Matthew P. Kronman

Antibiotic Exposure and IBD Development Among Children: A Population-Based Cohort Study

OBJECTIVE: To determine whether childhood antianaerobic antibiotic exposure is associated with the development of inflammatory bowel disease (IBD). METHODS: This retrospective cohort study employed data from 464 UK ambulatory practices participating in The Health Improvement Network. All children with ≥2 years of follow-up from 1994 to 2009 were followed between practice enrollment and IBD development, practice deregistration, 19 years of age, or death; those with previous IBD were excluded. All antibiotic prescriptions were captured. Antianaerobic antibiotic agents were defined as penicillin, amoxicillin, ampicillin, penicillin/β-lactamase inhibitor combinations, tetracyclines, clindamycin, metronidazole, cefoxitin, carbapenems, and oral vancomycin. RESULTS: A total of 1 072 426 subjects contributed 6.6 million person-years of follow-up; 748 developed IBD. IBD incidence rates among antianaerobic antibiotic unexposed and exposed subjects were 0.83 and 1.52/10 000 person-years, respectively, for an 84% relative risk increase. Exposure throughout childhood was associated with developing IBD, but this relationship decreased with increasing age at exposure. Exposure before 1 year of age had an adjusted hazard ratio of 5.51 (95% confidence interval [CI]: 1.66–18.28) but decreased to 2.62 (95% CI: 1.61–4.25) and 1.57 (95% CI: 1.35–1.84) by 5 and 15 years, respectively. Each antibiotic course increased the IBD hazard by 6% (4%–8%). A dose-response effect existed, with receipt of >2 antibiotic courses more highly associated with IBD development than receipt of 1 to 2 courses, with adjusted hazard ratios of 4.77 (95% CI: 2.13–10.68) versus 3.33 (95% CI: 1.69–6.58). CONCLUSIONS: Childhood antianaerobic antibiotic exposure is associated with IBD development.

Ambulatory visit rates and antibiotic prescribing for children with pneumonia, 1994-2007

BACKGROUND: The incidence of pediatric hospitalizations for community-acquired pneumonia (CAP) has declined after the widespread use of the heptavalent pneumococcal conjugate vaccine. The national incidence of outpatient visits for CAP, however, is not well established. Although no pediatric CAP treatment guidelines are available, current data support narrow-spectrum antibiotics as the first-line treatment for most patients with CAP. OBJECTIVE: To estimate the incidence rates of outpatient CAP, examine time trends in antibiotics prescribed for CAP, and determine factors associated with broad-spectrum antibiotic prescribing for CAP. PATIENTS AND METHODS: The National Ambulatory and National Hospital Ambulatory Medical Care Surveys (1994–2007) were used to identify children aged 1 to 18 years with CAP using a validated algorithm. We determined age group–specific rates of outpatient CAP and examined trends in antibiotic prescribing for CAP. Data from 2006–2007 were used to study factors associated with broad-spectrum antibiotic prescribing. RESULTS: Overall, annual CAP visit rates ranged from 16.9 to 22.4 per 1000 population, with the highest rates occurring in children aged 1 to 5 years (range: 32.3–49.6 per 1000). Ambulatory CAP visit rates did not change between 1994 and 2007. Antibiotics commonly prescribed for CAP included macrolides (34% of patients overall), cephalosporins (22% overall), and penicillins (14% overall). Cephalosporin use increased significantly between 2000 and 2007 (P = .002). Increasing age, a visit to a nonemergency department office, and obtaining a radiograph or complete blood count were associated with broad-spectrum antibiotic prescribing. CONCLUSIONS: The incidence of pediatric ambulatory CAP visits has not changed significantly between 1994 and 2007, despite the introduction of heptavalent pneumococcal conjugate vaccine in 2000. Broad-spectrum antibiotics, particularly macrolides, were frequently prescribed despite evidence that they provide little benefit over penicillins.

