Time for a Change: Considering Vancomycin Alternatives for Pediatric Methicillin-Resistant Staphylococcus aureus Bacteremia.

Vancomycin remains the standard of care for treating methicillin-resistant Staphylococcus aureus (MRSA) bacteremia in pediatrics largely because no alternative antibiotic is definitively superior. Long-standing historical precedent and S. aureus' notable lack of vancomycin resistance are clear benefits, but vancomycin's use remains plagued by nephrotoxicity and the need for therapeutic drug monitoring, with inadequate consensus on how best to dose or monitor vancomycin in pediatrics. Daptomycin, ceftaroline, and linezolid are all promising alternatives, with improved safety relative to vancomycin. However, inadequate and variable efficacy data limit confidence in their use. Despite this, we contend that it is time for clinicians to reconsider vancomycin's place in clinical use. In this review, we summarize the supporting data for using vancomycin versus these other anti-MRSA antibiotics, present a framework for antibiotic decision-making that considers patient-specific factors, and discuss approaches to antibiotic selection for various etiologies of MRSA bacteremia. This review aims to help pediatric clinicians choose among the various treatment options for MRSA bacteremia, acknowledging that the optimal antibiotic choice is sometimes uncertain.

Antimicrobial Stewardship in Cystic Fibrosis.

The chronic airway infection and inflammation characteristic of cystic fibrosis (CF) ultimately leads to progressive lung disease, the primary cause of death in persons with CF (pwCF). Despite many recent advances in CF clinical care, efforts to preserve lung function in many pwCF still necessitate frequent antimicrobial use. Incorporating antimicrobial stewardship (AMS) principles into management of pulmonary exacerbations (PEx) would facilitate development of best practices for antimicrobial utilization at CF care centers. However, AMS can be challenging in CF given the unique aspects of chronic, polymicrobial infection in the CF airways, lack of evidence-based guidelines for managing PEx, limited utility for antimicrobial susceptibility testing, and increased frequency of adverse drug events in pwCF. This article describes current evidence-based antimicrobial treatment strategies for pwCF, highlights the potential for AMS to beneficially impact CF care, and provides practical strategies for integrating AMS programs into the management of PEx in pwCF.

Lactococcus Species Central Line-Associated Bloodstream Infection in Pediatrics: A Case Series.

Lactococcus spp. is typically thought to be of low virulence and seldom considered pathogenic. Few cases of significant infections in children have been reported, all outside of the United States. There is also limited data on antimicrobial susceptibility testing for Lactococcus spp. We present three pediatric patients with central line bloodstream infections due to Lactococcus spp. between 2018 and 2020, along with a review of the pediatric literature.

Therapeutic Monitoring of Vancomycin for Serious Methicillin-resistant Staphylococcus aureus Infections: A Revised Consensus Guideline and Review by the American Society of Health-system Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists.

Recent clinical data on vancomycin pharmacokinetics and pharmacodynamics suggest a reevaluation of current dosing and monitoring recommendations. The previous 2009 vancomycin consensus guidelines recommend trough monitoring as a surrogate marker for the target area under the curve over 24 hours to minimum inhibitory concentration (AUC/MIC). However, recent data suggest that trough monitoring is associated with higher nephrotoxicity. This document is an executive summary of the new vancomycin consensus guidelines for vancomycin dosing and monitoring. It was developed by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists vancomycin consensus guidelines committee. These consensus guidelines recommend an AUC/MIC ratio of 400-600 mg*hour/L (assuming a broth microdilution MIC of 1 mg/L) to achieve clinical efficacy and ensure safety for patients being treated for serious methicillin-resistant Staphylococcus aureus infections.

Executive Summary: Therapeutic Monitoring of Vancomycin for Serious Methicillin-Resistant Staphylococcus aureus Infections: A Revised Consensus Guideline and Review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists.

BACKGROUND: Recent vancomycin PK/PD and toxicodynamic studies enable a reassessment of the current dosing and monitoring guideline in an attempt to further optimize the efficacy and safety of vancomycin therapy. The area-under-the-curve to minimum inhibitory concentration (AUC/MIC) has been identified as the most appropriate pharmacokinetic/pharmacodynamic (PK/PD) target for vancomycin. The 2009 vancomycin consenus guidelines recommended specific trough concentrations as a surrogate marker for AUC/MIC. However, more recent toxicodynamic studies have reported an increase in nephrotoxicity associated with trough monitoring. METHODS AND RESULTS: This is the executive summary of the new vancomycin consensus guidelines for dosing and monitoring vancomycin therapy and was developed by the American Society of Health-Systems Pharmacists, Infectious Diseases Society of America, Pediatric Infectious Diseases Society and the Society of Infectious Diseases Pharmacists vancomycin consensus guidelines committee. CONCLUSIONS: The recommendations provided in this document are intended to assist the clinician in optimizing vancomycin for the treatment of invasive MRSA infections in adult and pediatric patients. An AUC/MIC by broth microdilution (BMD) ratio of 400 to 600 (assuming MICBMD of 1 mg/L) should be advocated as the target to achieve clinical efficacy while improving patient safety for patients with serious MRSA infections. In such cases, AUC-guided dosing and monitoring is the most accurate and optimal way to manage vancomycin therapy.

