Antimicrobial-resistant infections

Clinical question: Is trimethoprim-sulfamethoxazole equivalent to vancomycin for the treatment of severe infections caused by methicillin-resistant Staphyloccus aureus?

Bottom line: Trimethoprim-sulfamethoxazole (TMP-SMX) did not achieve noninferiority as compared with vancomycin for the treatment of severe methicillin-resistant Staphyloccus aureus (MRSA) infections in hospitalized patients, and it may lead to increased mortality in the subset of patients with bacteremia. (LOE = 1b)

Reference: Paul M, Bishara J, Yahav D, et al. Trimethoprim-sulfamethoxazole versus vancomycin for severe infections caused by meticillin-resistant Staphylococcus aureus. BMJ 2015;350:h2219.

Study design: Randomized controlled trial (nonblinded)

Funding source: Foundation

Allocation: Concealed

Setting: Inpatient (any location)

Synopsis

Although TMP-SMX can be used to treat uncomplicated skin and soft-tissue infections caused by MRSA, it is not currently recommended for more serious MRSA infections such as bacteremia or pneumonia. In this study, investigators tested whether TMP-SMX is noninferior to vancomycin for the treatment of hospitalized patients with severe MRSA infections. Patients included in the study (N = 252) had microbiologically documented MRSA infections, including complicated skin and soft-tissue infections, bone or joint infections, pneumonia, or primary bacteremia. Patients with MRSA isolates resistant to TMP-SMX or vancomycin were excluded.

Using concealed allocation, the investigators randomized the patients to receive either high-dose TMP-SMX (320 mg trimethoprim/1600 mg sulfamethoxazole intravenously twice daily) or vancomycin (1 mg intravenously twice daily) for at least 7 days. In the TMP-SMX group, treatment could be transitioned to an oral regimen of an equivalent dose at the clinician's discretion. The 2 groups had similar baseline characteristics with a mean age of 66 years and similar comorbidities, though the vancomycin group had a higher percentage of patients with bacteremia than the TMP-SMX group (30% vs 43%; P = .042). The primary outcome was treatment failure at 7 days, defined as a composite of death, persistent fever or hypotension, stable or worsening Sequential Organ Failure Assessment score, or persistent bacteremia. There was no statistically significant difference detected between the 2 groups for this outcome (38% treatment failure with TMP-SMX vs 27% with vancomycin; absolute difference 10.4%, 95% CI -1.2% to 21.5%).

However, since the 95% confidence interval for the absolute difference fell outside the predefined lower limit of noninferiority of 15%, the authors concluded that TMP-SMX failed to achieve noninferiority as compared with vancomycin. Additionally, in the subgroup of patients with bacteremia, patients were more likely to die in the TMP-SMX group as compared with the vancomycin group, although this difference again was not statistically significant (34% with TMP-SMX vs 18% with vancomycin; relative risk 1.90, 0.92-3.93).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Is trimethoprim-sulfamethoxazole equivalent to vancomycin for the treatment of severe infections caused by methicillin-resistant Staphyloccus aureus?

Bottom line: Trimethoprim-sulfamethoxazole (TMP-SMX) did not achieve noninferiority as compared with vancomycin for the treatment of severe methicillin-resistant Staphyloccus aureus (MRSA) infections in hospitalized patients, and it may lead to increased mortality in the subset of patients with bacteremia. (LOE = 1b)

Reference: Paul M, Bishara J, Yahav D, et al. Trimethoprim-sulfamethoxazole versus vancomycin for severe infections caused by meticillin-resistant Staphylococcus aureus. BMJ 2015;350:h2219.

Study design: Randomized controlled trial (nonblinded)

Funding source: Foundation

Allocation: Concealed

Setting: Inpatient (any location)

Synopsis

Although TMP-SMX can be used to treat uncomplicated skin and soft-tissue infections caused by MRSA, it is not currently recommended for more serious MRSA infections such as bacteremia or pneumonia. In this study, investigators tested whether TMP-SMX is noninferior to vancomycin for the treatment of hospitalized patients with severe MRSA infections. Patients included in the study (N = 252) had microbiologically documented MRSA infections, including complicated skin and soft-tissue infections, bone or joint infections, pneumonia, or primary bacteremia. Patients with MRSA isolates resistant to TMP-SMX or vancomycin were excluded.

Using concealed allocation, the investigators randomized the patients to receive either high-dose TMP-SMX (320 mg trimethoprim/1600 mg sulfamethoxazole intravenously twice daily) or vancomycin (1 mg intravenously twice daily) for at least 7 days. In the TMP-SMX group, treatment could be transitioned to an oral regimen of an equivalent dose at the clinician's discretion. The 2 groups had similar baseline characteristics with a mean age of 66 years and similar comorbidities, though the vancomycin group had a higher percentage of patients with bacteremia than the TMP-SMX group (30% vs 43%; P = .042). The primary outcome was treatment failure at 7 days, defined as a composite of death, persistent fever or hypotension, stable or worsening Sequential Organ Failure Assessment score, or persistent bacteremia. There was no statistically significant difference detected between the 2 groups for this outcome (38% treatment failure with TMP-SMX vs 27% with vancomycin; absolute difference 10.4%, 95% CI -1.2% to 21.5%).

However, since the 95% confidence interval for the absolute difference fell outside the predefined lower limit of noninferiority of 15%, the authors concluded that TMP-SMX failed to achieve noninferiority as compared with vancomycin. Additionally, in the subgroup of patients with bacteremia, patients were more likely to die in the TMP-SMX group as compared with the vancomycin group, although this difference again was not statistically significant (34% with TMP-SMX vs 18% with vancomycin; relative risk 1.90, 0.92-3.93).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Is trimethoprim-sulfamethoxazole equivalent to vancomycin for the treatment of severe infections caused by methicillin-resistant Staphyloccus aureus?

Bottom line: Trimethoprim-sulfamethoxazole (TMP-SMX) did not achieve noninferiority as compared with vancomycin for the treatment of severe methicillin-resistant Staphyloccus aureus (MRSA) infections in hospitalized patients, and it may lead to increased mortality in the subset of patients with bacteremia. (LOE = 1b)

Reference: Paul M, Bishara J, Yahav D, et al. Trimethoprim-sulfamethoxazole versus vancomycin for severe infections caused by meticillin-resistant Staphylococcus aureus. BMJ 2015;350:h2219.

Study design: Randomized controlled trial (nonblinded)

Funding source: Foundation

Allocation: Concealed

Setting: Inpatient (any location)

Synopsis

Although TMP-SMX can be used to treat uncomplicated skin and soft-tissue infections caused by MRSA, it is not currently recommended for more serious MRSA infections such as bacteremia or pneumonia. In this study, investigators tested whether TMP-SMX is noninferior to vancomycin for the treatment of hospitalized patients with severe MRSA infections. Patients included in the study (N = 252) had microbiologically documented MRSA infections, including complicated skin and soft-tissue infections, bone or joint infections, pneumonia, or primary bacteremia. Patients with MRSA isolates resistant to TMP-SMX or vancomycin were excluded.

Using concealed allocation, the investigators randomized the patients to receive either high-dose TMP-SMX (320 mg trimethoprim/1600 mg sulfamethoxazole intravenously twice daily) or vancomycin (1 mg intravenously twice daily) for at least 7 days. In the TMP-SMX group, treatment could be transitioned to an oral regimen of an equivalent dose at the clinician's discretion. The 2 groups had similar baseline characteristics with a mean age of 66 years and similar comorbidities, though the vancomycin group had a higher percentage of patients with bacteremia than the TMP-SMX group (30% vs 43%; P = .042). The primary outcome was treatment failure at 7 days, defined as a composite of death, persistent fever or hypotension, stable or worsening Sequential Organ Failure Assessment score, or persistent bacteremia. There was no statistically significant difference detected between the 2 groups for this outcome (38% treatment failure with TMP-SMX vs 27% with vancomycin; absolute difference 10.4%, 95% CI -1.2% to 21.5%).

However, since the 95% confidence interval for the absolute difference fell outside the predefined lower limit of noninferiority of 15%, the authors concluded that TMP-SMX failed to achieve noninferiority as compared with vancomycin. Additionally, in the subgroup of patients with bacteremia, patients were more likely to die in the TMP-SMX group as compared with the vancomycin group, although this difference again was not statistically significant (34% with TMP-SMX vs 18% with vancomycin; relative risk 1.90, 0.92-3.93).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Have the causative organisms in pediatric bacteremia changed over time concurrent with introduction of the pneumococcal conjugate vaccine?

Background: Previous research has shown introduction of polyvalent pneumococcal conjugate vaccine led to changes in the organisms causing meningitis and otitis media, and patterns of nasopharyngeal colonization. Pneumococcus, historically, was a common cause of bacteremia. The availability of pneumococcal conjugate vaccine may have changed the organisms causing bacteremia in children.

Study design: Retrospective chart review and time series.

Setting: Children presenting to the ED of Alder Hey Children’s Hospital in Liverpool, England, from 2001 to 2011.

Synopsis: Five hundred seventy-five episodes of bacteremia were found in 525 children. Infants most commonly had E. coli and Group B streptococcal infections; children over age five most commonly had S. aureus. The introduction of the pneumococcal conjugate vaccine decreased pneumococcal bacteremia by 49% over the study period. This decrease was accompanied by an increase in Gram-negative bacteremia. Susceptibility to empiric antibiotics (third-generation cephalosporins) dropped from 96% to 83%. Over the study period, more children presented with central venous lines, which was felt to be due to increasing outpatient use of total parenteral nutrition (TPN).

Bottom line: Vaccination against pneumococcus is changing the microbiology of pediatric bacteremia, with fewer vaccine-preventable Gram-positive infections and more Gram-negative infections. This increases the likelihood of resistance to third-generation cephalosporins as empiric antibiotic.

Citation: Irwin AD, Drew RJ, Marshall P, et al. Etiology of childhood bacteremia and timely antibiotics administration in the emergency department. Pediatrics. 2015;135(4): 635-642.

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Dr. Stubblefield is a pediatric hospitalist at Nemours/Alfred I. Dupont Hospital for Children in Wilmington, Del., and assistant professor of pediatrics at Thomas Jefferson Medical College in Philadelphia

Clinical question: Have the causative organisms in pediatric bacteremia changed over time concurrent with introduction of the pneumococcal conjugate vaccine?