Bacterial Prevalence and Antimicrobial Prescribing Trends for Acute Respiratory Tract Infections

BACKGROUND AND OBJECTIVES: Antimicrobials are frequently prescribed for acute respiratory tract infections (ARTI), although many are viral. We aimed to determine bacterial prevalence rates for 5 common childhood ARTI - acute otitis media (AOM), sinusitis, bronchitis, upper respiratory tract infection, and pharyngitis- and to compare these rates to nationally representative antimicrobial prescription rates for these ARTI. METHODS: We performed (1) a meta-analysis of English language pediatric studies published between 2000 and 2011 in Medline, Embase, and the Cochrane library to determine ARTI bacterial prevalence rates; and (2) a retrospective cohort analysis of children age <18 years evaluated in ambulatory clinics sampled by the 2000–2010 National Ambulatory Medical Care Survey (NAMCS) to determine estimated US ARTI antimicrobial prescribing rates. RESULTS: From the meta-analysis, the AOM bacterial prevalence was 64.7% (95% confidence interval [CI], 50.5%–77.7%); Streptococcus pyogenes prevalence during pharyngitis was 20.2% (95% CI, 15.9%–25.2%). No URI or bronchitis studies met inclusion criteria, and 1 sinusitis study met inclusion criteria, identifying bacteria in 78% of subjects. Based on these condition-specific bacterial prevalence rates, the expected antimicrobial rescribing rate for ARTI overall was 27.4% (95% CI, 26.5%–28.3%). However, antimicrobial agents were prescribed in NAMCS during 56.9% (95% CI, 50.8%–63.1%) of ARTI encounters, representing an estimated 11.4 million potentially preventable antimicrobial prescriptions annually. CONCLUSIONS: An estimated 27.4% of US children who have ARTI have bacterial illness in the post-pneumococcal conjugate vaccine era. Antimicrobials are prescribed almost twice as often as expected during outpatient ARTI visits, representing an important target for ongoing antimicrobial stewardship interventions.

Antimicrobial Stewardship Programs in Freestanding Children’s Hospitals

BACKGROUND AND OBJECTIVE: Single-center evaluations of pediatric antimicrobial stewardship programs (ASPs) suggest that ASPs are effective in reducing and improving antibiotic prescribing, but studies are limited. Our objective was to compare antibiotic prescribing rates in a group of pediatric hospitals with formalized ASPs (ASP+) to a group of concurrent control hospitals without formalized stewardship programs (ASP−). METHODS: We evaluated the impact of ASPs on antibiotic prescribing over time measured by days of therapy/1000 patient-days in a group of 31 freestanding children’s hospitals (9 ASP+, 22 ASP−). We compared differences in average antibiotic use for all ASP+ and ASP− hospitals from 2004 to 2012 before and after release of 2007 Infectious Diseases Society of America guidelines for developing ASPs. Antibiotic use was compared for both all antibacterials and for a select subset (vancomycin, carbapenems, linezolid). For each ASP+ hospital, we determined differences in the average monthly changes in antibiotic use before and after the program was started by using interrupted time series via dynamic regression. RESULTS: In aggregate, as compared with those years preceding the guidelines, there was a larger decline in average antibiotic use in ASP+ hospitals than in ASP− hospitals from 2007 to 2012, the years after the release of Infectious Diseases Society of America guidelines (11% vs 8%, P = .04). When examined individually, relative to preimplementation trends, 8 of 9 ASP+ hospitals revealed declines in antibiotic use, with an average monthly decline in days of therapy/1000 patient-days of 5.7%. For the select subset of antibiotics, the average monthly decline was 8.2%. CONCLUSIONS: Formalized ASPs in children’s hospitals are effective in reducing antibiotic prescribing.

