Joshua Courter

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.

Prevalence and Characteristics of Antimicrobial Stewardship Programs at Freestanding Children's Hospitals in the United States

BACKGROUND AND OBJECTIVE Antimicrobial stewardship programs (ASPs) are a mechanism to ensure the appropriate use of antimicrobials. The extent to which ASPs are formally implemented in freestanding childrens hospitals is unknown. The objective of this study was to determine the prevalence and characteristics of ASPs in freestanding childrens hospitals. METHODS We conducted an electronic survey of 42 freestanding childrens hospitals that are members of the Childrens Hospital Association to determine the presence and characteristics of their ASPs. For hospitals without an ASP, we determined whether stewardship strategies were in place and whether there were barriers to implementing a formal ASP. RESULTS We received responses from 38 (91%) of 42. Among responding institutions, 16 (38%) had a formal ASP, and 15 (36%) were in the process of implementing a program. Most ASPs (13 [81%] of 16) were started after 2007. The median number of full-time equivalents dedicated to ASPs was 0.63 (range, 0.1-1.8). The most common antimicrobials monitored by ASPs were linezolid, vancomycin, and carbapenems. Many hospitals without a formal ASP were performing stewardship activities, including elements of prospective audit and feedback (9 [41%] of 22), formulary restriction (9 [41%] of 22), and use of clinical guidelines (17 [77%] of 22). Antimicrobial outcomes were more likely to be monitored by hospitals with ASPs (100% vs 68%; P = .01), although only 1 program provided support for a data analyst. CONCLUSIONS Most freestanding childrens hospitals have implemented or are developing an ASP. These programs differ in structure and function, and more data are needed to identify program characteristics that have the greatest impact.

Quality Improvement Methods Increase Appropriate Antibiotic Prescribing for Childhood Pneumonia

OBJECTIVE: In August 2011, the Pediatric Infectious Disease Society and Infectious Disease Society of America published an evidence-based guideline for the management of community-acquired pneumonia (CAP) in children ≥3 months. Our objective was to evaluate if quality improvement (QI) methods could improve appropriate antibiotic prescribing in a setting without a formal antimicrobial stewardship program. METHODS: At a tertiary children’s hospital, QI methods were used to rapidly implement the Pediatric Infectious Disease Society/Infectious Disease Society of America guideline recommendations for appropriate first-line antibiotic therapy in children with CAP. QI interventions focused on 4 key drivers and were tested separately in the emergency department and on the hospital medicine resident teams, using multiple plan-do-study-act cycles. Medical records of eligible patients were reviewed weekly to determine the success of prescribing recommended antibiotic therapy. The impact of these interventions on our outcome was tracked over time on run charts. RESULTS: Appropriate first-line antibiotic prescribing for children admitted with the diagnosis of CAP increased in the emergency department from a median baseline of 0% to 100% and on the hospital medicine resident teams from 30% to 100% within 6 months of introducing the guidelines locally at Cincinnati Children’s Hospital Medical Center and has been sustained for 3 months. CONCLUSIONS: Our study demonstrates that QI methods can rapidly improve adherence to national guidelines even in settings without a formal antimicrobial stewardship program to encourage judicious antibiotic prescribing for CAP.

Increased Clinical Failures When Treating Acute Otitis Media with Macrolides: A Meta-Analysis