Background: Previous research has shown introduction of polyvalent pneumococcal conjugate vaccine led to changes in the organisms causing meningitis and otitis media, and patterns of nasopharyngeal colonization. Pneumococcus, historically, was a common cause of bacteremia. The availability of pneumococcal conjugate vaccine may have changed the organisms causing bacteremia in children.

Study design: Retrospective chart review and time series.

Setting: Children presenting to the ED of Alder Hey Children’s Hospital in Liverpool, England, from 2001 to 2011.

Synopsis: Five hundred seventy-five episodes of bacteremia were found in 525 children. Infants most commonly had E. coli and Group B streptococcal infections; children over age five most commonly had S. aureus. The introduction of the pneumococcal conjugate vaccine decreased pneumococcal bacteremia by 49% over the study period. This decrease was accompanied by an increase in Gram-negative bacteremia. Susceptibility to empiric antibiotics (third-generation cephalosporins) dropped from 96% to 83%. Over the study period, more children presented with central venous lines, which was felt to be due to increasing outpatient use of total parenteral nutrition (TPN).

Bottom line: Vaccination against pneumococcus is changing the microbiology of pediatric bacteremia, with fewer vaccine-preventable Gram-positive infections and more Gram-negative infections. This increases the likelihood of resistance to third-generation cephalosporins as empiric antibiotic.

Citation: Irwin AD, Drew RJ, Marshall P, et al. Etiology of childhood bacteremia and timely antibiotics administration in the emergency department. Pediatrics. 2015;135(4): 635-642.

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Dr. Stubblefield is a pediatric hospitalist at Nemours/Alfred I. Dupont Hospital for Children in Wilmington, Del., and assistant professor of pediatrics at Thomas Jefferson Medical College in Philadelphia

Clinical question: Have the causative organisms in pediatric bacteremia changed over time concurrent with introduction of the pneumococcal conjugate vaccine?

Background: Previous research has shown introduction of polyvalent pneumococcal conjugate vaccine led to changes in the organisms causing meningitis and otitis media, and patterns of nasopharyngeal colonization. Pneumococcus, historically, was a common cause of bacteremia. The availability of pneumococcal conjugate vaccine may have changed the organisms causing bacteremia in children.

Study design: Retrospective chart review and time series.

Setting: Children presenting to the ED of Alder Hey Children’s Hospital in Liverpool, England, from 2001 to 2011.

Synopsis: Five hundred seventy-five episodes of bacteremia were found in 525 children. Infants most commonly had E. coli and Group B streptococcal infections; children over age five most commonly had S. aureus. The introduction of the pneumococcal conjugate vaccine decreased pneumococcal bacteremia by 49% over the study period. This decrease was accompanied by an increase in Gram-negative bacteremia. Susceptibility to empiric antibiotics (third-generation cephalosporins) dropped from 96% to 83%. Over the study period, more children presented with central venous lines, which was felt to be due to increasing outpatient use of total parenteral nutrition (TPN).

Bottom line: Vaccination against pneumococcus is changing the microbiology of pediatric bacteremia, with fewer vaccine-preventable Gram-positive infections and more Gram-negative infections. This increases the likelihood of resistance to third-generation cephalosporins as empiric antibiotic.

Citation: Irwin AD, Drew RJ, Marshall P, et al. Etiology of childhood bacteremia and timely antibiotics administration in the emergency department. Pediatrics. 2015;135(4): 635-642.

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Dr. Stubblefield is a pediatric hospitalist at Nemours/Alfred I. Dupont Hospital for Children in Wilmington, Del., and assistant professor of pediatrics at Thomas Jefferson Medical College in Philadelphia

Clinical question: What is the influence of patient complexities on providers’ decisions to prescribe antibiotics in three common hospital-based clinical vignettes?

Background: Antibiotic treatment decisions for medically complex patients are complicated, because the risk of undertreatment may be severe, while overtreatment may be associated with adverse effects and the emergence of resistant pathogens. It is believed that physicians are more likely than not to prescribe antibiotics for complex patients.

Study design: Hospital-based, physician survey.

Setting: Three urban academic medical centers in Los Angeles County, Calif.

Synopsis: Physicians were presented with three clinical vignettes, with variations by age, comorbidity, functional status, and follow-up, and asked to choose the best antibiotic regimen. Of the 874 invited physicians, 255 (29%) responded to the survey; 245 physicians were eligible for the study.

Study results showed 28% to 49% of physicians recommended antibiotics that were inconsistent with national guidelines. This percentage increased to 48% to 63% for medically complex patients, defined as those with older age, high medical comorbidity burden, poor functional status, or limited follow-up after hospital discharge (P<0.01). Resident physicians (n=183) were more likely than attending physicians (n=57) to have recommended antibiotics in the baseline vignettes (43% vs. 34%, P<0.05) and in all four vignettes with patient complexities.

Bottom line: Inappropriate antibiotic use was prevalent and occurred more often for patients with medical complexities.

Citation: Wooten D, Kahn K, Grein JD, Eells SJ, Miller LG. The association of patient complexities with antibiotic ordering. J Hosp Med. 2015;10:1-7.

Clinical question: What is the influence of patient complexities on providers’ decisions to prescribe antibiotics in three common hospital-based clinical vignettes?

Background: Antibiotic treatment decisions for medically complex patients are complicated, because the risk of undertreatment may be severe, while overtreatment may be associated with adverse effects and the emergence of resistant pathogens. It is believed that physicians are more likely than not to prescribe antibiotics for complex patients.

Study design: Hospital-based, physician survey.

Setting: Three urban academic medical centers in Los Angeles County, Calif.

Synopsis: Physicians were presented with three clinical vignettes, with variations by age, comorbidity, functional status, and follow-up, and asked to choose the best antibiotic regimen. Of the 874 invited physicians, 255 (29%) responded to the survey; 245 physicians were eligible for the study.

Study results showed 28% to 49% of physicians recommended antibiotics that were inconsistent with national guidelines. This percentage increased to 48% to 63% for medically complex patients, defined as those with older age, high medical comorbidity burden, poor functional status, or limited follow-up after hospital discharge (P<0.01). Resident physicians (n=183) were more likely than attending physicians (n=57) to have recommended antibiotics in the baseline vignettes (43% vs. 34%, P<0.05) and in all four vignettes with patient complexities.

Bottom line: Inappropriate antibiotic use was prevalent and occurred more often for patients with medical complexities.

Citation: Wooten D, Kahn K, Grein JD, Eells SJ, Miller LG. The association of patient complexities with antibiotic ordering. J Hosp Med. 2015;10:1-7.

Clinical question: What is the influence of patient complexities on providers’ decisions to prescribe antibiotics in three common hospital-based clinical vignettes?

Background: Antibiotic treatment decisions for medically complex patients are complicated, because the risk of undertreatment may be severe, while overtreatment may be associated with adverse effects and the emergence of resistant pathogens. It is believed that physicians are more likely than not to prescribe antibiotics for complex patients.

Study design: Hospital-based, physician survey.

Setting: Three urban academic medical centers in Los Angeles County, Calif.

Synopsis: Physicians were presented with three clinical vignettes, with variations by age, comorbidity, functional status, and follow-up, and asked to choose the best antibiotic regimen. Of the 874 invited physicians, 255 (29%) responded to the survey; 245 physicians were eligible for the study.

Study results showed 28% to 49% of physicians recommended antibiotics that were inconsistent with national guidelines. This percentage increased to 48% to 63% for medically complex patients, defined as those with older age, high medical comorbidity burden, poor functional status, or limited follow-up after hospital discharge (P<0.01). Resident physicians (n=183) were more likely than attending physicians (n=57) to have recommended antibiotics in the baseline vignettes (43% vs. 34%, P<0.05) and in all four vignettes with patient complexities.

Bottom line: Inappropriate antibiotic use was prevalent and occurred more often for patients with medical complexities.

Citation: Wooten D, Kahn K, Grein JD, Eells SJ, Miller LG. The association of patient complexities with antibiotic ordering. J Hosp Med. 2015;10:1-7.

 

Clinical question: What are the efficacy and safety of clindamycin and trimethoprim-sulfamethoxazole (TMP-SMX) for treatment of uncomplicated soft tissue infections in adults and children?

Background: Clindamycin and TMP-SMX are commonly used treatments for uncomplicated skin infections in adults and children, but no head-to-head comparison of efficacy or side effect profile for these medications exists.

Study design: Multi-center, prospective, double-blind, randomized clinical trial of superiority.

Setting: Four academic medical centers.

Synopsis: A group of 524 adults (n=369) and children with uncomplicated cellulitis, abscess, or both was enrolled. For patients with abscess, only those with larger lesions (based on age) were included. All abscesses were incised and drained, and patients were randomly treated with either clindamycin or TMP-SMX for 10 days. A total of 41% of cultures from suppurative wounds grew Staphylococcus aureus; 77% of these were methicillin-resistant.

The primary outcome was clinical cure assessed at 7 to 10 days and one month after completing treatment. No significant difference in cure or reported side effects was seen between drug treatment groups, age groups, lesion types, or isolates cultured. Some 80.3% of patients in the clindamycin group and 77.3% of patients in the TMP-SMX group were cured. Side effect profiles assessed by patient questionnaires showed similar rates of self-limited gastrointestinal (~19%) and dermatologic (~1%) complaints. No cases of Clostridium difficile–associated diarrhea were found.

Limitations include exclusion of patients with significant comorbidities and hospitalized patients. Also, other antibiotic regimens were not compared. Patients were followed for only one month to assess recurrence. Finally, no attempt was made to optimize antibiotic dose.

Bottom line: Clindamycin and TMP-SMX had similar cure rates and side effect profiles in otherwise healthy patients with uncomplicated skin infections.

Citation: Miller LG, Daum RS, Creech CB, et al. Clindamycin versus trimethoprim-sulfamethoxazole for uncomplicated skin infections. N Engl J Med. 2015;372:1093–1103.

Visit our website for more hospitalist-focused literature reviews.

 

Clinical question: What are the efficacy and safety of clindamycin and trimethoprim-sulfamethoxazole (TMP-SMX) for treatment of uncomplicated soft tissue infections in adults and children?

Background: Clindamycin and TMP-SMX are commonly used treatments for uncomplicated skin infections in adults and children, but no head-to-head comparison of efficacy or side effect profile for these medications exists.

Study design: Multi-center, prospective, double-blind, randomized clinical trial of superiority.

Setting: Four academic medical centers.

