Jason Child

Intravenous acyclovir and renal dysfunction in children: a matched case control study.

OBJECTIVES A cluster of children receiving intravenous (IV) acyclovir for meningoencephalitis developed acute renal failure in April-May 2008, which prompted a retrospective case-control study to determine the rate of and risk factors for acute nephrotoxicity during IV acyclovir treatment in children. STUDY DESIGN The percentage decrease in glomerular filtration rate in children receiving IV acyclovir who had ≥ 1 creatinine measurement after acyclovir initiation from October 2006 to January 2009 was classified as renal risk, injury, or failure according to modified Pediatric Risk Injury, Failure, Loss, End-Stage Renal Disease criteria. Univariate and multivariate matched analyses were conducted to identify risk factors contributing to nephrotoxicity. RESULTS In the selected study group, renal dysfunction was seen in 131 of 373 (35%) treatment courses studied: 81 of 373 (22%) risk, 36 of 373 (9.7%) injury, and 14 of 373 (3.8%) failure. Most renal dysfunction occurred within 48 hours of the initiation of acyclovir. Renal function returned to the normal range but not to baseline in most cases during the follow-up period. Risk factors for renal dysfunction included acyclovir dose >15 mg/kg (OR 3.81, 95% CI 1.55-9.37) for risk; cumulative exposure greater than calculated cumulative exposure based on 500 mg/m(2)/dose (OR 6.00, 95% CI 1.95-18.46) for injury; and age >8 years (OR 21.5, 95% CI 2.2, >1000) and ceftriaxone coadministration (OR 19.3, 95% CI 1.8, >1000) for failure. CONCLUSIONS Nephrotoxicity associated with IV acyclovir is common and necessitates renal function monitoring. Risk factors include greater dose, older age, and concomitant ceftriaxone administration. Outside the neonatal period, renal dysfunction may be minimized by dosing IV acyclovir below thresholds associated with nephrotoxicity (ie, ≤ 500 mg/m(2)/dose or ≤ 15 mg/kg/dose), particularly in older patients.

Handshake Stewardship: A Highly Effective Rounding-Based Antimicrobial Optimization Service.

Background: Implementation of an antimicrobial stewardship program is recommended as one solution to combat increasing antimicrobial resistance. Most antimicrobial stewardship programs use preauthorization or restrictive strategies recommended in national guidelines. We describe a unique, rounding-based strategy, handshake stewardship. Handshake stewardship is distinguished by: (1) lack of restriction and preauthorization, (2) review of all prescribed antimicrobials and (3) a rounding-based, in-person approach to feedback by a pharmacist–physician team. Methods: We retrospectively measured antimicrobial use hospital-wide and by unit during preimplementation, planning, and postimplementation phases of the handshake stewardship approach to determine the efficacy of this strategy in decreasing use in a freestanding children’s hospital. All antimicrobials prescribed on the inpatient services between October 2010 and September 2014 were included in the review. Monthly antimicrobial use (hospital-wide and by unit) was measured in days of therapy per 1000 patient days (DOT/1000 PD). Results: Overall antimicrobial use decreased by 10.9% during the 4 years of the analysis (942 to 839 DOT/1000 PD, P < 0.01), with an impact of 10.3% on antibacterials (750 to 673 DOT/1000 PD, P < 0.01). Vancomycin use decreased by 25.7% (105 to 78 DOT/1000 PD, P < 0.01). Meropenem use decreased by 22.2% (45 to 35 DOT/1000 PD, P = 0.04) without a compensatory increase of other antipseudomonal agents. Decreased usage was observed both hospital-wide and on individual units for most agents. Conclusions: The handshake stewardship approach is an effective strategy for an antimicrobial stewardship program, as demonstrated by the widespread and significant decrease in antimicrobial use after implementation.