Background: Macrolide antibiotics are often used to treat children with acute otitis media (AOM); however, the 2004 American Academy of Pediatrics (AAP) and American Academy of Family Physicians guidelines recommend against their use in patients without history of a type I allergic reaction to penicillins. Objective: To evaluate via meta-analysis the comparative efficacy of amoxicillin or amoxicillin/clavulanate to that of macrolide antibiotics in the treatment of children with AOM. Methods: A systematic literature search of MEDLINE, EMBASE, and International Pharmaceutical Abstracts was conducted from the earliest available date through September 2008. We used the following MeSH and key words: amoxicillin, amoxlcillin/clavulanate, Augmentin, azithromycin, ceftriaxone, clarithromycin, macrolides, AND media, otitis media, and effusion. Included studies were randomized, blinded, and controlled trials evaluating guideline-recommended antibiotics (amoxicillin or amoxicillin/clavulanate) compared to macrolide antibiotics (azithromycin or clarithromycin) in AOM in children. The primary outcome assessed was clinical failure measured between days 10 and 16 after starting antibiotic therapy. Results are reported as relative risks (RRs) with 95% confidence intervals and were calculated using a random-effects model. Results: A total of 10 trials (N = 2766) evaluating children 6 months–15 years old were included in the meta-analysis. Upon meta-analysis, the use of macrolide antibiotics was associated with an increased risk of clinical failure (RR 1.31 [95% CI 1.07 to 1.60]: p = 0.008) corresponding to a number needed to harm of 32. Upon safety analysis, rates of any adverse reaction (RR 0.74 [95% CI 0.60 to 0.90]: p = 0.003) and diarrhea (RR 0.41 [95% CI 0.32 to 0.52]: p < 0.0001) were significantly lower in the macrolide group. Conclusions: The meta-analysis suggests that patients treated with macrolides for AOM may be more likely to have clinical failures. As such, it supports the current AAP AOM recommendation that macrolides be reserved for patients who can not receive amoxicillin or amoxicillin/clavulanate.

Considerations in the Pharmacologic Treatment and Prevention of Neonatal Sepsis

The management of neonatal sepsis is challenging owing to complex developmental and environmental factors that contribute to inter-individual variability in the pharmacokinetics and pharmacodynamics of many antimicrobial agents. In this review, we describe (i) the changing epidemiology of early- and late-onset neonatal sepsis; (ii) the pharmacologic considerations that influence the safety and efficacy of antibacterials, antifungals, and immunomodulatory adjuvants; and (iii) the recommended dosing regimens for pharmacologic agents commonly used in the treatment and prevention of neonatal sepsis. Neonatal sepsis is marked by high morbidity and mortality, such that prompt initiation of antimicrobial therapy is essential following culture collection. Before culture results are available, combination therapy with ampicillin and an aminoglycoside is recommended. When meningitis is suspected, ampicillin and cefotaxime may be considered. Following identification of the causative organism and in vitro susceptibility testing, antimicrobial therapy may be narrowed to provide targeted coverage. Therapeutic drug monitoring should be considered for neonates receiving vancomycin or aminoglycoside therapies. For neonates with invasive fungal infections, the development of new antifungal agents has significantly improved therapeutic outcomes in recent years. Liposomal amphotericin B has been found to be safe and efficacious in patients with renal impairment or toxicity caused by conventional amphotericin B. Antifungal prophylaxis with fluconazole has also been reported to dramatically reduce rates of neonatal invasive fungal infections and to improve long-term neurodevelopmental outcomes among treated children. Additionally, several large multicenter studies are currently investigating the safety and efficacy of oral lactoferrin as an immunoprophylactic agent for the prevention of neonatal sepsis.

Dose optimisation of antibiotics in children: application of pharmacokinetics/pharmacodynamics in paediatrics

The judicious use of antibiotics to combat infections in children relies upon appropriate selection of an agent, dose and duration to maximise efficacy and to minimise toxicity. Critical to dose optimisation is an understanding of the pharmacokinetics and pharmacodynamics of available drugs. Optimal dosing strategies may take advantage of pharmacokinetic/pharmacodynamic (PK/PD) principles so that antibiotic dosing can be individualised to assure effective bacterial killing in patients who have altered pharmacokinetics or who have infections with less susceptible or resistant organisms. This review will outline the fundamentals of antimicrobial pharmacokinetics/pharmacodynamics through discussion of antibacterial agents most often used in children. We aim to highlight the importance of dose optimisation in paediatrics and describe non-conventional dosing strategies that can take advantage of PK/PD principles at the bedside.