Synopsis: A group of 524 adults (n=369) and children with uncomplicated cellulitis, abscess, or both was enrolled. For patients with abscess, only those with larger lesions (based on age) were included. All abscesses were incised and drained, and patients were randomly treated with either clindamycin or TMP-SMX for 10 days. A total of 41% of cultures from suppurative wounds grew Staphylococcus aureus; 77% of these were methicillin-resistant.

The primary outcome was clinical cure assessed at 7 to 10 days and one month after completing treatment. No significant difference in cure or reported side effects was seen between drug treatment groups, age groups, lesion types, or isolates cultured. Some 80.3% of patients in the clindamycin group and 77.3% of patients in the TMP-SMX group were cured. Side effect profiles assessed by patient questionnaires showed similar rates of self-limited gastrointestinal (~19%) and dermatologic (~1%) complaints. No cases of Clostridium difficile–associated diarrhea were found.

Limitations include exclusion of patients with significant comorbidities and hospitalized patients. Also, other antibiotic regimens were not compared. Patients were followed for only one month to assess recurrence. Finally, no attempt was made to optimize antibiotic dose.

Bottom line: Clindamycin and TMP-SMX had similar cure rates and side effect profiles in otherwise healthy patients with uncomplicated skin infections.

Citation: Miller LG, Daum RS, Creech CB, et al. Clindamycin versus trimethoprim-sulfamethoxazole for uncomplicated skin infections. N Engl J Med. 2015;372:1093–1103.

Visit our website for more hospitalist-focused literature reviews.

 

Clinical question: What are the efficacy and safety of clindamycin and trimethoprim-sulfamethoxazole (TMP-SMX) for treatment of uncomplicated soft tissue infections in adults and children?

Background: Clindamycin and TMP-SMX are commonly used treatments for uncomplicated skin infections in adults and children, but no head-to-head comparison of efficacy or side effect profile for these medications exists.

Study design: Multi-center, prospective, double-blind, randomized clinical trial of superiority.

Setting: Four academic medical centers.

Synopsis: A group of 524 adults (n=369) and children with uncomplicated cellulitis, abscess, or both was enrolled. For patients with abscess, only those with larger lesions (based on age) were included. All abscesses were incised and drained, and patients were randomly treated with either clindamycin or TMP-SMX for 10 days. A total of 41% of cultures from suppurative wounds grew Staphylococcus aureus; 77% of these were methicillin-resistant.

The primary outcome was clinical cure assessed at 7 to 10 days and one month after completing treatment. No significant difference in cure or reported side effects was seen between drug treatment groups, age groups, lesion types, or isolates cultured. Some 80.3% of patients in the clindamycin group and 77.3% of patients in the TMP-SMX group were cured. Side effect profiles assessed by patient questionnaires showed similar rates of self-limited gastrointestinal (~19%) and dermatologic (~1%) complaints. No cases of Clostridium difficile–associated diarrhea were found.

Limitations include exclusion of patients with significant comorbidities and hospitalized patients. Also, other antibiotic regimens were not compared. Patients were followed for only one month to assess recurrence. Finally, no attempt was made to optimize antibiotic dose.

Bottom line: Clindamycin and TMP-SMX had similar cure rates and side effect profiles in otherwise healthy patients with uncomplicated skin infections.

Citation: Miller LG, Daum RS, Creech CB, et al. Clindamycin versus trimethoprim-sulfamethoxazole for uncomplicated skin infections. N Engl J Med. 2015;372:1093–1103.

Visit our website for more hospitalist-focused literature reviews.

Clinical question: After hospitalization for acute hematogenous osteomyelitis (AHOM), do children discharged with oral antibiotics have similar clinical outcomes compared to those discharged with home IV antibiotics?

Background: AHOM occurs in one in 5,000 children yearly and makes up approximately 1% of pediatric hospitalizations in the U.S.¹ The incidence of AHOM might be increasing in some communities, concurrent with the increasing prevalence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA).² Uncomplicated AHOM typically is defined as osteomyelitis not associated with trauma, with less than 14 days of symptoms and not requiring surgical intervention beyond diagnostic sampling.¹ Most recent published studies support a seven-day inpatient course of IV antibiotics for uncomplicated AHOM, followed by 21 to 28 days of oral therapy for patients who continue to improve clinically.¹ Significant variability exists in practice, with a recent study of free-standing children’s hospitals showing rates of transition to oral antibiotics after hospitalization for AHOM ranging from approximately 10% to more than 90%.³

Study design: Multi-center, retrospective, cohort study.

Setting: Thirty-eight U.S. children’s hospitals.

Synopsis: Researchers used clinical and billing data from the Pediatric Health Information System (PHIS) to identify children between the ages of two months and 18 years over a 48-month period who were discharged with a diagnosis of acute or unspecified osteomyelitis based on ICD-9-CM coding.

PHIS is a database of administrative, billing, and clinical details derived from hospitalizations at 44 U.S. children’s hospitals.

Exclusions from the study were numerous, and included:

• Hospitalization in the six months prior with acute, unspecified, or chronic osteomyelitis;
• Chronic cardiac, hematologic, immunologic, oncologic, or respiratory conditions that would increase the risk of treatment failure;
• Transfer either to or from the hospital at any point during hospitalization;
• More than one site of osteomyelitis;
• Length of stay of less than two or more than 14 days;
• Inability to take antibiotics orally or enterally;
• Malabsorption disorders;
• Primary diagnosis of cellulitis or septic arthritis;
• Orthopedic hardware or bone fractures;
• Prolonged immobilization or developed pressure ulcers; and
• Osteomyelitis of the head, face, and orbits.

Local physicians and research assistants at each hospital site reviewed medical records to confirm the validity of the ICD-9-CM diagnosis, determine the post-discharge antibiotic details, review for return ED visits or readmission within six months, and extract culture results. Primary outcome was treatment failure, defined as revisit to the ED or readmission for a change in antibiotic treatment (type, dosage, or prolongation), drainage of abscess, debridement, bone biopsy, or conversion to PICC route. Secondary outcomes included a return to ED or rehospitalization for adverse drug reactions (vomiting/diarrhea, dehydration, C. difficile infection, allergic reactions, drug-induced neutropenia, acute kidney injury) or PICC complication (fever evaluation, PICC site infection, blood stream infection, sepsis, thrombosis, breakage, repair, adjustment, manipulation, or PICC removal).

Of 8,555 patients from 38 hospitals who satisfied inclusion criteria, 2,060 patients from 36 hospitals remained after application of exclusion criteria, with 1,005 receiving antibiotics orally and 1,055 via a peripherally inserted central catheter (PICC) upon discharge. Median length of stay was six days, and the percentage of patients discharged on oral antibiotics ranged widely at the hospital level, from zero to 100%. Patients were most commonly discharged on clindamycin (50%) and cephalexin (37%) in the oral cohort, and clindamycin (36%) and cefazolin (33%) in the PICC cohort.

The rate of treatment failure was similar in unmatched analyses of the oral cohort (5%) versus the PICC cohort (6%). This similarity persisted in across-hospital and within-hospital matched analyses. Rates of adverse drug reactions were low (<4%) in both groups, but 15% of the PICC cohort returned to the ED or were readmitted for a PICC complication.

Bottom line: Previously healthy children hospitalized with a single focus of AHOM have similarly low rates of treatment failure whether discharged on oral- or PICC-administered antibiotics. Patients discharged with PICC-administered antibiotics suffer from a higher rate of return ED visit or readmission due to PICC-related complications.

 

Citation: Keren R, Shah SS, Srivastava R. Comparative effectiveness of intravenous vs oral antibiotics for postdischarge treatment of acute osteomyelitis in children. JAMA Pediatr. 2015;169(2):120-128.

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Reviewed by Pediatric Editor Weijen Chang, MD, SFHM, FAAP, associate clinical professor of medicine and pediatrics at the University of California at San Diego School of Medicine, and a hospitalist at both UCSD Medical Center and Rady Children’s Hospital.

References

1. Majewski J, Del Vecchio M, Aronoff S. Route and length of therapy of acute uncomplicated hematogenous osteomyelitis: do we have the answers yet? Hosp Pediatr. 2014;4(1):44-47.
2. Arnold SR, Elias D, Buckingham SC, et al. Changing patterns of acute hematogenous osteomyelitis and septic arthritis: emergence of community-associated methicillin-resistant Staphylococcus aureus. J Pediatr Orthop. 2006;26(6):703-708.
3. Zaoutis T, Localio AR, Leckerman K, Saddlemire S, Bertoch D, Keren R. Prolonged intravenous therapy versus eraly transtion to oral antimicrobial therapy for acute osteomyelitis in children. Pediatrics. 2009;123(2):636-642.

Clinical question: After hospitalization for acute hematogenous osteomyelitis (AHOM), do children discharged with oral antibiotics have similar clinical outcomes compared to those discharged with home IV antibiotics?

Background: AHOM occurs in one in 5,000 children yearly and makes up approximately 1% of pediatric hospitalizations in the U.S.¹ The incidence of AHOM might be increasing in some communities, concurrent with the increasing prevalence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA).² Uncomplicated AHOM typically is defined as osteomyelitis not associated with trauma, with less than 14 days of symptoms and not requiring surgical intervention beyond diagnostic sampling.¹ Most recent published studies support a seven-day inpatient course of IV antibiotics for uncomplicated AHOM, followed by 21 to 28 days of oral therapy for patients who continue to improve clinically.¹ Significant variability exists in practice, with a recent study of free-standing children’s hospitals showing rates of transition to oral antibiotics after hospitalization for AHOM ranging from approximately 10% to more than 90%.³

Study design: Multi-center, retrospective, cohort study.

Setting: Thirty-eight U.S. children’s hospitals.

Synopsis: Researchers used clinical and billing data from the Pediatric Health Information System (PHIS) to identify children between the ages of two months and 18 years over a 48-month period who were discharged with a diagnosis of acute or unspecified osteomyelitis based on ICD-9-CM coding.

PHIS is a database of administrative, billing, and clinical details derived from hospitalizations at 44 U.S. children’s hospitals.

Exclusions from the study were numerous, and included:

• Hospitalization in the six months prior with acute, unspecified, or chronic osteomyelitis;
• Chronic cardiac, hematologic, immunologic, oncologic, or respiratory conditions that would increase the risk of treatment failure;
• Transfer either to or from the hospital at any point during hospitalization;
• More than one site of osteomyelitis;
• Length of stay of less than two or more than 14 days;
• Inability to take antibiotics orally or enterally;
• Malabsorption disorders;
• Primary diagnosis of cellulitis or septic arthritis;
• Orthopedic hardware or bone fractures;
• Prolonged immobilization or developed pressure ulcers; and
• Osteomyelitis of the head, face, and orbits.