Clinical Impact and Provider Acceptability of Real-Time Antimicrobial Stewardship Decision Support for Rapid Diagnostics in Children With Positive Blood Culture Results

Background Rapid diagnostic technologies for infectious diseases have the potential to improve clinical outcomes, but guideline-recommended antimicrobial stewardship (AS) strategies are not currently optimized for rapid intervention. We evaluated the clinical impact and provider acceptability of implementing real-time AS decision support for children with positive blood culture results according to the FilmArray blood culture identification panel (BCID [BioFire Diagnostics]) at Childrens Hospital Colorado. Methods A pre-post quasi-experimental design was used to compare the outcomes of 100 postintervention children with positive blood culture results matched with 200 preintervention control children. Causative organisms in the preintervention group were identified using conventional microbiologic techniques and communicated to providers by a microbiology technologist. Postintervention organisms were identified by the BCID and communicated by an AS provider in real time with interpretation and antimicrobial recommendations. The primary outcome was time to optimal antimicrobial therapy (time from blood culture collection to start of predetermined pathogen-specific regimen or antimicrobial discontinuation for contaminants) compared by a log-rank test and Kaplan-Meier analysis. Provider acceptability of the intervention was assessed via E-mailed surveys. Results The median time to optimal therapy decreased from 60.2 hours before intervention to 26.7 hours after intervention (P = .001). Among children with blood cultures that contained true pathogens, the time to effective antimicrobial therapy decreased from 6.9 to 3.4 hours (P = .03). Unnecessary antibiotic initiation for children with a culture that contained organisms considered to be contaminants decreased from 76% to 26% (P < .001). Providers reported a change in management as a result of BCID results in 73% of the cases and a mean overall satisfaction rating of 4.8 on a 5-point Likert scale. Conclusions Real-time AS decision support for rapid diagnostics is associated with improved antimicrobial use and high satisfaction ratings by providers.

Cost of management of severe pneumonia in young children: systematic analysis

Background Childhood pneumonia is a major cause of childhood illness and the second leading cause of child death globally. Understanding the costs associated with the management of childhood pneumonia is essential for resource allocation and priority setting for child health. Methods We conducted a systematic review to identify studies reporting data on the cost of management of pneumonia in children younger than 5 years old. We collected unpublished cost data on non–severe, severe and very severe pneumonia through collaboration with an international working group. We extracted data on cost per episode, duration of hospital stay and unit cost of interventions for the management of pneumonia. The mean (95% confidence interval, CI) and median (interquartile range, IQR) treatment costs were estimated and reported where appropriate. Results We identified 24 published studies eligible for inclusion and supplemented these with data from 10 unpublished studies. The 34 studies included in the cost analysis contained data on more than 95 000 children with pneumonia from both low– and–middle income countries (LMIC) and high–income countries (HIC) covering all 6 WHO regions. The total cost (per episode) for management of severe pneumonia was US

A Handshake From Antimicrobial Stewardship Opens Doors for Infectious Disease Consultations

4.3 (95% CI 1.5–8.7), US

Adverse Events in Pediatric Patients Receiving Long-term Oral and Intravenous Antibiotics

51.7 (95% CI 17.4–91.0) and US

Cephem antibiotics: wise use today preserves cure for tomorrow.

242.7 (95% CI 153.6–341.4)–559.4 (95% CI 268.9–886.3) in community, out–patient facilities and different levels of hospital in–patient settings in LMIC. Direct medical cost for severe pneumonia in hospital inpatient settings was estimated to be 26.6%–115.8% of patients’ monthly household income in LMIC. The mean direct non–medical cost and indirect cost for severe pneumonia management accounted for 0.5–31% of weekly household income. The mean length of stay (LOS) in hospital for children with severe pneumonia was 5.8 (IQR 5.3–6.4) and 7.7 (IQR 5.5–9.9) days in LMIC and HIC respectively for these children. Conclusion This is the most comprehensive review to date of cost data from studies on the management of childhood pneumonia and these data should be helpful for health services planning and priority setting by national programmes and international agencies.

Anti-Xa Stability of Diluted Dalteparin for Pediatric Use

Implementation of a unique in-person pediatric antimicrobial stewardship program was associated with a significant increase in infectious disease consultations at a quaternary care childrens hospital. This study demonstrates that antimicrobial stewardship programs support, and do not compete with, infectious disease programs.

Once-Daily Ceftriaxone Plus Metronidazole Versus Ertapenem and/or Cefoxitin for Pediatric Appendicitis.