Evaluation of Pediatric Surgical Site Infections Associated with Colorectal Surgeries at an Academic Children's Hospital.

Appropriate use of antibiotic prophylaxis (AP) is a key measure for the prevention of surgical site infections (SSI) in colorectal surgeries; however, despite the presence of national and international guidelines, compliance with AP recommendations remains low. The purpose of this study is to evaluate compliance with recommendations for the use of AP in children undergoing colorectal surgeries and to evaluate the effectiveness of antibiotics in the prevention of SSI. We collected demographic and clinical characteristics of patients who underwent colorectal surgeries, as well as microbiological and antimicrobial susceptibility data for patients who developed SSI. AP data were collected and compared with national guidelines. Antibiotic dosing and duration were most frequently in concordance with national guidelines, while antibiotic timing and selection had the lowest rates of compliance. Twelve of the 192 colorectal procedures evaluated resulted in SSI. Only 2 of the 12 children with SSI received appropriate AP for all four categories evaluated. Eight cases that resulted in SSI were due to organisms not covered by the recommended AP. We identified multiple areas for the improvement of AP in children undergoing colorectal surgery. A multidisciplinary approach to development of standardized protocols, educational interventions, and EHR-based algorithms may facilitate or improve appropriate AP use.

Finding the relevance of antimicrobial stewardship for cystic fibrosis.

Antimicrobials have undoubtedly improved the lives of people with CF, but important antimicrobial-related toxicities and the emergence of antimicrobial-resistant bacteria associated with their use must be considered. Antimicrobial stewardship (AMS) is advocated across the spectrum of healthcare to promote the appropriate use of antimicrobials to preserve their current effectiveness and to optimise treatment, and it is clear that AMS strategies are applicable to and can benefit both non-CF and CF populations. This perspective explores the definition and components of an AMS program, the current evidence for AMS, and the reasons why AMS is a challenging concept in the provision of CF care. We also discuss the elements of CF care which align with AMS programs and principles and propose research priorities for AMS in CF.

Expanding Existing Antimicrobial Stewardship Programs in Pediatrics: What Comes Next.

The prevalence of pediatric antimicrobial stewardship programs (ASPs) is increasing in acute care facilities across the United States. Over the past several years, the evidence base used to inform effective stewardship practices has expanded, and regulatory interest in stewardship programs has increased. Here, we review approaches for established, hospital-based pediatric ASPs to adapt and report standardized metrics, broaden their reach to specialized populations, expand to undertake novel stewardship initiatives, and implement rapid diagnostics to continue their evolution in improving antimicrobial use and patient outcomes.

Description of Respiratory Microbiology of Children With Long-Term Tracheostomies.

BACKGROUND: There is little evidence in the medical literature to guide empiric treatment of pediatric patients with long-term tracheostomies who present with signs and symptoms of a bacterial respiratory infection. The overall goal of this study was to describe the respiratory microbiology in this study population at our institution. METHODS: This study was a retrospective chart review of all subjects with tracheostomies currently receiving care at the Arkansas Center for Respiratory Technology Dependent Children. Descriptive statistics were used to describe the respiratory microbiology of the full study group. Several subgroup analyses were conducted, including description of microbiology according to time with tracheostomy, mean time to isolation of specific organisms after the tracheostomy tube was placed, association between Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus isolation and prescribed antibiotic courses, and description of microbiology according to level of chronic respiratory support. Available respiratory culture results up to July 2011 were collected for all eligible subjects. Descriptive statistics were used to describe subject characteristics, and chi-square analysis was used to analyze associations between categorical data. P < .05 was considered statistically significant. RESULTS: A total of 93 subjects met inclusion criteria for the study. The median (interquartile range) age at time of tracheotomy was 0.84 (0.36-3.25) y, and the median (interquartile range) time with tracheostomy was 4.29 (2.77-9.49) y. The most common organism isolated was P. aeruginosa (90.3%), with Gram-negative organisms predominating. However, 55.9% of the study population had a respiratory culture positive for methicillin-resistant S. aureus. The first organism isolated after tracheostomy placement was Methiciliin-sensitive S. aureus was isolated the soonest after tracheostomy placement. Specific organisms were not related to level of chronic respiratory support or likelihood of receiving antibiotics. CONCLUSIONS: This study provides an updated overview of the variety of potential pathogens isolated from respiratory cultures of pediatric subjects with long-term tracheostomies.