Local physicians and research assistants at each hospital site reviewed medical records to confirm the validity of the ICD-9-CM diagnosis, determine the post-discharge antibiotic details, review for return ED visits or readmission within six months, and extract culture results. Primary outcome was treatment failure, defined as revisit to the ED or readmission for a change in antibiotic treatment (type, dosage, or prolongation), drainage of abscess, debridement, bone biopsy, or conversion to PICC route. Secondary outcomes included a return to ED or rehospitalization for adverse drug reactions (vomiting/diarrhea, dehydration, C. difficile infection, allergic reactions, drug-induced neutropenia, acute kidney injury) or PICC complication (fever evaluation, PICC site infection, blood stream infection, sepsis, thrombosis, breakage, repair, adjustment, manipulation, or PICC removal).

Of 8,555 patients from 38 hospitals who satisfied inclusion criteria, 2,060 patients from 36 hospitals remained after application of exclusion criteria, with 1,005 receiving antibiotics orally and 1,055 via a peripherally inserted central catheter (PICC) upon discharge. Median length of stay was six days, and the percentage of patients discharged on oral antibiotics ranged widely at the hospital level, from zero to 100%. Patients were most commonly discharged on clindamycin (50%) and cephalexin (37%) in the oral cohort, and clindamycin (36%) and cefazolin (33%) in the PICC cohort.

The rate of treatment failure was similar in unmatched analyses of the oral cohort (5%) versus the PICC cohort (6%). This similarity persisted in across-hospital and within-hospital matched analyses. Rates of adverse drug reactions were low (<4%) in both groups, but 15% of the PICC cohort returned to the ED or were readmitted for a PICC complication.

Bottom line: Previously healthy children hospitalized with a single focus of AHOM have similarly low rates of treatment failure whether discharged on oral- or PICC-administered antibiotics. Patients discharged with PICC-administered antibiotics suffer from a higher rate of return ED visit or readmission due to PICC-related complications.

 

Citation: Keren R, Shah SS, Srivastava R. Comparative effectiveness of intravenous vs oral antibiotics for postdischarge treatment of acute osteomyelitis in children. JAMA Pediatr. 2015;169(2):120-128.

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Reviewed by Pediatric Editor Weijen Chang, MD, SFHM, FAAP, associate clinical professor of medicine and pediatrics at the University of California at San Diego School of Medicine, and a hospitalist at both UCSD Medical Center and Rady Children’s Hospital.

References

1. Majewski J, Del Vecchio M, Aronoff S. Route and length of therapy of acute uncomplicated hematogenous osteomyelitis: do we have the answers yet? Hosp Pediatr. 2014;4(1):44-47.
2. Arnold SR, Elias D, Buckingham SC, et al. Changing patterns of acute hematogenous osteomyelitis and septic arthritis: emergence of community-associated methicillin-resistant Staphylococcus aureus. J Pediatr Orthop. 2006;26(6):703-708.
3. Zaoutis T, Localio AR, Leckerman K, Saddlemire S, Bertoch D, Keren R. Prolonged intravenous therapy versus eraly transtion to oral antimicrobial therapy for acute osteomyelitis in children. Pediatrics. 2009;123(2):636-642.

Clinical question: After hospitalization for acute hematogenous osteomyelitis (AHOM), do children discharged with oral antibiotics have similar clinical outcomes compared to those discharged with home IV antibiotics?

Background: AHOM occurs in one in 5,000 children yearly and makes up approximately 1% of pediatric hospitalizations in the U.S.¹ The incidence of AHOM might be increasing in some communities, concurrent with the increasing prevalence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA).² Uncomplicated AHOM typically is defined as osteomyelitis not associated with trauma, with less than 14 days of symptoms and not requiring surgical intervention beyond diagnostic sampling.¹ Most recent published studies support a seven-day inpatient course of IV antibiotics for uncomplicated AHOM, followed by 21 to 28 days of oral therapy for patients who continue to improve clinically.¹ Significant variability exists in practice, with a recent study of free-standing children’s hospitals showing rates of transition to oral antibiotics after hospitalization for AHOM ranging from approximately 10% to more than 90%.³

Study design: Multi-center, retrospective, cohort study.

Setting: Thirty-eight U.S. children’s hospitals.

Synopsis: Researchers used clinical and billing data from the Pediatric Health Information System (PHIS) to identify children between the ages of two months and 18 years over a 48-month period who were discharged with a diagnosis of acute or unspecified osteomyelitis based on ICD-9-CM coding.

PHIS is a database of administrative, billing, and clinical details derived from hospitalizations at 44 U.S. children’s hospitals.

Exclusions from the study were numerous, and included:

• Hospitalization in the six months prior with acute, unspecified, or chronic osteomyelitis;
• Chronic cardiac, hematologic, immunologic, oncologic, or respiratory conditions that would increase the risk of treatment failure;
• Transfer either to or from the hospital at any point during hospitalization;
• More than one site of osteomyelitis;
• Length of stay of less than two or more than 14 days;
• Inability to take antibiotics orally or enterally;
• Malabsorption disorders;
• Primary diagnosis of cellulitis or septic arthritis;
• Orthopedic hardware or bone fractures;
• Prolonged immobilization or developed pressure ulcers; and
• Osteomyelitis of the head, face, and orbits.

Local physicians and research assistants at each hospital site reviewed medical records to confirm the validity of the ICD-9-CM diagnosis, determine the post-discharge antibiotic details, review for return ED visits or readmission within six months, and extract culture results. Primary outcome was treatment failure, defined as revisit to the ED or readmission for a change in antibiotic treatment (type, dosage, or prolongation), drainage of abscess, debridement, bone biopsy, or conversion to PICC route. Secondary outcomes included a return to ED or rehospitalization for adverse drug reactions (vomiting/diarrhea, dehydration, C. difficile infection, allergic reactions, drug-induced neutropenia, acute kidney injury) or PICC complication (fever evaluation, PICC site infection, blood stream infection, sepsis, thrombosis, breakage, repair, adjustment, manipulation, or PICC removal).

Of 8,555 patients from 38 hospitals who satisfied inclusion criteria, 2,060 patients from 36 hospitals remained after application of exclusion criteria, with 1,005 receiving antibiotics orally and 1,055 via a peripherally inserted central catheter (PICC) upon discharge. Median length of stay was six days, and the percentage of patients discharged on oral antibiotics ranged widely at the hospital level, from zero to 100%. Patients were most commonly discharged on clindamycin (50%) and cephalexin (37%) in the oral cohort, and clindamycin (36%) and cefazolin (33%) in the PICC cohort.

The rate of treatment failure was similar in unmatched analyses of the oral cohort (5%) versus the PICC cohort (6%). This similarity persisted in across-hospital and within-hospital matched analyses. Rates of adverse drug reactions were low (<4%) in both groups, but 15% of the PICC cohort returned to the ED or were readmitted for a PICC complication.

Bottom line: Previously healthy children hospitalized with a single focus of AHOM have similarly low rates of treatment failure whether discharged on oral- or PICC-administered antibiotics. Patients discharged with PICC-administered antibiotics suffer from a higher rate of return ED visit or readmission due to PICC-related complications.

 

Citation: Keren R, Shah SS, Srivastava R. Comparative effectiveness of intravenous vs oral antibiotics for postdischarge treatment of acute osteomyelitis in children. JAMA Pediatr. 2015;169(2):120-128.

---

Reviewed by Pediatric Editor Weijen Chang, MD, SFHM, FAAP, associate clinical professor of medicine and pediatrics at the University of California at San Diego School of Medicine, and a hospitalist at both UCSD Medical Center and Rady Children’s Hospital.

References

1. Majewski J, Del Vecchio M, Aronoff S. Route and length of therapy of acute uncomplicated hematogenous osteomyelitis: do we have the answers yet? Hosp Pediatr. 2014;4(1):44-47.
2. Arnold SR, Elias D, Buckingham SC, et al. Changing patterns of acute hematogenous osteomyelitis and septic arthritis: emergence of community-associated methicillin-resistant Staphylococcus aureus. J Pediatr Orthop. 2006;26(6):703-708.
3. Zaoutis T, Localio AR, Leckerman K, Saddlemire S, Bertoch D, Keren R. Prolonged intravenous therapy versus eraly transtion to oral antimicrobial therapy for acute osteomyelitis in children. Pediatrics. 2009;123(2):636-642.

Clinical question

Can a procalcitonin-based algorithm reduce antibiotic use in critically ill patients?

Bottom line

A procalcitonin-based algorithm using a 0.1 ng/mL cutoff does not significantly decrease the duration of antibiotic treatment in critically ill patients nor does it reduce length of stay or number of deaths. The rate of decline in the procalcitonin level over the first 72 hours, however, does serve as an independent predictor of short-term and long-term all-cause mortality. (LOE = 1b-)

Reference

Shehabi Y, Sterba M, Garrett PM, et al, for the ProGUARD Study Investigators and the ANZICS Clinical Trials Group. Procalcitonin algorithm in critically ill adults with undifferentiated infection or suspected sepsis. Am J Respir Crit Care Med 2014;190(10):1102-1110.

Study design: Randomized controlled trial (nonblinded)

Funding source: Foundation

Allocation: Concealed

Setting: Inpatient (ICU only)

Synopsis

Procalcitonin (PCT) is a sepsis biomarker that has been utilized to guide antibiotic use in different patient populations. In this study, the authors tested a PCT-algorithm using a 0.1 ng/mL cut-off to reduce antibiotic exposure in critically ill patients. Patients newly admitted to intensive care units (ICUs) who were receiving antibiotics for suspected infections were randomized, using concealed allocation, to receive PCT-guided care (n = 196) or standard care (n = 198). All patients had PCT levels drawn daily until discharge from the ICU or up to a maximum of 7 days. In the PCT group, antibiotics were stopped if PCT levels were negative (< 0.1 ng/mL), if PCT levels were borderline (0.1 - 0.25 ng/mL) and infection was unlikely, or if PCT levels decreased more than 90% from baseline values. In the standard care group, the treating clinician determined antibiotic use without knowledge of the PCT results. Baseline characteristics of the 2 groups were similar with regard to severity-of-disease scores and baseline PCT values. There was high compliance with the PCT algorithm, with less than 3% of study days when the algorithm was not followed. There was no significant difference detected between the 2 groups for the primary outcome of time to antibiotic cessation. However, duration of antibiotic use was longer than expected in the control group (11 days actual vs 9 days expected), so the study may have been underpowered to detect an expected 25% reduction. Nevertheless, the 2 groups were similar with regard to ICU and hospital lengths of stay, as well as ICU, hospital, and 90-day mortality rates. Of note, the rate of decline in PCT level over the first 72 hours was an independent predictor of hospital mortality and 90-day mortality, with a slower decline corresponding to a higher mortality.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Can a procalcitonin-based algorithm reduce antibiotic use in critically ill patients?

