Retrospective Observational Assessment of the Impact of Cefepime Prophylaxis in Neutropenic Pediatric Patients With Acute Myelogenous Leukemia.

BACKGROUND: The potential for cefepime prophylaxis to reduce bloodstream infections (BSIs) in pediatric patients with acute myelogenous leukemia (AML) has been incompletely characterized. METHODS: A retrospective quasi-experimental study of patients under 21 years of age admitted with AML from 2010 through 2018 at two affiliated pediatric tertiary-care hospitals before and after the adoption of routine cefepime prophylaxis for afebrile AML patients during profound neutropenia. RESULTS: The rate of BSIs per 1000 neutropenia days was significantly lower in the prophylaxis group than the baseline group (2.6 vs 15.5, incidence rate ratio [IRR] 0.17, 95% CI 0.09-0.32). Interrupted time-series analysis showed that a sharp reduction in BSIs coincided with the implementation of prophylaxis. Bacteremia with viridans group streptococci was frequent in the baseline group but not observed after adopting prophylaxis. Despite the increased use of cefepime, the rate of cefepime-nonsusceptible BSIs per 1000 neutropenia days decreased (1.6 vs 4.1, IRR 0.40, 95% CI 0.16-0.99). The median number of febrile neutropenia episodes per patient also decreased in the prophylaxis group, as did the proportion of patients admitted to the intensive care unit (ICU) (22/51 (43.1%) vs 26/38 (68.4%); risk difference -25.3%, 95% CI -44.4 to -2.8). A trend was observed toward an increased proportion of patients with Clostridioides difficile infection in the prophylaxis group (10/51 (19.6%) vs 3/38 (7.9%); risk difference 11.7%, 95% CI -3.4 to 29.0). CONCLUSIONS: Cefepime prophylaxis was associated with a significant reduction in BSIs, febrile neutropenia, and ICU admission among pediatric AML patients.

Safety and Tolerability of Monoclonal Antibody Therapies for Treatment of COVID-19 in Pediatric Patients.

There is a little data regarding safety or efficacy of monoclonal antibody treatment for mild-to-moderate COVID-19 in pediatric patients despite it being frequently used in adults. This retrospective study of 17 patients with mild-to-moderate COVID-19 who received monoclonal antibody therapy found that the treatment was well tolerated, safe, and may be effective in halting progression to severe disease.

One Size Fits All? Application of Susceptible-Dose-Dependent Breakpoints to Pediatric Patients and Laboratory Reporting.

The Clinical and Laboratory Standards Institute antimicrobial and antifungal standards define a susceptible-dose-dependent (SDD) category for certain organisms and drug combinations. Reporting MICs within the SDD category suggests that treatment success is likely with increased drug exposure. These breakpoints are based on pharmacokinetic, pharmacodynamic, and clinical outcome data from adults and not pediatric patients. This commentary aims to discuss the implications of reporting SDD interpretations for pediatric patients and recommends laboratory reporting comments.

Evaluation of a Second-Sign Process for Antimicrobial Prior Authorization.

BACKGROUND: A second-sign prospective restriction of select broad-spectrum antimicrobials was fully implemented in January 2015 as a pediatric antimicrobial stewardship program (ASP) initiative to help ensure the most appropriate empiric use of ceftaroline, cefepime, fidaxomicin, linezolid, and vancomycin (intravenous). The objective of this evaluation is to assess the effectiveness of a forced second-sign process in the electronic medical record as a pediatric ASP strategy. We anticipated that the second-sign process for antibiotics would increase the appropriateness of empiric antibiotic use, as defined by preapproved criteria, clinical pathways, national guidelines, and pediatric-specific infectious diseases reference texts, while not causing significant delay in the initial administration of antibiotic therapy. METHODS: This was a retrospective before and after intervention chart review conducted from July 2014 to June 2015. The study was conducted at a 187-bed, freestanding teaching children's hospital that included the following: level-1 pediatric trauma center, 18-bed pediatric intensive care unit, and 32-bed neonatal intensive care unit. RESULTS: A total of 1178 orders were identified, and 389 met inclusion criteria. The vast majority of second-sign orders were for vancomycin (92%), 61% were written for males, and the median age was 6 years old. Appropriateness of second-sign restricted antibiotic use significantly increased after second-sign implementation (84.5% to 92.9%, P = .01). The secondary outcome of time from initial order entry to medication administration was not different between the before and after groups (median time, 184.5 [interquartile range, 110.25-280.75] vs 174 [interquartile range, 104-228] minutes; P = .342). CONCLUSIONS: The use of a second-sign approval process for antimicrobial restriction can lead to increased appropriateness of antibiotic use at a pediatric hospital, without causing a delay in administration.