Adjunct Corticosteroids in Children Hospitalized With Community-Acquired Pneumonia

OBJECTIVE: To determine if systemic corticosteroid therapy is associated with improved outcomes for children hospitalized with community-acquired pneumonia (CAP). METHODS: In this multicenter, retrospective cohort study we used data from 36 childrens hospitals for children aged 1 to 18 years with CAP. Main outcome measures were length of stay (LOS), readmission, and total hospitalization cost. The primary exposure was the use of adjunct systemic corticosteroids. Multivariable regression models and propensity scores were used to adjust for confounders. RESULTS: The 20 703 patients whose data were included had a median age of 4 years. Adjunct corticosteroid therapy was administered to 7234 patients (35%). The median LOS was 3 days, and 245 patients (1.2%) required readmission. Systemic corticosteroid therapy was associated with shorter LOS overall (adjusted hazard ratio [HR]: 1.24 [95% confidence interval (CI): 1.18–1.30]). Among children who received treatment with β-agonists, the LOS was shorter for children who had received corticosteroids compared with children who had not (adjusted HR: 1.36 [95% CI: 1.28–1.45]). Among children who did not receive β-agonists, the LOS was longer for those who received corticosteroids compared with those who did not (adjusted HR: 0.85 [95% CI: 0.75–0.96]). Corticosteroids were associated with readmission of patients who did not receive concomitant β-agonist therapy (adjusted odds ratio: 1.97 [95% CI: 1.09–3.57]). CONCLUSIONS: For children hospitalized with CAP, adjunct corticosteroids were associated with a shorter hospital LOS among patients who received concomitant β-agonist therapy. Among patients who did not receive this therapy, systemic corticosteroids were associated with a longer LOS and a greater odds of readmission. If β-agonist therapy is considered a proxy for wheezing, our findings suggest that among patients admitted to the hospital with a diagnosis of CAP, only those with acute wheezing benefit from adjunct systemic corticosteroid therapy.

Fecal microbiota transplantation via nasogastric tube for recurrent clostridium difficile infection in pediatric patients.

ABSTRACT Fecal microbiota transplantation (FMT) is a safe and effective therapy for adults with recurrent Clostridium difficile colitis, but data regarding FMT in children are limited and focus on colonoscopic administration of FMT. We present 10 consecutive children who received FMT via nasogastric tube for treatment of recurrent C difficile infection. Median age was 5.4 years, and 30% were receiving simultaneous immunosuppression. Median follow-up was 44 days, and 90% of patients resolved their C difficile infection; one patient relapsed 2 months later after receiving antibiotics. FMT via nasogastric tube appears safe, well tolerated, and effective in treating pediatric recurrent C difficile colitis.

Charges and Lengths of Stay Attributable to Adverse Patient-Care Events Using Pediatric-Specific Quality Indicators: A Multicenter Study of Freestanding Children's Hospitals

OBJECTIVE. The purpose of this work was to determine the excess charges, both overall and according to category, and lengths of stay attributable to adverse patient-care events during pediatric hospitalization. METHODS. Agency for Healthcare Research and Quality pediatric-specific quality indicators were used to identify adverse events in 431524 discharges from 38 freestanding, academic, not-for-profit, tertiary care pediatric hospitals in the United States participating in the Pediatric Health Information System database in 2006. All of the discharges from any of the 38 hospitals participating in the Pediatric Health Information System between January 1 and December 31, 2006, were eligible for inclusion. The primary outcomes were excess lengths of stay and charges (both overall and according to pharmacy, laboratory, imaging, clinical, supply, and other categories) were attributable to adverse patient-safety events as determined by 12 pediatric-specific quality indicators. RESULTS. Statistically significant excess lengths of stay attributable to pediatric-specific quality indicator events ranged from 2.8 days for accidental puncture and laceration to 23.5 days for postoperative sepsis, and statistically significant excess overall charges ranged from

Upper Versus Lower Gastrointestinal Delivery for Transplantation of Fecal Microbiota in Recurrent or Refractory Clostridium difficile Infection: A Collaborative Analysis of Individual Patient Data From 14 Studies.

34884 for accidental puncture and laceration to

Characterization of Inpatient Cystic Fibrosis Pulmonary Exacerbations.

337226 for in-hospital mortality after pediatric heart surgery. Each charge category had significant charge increases caused by pediatric-specific quality indicator events, with the largest being laboratory and other charges, ranging from

Childhood Vaccine Exemption Policy: The Case for a Less Restrictive Alternative.

7622 to