Bottom line

A procalcitonin-based algorithm using a 0.1 ng/mL cutoff does not significantly decrease the duration of antibiotic treatment in critically ill patients nor does it reduce length of stay or number of deaths. The rate of decline in the procalcitonin level over the first 72 hours, however, does serve as an independent predictor of short-term and long-term all-cause mortality. (LOE = 1b-)

Reference

Shehabi Y, Sterba M, Garrett PM, et al, for the ProGUARD Study Investigators and the ANZICS Clinical Trials Group. Procalcitonin algorithm in critically ill adults with undifferentiated infection or suspected sepsis. Am J Respir Crit Care Med 2014;190(10):1102-1110.

Study design: Randomized controlled trial (nonblinded)

Funding source: Foundation

Allocation: Concealed

Setting: Inpatient (ICU only)

Synopsis

Procalcitonin (PCT) is a sepsis biomarker that has been utilized to guide antibiotic use in different patient populations. In this study, the authors tested a PCT-algorithm using a 0.1 ng/mL cut-off to reduce antibiotic exposure in critically ill patients. Patients newly admitted to intensive care units (ICUs) who were receiving antibiotics for suspected infections were randomized, using concealed allocation, to receive PCT-guided care (n = 196) or standard care (n = 198). All patients had PCT levels drawn daily until discharge from the ICU or up to a maximum of 7 days. In the PCT group, antibiotics were stopped if PCT levels were negative (< 0.1 ng/mL), if PCT levels were borderline (0.1 - 0.25 ng/mL) and infection was unlikely, or if PCT levels decreased more than 90% from baseline values. In the standard care group, the treating clinician determined antibiotic use without knowledge of the PCT results. Baseline characteristics of the 2 groups were similar with regard to severity-of-disease scores and baseline PCT values. There was high compliance with the PCT algorithm, with less than 3% of study days when the algorithm was not followed. There was no significant difference detected between the 2 groups for the primary outcome of time to antibiotic cessation. However, duration of antibiotic use was longer than expected in the control group (11 days actual vs 9 days expected), so the study may have been underpowered to detect an expected 25% reduction. Nevertheless, the 2 groups were similar with regard to ICU and hospital lengths of stay, as well as ICU, hospital, and 90-day mortality rates. Of note, the rate of decline in PCT level over the first 72 hours was an independent predictor of hospital mortality and 90-day mortality, with a slower decline corresponding to a higher mortality.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Can a procalcitonin-based algorithm reduce antibiotic use in critically ill patients?

Bottom line

A procalcitonin-based algorithm using a 0.1 ng/mL cutoff does not significantly decrease the duration of antibiotic treatment in critically ill patients nor does it reduce length of stay or number of deaths. The rate of decline in the procalcitonin level over the first 72 hours, however, does serve as an independent predictor of short-term and long-term all-cause mortality. (LOE = 1b-)

Reference

Shehabi Y, Sterba M, Garrett PM, et al, for the ProGUARD Study Investigators and the ANZICS Clinical Trials Group. Procalcitonin algorithm in critically ill adults with undifferentiated infection or suspected sepsis. Am J Respir Crit Care Med 2014;190(10):1102-1110.

Study design: Randomized controlled trial (nonblinded)

Funding source: Foundation

Allocation: Concealed

Setting: Inpatient (ICU only)

Synopsis

Procalcitonin (PCT) is a sepsis biomarker that has been utilized to guide antibiotic use in different patient populations. In this study, the authors tested a PCT-algorithm using a 0.1 ng/mL cut-off to reduce antibiotic exposure in critically ill patients. Patients newly admitted to intensive care units (ICUs) who were receiving antibiotics for suspected infections were randomized, using concealed allocation, to receive PCT-guided care (n = 196) or standard care (n = 198). All patients had PCT levels drawn daily until discharge from the ICU or up to a maximum of 7 days. In the PCT group, antibiotics were stopped if PCT levels were negative (< 0.1 ng/mL), if PCT levels were borderline (0.1 - 0.25 ng/mL) and infection was unlikely, or if PCT levels decreased more than 90% from baseline values. In the standard care group, the treating clinician determined antibiotic use without knowledge of the PCT results. Baseline characteristics of the 2 groups were similar with regard to severity-of-disease scores and baseline PCT values. There was high compliance with the PCT algorithm, with less than 3% of study days when the algorithm was not followed. There was no significant difference detected between the 2 groups for the primary outcome of time to antibiotic cessation. However, duration of antibiotic use was longer than expected in the control group (11 days actual vs 9 days expected), so the study may have been underpowered to detect an expected 25% reduction. Nevertheless, the 2 groups were similar with regard to ICU and hospital lengths of stay, as well as ICU, hospital, and 90-day mortality rates. Of note, the rate of decline in PCT level over the first 72 hours was an independent predictor of hospital mortality and 90-day mortality, with a slower decline corresponding to a higher mortality.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Hospitalists need not fear negative consequences when prescribing guideline-recommended antibiotic therapy for children hospitalized with community-acquired pneumonia (CAP), according to a recent study conducted at Cincinnati Children’s Hospital Medical Center (CCHMC).

"Guideline-recommended therapy for pediatric pneumonia did not result in different outcomes than nonrecommended [largely cephalosporin] therapy," lead author and CCHMC-based hospitalist Joanna Thomson MD, MPH, says in an email to The Hospitalist.

Published in the Journal of Hospital Medicine, the study followed the outcomes of 168 pediatric inpatients ages 3 months to 18 years who were prescribed empiric guideline-recommended therapy, which advises using an aminopenicillin first rather than a broad-spectrum antibiotic. The study focused on patients’ outcomes, specifically length of stay (LOS), total cost of hospitalization, and inpatient pharmacy costs, and found no difference in LOS or costs for patients treated according to guidelines compared with those whose treatment varied from the recommendations.

"Given growing concerns regarding antimicrobial resistance, it is pretty easy to extrapolate the benefits of using narrow-spectrum therapy, but we wanted to make sure that it wasn't resulting in negative unintended consequences," Dr. Thomson says. "Indeed, use of guideline-recommended therapy did not change our outcomes."

However, most patients hospitalized with CAP do not currently receive guideline-recommended therapy, according to Dr. Thomson. CCHMC had been one of those institutions overprescribing cephalosporin, with nearly 70% of children admitted with pneumonia receiving the antibiotic. That practice has since changed, she notes.

"The majority of hospitalized patients in the U.S. still receive broad-spectrum cephalosporins," Dr. Thomson says. "I suspect that this may partially be due to fears of unintended negative consequences. We should all be good stewards and prescribe guideline-recommended therapy whenever possible."

Visit our website for more information on antibiotic prescription practices.

Hospitalists need not fear negative consequences when prescribing guideline-recommended antibiotic therapy for children hospitalized with community-acquired pneumonia (CAP), according to a recent study conducted at Cincinnati Children’s Hospital Medical Center (CCHMC).

"Guideline-recommended therapy for pediatric pneumonia did not result in different outcomes than nonrecommended [largely cephalosporin] therapy," lead author and CCHMC-based hospitalist Joanna Thomson MD, MPH, says in an email to The Hospitalist.

Published in the Journal of Hospital Medicine, the study followed the outcomes of 168 pediatric inpatients ages 3 months to 18 years who were prescribed empiric guideline-recommended therapy, which advises using an aminopenicillin first rather than a broad-spectrum antibiotic. The study focused on patients’ outcomes, specifically length of stay (LOS), total cost of hospitalization, and inpatient pharmacy costs, and found no difference in LOS or costs for patients treated according to guidelines compared with those whose treatment varied from the recommendations.

"Given growing concerns regarding antimicrobial resistance, it is pretty easy to extrapolate the benefits of using narrow-spectrum therapy, but we wanted to make sure that it wasn't resulting in negative unintended consequences," Dr. Thomson says. "Indeed, use of guideline-recommended therapy did not change our outcomes."

However, most patients hospitalized with CAP do not currently receive guideline-recommended therapy, according to Dr. Thomson. CCHMC had been one of those institutions overprescribing cephalosporin, with nearly 70% of children admitted with pneumonia receiving the antibiotic. That practice has since changed, she notes.

"The majority of hospitalized patients in the U.S. still receive broad-spectrum cephalosporins," Dr. Thomson says. "I suspect that this may partially be due to fears of unintended negative consequences. We should all be good stewards and prescribe guideline-recommended therapy whenever possible."

Visit our website for more information on antibiotic prescription practices.

Hospitalists need not fear negative consequences when prescribing guideline-recommended antibiotic therapy for children hospitalized with community-acquired pneumonia (CAP), according to a recent study conducted at Cincinnati Children’s Hospital Medical Center (CCHMC).

"Guideline-recommended therapy for pediatric pneumonia did not result in different outcomes than nonrecommended [largely cephalosporin] therapy," lead author and CCHMC-based hospitalist Joanna Thomson MD, MPH, says in an email to The Hospitalist.

Published in the Journal of Hospital Medicine, the study followed the outcomes of 168 pediatric inpatients ages 3 months to 18 years who were prescribed empiric guideline-recommended therapy, which advises using an aminopenicillin first rather than a broad-spectrum antibiotic. The study focused on patients’ outcomes, specifically length of stay (LOS), total cost of hospitalization, and inpatient pharmacy costs, and found no difference in LOS or costs for patients treated according to guidelines compared with those whose treatment varied from the recommendations.

"Given growing concerns regarding antimicrobial resistance, it is pretty easy to extrapolate the benefits of using narrow-spectrum therapy, but we wanted to make sure that it wasn't resulting in negative unintended consequences," Dr. Thomson says. "Indeed, use of guideline-recommended therapy did not change our outcomes."

However, most patients hospitalized with CAP do not currently receive guideline-recommended therapy, according to Dr. Thomson. CCHMC had been one of those institutions overprescribing cephalosporin, with nearly 70% of children admitted with pneumonia receiving the antibiotic. That practice has since changed, she notes.

