or vaginitis.

WHAT’S NEW
Even severe sinusitis resolves without antibiotics
Previous studies recommended foregoing antibiotics for acute sinusitis, except when symptoms are severe. This study—in which more than half (52%) of patients in each group had symptoms rated severe or very severe—found no benefit to adding amoxicillin to supportive treatments.¹ Antibiotics did not shorten the duration of illness, prevent relapse and recurrence, or improve satisfaction with treatment. The researchers found a statistically significant difference between groups on day 7 of 0.19 points, but no clinically meaningful difference (≥ 0.5) based on the SNOT-16 mean score.

CAVEATS
Guidelines, risk of complications may give reason to pause
The 2012 Infectious Diseases Society of America guidelines recommend amoxicillin with clavulanic acid as empiric therapy for acute bacterial rhinosinusitis.⁷ The findings of the study by Garbutt et al—conducted at a time when the incidence of beta-lactamase-producing organisms was low and amoxicillin was the treatment of choice—suggest otherwise.

Serious complications of sinusitis, such as brain abscess, periorbital cellulitis, and meningitis, can occur, however. Patients who deteriorate clinically or develop high fever or severe headache require close follow-up, which may include further diagnostic evaluation or consultation with an otolaryngologist. Evidence is lacking as to whether antibiotics prevent such complications.⁵

CHALLENGES TO IMPLEMENTATION
Managing patient expectations
Many patients with symptoms of acute rhinosinusitis think they need an antibiotic. Managing their expectations and providing instructions about supportive treatments are time consuming and may be

difficult.

Nonetheless, we’re optimistic: We think that most patients today are aware of the problems associated with antibiotic resistance and wary of “superbugs,” and will therefore be receptive to this practice change. Clinicians can help by reminding patients of the adverse effects of antibiotics and the natural course of rhinosinusitis, as well as by offering symptomatic treatments.

REFERENCES
1. Garbutt J, Banister C, Spitznagel E, et al. Amoxicillin for acute rhinosinusitis: a randomized controlled trial. JAMA. 2012;307:685-692.

2. Centers for Disease Control and Prevention. Summary health statistics for US adults: National Health Interview Survey 2010. January 2012. www.cdc.gov/nchs/data/series/sr_10/sr10_252.pdf. Accessed July 9, 2012.

3. Rosenfeld RM, Andes D, Bhattacharyya N, et al. Clinical practice guideline: adult sinusitis. Otolaryngol Head Neck Surg. 2007:137(3 suppl):S1-S31.

4. Hickner JM, Bartlett JG, Besser RE, et al; American Academy of Family Physians; American College of Physicians; American Society of Internal Medicine; Centers for Disease Control; Infectious Disease Society of America. Principles of appropriate antibiotic use for acute rhinosinusitis in adults; background. Ann Intern Med. 2001;134:498-505.

5. Ahovuo-Saloranta A, Borisenk OV, Kovanen N, et al. Antibiotics for acute maxillary sinusitis. Cochrane Database Sys Rev. 2008(2):CD000243.

6. Allen G, Kelsberg G, Jankowski TA. Do nasal decongestants relieve symptoms? J Fam Pract. 2003;52:714-724.

7. Chow AW, Benninger MS, Brook I, et al. IDSA clinical practice guideline for acute bacterial rhinosinusitis in children and adults. Clin Infect Dis. 2012;54:e72-e112.

8. Zalmanovici A, Yaphe J. Intranasal steroids for acute sinusitis. Cochrane Database Syst Rev. 2009(4):CD005149.

9. Schumann A, Hickner, J. Patients insist on antibiotics for sinusitis? Here is a good reason to say “no.” J Fam Pract. 2008;57:464-468.

10. Young J, De Sutter A, Merenstein D, et al. Antibiotics for adults with clinically diagnosed acute rhinosinusitis: a meta-analysis of individual patient data. Lancet. 2008;371:908-914.

11. Gill JM, Fleischut P, Haas S. Use of antibiotics for adult upper respiratory infections in outpatient settings: a national ambulatory network study. Fam Med. 2006;38:349-354.