In vitro Activity of Ceftolozane/Tazobactam Alone or with an Aminoglycoside Against Multi-Drug-Resistant Pseudomonas aeruginosa from Pediatric Cystic Fibrosis Patients.

INTRODUCTION: Gram-negative multi-drug resistance is an emerging threat among pediatric patients with cystic fibrosis (CF). Ceftolozane/tazobactam (C/T) is an extended-spectrum cephalosporin/beta-lactamase inhibitor combination that has been shown to maintain activity against MDR P. aeruginosa isolates. The understanding of C/T effectiveness in pediatric patients is extremely limited. Minimum inhibitory concentration (MIC) testing and time-kill analyses were performed to better understand the antimicrobial susceptibility and potential role of C/T. METHODS: Non-duplicate clinical respiratory MDR P. aeruginosa isolates (n = 5) from four pediatric CF patients were identified. MICs were determined for these isolates using CLSI broth microdilution methods. Time-kill analyses were performed using multiples of C/T alone, and combinations of C/T 2× and 8× the MIC with 30 mg/L tobramycin or 80 mg/L amikacin for all isolates. Cell counts were determined by serial dilution plating. RESULTS: Isolates had variable susceptibilities to C/T (range 0.5-8 mg/L), tobramycin (range 2 to >64 mg/L) and amikacin (range 8 to >256 mg/L). Time-kill analyses revealed an average of 0.71 (range -0.6 to 4.4), 1.50 (range 0.8-2.0) and 2.1 (range 1.2-3.4) log-kill at 4×, 8× and 16× the C/T MIC, respectively. At a tobramycin MIC of 32 mg/L, combination therapy showed synergistic benefit when the isolate was C/T susceptible. C/T and amikacin combination therapy showed synergistic activity at an amikacin MIC >256 mg/L when C/T MIC was 2 mg/L (4.7 log-kill at 2× C/T MIC and 4.0 log-kill at 8× C/T MIC). CONCLUSION: C/T appears to be a promising treatment option for treatment of MDR P. aeruginosa in pediatric CF patients, both alone and in combination with tobramycin or amikacin. Interestingly, the benefit of C/T combination therapy with amikacin may be more pronounced than with the addition of tobramycin. Further evaluation of such combination regimens in pediatric CF patients is warranted.

Management of Pneumonia in the Pediatric Critical Care Unit: An Area for Antimicrobial Stewardship.

BACKGROUND: Pediatric pneumonia is one of the most common causes of childhood infection requiring hospitalization and is a substantial driver of antimicrobial use among hospitalized children. About 12-20% of pediatric patients hospitalized with community-acquired pneumonia (CAP) require critical care. Additionally, nosocomial pneumonias (i.e. hospital-acquired and ventilator- associated pneumonias) are responsible for 15-53% of hospital-associated infections and are the most common indication for empiric antibiotics in the pediatric intensive care unit. OBJECTIVE: Respiratory infections, especially pneumonias, are a strong area for antimicrobial stewardship program (ASP) interventions, as they have been shown to improve patient outcomes while reducing inappropriate antimicrobial use, antimicrobial resistance, and overall costs. METHOD: Optimizing the selection of appropriate antimicrobial therapies is difficult for pediatric pneumonias because of the ill-defined definitive diagnostic criteria and difficulty differentiating between viral and bacterial etiology. RESULT: The aim of this review is to highlight the role of antimicrobial stewardship efforts in the treatment of pneumonias in critically ill children by discussing the emerging role of diagnostic criteria, the etiology of disease, appropriate targeted antimicrobial selection, and the optimization of antibiotic dosing and pharmacodynamic targets.