"The majority of hospitalized patients in the U.S. still receive broad-spectrum cephalosporins," Dr. Thomson says. "I suspect that this may partially be due to fears of unintended negative consequences. We should all be good stewards and prescribe guideline-recommended therapy whenever possible."

Visit our website for more information on antibiotic prescription practices.

Antibiotic overprescription remains a problem in the U.S. and abroad and shows no signs of slowing. A study published in the October 2014 issue of JAMA reports that nearly half of all hospitalized patients receive antibiotics, and the drugs most commonly prescribed are broad-spectrum antibiotics, which have been linked with promoting the spread of antibiotic-resistant bacteria. Based on a one-day prevalence survey of more than 11,000 patients in 183 U.S. hospitals in 2011, the study notes that half of inpatients prescribed antibiotics received two or more of them. The CDC estimates that 20% to 50% of all antibiotics prescribed in U.S. hospitals are either unnecessary or inappropriate, and many of them count adverse drug reactions among their side effects .

While a growing body of evidence suggests that hospital-based antibiotic stewardship programs can optimize treatment, reduce antibacterial side effects, and save money, a study published September 2014 in JAMA says those benefits may be lost post-discharge. Results of a randomized trial of an outpatient antimicrobial stewardship intervention found that an initial 50% reduction in antibiotic prescriptions was lost when their targeted interventions ceased.

“These data suggest that audit and feedback was a vital element of this intervention and that antimicrobial stewardship requires continued, active efforts to sustain initial improvements,” says lead author Jeffrey S. Gerber, MD, PhD, CHCP, attending physician in infectious diseases at the Children’s Hospital of Philadelphia.

The federal government has taken a three-pronged approach to the problem: a report from the President’s Council of Advisors on Science and Technology with recommendations for monitoring superbugs and slowing their spread; an executive order issued by President Obama on September 18, 2014 with a commitment to “accelerate scientific research and facilitate the development of new antibacterial drugs;” and the creation of a national task force charged with designing a national strategy to combat antibiotic overuse by February 2015.

The President’s Council report notes that bacteria are becoming resistant to antibiotics in large part because these drugs are overprescribed to patients and overused in animals raised for food. The report recommends the CDC develop rules by 2017 requiring hospitals and nursing homes to implement best practices for antibiotic use.

Antibiotic overprescription remains a problem in the U.S. and abroad and shows no signs of slowing. A study published in the October 2014 issue of JAMA reports that nearly half of all hospitalized patients receive antibiotics, and the drugs most commonly prescribed are broad-spectrum antibiotics, which have been linked with promoting the spread of antibiotic-resistant bacteria. Based on a one-day prevalence survey of more than 11,000 patients in 183 U.S. hospitals in 2011, the study notes that half of inpatients prescribed antibiotics received two or more of them. The CDC estimates that 20% to 50% of all antibiotics prescribed in U.S. hospitals are either unnecessary or inappropriate, and many of them count adverse drug reactions among their side effects .

While a growing body of evidence suggests that hospital-based antibiotic stewardship programs can optimize treatment, reduce antibacterial side effects, and save money, a study published September 2014 in JAMA says those benefits may be lost post-discharge. Results of a randomized trial of an outpatient antimicrobial stewardship intervention found that an initial 50% reduction in antibiotic prescriptions was lost when their targeted interventions ceased.

“These data suggest that audit and feedback was a vital element of this intervention and that antimicrobial stewardship requires continued, active efforts to sustain initial improvements,” says lead author Jeffrey S. Gerber, MD, PhD, CHCP, attending physician in infectious diseases at the Children’s Hospital of Philadelphia.

The federal government has taken a three-pronged approach to the problem: a report from the President’s Council of Advisors on Science and Technology with recommendations for monitoring superbugs and slowing their spread; an executive order issued by President Obama on September 18, 2014 with a commitment to “accelerate scientific research and facilitate the development of new antibacterial drugs;” and the creation of a national task force charged with designing a national strategy to combat antibiotic overuse by February 2015.

The President’s Council report notes that bacteria are becoming resistant to antibiotics in large part because these drugs are overprescribed to patients and overused in animals raised for food. The report recommends the CDC develop rules by 2017 requiring hospitals and nursing homes to implement best practices for antibiotic use.

Antibiotic overprescription remains a problem in the U.S. and abroad and shows no signs of slowing. A study published in the October 2014 issue of JAMA reports that nearly half of all hospitalized patients receive antibiotics, and the drugs most commonly prescribed are broad-spectrum antibiotics, which have been linked with promoting the spread of antibiotic-resistant bacteria. Based on a one-day prevalence survey of more than 11,000 patients in 183 U.S. hospitals in 2011, the study notes that half of inpatients prescribed antibiotics received two or more of them. The CDC estimates that 20% to 50% of all antibiotics prescribed in U.S. hospitals are either unnecessary or inappropriate, and many of them count adverse drug reactions among their side effects .

While a growing body of evidence suggests that hospital-based antibiotic stewardship programs can optimize treatment, reduce antibacterial side effects, and save money, a study published September 2014 in JAMA says those benefits may be lost post-discharge. Results of a randomized trial of an outpatient antimicrobial stewardship intervention found that an initial 50% reduction in antibiotic prescriptions was lost when their targeted interventions ceased.

“These data suggest that audit and feedback was a vital element of this intervention and that antimicrobial stewardship requires continued, active efforts to sustain initial improvements,” says lead author Jeffrey S. Gerber, MD, PhD, CHCP, attending physician in infectious diseases at the Children’s Hospital of Philadelphia.

The federal government has taken a three-pronged approach to the problem: a report from the President’s Council of Advisors on Science and Technology with recommendations for monitoring superbugs and slowing their spread; an executive order issued by President Obama on September 18, 2014 with a commitment to “accelerate scientific research and facilitate the development of new antibacterial drugs;” and the creation of a national task force charged with designing a national strategy to combat antibiotic overuse by February 2015.

The President’s Council report notes that bacteria are becoming resistant to antibiotics in large part because these drugs are overprescribed to patients and overused in animals raised for food. The report recommends the CDC develop rules by 2017 requiring hospitals and nursing homes to implement best practices for antibiotic use.

Case

A 45-year-old previously healthy female was admitted to the ICU with sepsis caused by community-acquired pneumonia. Per hospital policy, all patients admitted to the ICU are screened for MRSA colonization. If the nasal screen is positive, contact isolation is initiated and the hospital’s MRSA decolonization protocol is implemented. Her nasal screen was positive for MRSA.

Overview

MRSA infections are associated with significant morbidity and mortality, and death occurs in almost 5% of patients who develop a MRSA infection. In 2005, invasive MRSA was responsible for approximately 278,000 hospitalizations and 19,000 deaths. MRSA is a common cause of healthcare-associated infections (HAIs) and is the most common pathogen in surgical site infections (SSIs) and ventilator-associated pneumonias. The cost of treating MRSA infections is substantial; in 2003, $14.5 billion was spent on MRSA-related hospitalizations.

It is well known that MRSA colonization is a risk factor for the subsequent development of a MRSA infection. This risk persists over time, and approximately 25% of individuals who are colonized with MRSA for more than one year will develop a late-onset MRSA infection.¹ It is estimated that between 0.8% and 6% of people in the U.S. are asymptomatically colonized with MRSA.

One infection control strategy for reducing the transmission of MRSA among hospitalized patients involves screening for the presence of this organism and then placing colonized and/or infected patients in isolation; however, there is considerable controversy about which patients should be screened.

An additional element of many infection control strategies involves MRSA decolonization, but there is uncertainty about which patients benefit from it and significant variability in its reported success rates.² Additionally, several studies have indicated that MRSA decolonization is only temporary and that patients become recolonized over time.

Treatment

It is estimated that 10% to 20% of MRSA carriers will develop an infection while they are hospitalized. Furthermore, even after they have been discharged from the hospital, their risk for developing a MRSA infection persists.

Most patients who develop a MRSA infection have been colonized prior to infection, and these patients usually develop an infection caused by the same strain as the colonization. In view of this fact, a primary goal of decolonization is reducing the likelihood of “auto-infection.” Another goal of decolonization is reducing the transmission of MRSA to other patients.

In order to determine whether MRSA colonization is present, patients undergo screening, and specimens are collected from the nares using nasal swabs. Specimens from extranasal sites, such as the groin, are sometimes also obtained for screening. These screening tests are usually done with either cultures or polymerase chain reaction testing.

There is significant variability in the details of screening and decolonization protocols among different healthcare facilities. Typically, the screening test costs more than the agents used for decolonization. Partly for this reason, some facilities forego screening altogether, instead treating all patients with a decolonization regimen; however, there is concern that administering decolonizing medications to all patients would lead to the unnecessary treatment of large numbers of patients. Such widespread use of the decolonizing agents might promote the development of resistance to these medications.

Medications. Decolonization typically involves the use of a topical antibiotic, most commonly mupirocin, which is applied to the nares. This may be used in conjunction with an oral antimicrobial agent. While the nares are the anatomical locations most commonly colonized by MRSA, extranasal colonization occurs in 50% of those who are nasally colonized.

 

Of the topical medications available for decolonization, mupirocin has the highest efficacy, with eradication of MRSA and methicillin-sensitive Staphylococcus aureus (MSSA) colonization ranging from 81% to 93%. To increase the likelihood of successful decolonization, an antiseptic agent, such as chlorhexidine gluconate, may also be applied to the skin. Chlorhexidine gluconate is also commonly used to prevent other HAIs.

Neomycin is sometimes used for decolonization, but its efficacy for this purpose is questionable. There are also concerns about resistance, but it may be an option in cases of documented mupirocin resistance. Preparations that contain tea tree oil appear to be more effective for decolonization of skin sites than for nasal decolonization. Table 1 lists the topical antibiotics and antiseptics that may be utilized for decolonization, while Table 2 lists the oral medications that can be used for this purpose. Table 3 lists investigational agents being evaluated for their ability to decolonize patients.

It has been suggested that the patients who might derive the most benefit from decolonization are those at increased risk for developing a MRSA infection during a specific time interval. This would include patients who are admitted to the ICU for an acute illness and cardiothoracic surgery patients. A benefit from decolonization has also been observed in hemodialysis patients, who have an incidence of invasive MRSA infections 100 times greater than the general population. Otherwise, there are no data to support the routine use of decolonization in nonsurgical patients.