Population pharmacokinetics of sirolimus in pediatric patients with neurofibromatosis type 1

Purpose: The narrow therapeutic index and large interpatient variability in sirolimus pharmacokinetics (PK) make therapeutic drug monitoring necessary. Factors responsible for PK variability are not well understood, and published PK studies do not include pediatric patients with neurofibromatosis type 1 (NF1). The objectives of this study were to estimate sirolimus clearance in a cohort of children with NF1 using data collected in a concentration-guided trial, to evaluate the effect of treatment duration on clearance and dose requirements, and to evaluate the association of sirolimus clearance with patient-specific factors, including age, weight, body surface area (BSA), race, and sex. Methods: Sirolimus concentration–time data were collected from an ongoing prospective trial in children with NF1. An iterative 2-stage Bayesian method was used for the PK parameter analyses. Results: Data from 44 patients with NF1 were included in the analyses. Mean age was 8.4 years (SD 4.5, range 3–18), and mean weight was 29.8 kg (SD 16.7, range 12–85.8). Mean sirolimus clearance was 11.8 L/h (SD 4.6, range 2.2–24.1), and the mean dose to obtain a target trough concentration of 10–15 ng/mL was 2.0 mg/m2 administered twice daily (SD 0.72, range 0.77–3.85). A nonlinear relationship between age and clearance was observed. Total body weight and BSA were strong predictors of sirolimus clearance (r2 = 0.67 and 0.65, respectively). Conclusions: Sirolimus clearance in children with NF1 is comparable with that in pediatric transplant patients. Clearance was most associated with body size parameters (BSA and total body weight) in children with NF1. When normalized for size, an age effect on clearance was observed in the youngest patients, most likely because of the maturational changes in drug absorption and metabolism. A mean dose of 2.0 mg/m2 twice a day was required for attainment of target trough concentrations of 10–15 ng/mL in children greater than 3 years of age who have NF1. The updated model will allow PK-guided individualized dosing of sirolimus in patients with NF1.

Decreasing Duration of Antibiotic Prescribing for Uncomplicated Skin and Soft Tissue Infections.

BACKGROUND AND OBJECTIVE: Short courses of antibiotics are often indicated for uncomplicated skin and soft tissue infections (uSSTIs). Our objective was to decrease duration of antibiotics prescribed in children hospitalized for uSSTIs by using quality improvement (QI) methods. METHODS: QI methods were used to decrease duration of antibiotics prescribed upon hospital discharge for uSSTIs. We sought to accomplish this goal by increasing outpatient prescriptions for short courses of therapy (≤7 days). Key drivers included awareness of evidence among physicians, changing the culture of prescribing, buy-in from prescribers, and monitoring of prescribing. Physician education, modification of antibiotic order sets for discharge prescriptions, and continual identification and mitigation of therapy plans, were key interventions implemented by using plan-do-study-act cycles. A run chart assessed the impact of the interventions over time. RESULTS: We identified 641 index admissions for uSSTIs over a 23-month period for patients aged >90 days to 18 years. The proportion of children discharged with short courses of antibiotics increased from a baseline median of 23% to 74%, which was sustained for 6 months. Differences in the proportion of children admitted for treatment failure or recurrence before and after project initiation were not significant. CONCLUSIONS: Using QI methodology, we decreased duration of antibiotics prescribed in children hospitalized for uSSTIs by increasing prescriptions for short courses of antibiotics. Modification of electronic order sets for discharge prescriptions allowed for sustained improvement in prescribing practices. Our findings support the use of shorter outpatient antibiotic courses in most children with uSSTIs, and suggest criteria for complicated SSTIs.

Hospital outcomes associated with guideline-recommended antibiotic therapy for pediatric pneumonia

BACKGROUND Recent national guidelines recommend use of narrow-spectrum antibiotic therapy as empiric treatment for children hospitalized with community-acquired pneumonia (CAP). However, clinical outcomes associated with adoption of this recommendation have not been studied. METHODS This retrospective cohort study included children age 3 months to 18 years, hospitalized with CAP from May 2, 2011 through July 30, 2012. Primary exposure of interest was empiric antibiotic therapy, classified as guideline recommended or not. Primary outcomes were length of stay (LOS), total hospital costs, and inpatient pharmacy costs. Secondary outcomes included broadened antibiotic therapy, emergency department revisits, and readmissions. Multivariable linear regression and Fisher exact test were performed to determine the association of guideline-recommended antibiotic therapy on outcomes. RESULTS Empiric guideline-recommended therapy was prescribed to 168 (76%) of 220 patients. Median hospital LOS was 1.3 days (interquartile range [IQR]: 0.9-1.9 days), median total cost of index hospitalization was

Automated identification of antibiotic overdoses and adverse drug events via analysis of prescribing alerts and medication administration records

4097 (IQR: