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3-year interval between Pap smears adequate for women with prior negative results
This study predicts that among women aged 30 to 64 years with 3 recent, negative Papanicolaou (Pap) smears, extending the interval for cervical cancer screening from 1 to 3 years would lead to an excess risk of cervical cancer of 3 in 100,000.
For women aged 30 to 44 years, preventing 1 case of cervical cancer through yearly Pap smears would require an additional 69,665 Pap smears and 3861 colposcopies (compared with screening 3 years after the last negative Pap smear). Clinicians should feel comfortable extending the interval for Pap smears from 1 to 3 years in women with prior normal results and a high likelihood of follow-up.
This study predicts that among women aged 30 to 64 years with 3 recent, negative Papanicolaou (Pap) smears, extending the interval for cervical cancer screening from 1 to 3 years would lead to an excess risk of cervical cancer of 3 in 100,000.
For women aged 30 to 44 years, preventing 1 case of cervical cancer through yearly Pap smears would require an additional 69,665 Pap smears and 3861 colposcopies (compared with screening 3 years after the last negative Pap smear). Clinicians should feel comfortable extending the interval for Pap smears from 1 to 3 years in women with prior normal results and a high likelihood of follow-up.
This study predicts that among women aged 30 to 64 years with 3 recent, negative Papanicolaou (Pap) smears, extending the interval for cervical cancer screening from 1 to 3 years would lead to an excess risk of cervical cancer of 3 in 100,000.
For women aged 30 to 44 years, preventing 1 case of cervical cancer through yearly Pap smears would require an additional 69,665 Pap smears and 3861 colposcopies (compared with screening 3 years after the last negative Pap smear). Clinicians should feel comfortable extending the interval for Pap smears from 1 to 3 years in women with prior normal results and a high likelihood of follow-up.
Ezetimibe plus atorvastatin lowers cholesterol
Ezetimibe plus atorvastatin lowers low-density lipoprotein (LDL) cholesterol more than either alone. When combined with low-dose atorvastatin (10 mg), ezetimibe achieves reductions similar to those seen with atorvastatin (80 mg) alone in LDL cholesterol, the ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol, and triglycerides.
Despite these modest reductions in cholesterol, this study does not provide evidence that this combination lessens cardiovascular morbidity or mortality. With this caveat, adding ezetimibe to atorvastatin may be a reasonable alternative for patients already on high-dose atorvastatin who either can’t reach target cholesterol levels or experience significant side effects.
Ezetimibe plus atorvastatin lowers low-density lipoprotein (LDL) cholesterol more than either alone. When combined with low-dose atorvastatin (10 mg), ezetimibe achieves reductions similar to those seen with atorvastatin (80 mg) alone in LDL cholesterol, the ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol, and triglycerides.
Despite these modest reductions in cholesterol, this study does not provide evidence that this combination lessens cardiovascular morbidity or mortality. With this caveat, adding ezetimibe to atorvastatin may be a reasonable alternative for patients already on high-dose atorvastatin who either can’t reach target cholesterol levels or experience significant side effects.
Ezetimibe plus atorvastatin lowers low-density lipoprotein (LDL) cholesterol more than either alone. When combined with low-dose atorvastatin (10 mg), ezetimibe achieves reductions similar to those seen with atorvastatin (80 mg) alone in LDL cholesterol, the ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol, and triglycerides.
Despite these modest reductions in cholesterol, this study does not provide evidence that this combination lessens cardiovascular morbidity or mortality. With this caveat, adding ezetimibe to atorvastatin may be a reasonable alternative for patients already on high-dose atorvastatin who either can’t reach target cholesterol levels or experience significant side effects.
Clindamycin for vaginosis reduces prematurity and late miscarriage
Using oral clindamycin to treat women with asymptomatic bacterial vaginosis during their second trimester (between 12 and 22 weeks estimated gestational age) reduces the number of premature births and late miscarriages. The study did not demonstrate a difference in the number of neonatal intensive care unit admissions, mean birth weight, or gestational age.
This is the first study demonstrating benefits in treating asymptomatic bacterial vaginosis early in pregnancy. It still needs to be determined, in larger trials, whether generalized screening and treatment for asymptomatic bacterial vaginosis in the early second trimester is beneficial and cost-effective.