It is not uncommon for hospitals to screen patients admitted to the ICU for MRSA nasal colonization; in fact, screening is mandatory in nine states. If the nasal screen is positive, contact precautions are instituted. The decision about whether or not to initiate a decolonization protocol varies among different ICUs, but most do not carry out universal decolonization.

Some studies show decolonization is beneficial for ICU patients. These studies include a large cluster-randomized trial called REDUCE MRSA,³ which took place in 43 hospitals and involved 74,256 patients in 74 ICUs. The study showed that universal (i.e., without screening) decolonization using mupirocin and chlorhexidine was effective in reducing rates of MRSA clinical isolates, as well as bloodstream infection from any pathogen. Other studies have demonstrated benefits from the decolonization of ICU patients.^4,5

Surgical Site Infections. Meanwhile, SSIs are often associated with increased mortality rates and substantial healthcare costs, including increased hospital lengths of stay and readmission rates. Staphylococcus aureus is the pathogen most commonly isolated from SSIs. In surgical patients, colonization with MRSA is associated with an elevated rate of MRSA SSIs. The goal of decolonization in surgical patients is not to permanently eliminate MRSA but to prevent SSIs by suppressing the presence of this organism for a relatively brief duration.

There is evidence that decolonization reduces SSIs for cardiothoracic surgeries.⁶ For these patients, it is cost effective to screen for nasal carriage of MRSA and then treat carriers with a combination of pre-operative mupirocin and chlorhexidine. It may be reasonable to delay cardiothoracic surgery in colonized patients who will require implantation of prosthetic material until they complete MRSA decolonization.

In addition to reducing the risk of auto-infection, another goal of decolonization is limiting the possibility of transmission of MRSA from a colonized patient to a susceptible individual; however, there are only limited data available that measure the efficacy of decolonization for preventing transmission.

Concerns about the potential hazards of decolonization therapy have impacted its widespread implementation. The biggest concern is that patients may develop resistance to the antimicrobial agents used for decolonization, particularly if they are used at increased frequency. Mupirocin resistance monitoring is valuable, but, unfortunately, the susceptibility of Staphylococcus aureus to mupirocin is not routinely evaluated, so the prevalence of mupirocin resistance in local strains is often unknown. Another concern about decolonization is the cost of screening and decolonizing patients.

 

Back to the Case

The patient in this case required admission to an ICU and, based on the results of the REDUCE MRSA clinical trial, she would likely benefit from undergoing decolonization to reduce her risk of both MRSA-positive clinical cultures and bloodstream infections caused by any pathogen.

Bottom Line

Decolonization is beneficial for patients at increased risk of developing a MRSA infection during a specific period, such as patients admitted to the ICU and those undergoing cardiothoracic surgery.

---

Dr. Clarke is assistant professor in the division of hospital medicine at Emory University Hospital and a faculty member in the Emory University Department of Medicine, both in Atlanta.

References

1. Dow G, Field D, Mancuso M, Allard J. Decolonization of methicillin-resistant Staphylococcus aureus during routine hospital care: Efficacy and long-term follow-up. Can J Infect Dis Med Microbiol. 2010;21(1):38-44.
2. Simor AE. Staphylococcal decolonisation: An effective strategy for prevention of infection? Lancet Infect Dis. 2011;11(12):952-962.
3. Huang SS, Septimus E, Kleinman K, et al. Targeted versus universal decolonization to prevent ICU infection. N Engl J Med. 2013;368(24):2255-2265.
4. Fraser T, Fatica C, Scarpelli M, et al. Decrease in Staphylococcus aureus colonization and hospital-acquired infection in a medical intensive care unit after institution of an active surveillance and decolonization program. Infect Control Hosp Epidemiol. 2010;31(8):779-783.
5. Robotham J, Graves N, Cookson B, et al. Screening, isolation, and decolonisation strategies in the control of methicillin-resistant Staphylococcus aureus in intensive care units: Cost effectiveness evaluation. BMJ. 2011;343:d5694.
6. Schweizer M, Perencevich E, McDanel J, et al. Effectiveness of a bundled intervention of decolonization and prophylaxis to decrease Gram positive surgical site infections after cardiac or orthopedic surgery: Systematic review and meta-analysis. BMJ. 2013;346:f2743.

Case

A 45-year-old previously healthy female was admitted to the ICU with sepsis caused by community-acquired pneumonia. Per hospital policy, all patients admitted to the ICU are screened for MRSA colonization. If the nasal screen is positive, contact isolation is initiated and the hospital’s MRSA decolonization protocol is implemented. Her nasal screen was positive for MRSA.

Overview

MRSA infections are associated with significant morbidity and mortality, and death occurs in almost 5% of patients who develop a MRSA infection. In 2005, invasive MRSA was responsible for approximately 278,000 hospitalizations and 19,000 deaths. MRSA is a common cause of healthcare-associated infections (HAIs) and is the most common pathogen in surgical site infections (SSIs) and ventilator-associated pneumonias. The cost of treating MRSA infections is substantial; in 2003, $14.5 billion was spent on MRSA-related hospitalizations.

It is well known that MRSA colonization is a risk factor for the subsequent development of a MRSA infection. This risk persists over time, and approximately 25% of individuals who are colonized with MRSA for more than one year will develop a late-onset MRSA infection.¹ It is estimated that between 0.8% and 6% of people in the U.S. are asymptomatically colonized with MRSA.

One infection control strategy for reducing the transmission of MRSA among hospitalized patients involves screening for the presence of this organism and then placing colonized and/or infected patients in isolation; however, there is considerable controversy about which patients should be screened.

An additional element of many infection control strategies involves MRSA decolonization, but there is uncertainty about which patients benefit from it and significant variability in its reported success rates.² Additionally, several studies have indicated that MRSA decolonization is only temporary and that patients become recolonized over time.

Treatment

It is estimated that 10% to 20% of MRSA carriers will develop an infection while they are hospitalized. Furthermore, even after they have been discharged from the hospital, their risk for developing a MRSA infection persists.

Most patients who develop a MRSA infection have been colonized prior to infection, and these patients usually develop an infection caused by the same strain as the colonization. In view of this fact, a primary goal of decolonization is reducing the likelihood of “auto-infection.” Another goal of decolonization is reducing the transmission of MRSA to other patients.

In order to determine whether MRSA colonization is present, patients undergo screening, and specimens are collected from the nares using nasal swabs. Specimens from extranasal sites, such as the groin, are sometimes also obtained for screening. These screening tests are usually done with either cultures or polymerase chain reaction testing.

There is significant variability in the details of screening and decolonization protocols among different healthcare facilities. Typically, the screening test costs more than the agents used for decolonization. Partly for this reason, some facilities forego screening altogether, instead treating all patients with a decolonization regimen; however, there is concern that administering decolonizing medications to all patients would lead to the unnecessary treatment of large numbers of patients. Such widespread use of the decolonizing agents might promote the development of resistance to these medications.

Medications. Decolonization typically involves the use of a topical antibiotic, most commonly mupirocin, which is applied to the nares. This may be used in conjunction with an oral antimicrobial agent. While the nares are the anatomical locations most commonly colonized by MRSA, extranasal colonization occurs in 50% of those who are nasally colonized.

 

Of the topical medications available for decolonization, mupirocin has the highest efficacy, with eradication of MRSA and methicillin-sensitive Staphylococcus aureus (MSSA) colonization ranging from 81% to 93%. To increase the likelihood of successful decolonization, an antiseptic agent, such as chlorhexidine gluconate, may also be applied to the skin. Chlorhexidine gluconate is also commonly used to prevent other HAIs.

Neomycin is sometimes used for decolonization, but its efficacy for this purpose is questionable. There are also concerns about resistance, but it may be an option in cases of documented mupirocin resistance. Preparations that contain tea tree oil appear to be more effective for decolonization of skin sites than for nasal decolonization. Table 1 lists the topical antibiotics and antiseptics that may be utilized for decolonization, while Table 2 lists the oral medications that can be used for this purpose. Table 3 lists investigational agents being evaluated for their ability to decolonize patients.

It has been suggested that the patients who might derive the most benefit from decolonization are those at increased risk for developing a MRSA infection during a specific time interval. This would include patients who are admitted to the ICU for an acute illness and cardiothoracic surgery patients. A benefit from decolonization has also been observed in hemodialysis patients, who have an incidence of invasive MRSA infections 100 times greater than the general population. Otherwise, there are no data to support the routine use of decolonization in nonsurgical patients.

It is not uncommon for hospitals to screen patients admitted to the ICU for MRSA nasal colonization; in fact, screening is mandatory in nine states. If the nasal screen is positive, contact precautions are instituted. The decision about whether or not to initiate a decolonization protocol varies among different ICUs, but most do not carry out universal decolonization.

Some studies show decolonization is beneficial for ICU patients. These studies include a large cluster-randomized trial called REDUCE MRSA,³ which took place in 43 hospitals and involved 74,256 patients in 74 ICUs. The study showed that universal (i.e., without screening) decolonization using mupirocin and chlorhexidine was effective in reducing rates of MRSA clinical isolates, as well as bloodstream infection from any pathogen. Other studies have demonstrated benefits from the decolonization of ICU patients.^4,5

Surgical Site Infections. Meanwhile, SSIs are often associated with increased mortality rates and substantial healthcare costs, including increased hospital lengths of stay and readmission rates. Staphylococcus aureus is the pathogen most commonly isolated from SSIs. In surgical patients, colonization with MRSA is associated with an elevated rate of MRSA SSIs. The goal of decolonization in surgical patients is not to permanently eliminate MRSA but to prevent SSIs by suppressing the presence of this organism for a relatively brief duration.

There is evidence that decolonization reduces SSIs for cardiothoracic surgeries.⁶ For these patients, it is cost effective to screen for nasal carriage of MRSA and then treat carriers with a combination of pre-operative mupirocin and chlorhexidine. It may be reasonable to delay cardiothoracic surgery in colonized patients who will require implantation of prosthetic material until they complete MRSA decolonization.

In addition to reducing the risk of auto-infection, another goal of decolonization is limiting the possibility of transmission of MRSA from a colonized patient to a susceptible individual; however, there are only limited data available that measure the efficacy of decolonization for preventing transmission.

Concerns about the potential hazards of decolonization therapy have impacted its widespread implementation. The biggest concern is that patients may develop resistance to the antimicrobial agents used for decolonization, particularly if they are used at increased frequency. Mupirocin resistance monitoring is valuable, but, unfortunately, the susceptibility of Staphylococcus aureus to mupirocin is not routinely evaluated, so the prevalence of mupirocin resistance in local strains is often unknown. Another concern about decolonization is the cost of screening and decolonizing patients.