12. Shehab N, Patel PR, Srinivasan A, et al. Emergency department visits for antibiotic-associated adverse events. Clin Infect Dis. 2008; 47:735-743.

ACKNOWLEDGEMENT
The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Copyright © 2012 The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2012;61(10):610-612.

ILLUSTRATIVE CASE

A 28-year-old man comes to your clinic after suffering from fatigue, purulent nasal discharge, and unilateral facial pain for nearly 10 days. Overall, he appears healthy, and you diagnose acute rhinosinusitis. You suggest OTC remedies for supportive care and wonder if a course of amoxicillin would speed his recovery.

Each year, more than 30 million Americans—about one in 7 adults—are diagnosed with sinusitis.² No more than 2% of these cases are thought to be bacterial.³

Centers for Disease Control and Prevention (CDC) guidelines for the diagnosis of acute bacterial rhinosinusitis include symptoms that last 7 days or more, with maxillary pain or tenderness in the face or teeth and purulent nasal secretions.⁴ Patients with symptoms lasting less than 7 days are unlikely to have a bacterial infection. But the non-specific signs and symptoms included in the CDC guidelines limit their usefulness in determining whether the cause of the sinusitis is bacterial or viral on clinical grounds alone.

Most cases of sinusitis spontaneously resolve
In patients with acute bacterial sinusitis, the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) guidelines advocate watchful waiting and symptom relief with nasal oxymetazoline, pseudoephedrine, and saline nasal irrigation.³ The rate of spontaneous resolution is high: 80% of patients with clinically diagnosed sinusitis improve without treatment within 2 weeks.^1,5

Traditional decongestants and mucolytics have not demonstrated efficacy in resolving sinusitis, although rigorous evaluation is lacking. Other treatments, such as saline irrigation and intranasal corticosteroids, are of unclear benefit and need further study.^6-8

Lack of evidence has done little to curtail antibiotic use
An earlier PURL based on a meta-analysis of antibiotic treatment trials for sinusitis recommended that we stop prescribing antibiotics for adults with acute sinusitis unless their symptoms are severe.^9,10 Yet antibiotics remain the mainstay of treatment.

Despite the AAO-HNS guidelines, evidence of spontaneous resolution, and accumulating data on the lack of efficacy of antimicrobials for sinusitis, 81% of patients diagnosed with acute sinusitis were given prescriptions for antibiotics, a study of primary care practices showed.¹¹ Frequent use of antibiotics contributes to high rates of drug resistance, and adverse events related to antibiotic use account for an estimated 142,500 emergency department visits annually.¹²

STUDY SUMMARY: Little benefit from amoxicillin, even for severe cases

Garbutt and colleagues revisited the issue, randomizing 166 patients from 10 primary care practices to amoxicillin plus symptomatic treatment or placebo plus symptomatic treatment for acute rhinosinusitis.¹ To be eligible for the study, patients had to be between the ages of 18 and 70 years, meet CDC diagnostic criteria for acute rhinosinusitis, and have moderate to very severe symptoms that were of 7- to-28-day duration and worsening or not improving or of <7-day duration but had worsened after an initial improvement. Exclusion criteria included complications from sinusitis, a history of allergy to penicillin or amoxicillin, antibiotic use in the past 4 weeks, comorbidities that impair immune function, cystic fibrosis, pregnancy, and mild symptoms.

Both groups had similar baseline characteristics, with participants who were predominantly white (79%) and female (64%). All the participants received a supply of symptomatic treatments: acetaminophen, guaifenesin, dextromethorphan, and sustained-release pseudoephedrine. The treatment group also received amoxicillin 1500 mg/d, divided into 3 doses; the placebo group received identical-looking placebo pills.

Patients were assessed with the Sino-nasal Outcome Test-16 (SNOT-16), a validated measure that asks patients to assess both the severity and frequency of 16 sinus symptoms. SNOT-16 uses a 0-to-3 rating scale (0=no problem; 3=severe problem), with a clinically important difference of ≥0.5 on the mean score. The test was administered at enrollment and at Days 3, 7, and 10. The disease-specific quality of life at Day 3 was the primary outcome.