BACKGROUND AND OBJECTIVE Children receiving long-term antibiotic therapy (LTAT) at Childrens Hospital Colorado (CHCO) are treated with both oral and intravenous (i.v.) agents and often experience complications not comprehensively described by the literature. We sought to describe adverse drug events (ADEs) and venous access complications (VACs) in pediatric patients managed with oral and i.v. antibiotics so as to inform clinical decision-making, drug monitoring, and patient counseling at CHCO. METHODS We conducted a retrospective review of children receiving LTAT through the CHCO infectious disease service from 2006 to 2012. Demographic, microbiologic, diagnostic data, ADEs, and VACs were recorded for each patient. RESULTS From 2006 to 2012, 521 patients received 1876 courses, accounting for 71,306 days of antimicrobial therapy. A total of 219 patients (42%) developed an ADE with discontinuation of the offending agent in 65% of courses associated with an ADE. The most common ADEs were neutropenia, rash, and diarrhea. Central lines were placed in 376 patients with 106 (28%) experiencing ≥1 VACs. I.v. agents were associated with a fourfold increase in the rate of ADEs compared with oral agents, and a fivefold increase when VACs were included. CONCLUSIONS Practitioners may make more informed decisions and risk assessments by using descriptive ADE information for specific agents and mode of drug delivery to mitigate risk, thereby improving the quality of care. Patients should be counseled regarding risks of LTAT, including increased risk with i.v. therapy, and actively monitored for side effects.

An Intragastric Fecal Microbiota Transplantation Program for Treatment of Recurrent Clostridium difficile in Children is Efficacious, Safe, and Inexpensive

1. Sarah Parker, MD*,† 2. Michelle Mitchell, MD* 3. Jason Child, PharmD†‡ 1. *Division of Pediatric Infectious Diseases, University of Colorado School of Medicine/Children’s Hospital Colorado, Aurora, CO. 2. †Antimicrobial Stewardship Program, Children’s Hospital Colorado, Aurora, CO. 3. ‡Department of Pharmacy, Children’s Hospital Colorado, Aurora, CO. * Abbreviations: CAP: : community-acquired pneumonia CLSI: : Clinical Laboratory Standards Institute CSF: : cerebrospinal fluid FDA: : Food and Drug Administration GAS: : group A streptococcus IM: : intramuscular IV: : intravenous MIC: : mean inhibitory concentration MRSA: : methicillin-resistant Staphylococcus aureus MSSA: : methicillin-susceptible Staphylococcus aureus PBP: : penicillin-binding protein PD: : pharmacodynamic PK: : pharmacokinetic PRSP: : penicillin-resistant Streptococcus pneumoniae UTI: : urinary tract infection In the spirit of last month’s issue emphasizing “Doing Less” and using evidenced-based guidelines for treating pneumonia and sinusitis, we present the following feature on the judicious use of cephalosporins. Joseph A. Zenel, MD Editor-in-Chief Although cephem antibiotics are important in a pediatrician’s armamentarium, they are overused to the detriment of patients, hospitals, and communities, despite the availability of sound alternatives. Going back to the basics on mechanisms of action, resistance, and pharmacokinetic and pharmacodynamic principles facilitates smarter use and preserves cures for tomorrow. After reading this article, readers should be able to: 1. Describe in a general manner the mechanism of action, resistance, and pharmacokinetic and pharmacodynamic principles of cephem antibiotics. 2. Describe the advantages and disadvantages of oral cephem antibiotics compared with amoxicillin and amoxicillin–clavulanic acid. 3. Describe appropriate clinical situations in which to use cephem antibiotics. 4. Describe appropriate clinical situations where cephems are commonly used but could reasonably be replaced with an alternative, non-cephem antimicrobial. The cephem antibiotics were first deployed in the 1960s but did not expand into broad use until the 1970s with the development of useful semisynthetic derivatives. The cephem class includes the cephalosporins and the cephamycins, of which more than 22 antibiotics are now in clinical use (Table 1). There is no doubt that the cephem antibiotics are important weapons in a practitioner’s armamentarium; they are the most widely prescribed and largest selling class of antibiotics, with