 

Back to the Case

The patient in this case required admission to an ICU and, based on the results of the REDUCE MRSA clinical trial, she would likely benefit from undergoing decolonization to reduce her risk of both MRSA-positive clinical cultures and bloodstream infections caused by any pathogen.

Bottom Line

Decolonization is beneficial for patients at increased risk of developing a MRSA infection during a specific period, such as patients admitted to the ICU and those undergoing cardiothoracic surgery.

---

Dr. Clarke is assistant professor in the division of hospital medicine at Emory University Hospital and a faculty member in the Emory University Department of Medicine, both in Atlanta.

References

1. Dow G, Field D, Mancuso M, Allard J. Decolonization of methicillin-resistant Staphylococcus aureus during routine hospital care: Efficacy and long-term follow-up. Can J Infect Dis Med Microbiol. 2010;21(1):38-44.
2. Simor AE. Staphylococcal decolonisation: An effective strategy for prevention of infection? Lancet Infect Dis. 2011;11(12):952-962.
3. Huang SS, Septimus E, Kleinman K, et al. Targeted versus universal decolonization to prevent ICU infection. N Engl J Med. 2013;368(24):2255-2265.
4. Fraser T, Fatica C, Scarpelli M, et al. Decrease in Staphylococcus aureus colonization and hospital-acquired infection in a medical intensive care unit after institution of an active surveillance and decolonization program. Infect Control Hosp Epidemiol. 2010;31(8):779-783.
5. Robotham J, Graves N, Cookson B, et al. Screening, isolation, and decolonisation strategies in the control of methicillin-resistant Staphylococcus aureus in intensive care units: Cost effectiveness evaluation. BMJ. 2011;343:d5694.
6. Schweizer M, Perencevich E, McDanel J, et al. Effectiveness of a bundled intervention of decolonization and prophylaxis to decrease Gram positive surgical site infections after cardiac or orthopedic surgery: Systematic review and meta-analysis. BMJ. 2013;346:f2743.

Case

A 45-year-old previously healthy female was admitted to the ICU with sepsis caused by community-acquired pneumonia. Per hospital policy, all patients admitted to the ICU are screened for MRSA colonization. If the nasal screen is positive, contact isolation is initiated and the hospital’s MRSA decolonization protocol is implemented. Her nasal screen was positive for MRSA.

Overview

MRSA infections are associated with significant morbidity and mortality, and death occurs in almost 5% of patients who develop a MRSA infection. In 2005, invasive MRSA was responsible for approximately 278,000 hospitalizations and 19,000 deaths. MRSA is a common cause of healthcare-associated infections (HAIs) and is the most common pathogen in surgical site infections (SSIs) and ventilator-associated pneumonias. The cost of treating MRSA infections is substantial; in 2003, $14.5 billion was spent on MRSA-related hospitalizations.

It is well known that MRSA colonization is a risk factor for the subsequent development of a MRSA infection. This risk persists over time, and approximately 25% of individuals who are colonized with MRSA for more than one year will develop a late-onset MRSA infection.¹ It is estimated that between 0.8% and 6% of people in the U.S. are asymptomatically colonized with MRSA.

One infection control strategy for reducing the transmission of MRSA among hospitalized patients involves screening for the presence of this organism and then placing colonized and/or infected patients in isolation; however, there is considerable controversy about which patients should be screened.

An additional element of many infection control strategies involves MRSA decolonization, but there is uncertainty about which patients benefit from it and significant variability in its reported success rates.² Additionally, several studies have indicated that MRSA decolonization is only temporary and that patients become recolonized over time.

Treatment

It is estimated that 10% to 20% of MRSA carriers will develop an infection while they are hospitalized. Furthermore, even after they have been discharged from the hospital, their risk for developing a MRSA infection persists.

Most patients who develop a MRSA infection have been colonized prior to infection, and these patients usually develop an infection caused by the same strain as the colonization. In view of this fact, a primary goal of decolonization is reducing the likelihood of “auto-infection.” Another goal of decolonization is reducing the transmission of MRSA to other patients.

In order to determine whether MRSA colonization is present, patients undergo screening, and specimens are collected from the nares using nasal swabs. Specimens from extranasal sites, such as the groin, are sometimes also obtained for screening. These screening tests are usually done with either cultures or polymerase chain reaction testing.

There is significant variability in the details of screening and decolonization protocols among different healthcare facilities. Typically, the screening test costs more than the agents used for decolonization. Partly for this reason, some facilities forego screening altogether, instead treating all patients with a decolonization regimen; however, there is concern that administering decolonizing medications to all patients would lead to the unnecessary treatment of large numbers of patients. Such widespread use of the decolonizing agents might promote the development of resistance to these medications.

Medications. Decolonization typically involves the use of a topical antibiotic, most commonly mupirocin, which is applied to the nares. This may be used in conjunction with an oral antimicrobial agent. While the nares are the anatomical locations most commonly colonized by MRSA, extranasal colonization occurs in 50% of those who are nasally colonized.

 

Of the topical medications available for decolonization, mupirocin has the highest efficacy, with eradication of MRSA and methicillin-sensitive Staphylococcus aureus (MSSA) colonization ranging from 81% to 93%. To increase the likelihood of successful decolonization, an antiseptic agent, such as chlorhexidine gluconate, may also be applied to the skin. Chlorhexidine gluconate is also commonly used to prevent other HAIs.

Neomycin is sometimes used for decolonization, but its efficacy for this purpose is questionable. There are also concerns about resistance, but it may be an option in cases of documented mupirocin resistance. Preparations that contain tea tree oil appear to be more effective for decolonization of skin sites than for nasal decolonization. Table 1 lists the topical antibiotics and antiseptics that may be utilized for decolonization, while Table 2 lists the oral medications that can be used for this purpose. Table 3 lists investigational agents being evaluated for their ability to decolonize patients.

It has been suggested that the patients who might derive the most benefit from decolonization are those at increased risk for developing a MRSA infection during a specific time interval. This would include patients who are admitted to the ICU for an acute illness and cardiothoracic surgery patients. A benefit from decolonization has also been observed in hemodialysis patients, who have an incidence of invasive MRSA infections 100 times greater than the general population. Otherwise, there are no data to support the routine use of decolonization in nonsurgical patients.

It is not uncommon for hospitals to screen patients admitted to the ICU for MRSA nasal colonization; in fact, screening is mandatory in nine states. If the nasal screen is positive, contact precautions are instituted. The decision about whether or not to initiate a decolonization protocol varies among different ICUs, but most do not carry out universal decolonization.

Some studies show decolonization is beneficial for ICU patients. These studies include a large cluster-randomized trial called REDUCE MRSA,³ which took place in 43 hospitals and involved 74,256 patients in 74 ICUs. The study showed that universal (i.e., without screening) decolonization using mupirocin and chlorhexidine was effective in reducing rates of MRSA clinical isolates, as well as bloodstream infection from any pathogen. Other studies have demonstrated benefits from the decolonization of ICU patients.^4,5

Surgical Site Infections. Meanwhile, SSIs are often associated with increased mortality rates and substantial healthcare costs, including increased hospital lengths of stay and readmission rates. Staphylococcus aureus is the pathogen most commonly isolated from SSIs. In surgical patients, colonization with MRSA is associated with an elevated rate of MRSA SSIs. The goal of decolonization in surgical patients is not to permanently eliminate MRSA but to prevent SSIs by suppressing the presence of this organism for a relatively brief duration.

There is evidence that decolonization reduces SSIs for cardiothoracic surgeries.⁶ For these patients, it is cost effective to screen for nasal carriage of MRSA and then treat carriers with a combination of pre-operative mupirocin and chlorhexidine. It may be reasonable to delay cardiothoracic surgery in colonized patients who will require implantation of prosthetic material until they complete MRSA decolonization.

In addition to reducing the risk of auto-infection, another goal of decolonization is limiting the possibility of transmission of MRSA from a colonized patient to a susceptible individual; however, there are only limited data available that measure the efficacy of decolonization for preventing transmission.

Concerns about the potential hazards of decolonization therapy have impacted its widespread implementation. The biggest concern is that patients may develop resistance to the antimicrobial agents used for decolonization, particularly if they are used at increased frequency. Mupirocin resistance monitoring is valuable, but, unfortunately, the susceptibility of Staphylococcus aureus to mupirocin is not routinely evaluated, so the prevalence of mupirocin resistance in local strains is often unknown. Another concern about decolonization is the cost of screening and decolonizing patients.

 

Back to the Case

The patient in this case required admission to an ICU and, based on the results of the REDUCE MRSA clinical trial, she would likely benefit from undergoing decolonization to reduce her risk of both MRSA-positive clinical cultures and bloodstream infections caused by any pathogen.

Bottom Line

Decolonization is beneficial for patients at increased risk of developing a MRSA infection during a specific period, such as patients admitted to the ICU and those undergoing cardiothoracic surgery.

---

Dr. Clarke is assistant professor in the division of hospital medicine at Emory University Hospital and a faculty member in the Emory University Department of Medicine, both in Atlanta.

References

1. Dow G, Field D, Mancuso M, Allard J. Decolonization of methicillin-resistant Staphylococcus aureus during routine hospital care: Efficacy and long-term follow-up. Can J Infect Dis Med Microbiol. 2010;21(1):38-44.
2. Simor AE. Staphylococcal decolonisation: An effective strategy for prevention of infection? Lancet Infect Dis. 2011;11(12):952-962.
3. Huang SS, Septimus E, Kleinman K, et al. Targeted versus universal decolonization to prevent ICU infection. N Engl J Med. 2013;368(24):2255-2265.
4. Fraser T, Fatica C, Scarpelli M, et al. Decrease in Staphylococcus aureus colonization and hospital-acquired infection in a medical intensive care unit after institution of an active surveillance and decolonization program. Infect Control Hosp Epidemiol. 2010;31(8):779-783.
5. Robotham J, Graves N, Cookson B, et al. Screening, isolation, and decolonisation strategies in the control of methicillin-resistant Staphylococcus aureus in intensive care units: Cost effectiveness evaluation. BMJ. 2011;343:d5694.
6. Schweizer M, Perencevich E, McDanel J, et al. Effectiveness of a bundled intervention of decolonization and prophylaxis to decrease Gram positive surgical site infections after cardiac or orthopedic surgery: Systematic review and meta-analysis. BMJ. 2013;346:f2743.