Using oral clindamycin to treat women with asymptomatic bacterial vaginosis during their second trimester (between 12 and 22 weeks estimated gestational age) reduces the number of premature births and late miscarriages. The study did not demonstrate a difference in the number of neonatal intensive care unit admissions, mean birth weight, or gestational age.
This is the first study demonstrating benefits in treating asymptomatic bacterial vaginosis early in pregnancy. It still needs to be determined, in larger trials, whether generalized screening and treatment for asymptomatic bacterial vaginosis in the early second trimester is beneficial and cost-effective.
Using oral clindamycin to treat women with asymptomatic bacterial vaginosis during their second trimester (between 12 and 22 weeks estimated gestational age) reduces the number of premature births and late miscarriages. The study did not demonstrate a difference in the number of neonatal intensive care unit admissions, mean birth weight, or gestational age.
This is the first study demonstrating benefits in treating asymptomatic bacterial vaginosis early in pregnancy. It still needs to be determined, in larger trials, whether generalized screening and treatment for asymptomatic bacterial vaginosis in the early second trimester is beneficial and cost-effective.
Children with fever and vomiting benefit from immediate antibiotics for acute otitis media
Starting antibiotics immediately in children with acute otitis media accompanied by fever or vomiting results in better symptom relief and decreased sleep disturbance when measured after 3 days, as compared with no treatment. Parents who consider these outcomes important may prefer not to delay antibiotic treatment. Conversely, children without fever or vomiting tend to have the same duration of symptoms regardless of antibiotic treatment and are suitable for a “wait and see” approach.
Starting antibiotics immediately in children with acute otitis media accompanied by fever or vomiting results in better symptom relief and decreased sleep disturbance when measured after 3 days, as compared with no treatment. Parents who consider these outcomes important may prefer not to delay antibiotic treatment. Conversely, children without fever or vomiting tend to have the same duration of symptoms regardless of antibiotic treatment and are suitable for a “wait and see” approach.
Starting antibiotics immediately in children with acute otitis media accompanied by fever or vomiting results in better symptom relief and decreased sleep disturbance when measured after 3 days, as compared with no treatment. Parents who consider these outcomes important may prefer not to delay antibiotic treatment. Conversely, children without fever or vomiting tend to have the same duration of symptoms regardless of antibiotic treatment and are suitable for a “wait and see” approach.
When should acute nonvenereal conjunctivitis be treated with topical antibiotics?
Children with suspected or culture-proven acute nonvenereal bacterial conjunctivitis should be treated with topical antibiotics, which hastens clinical and microbiological remission and may prevent potentially serious morbidity. In light of recent evidence regarding the self-limiting nature of conjunctivitis in adults and the development of antibiotic resistance, a “wait-and-see” approach with careful follow-up may be reasonable for adults, but this approach has not been evaluated. (Grade of recommendation: C, based on extrapolation from systematic reviews of specialty clinic trials and cohort studies.)
Evidence summary
Conjunctivitis accounts for 1% to 2% of office visits to primary care practitioners.1 Conjunctivitis is more commonly caused by bacteria in children (50% in 1 study2) than in adults, in whom viral conjunctivitis predominates.3 Treating suspected or culture-proven acute bacterial conjunctivitis with topical antibiotics significantly shortens the clinical course of the disease and results in higher microbiological cure rates than placebo.1,4,5 A meta-analysis of 3 trials based in specialty clinics or hospitals reported significant clinical cure or improvement of bacterial conjunctivitis with 2 to 5 days of topical antibiotics compared with placebo (RR = 1.31, 95% CI, 1.11-1.55, number needed to treat = 5).1 Other articles have reported corneal or systemic complications of bacterial conjunctivitis. For example, 1 review reports that 25% of children with Haemophilus influenzae conjunctivitis develop otitis media.2
Although there is a small risk of complications and longer time course when bacterial conjunctivitis is left untreated, the disease is often self-limited, with a 64% clinical remission rate in patients treated for 2 to 5 days with placebo.1 The rate of spontaneous remission is much higher for adults than for children (71.6% vs 28%, respectively). The Cochrane meta-analysis reported a similar clinical cure rate in children for 6 to 10 days of treatment with topical antibiotics versus placebo. A systematic review of 5 placebo-controlled RCTs reported no serious adverse outcomes in conjunctivitis patients regardless of treatment group.4
Antibiotic resistance is a growing problem. Studies of fluoroquinolone resistance rates report a range of 4% to 50% for ocular bacteria.6 The 50% resistance rate occurred after 4 weeks of topical treatment in postcataract surgery patients.
Overall, this evidence suggests that for adults, watchful waiting rather than initially treating with antibiotics is reasonable, given the self-limited nature and lack of serious outcomes in untreated patients as well as growing concern about antibiotic resistance. Note that this recommendation applies only to acute nonvenereal conjunctivitis. It is generally accepted that conjunctivitis caused by gonococcus or chlamydia should be suspected in all newborns and in severe cases in sexually active young adults. These cases warrant culturing and antibiotic treatment to prevent serious complications.7
Recommendations from others
The American Optometric Association consensus guideline states that ideal treatment should be based on the specific causative organism. The guideline concludes that treatment of bacterial conjunctivitis with antibiotics can reduce symptoms, duration of illness, and chances of recurrence.8
Clinical Commentary by Carin Reust, MD, MSPH, at http://www.fpin.org.
1. Sheikh A, Hurwitz B, Cave J. Antibiotics versus placebo for acute bacterial conjunctivitis (Cochrane Review). In: The Cochrane Library, Issue 3, 2001. Oxford, England: Update Software.
2. Gigliotti F, Hendley JO, Morgan J, Michaels R, Dickens M, Lohr J. J Pediatr 1984;104:623-6.
3. Chung CW, Cohen EJ. West J Med 2000;173:202-5.
4. Sheikh A, Hurwitz B. Br J Gen Pract 2001;51:473-7.
5. Chung C, Cohen E. Bacterial conjunctivitis. Clinical evidence. London: BMJ Publishing Group, 2001: 436-41.
6. Baum J, Barza M. The evolution of antibiotic therapy for bacterial conjunctivitis and keratitis: 1970-2000. Cornea 2000;19:659-72.
7. Morrow GL, Abbott RL. Conjunctivitis. Am Fam Physician 1998;57:735-46.
8. American Optometric Association consensus panel on the care of the patient with conjunctivitis. Optometric clinical practice guideline no. 11, 1996.
Children with suspected or culture-proven acute nonvenereal bacterial conjunctivitis should be treated with topical antibiotics, which hastens clinical and microbiological remission and may prevent potentially serious morbidity. In light of recent evidence regarding the self-limiting nature of conjunctivitis in adults and the development of antibiotic resistance, a “wait-and-see” approach with careful follow-up may be reasonable for adults, but this approach has not been evaluated. (Grade of recommendation: C, based on extrapolation from systematic reviews of specialty clinic trials and cohort studies.)
Evidence summary
Conjunctivitis accounts for 1% to 2% of office visits to primary care practitioners.1 Conjunctivitis is more commonly caused by bacteria in children (50% in 1 study2) than in adults, in whom viral conjunctivitis predominates.3 Treating suspected or culture-proven acute bacterial conjunctivitis with topical antibiotics significantly shortens the clinical course of the disease and results in higher microbiological cure rates than placebo.1,4,5 A meta-analysis of 3 trials based in specialty clinics or hospitals reported significant clinical cure or improvement of bacterial conjunctivitis with 2 to 5 days of topical antibiotics compared with placebo (RR = 1.31, 95% CI, 1.11-1.55, number needed to treat = 5).1 Other articles have reported corneal or systemic complications of bacterial conjunctivitis. For example, 1 review reports that 25% of children with Haemophilus influenzae conjunctivitis develop otitis media.2
Although there is a small risk of complications and longer time course when bacterial conjunctivitis is left untreated, the disease is often self-limited, with a 64% clinical remission rate in patients treated for 2 to 5 days with placebo.1 The rate of spontaneous remission is much higher for adults than for children (71.6% vs 28%, respectively). The Cochrane meta-analysis reported a similar clinical cure rate in children for 6 to 10 days of treatment with topical antibiotics versus placebo. A systematic review of 5 placebo-controlled RCTs reported no serious adverse outcomes in conjunctivitis patients regardless of treatment group.4
Antibiotic resistance is a growing problem. Studies of fluoroquinolone resistance rates report a range of 4% to 50% for ocular bacteria.6 The 50% resistance rate occurred after 4 weeks of topical treatment in postcataract surgery patients.
Overall, this evidence suggests that for adults, watchful waiting rather than initially treating with antibiotics is reasonable, given the self-limited nature and lack of serious outcomes in untreated patients as well as growing concern about antibiotic resistance. Note that this recommendation applies only to acute nonvenereal conjunctivitis. It is generally accepted that conjunctivitis caused by gonococcus or chlamydia should be suspected in all newborns and in severe cases in sexually active young adults. These cases warrant culturing and antibiotic treatment to prevent serious complications.7
Recommendations from others
The American Optometric Association consensus guideline states that ideal treatment should be based on the specific causative organism. The guideline concludes that treatment of bacterial conjunctivitis with antibiotics can reduce symptoms, duration of illness, and chances of recurrence.8
Clinical Commentary by Carin Reust, MD, MSPH, at http://www.fpin.org.
Children with suspected or culture-proven acute nonvenereal bacterial conjunctivitis should be treated with topical antibiotics, which hastens clinical and microbiological remission and may prevent potentially serious morbidity. In light of recent evidence regarding the self-limiting nature of conjunctivitis in adults and the development of antibiotic resistance, a “wait-and-see” approach with careful follow-up may be reasonable for adults, but this approach has not been evaluated. (Grade of recommendation: C, based on extrapolation from systematic reviews of specialty clinic trials and cohort studies.)
Evidence summary
Conjunctivitis accounts for 1% to 2% of office visits to primary care practitioners.1 Conjunctivitis is more commonly caused by bacteria in children (50% in 1 study2) than in adults, in whom viral conjunctivitis predominates.3 Treating suspected or culture-proven acute bacterial conjunctivitis with topical antibiotics significantly shortens the clinical course of the disease and results in higher microbiological cure rates than placebo.1,4,5 A meta-analysis of 3 trials based in specialty clinics or hospitals reported significant clinical cure or improvement of bacterial conjunctivitis with 2 to 5 days of topical antibiotics compared with placebo (RR = 1.31, 95% CI, 1.11-1.55, number needed to treat = 5).1 Other articles have reported corneal or systemic complications of bacterial conjunctivitis. For example, 1 review reports that 25% of children with Haemophilus influenzae conjunctivitis develop otitis media.2
Although there is a small risk of complications and longer time course when bacterial conjunctivitis is left untreated, the disease is often self-limited, with a 64% clinical remission rate in patients treated for 2 to 5 days with placebo.1 The rate of spontaneous remission is much higher for adults than for children (71.6% vs 28%, respectively). The Cochrane meta-analysis reported a similar clinical cure rate in children for 6 to 10 days of treatment with topical antibiotics versus placebo. A systematic review of 5 placebo-controlled RCTs reported no serious adverse outcomes in conjunctivitis patients regardless of treatment group.4
Antibiotic resistance is a growing problem. Studies of fluoroquinolone resistance rates report a range of 4% to 50% for ocular bacteria.6 The 50% resistance rate occurred after 4 weeks of topical treatment in postcataract surgery patients.
Overall, this evidence suggests that for adults, watchful waiting rather than initially treating with antibiotics is reasonable, given the self-limited nature and lack of serious outcomes in untreated patients as well as growing concern about antibiotic resistance. Note that this recommendation applies only to acute nonvenereal conjunctivitis. It is generally accepted that conjunctivitis caused by gonococcus or chlamydia should be suspected in all newborns and in severe cases in sexually active young adults. These cases warrant culturing and antibiotic treatment to prevent serious complications.7
Recommendations from others
The American Optometric Association consensus guideline states that ideal treatment should be based on the specific causative organism. The guideline concludes that treatment of bacterial conjunctivitis with antibiotics can reduce symptoms, duration of illness, and chances of recurrence.8
Clinical Commentary by Carin Reust, MD, MSPH, at http://www.fpin.org.
1. Sheikh A, Hurwitz B, Cave J. Antibiotics versus placebo for acute bacterial conjunctivitis (Cochrane Review). In: The Cochrane Library, Issue 3, 2001. Oxford, England: Update Software.
2. Gigliotti F, Hendley JO, Morgan J, Michaels R, Dickens M, Lohr J. J Pediatr 1984;104:623-6.
3. Chung CW, Cohen EJ. West J Med 2000;173:202-5.
4. Sheikh A, Hurwitz B. Br J Gen Pract 2001;51:473-7.
5. Chung C, Cohen E. Bacterial conjunctivitis. Clinical evidence. London: BMJ Publishing Group, 2001: 436-41.
6. Baum J, Barza M. The evolution of antibiotic therapy for bacterial conjunctivitis and keratitis: 1970-2000. Cornea 2000;19:659-72.
7. Morrow GL, Abbott RL. Conjunctivitis. Am Fam Physician 1998;57:735-46.
8. American Optometric Association consensus panel on the care of the patient with conjunctivitis. Optometric clinical practice guideline no. 11, 1996.
1. Sheikh A, Hurwitz B, Cave J. Antibiotics versus placebo for acute bacterial conjunctivitis (Cochrane Review). In: The Cochrane Library, Issue 3, 2001. Oxford, England: Update Software.
2. Gigliotti F, Hendley JO, Morgan J, Michaels R, Dickens M, Lohr J. J Pediatr 1984;104:623-6.
3. Chung CW, Cohen EJ. West J Med 2000;173:202-5.
4. Sheikh A, Hurwitz B. Br J Gen Pract 2001;51:473-7.
5. Chung C, Cohen E. Bacterial conjunctivitis. Clinical evidence. London: BMJ Publishing Group, 2001: 436-41.
6. Baum J, Barza M. The evolution of antibiotic therapy for bacterial conjunctivitis and keratitis: 1970-2000. Cornea 2000;19:659-72.
7. Morrow GL, Abbott RL. Conjunctivitis. Am Fam Physician 1998;57:735-46.
8. American Optometric Association consensus panel on the care of the patient with conjunctivitis. Optometric clinical practice guideline no. 11, 1996.
Evidence-based answers from the Family Physicians Inquiries Network
Does long-term erythromycin treatment reduce the number of common cold infections and subsequent exacerbations in patients with chronic obstructive pulmonary disease (COPD)?
ABSTRACT
BACKGROUND: Simple viral respiratory infections (the common cold) often predispose patients with COPD to lower respiratory infections and subsequent exacerbations. Low-dose, long-term erythromycin therapy has been reported to treat diffuse panbronchiolitis and bronchiectasis by anti-inflammatory mechanisms rather than through its inherent antibacterial mechanisms. Macrolide antibiotics have also been reported to have antiviral protective mechanisms. This study investigated the frequency of common colds and COPD exacerbations in patients treated with low-dose, long-term erythromycin.
POPULATION STUDIED: This Japanese study included 109 patients with COPD as defined by the American Thoracic Society. Subjects could be treated with sustained-released theophylline and inhaled anticholinergic agents, but not corticosteroids. The investigators excluded patients with diffuse panbronchiolitis or bronchiectasis.
STUDY DESIGN AND VALIDITY: This was a randomized, nonblinded study conducted over 12 months. One group of 55 patients received erythromycin (200-400 mg daily); the control group of 54 patients received 10 mg riboflavin daily. The investigators were unaware which treatments would be given before enrolling patients into the study (ie, allocation was concealed). The groups were similar in age, sex, and baseline lung function. Patients self-reported daily symptoms, including sneezing, nasal discharge, malaise, headache, chills, fever, sore throat, hoarseness, and cough, and rated each for severity on a scale of 0 to 3. An episode of common cold was defined as a quantitative symptom score of >5. COPD exacerbations were defined as a worsening in symptoms requiring changes to the regular pharmacologic regimen, including the need for antimicrobial or systemic steroid therapy. Exacerbations were graded based on need for hospitalization: mild and moderate, if treatment did not require hospitalization; severe, if hospitalization was required. Physicians evaluated their patients every 2 weeks. Patients who had cold symptoms were encouraged to visit the hospital for investigator-initiated checks.
OUTCOMES MEASURED: The investigators measured the number of common colds and the frequency and severity of COPD exacerbations.
RESULTS: The number of common colds was significantly lower in the erythromycin group than in the control group (1.24 vs 4.54 episodes per person; P = .002). Over a 12-month period, 76% of the control group subjects experienced more than one cold, compared with 13% in the erythromycin group (relative risk = 9.26; 95% CI, 3.92-31.74, number needed to treat [NNT] = 1.6). The percentage of patients having one or more COPD exacerbations was significantly higher in the control group (54% vs 11%; RR = 4.71; 95% CI, 1.53-14.5; NNT = 2.2). The control group experienced 11 severe exacerbations; the erythromycin group had none. The total number and severity of COPD exacerbations were also significantly lower in the erythromycin group than in the control group. No deaths were reported during the study period. One patient in the erythromycin group was excluded because of adverse effects of treatment (diarrhea and anorexia).
The frequency of common colds and of subsequent COPD exacerbations was significantly lowered in patients taking a low-dose of erythromycin daily for 1 year. This effect may be a result of the anti-inflammatory and antiviral mechanisms of macrolide antibiotics. Unfortunately, because neither the investigators nor the study subjects were blinded, the reported magnitude of this benefit may not be accurate. Additionally, these patients were not using corticosteroid therapy, which would have provided an anti-inflammatory benefit. The potential risk of emerging erythromycin/macrolide–resistant pathogens should restrict liberal prophylactic use. Considering the limitations of the study design and the risk of antibiotic resistance, we do not recommend prophylactic erythromycin treatment for common cold prevention in COPD patients.
ABSTRACT
BACKGROUND: Simple viral respiratory infections (the common cold) often predispose patients with COPD to lower respiratory infections and subsequent exacerbations. Low-dose, long-term erythromycin therapy has been reported to treat diffuse panbronchiolitis and bronchiectasis by anti-inflammatory mechanisms rather than through its inherent antibacterial mechanisms. Macrolide antibiotics have also been reported to have antiviral protective mechanisms. This study investigated the frequency of common colds and COPD exacerbations in patients treated with low-dose, long-term erythromycin.
POPULATION STUDIED: This Japanese study included 109 patients with COPD as defined by the American Thoracic Society. Subjects could be treated with sustained-released theophylline and inhaled anticholinergic agents, but not corticosteroids. The investigators excluded patients with diffuse panbronchiolitis or bronchiectasis.
STUDY DESIGN AND VALIDITY: This was a randomized, nonblinded study conducted over 12 months. One group of 55 patients received erythromycin (200-400 mg daily); the control group of 54 patients received 10 mg riboflavin daily. The investigators were unaware which treatments would be given before enrolling patients into the study (ie, allocation was concealed). The groups were similar in age, sex, and baseline lung function. Patients self-reported daily symptoms, including sneezing, nasal discharge, malaise, headache, chills, fever, sore throat, hoarseness, and cough, and rated each for severity on a scale of 0 to 3. An episode of common cold was defined as a quantitative symptom score of >5. COPD exacerbations were defined as a worsening in symptoms requiring changes to the regular pharmacologic regimen, including the need for antimicrobial or systemic steroid therapy. Exacerbations were graded based on need for hospitalization: mild and moderate, if treatment did not require hospitalization; severe, if hospitalization was required. Physicians evaluated their patients every 2 weeks. Patients who had cold symptoms were encouraged to visit the hospital for investigator-initiated checks.
OUTCOMES MEASURED: The investigators measured the number of common colds and the frequency and severity of COPD exacerbations.
RESULTS: The number of common colds was significantly lower in the erythromycin group than in the control group (1.24 vs 4.54 episodes per person; P = .002). Over a 12-month period, 76% of the control group subjects experienced more than one cold, compared with 13% in the erythromycin group (relative risk = 9.26; 95% CI, 3.92-31.74, number needed to treat [NNT] = 1.6). The percentage of patients having one or more COPD exacerbations was significantly higher in the control group (54% vs 11%; RR = 4.71; 95% CI, 1.53-14.5; NNT = 2.2). The control group experienced 11 severe exacerbations; the erythromycin group had none. The total number and severity of COPD exacerbations were also significantly lower in the erythromycin group than in the control group. No deaths were reported during the study period. One patient in the erythromycin group was excluded because of adverse effects of treatment (diarrhea and anorexia).