There was no statistically significantly difference in SNOT-16 scores between the amoxicillin and placebo groups on Days 3 and 10. On Day 7, there was a small statistically significant improvement in the amoxicillin group, but it did not reach the level of clinical importance (≥0.5) based on SNOT-16’s mean score.

The authors also asked participants to retrospectively assess symptom change since enrollment on a 6-point scale. Those who reported that their symptoms were “a lot better” or “absent” were characterized as significantly improved. The results correlated with the data from the SNOT-16, showing no difference between the amoxicillin and control group at Days 3 and 10. On Day 7, 74% of patients treated with amoxicillin self- reported significant improvement in symptoms since the start of the study, vs 56% in the control group. The number needed to treat was 6 (95% confidence interval, 3-34; P= .02) for a reduction in symptoms at Day 7.

Patients in both groups had similar rates of absenteeism, inability to perform usual activities, relapse and recurrence, and use of additional health care. Satisfaction with treatment was similar, as well.

No serious adverse effects occurred. Both groups reported similar frequencies (<10%) of nausea, diarrhea, abdominal pain, or vaginitis.

WHAT’S NEW: Even severe sinusitis resolves without antibiotics

Previous studies recommended foregoing antibiotics for acute sinusitis, except when symptoms are severe. This study—in which more than half (52%) of patients in each group had symptoms rated severe or very severe—found no benefit to adding amoxicillin to supportive treatments.¹ Antibiotics did not shorten the duration of illness, prevent relapse and recurrence, or improve satisfaction with treatment. The researchers found a statistically significant difference between groups on Day 7 of 0.19 points, but no clinically meaningful difference (≥0.5) based on the SNOT-16 mean score.

CAVEATS: Guidelines, risk of complications may give reason to pause

The 2012 Infectious Diseases Society of America guidelines recommend amoxicillin with clavulanic acid as empiric therapy for acute bacterial rhinosinusitis.⁷ The findings of the study by Garbutt et al—conducted at a time when the incidence of beta-lactamase-producing organisms was low and amoxicillin was the treatment of choice—suggest otherwise.

Serious complications of sinusitis, such as brain abscess, periorbital cellulitis, and meningitis, can occur, however. Patients who deteriorate clinically or develop high fever or severe headache require close follow-up, which may include further diagnostic evaluation or consultation with an otolaryngologist. Evidence is lacking as to whether antibiotics prevent such complications.⁵

CHALLENGES TO IMPLEMENTATION: Managing patient expectations

Many patients with symptoms of acute rhinosinusitis think they need an antibiotic. Managing their expectations and providing instructions about supportive treatments are time consuming and may be difficult.

Nonetheless, we’re optimistic: We think that most patients today are aware of the problems associated with antibiotic resistance and wary of “superbugs,” and will therefore be receptive to this practice change. Physicians can help by reminding patients of the adverse effects of antibiotics and the natural course of rhino-sinusitis, as well as by offering symptomatic treatments.

Acknowledgement

The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 28-year-old man comes to your clinic after suffering from fatigue, purulent nasal discharge, and unilateral facial pain for nearly 10 days. Overall, he appears healthy, and you diagnose acute rhinosinusitis. You suggest OTC remedies for supportive care and wonder if a course of amoxicillin would speed his recovery.

Each year, more than 30 million Americans—about one in 7 adults—are diagnosed with sinusitis.² No more than 2% of these cases are thought to be bacterial.³

Centers for Disease Control and Prevention (CDC) guidelines for the diagnosis of acute bacterial rhinosinusitis include symptoms that last 7 days or more, with maxillary pain or tenderness in the face or teeth and purulent nasal secretions.⁴ Patients with symptoms lasting less than 7 days are unlikely to have a bacterial infection. But the non-specific signs and symptoms included in the CDC guidelines limit their usefulness in determining whether the cause of the sinusitis is bacterial or viral on clinical grounds alone.