Balancing vancomycin efficacy and nephrotoxicity: should we be aiming for trough or AUC/MIC?

Sixty years later, the question that still remains is how to appropriately utilize vancomycin in the pediatric population. The Infectious Diseases Society of America published guidelines in 2011 that provide guidance for dosing and monitoring of vancomycin in adults and pediatrics. However, goal vancomycin trough concentrations of 15-20 µg/mL for invasive infections caused by methicillin-resistant Staphylococcus aureus were based primarily on adult pharmacokinetic and pharmacodynamic data that achieved an area under the curve to minimum inhibitory concentration ratio (AUC/MIC) of ≥400. Recent pediatric literature shows that vancomycin trough concentrations needed to achieve the target AUC/MIC are different than the adult goal troughs cited in the guidelines. This paper addresses several thoughts, including the role of vancomycin AUC/MIC in dosing strategies and safety monitoring, consistency in laboratory reporting, and future directions for calculating AUC/MIC in pediatrics.

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 children's hospitals is unknown. The objective of this study was to determine the prevalence and characteristics of ASPs in freestanding children's hospitals. METHODS: We conducted an electronic survey of 42 freestanding children's hospitals that are members of the Children's 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 children's 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.

Antimicrobial stewardship in pediatrics: how every pediatrician can be a steward.

Antimicrobial stewardship (AS) programs are effective in improving clinical outcomes associated with antimicrobial therapies while improving patient safety by reducing adverse events and development of bacterial resistance. Understanding the basic principles of AS is essential to the successful development and implementation of AS strategies. Identifying and developing strategies to address barriers and challenges to AS can facilitate the establishment of financial, administrative, and organizational support, and agreement and participation by individual prescribers. Review of published outcomes of AS demonstrates the effectiveness in reducing unnecessary antimicrobial use and adverse events such as Clostridium difficile infections. We also illustrate the need for further research and expansion of AS activities to office-based practices and communities by using novel and innovative AS strategies and by influencing regional and national policies.

Intravenous voriconazole therapy in a preterm infant.

A preterm infant younger than 3 months developed a disseminated fluconazole-resistant Candida albicans infection that was treated with liposomal amphotericin B for 52 days, followed by the combination of intravenous voriconazole and liposomal amphotericin B for an additional 19 days. The infant received concomitant phenobarbital throughout the hospital stay. The infection resolved after addition of voriconazole to the treatment regimen. Intravenous voriconazole was begun at a high dosage, 6 mg/kg every 12 hours, for anticipated developmental and drug-induced changes in volume of distribution and clearance. On day 4 of therapy, serum concentrations of voriconazole were 3.27 microg/ml immediately after infusion and 0.33 microg/ml 6 hours after infusion. These levels were significantly lower than those achieved in adult pharmacokinetic and safety studies. After the infant's dosage was increased to 6 mg/kg every 8 hours, serum concentrations were 5.33 microg/ml 30 minutes after infusion and 2.67 microg/ml 6 hours after infusion. These levels were similar to those observed in adults. Intravenous voriconazole 6 mg/kg every 8 hours was administered safely, with concomitant phenobarbital therapy, in this preterm infant with developmentally diminished renal function.

Pharmacokinetics of intravenously administered azithromycin in pediatric patients.

BACKGROUND: The objective of this study was to characterize the pharmacokinetics and tolerance of a single intravenous (IV) azithromycin dose in children. METHODS: Subjects were stratified into 4 age groups: 0.5-2 years; >2-<6 years; 6-<12 years; and 12-<16 years. Each subject received a single 10 mg/kg dose (500 mg maximum) infused in 1 hour. Serial venous blood samples were obtained for a 168-hour period, and laboratory safety evaluations were performed immediately preceding azithromycin administration and at the conclusion of the study. Serum azithromycin concentrations were quantified with a validated high performance liquid chromatography method with mass spectrometric detection. Pharmacokinetic indices were calculated for each subject by noncompartmental techniques. RESULTS: Thirty-two subjects (6.7 +/- 5.0 years, 11 boys) participated. Mean serum concentration-time data were comparable for the 4 age groups. For all subjects with evaluable data, the mean area under the curve from 0 to 72 hours (AUC0-72) was 8.2 microg . h/mL (n = 26), the maximum concentration (Cmax) was 2.4 microg/mL and the elimination half-life (t1/2) was 65.2 hours (n = 25). The AUC0-72 and Cmax were not associated with age. The dose was well-tolerated with no serious adverse events. CONCLUSION: The disposition of azithromycin after a single 10-mg/kg IV dose (maximum labeled adult dose of 500 mg) is comparable in pediatric patients between 0.5 and 16 years of age. These pharmacokinetic data can be used to guide dose selection for future therapeutic trials of IV azithromycin in pediatric patients.