The frequency of common colds and of subsequent COPD exacerbations was significantly lowered in patients taking a low-dose of erythromycin daily for 1 year. This effect may be a result of the anti-inflammatory and antiviral mechanisms of macrolide antibiotics. Unfortunately, because neither the investigators nor the study subjects were blinded, the reported magnitude of this benefit may not be accurate. Additionally, these patients were not using corticosteroid therapy, which would have provided an anti-inflammatory benefit. The potential risk of emerging erythromycin/macrolide–resistant pathogens should restrict liberal prophylactic use. Considering the limitations of the study design and the risk of antibiotic resistance, we do not recommend prophylactic erythromycin treatment for common cold prevention in COPD patients.
ABSTRACT
BACKGROUND: Simple viral respiratory infections (the common cold) often predispose patients with COPD to lower respiratory infections and subsequent exacerbations. Low-dose, long-term erythromycin therapy has been reported to treat diffuse panbronchiolitis and bronchiectasis by anti-inflammatory mechanisms rather than through its inherent antibacterial mechanisms. Macrolide antibiotics have also been reported to have antiviral protective mechanisms. This study investigated the frequency of common colds and COPD exacerbations in patients treated with low-dose, long-term erythromycin.
POPULATION STUDIED: This Japanese study included 109 patients with COPD as defined by the American Thoracic Society. Subjects could be treated with sustained-released theophylline and inhaled anticholinergic agents, but not corticosteroids. The investigators excluded patients with diffuse panbronchiolitis or bronchiectasis.
STUDY DESIGN AND VALIDITY: This was a randomized, nonblinded study conducted over 12 months. One group of 55 patients received erythromycin (200-400 mg daily); the control group of 54 patients received 10 mg riboflavin daily. The investigators were unaware which treatments would be given before enrolling patients into the study (ie, allocation was concealed). The groups were similar in age, sex, and baseline lung function. Patients self-reported daily symptoms, including sneezing, nasal discharge, malaise, headache, chills, fever, sore throat, hoarseness, and cough, and rated each for severity on a scale of 0 to 3. An episode of common cold was defined as a quantitative symptom score of >5. COPD exacerbations were defined as a worsening in symptoms requiring changes to the regular pharmacologic regimen, including the need for antimicrobial or systemic steroid therapy. Exacerbations were graded based on need for hospitalization: mild and moderate, if treatment did not require hospitalization; severe, if hospitalization was required. Physicians evaluated their patients every 2 weeks. Patients who had cold symptoms were encouraged to visit the hospital for investigator-initiated checks.
OUTCOMES MEASURED: The investigators measured the number of common colds and the frequency and severity of COPD exacerbations.
RESULTS: The number of common colds was significantly lower in the erythromycin group than in the control group (1.24 vs 4.54 episodes per person; P = .002). Over a 12-month period, 76% of the control group subjects experienced more than one cold, compared with 13% in the erythromycin group (relative risk = 9.26; 95% CI, 3.92-31.74, number needed to treat [NNT] = 1.6). The percentage of patients having one or more COPD exacerbations was significantly higher in the control group (54% vs 11%; RR = 4.71; 95% CI, 1.53-14.5; NNT = 2.2). The control group experienced 11 severe exacerbations; the erythromycin group had none. The total number and severity of COPD exacerbations were also significantly lower in the erythromycin group than in the control group. No deaths were reported during the study period. One patient in the erythromycin group was excluded because of adverse effects of treatment (diarrhea and anorexia).
The frequency of common colds and of subsequent COPD exacerbations was significantly lowered in patients taking a low-dose of erythromycin daily for 1 year. This effect may be a result of the anti-inflammatory and antiviral mechanisms of macrolide antibiotics. Unfortunately, because neither the investigators nor the study subjects were blinded, the reported magnitude of this benefit may not be accurate. Additionally, these patients were not using corticosteroid therapy, which would have provided an anti-inflammatory benefit. The potential risk of emerging erythromycin/macrolide–resistant pathogens should restrict liberal prophylactic use. Considering the limitations of the study design and the risk of antibiotic resistance, we do not recommend prophylactic erythromycin treatment for common cold prevention in COPD patients.