Most cases of sinusitis spontaneously resolve
In patients with acute bacterial sinusitis, the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) guidelines advocate watchful waiting and symptom relief with nasal oxymetazoline, pseudoephedrine, and saline nasal irrigation.³ The rate of spontaneous resolution is high: 80% of patients with clinically diagnosed sinusitis improve without treatment within 2 weeks.^1,5

Traditional decongestants and mucolytics have not demonstrated efficacy in resolving sinusitis, although rigorous evaluation is lacking. Other treatments, such as saline irrigation and intranasal corticosteroids, are of unclear benefit and need further study.^6-8

Lack of evidence has done little to curtail antibiotic use
An earlier PURL based on a meta-analysis of antibiotic treatment trials for sinusitis recommended that we stop prescribing antibiotics for adults with acute sinusitis unless their symptoms are severe.^9,10 Yet antibiotics remain the mainstay of treatment.

Despite the AAO-HNS guidelines, evidence of spontaneous resolution, and accumulating data on the lack of efficacy of antimicrobials for sinusitis, 81% of patients diagnosed with acute sinusitis were given prescriptions for antibiotics, a study of primary care practices showed.¹¹ Frequent use of antibiotics contributes to high rates of drug resistance, and adverse events related to antibiotic use account for an estimated 142,500 emergency department visits annually.¹²

STUDY SUMMARY: Little benefit from amoxicillin, even for severe cases

Garbutt and colleagues revisited the issue, randomizing 166 patients from 10 primary care practices to amoxicillin plus symptomatic treatment or placebo plus symptomatic treatment for acute rhinosinusitis.¹ To be eligible for the study, patients had to be between the ages of 18 and 70 years, meet CDC diagnostic criteria for acute rhinosinusitis, and have moderate to very severe symptoms that were of 7- to-28-day duration and worsening or not improving or of <7-day duration but had worsened after an initial improvement. Exclusion criteria included complications from sinusitis, a history of allergy to penicillin or amoxicillin, antibiotic use in the past 4 weeks, comorbidities that impair immune function, cystic fibrosis, pregnancy, and mild symptoms.

Both groups had similar baseline characteristics, with participants who were predominantly white (79%) and female (64%). All the participants received a supply of symptomatic treatments: acetaminophen, guaifenesin, dextromethorphan, and sustained-release pseudoephedrine. The treatment group also received amoxicillin 1500 mg/d, divided into 3 doses; the placebo group received identical-looking placebo pills.

Patients were assessed with the Sino-nasal Outcome Test-16 (SNOT-16), a validated measure that asks patients to assess both the severity and frequency of 16 sinus symptoms. SNOT-16 uses a 0-to-3 rating scale (0=no problem; 3=severe problem), with a clinically important difference of ≥0.5 on the mean score. The test was administered at enrollment and at Days 3, 7, and 10. The disease-specific quality of life at Day 3 was the primary outcome.

There was no statistically significantly difference in SNOT-16 scores between the amoxicillin and placebo groups on Days 3 and 10. On Day 7, there was a small statistically significant improvement in the amoxicillin group, but it did not reach the level of clinical importance (≥0.5) based on SNOT-16’s mean score.

The authors also asked participants to retrospectively assess symptom change since enrollment on a 6-point scale. Those who reported that their symptoms were “a lot better” or “absent” were characterized as significantly improved. The results correlated with the data from the SNOT-16, showing no difference between the amoxicillin and control group at Days 3 and 10. On Day 7, 74% of patients treated with amoxicillin self- reported significant improvement in symptoms since the start of the study, vs 56% in the control group. The number needed to treat was 6 (95% confidence interval, 3-34; P= .02) for a reduction in symptoms at Day 7.

Patients in both groups had similar rates of absenteeism, inability to perform usual activities, relapse and recurrence, and use of additional health care. Satisfaction with treatment was similar, as well.

No serious adverse effects occurred. Both groups reported similar frequencies (<10%) of nausea, diarrhea, abdominal pain, or vaginitis.

WHAT’S NEW: Even severe sinusitis resolves without antibiotics

Previous studies recommended foregoing antibiotics for acute sinusitis, except when symptoms are severe. This study—in which more than half (52%) of patients in each group had symptoms rated severe or very severe—found no benefit to adding amoxicillin to supportive treatments.¹ Antibiotics did not shorten the duration of illness, prevent relapse and recurrence, or improve satisfaction with treatment. The researchers found a statistically significant difference between groups on Day 7 of 0.19 points, but no clinically meaningful difference (≥0.5) based on the SNOT-16 mean score.

CAVEATS: Guidelines, risk of complications may give reason to pause

The 2012 Infectious Diseases Society of America guidelines recommend amoxicillin with clavulanic acid as empiric therapy for acute bacterial rhinosinusitis.⁷ The findings of the study by Garbutt et al—conducted at a time when the incidence of beta-lactamase-producing organisms was low and amoxicillin was the treatment of choice—suggest otherwise.

Serious complications of sinusitis, such as brain abscess, periorbital cellulitis, and meningitis, can occur, however. Patients who deteriorate clinically or develop high fever or severe headache require close follow-up, which may include further diagnostic evaluation or consultation with an otolaryngologist. Evidence is lacking as to whether antibiotics prevent such complications.⁵

CHALLENGES TO IMPLEMENTATION: Managing patient expectations

Many patients with symptoms of acute rhinosinusitis think they need an antibiotic. Managing their expectations and providing instructions about supportive treatments are time consuming and may be difficult.

Nonetheless, we’re optimistic: We think that most patients today are aware of the problems associated with antibiotic resistance and wary of “superbugs,” and will therefore be receptive to this practice change. Physicians can help by reminding patients of the adverse effects of antibiotics and the natural course of rhino-sinusitis, as well as by offering symptomatic treatments.

Acknowledgement

The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 28-year-old man comes to your clinic after suffering from fatigue, purulent nasal discharge, and unilateral facial pain for nearly 10 days. Overall, he appears healthy, and you diagnose acute rhinosinusitis. You suggest OTC remedies for supportive care and wonder if a course of amoxicillin would speed his recovery.

Each year, more than 30 million Americans—about one in 7 adults—are diagnosed with sinusitis.² No more than 2% of these cases are thought to be bacterial.³

Centers for Disease Control and Prevention (CDC) guidelines for the diagnosis of acute bacterial rhinosinusitis include symptoms that last 7 days or more, with maxillary pain or tenderness in the face or teeth and purulent nasal secretions.⁴ Patients with symptoms lasting less than 7 days are unlikely to have a bacterial infection. But the non-specific signs and symptoms included in the CDC guidelines limit their usefulness in determining whether the cause of the sinusitis is bacterial or viral on clinical grounds alone.

Most cases of sinusitis spontaneously resolve
In patients with acute bacterial sinusitis, the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) guidelines advocate watchful waiting and symptom relief with nasal oxymetazoline, pseudoephedrine, and saline nasal irrigation.³ The rate of spontaneous resolution is high: 80% of patients with clinically diagnosed sinusitis improve without treatment within 2 weeks.^1,5

Traditional decongestants and mucolytics have not demonstrated efficacy in resolving sinusitis, although rigorous evaluation is lacking. Other treatments, such as saline irrigation and intranasal corticosteroids, are of unclear benefit and need further study.^6-8

Lack of evidence has done little to curtail antibiotic use
An earlier PURL based on a meta-analysis of antibiotic treatment trials for sinusitis recommended that we stop prescribing antibiotics for adults with acute sinusitis unless their symptoms are severe.^9,10 Yet antibiotics remain the mainstay of treatment.

Despite the AAO-HNS guidelines, evidence of spontaneous resolution, and accumulating data on the lack of efficacy of antimicrobials for sinusitis, 81% of patients diagnosed with acute sinusitis were given prescriptions for antibiotics, a study of primary care practices showed.¹¹ Frequent use of antibiotics contributes to high rates of drug resistance, and adverse events related to antibiotic use account for an estimated 142,500 emergency department visits annually.¹²

STUDY SUMMARY: Little benefit from amoxicillin, even for severe cases

Garbutt and colleagues revisited the issue, randomizing 166 patients from 10 primary care practices to amoxicillin plus symptomatic treatment or placebo plus symptomatic treatment for acute rhinosinusitis.¹ To be eligible for the study, patients had to be between the ages of 18 and 70 years, meet CDC diagnostic criteria for acute rhinosinusitis, and have moderate to very severe symptoms that were of 7- to-28-day duration and worsening or not improving or of <7-day duration but had worsened after an initial improvement. Exclusion criteria included complications from sinusitis, a history of allergy to penicillin or amoxicillin, antibiotic use in the past 4 weeks, comorbidities that impair immune function, cystic fibrosis, pregnancy, and mild symptoms.

Both groups had similar baseline characteristics, with participants who were predominantly white (79%) and female (64%). All the participants received a supply of symptomatic treatments: acetaminophen, guaifenesin, dextromethorphan, and sustained-release pseudoephedrine. The treatment group also received amoxicillin 1500 mg/d, divided into 3 doses; the placebo group received identical-looking placebo pills.

Patients were assessed with the Sino-nasal Outcome Test-16 (SNOT-16), a validated measure that asks patients to assess both the severity and frequency of 16 sinus symptoms. SNOT-16 uses a 0-to-3 rating scale (0=no problem; 3=severe problem), with a clinically important difference of ≥0.5 on the mean score. The test was administered at enrollment and at Days 3, 7, and 10. The disease-specific quality of life at Day 3 was the primary outcome.

There was no statistically significantly difference in SNOT-16 scores between the amoxicillin and placebo groups on Days 3 and 10. On Day 7, there was a small statistically significant improvement in the amoxicillin group, but it did not reach the level of clinical importance (≥0.5) based on SNOT-16’s mean score.

The authors also asked participants to retrospectively assess symptom change since enrollment on a 6-point scale. Those who reported that their symptoms were “a lot better” or “absent” were characterized as significantly improved. The results correlated with the data from the SNOT-16, showing no difference between the amoxicillin and control group at Days 3 and 10. On Day 7, 74% of patients treated with amoxicillin self- reported significant improvement in symptoms since the start of the study, vs 56% in the control group. The number needed to treat was 6 (95% confidence interval, 3-34; P= .02) for a reduction in symptoms at Day 7.

Patients in both groups had similar rates of absenteeism, inability to perform usual activities, relapse and recurrence, and use of additional health care. Satisfaction with treatment was similar, as well.

No serious adverse effects occurred. Both groups reported similar frequencies (<10%) of nausea, diarrhea, abdominal pain, or vaginitis.

WHAT’S NEW: Even severe sinusitis resolves without antibiotics

Previous studies recommended foregoing antibiotics for acute sinusitis, except when symptoms are severe. This study—in which more than half (52%) of patients in each group had symptoms rated severe or very severe—found no benefit to adding amoxicillin to supportive treatments.¹ Antibiotics did not shorten the duration of illness, prevent relapse and recurrence, or improve satisfaction with treatment. The researchers found a statistically significant difference between groups on Day 7 of 0.19 points, but no clinically meaningful difference (≥0.5) based on the SNOT-16 mean score.

CAVEATS: Guidelines, risk of complications may give reason to pause

The 2012 Infectious Diseases Society of America guidelines recommend amoxicillin with clavulanic acid as empiric therapy for acute bacterial rhinosinusitis.⁷ The findings of the study by Garbutt et al—conducted at a time when the incidence of beta-lactamase-producing organisms was low and amoxicillin was the treatment of choice—suggest otherwise.

Serious complications of sinusitis, such as brain abscess, periorbital cellulitis, and meningitis, can occur, however. Patients who deteriorate clinically or develop high fever or severe headache require close follow-up, which may include further diagnostic evaluation or consultation with an otolaryngologist. Evidence is lacking as to whether antibiotics prevent such complications.⁵

CHALLENGES TO IMPLEMENTATION: Managing patient expectations

Many patients with symptoms of acute rhinosinusitis think they need an antibiotic. Managing their expectations and providing instructions about supportive treatments are time consuming and may be difficult.

Nonetheless, we’re optimistic: We think that most patients today are aware of the problems associated with antibiotic resistance and wary of “superbugs,” and will therefore be receptive to this practice change. Physicians can help by reminding patients of the adverse effects of antibiotics and the natural course of rhino-sinusitis, as well as by offering symptomatic treatments.

Acknowledgement

The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.