Acute Kidney Injury During Treatment with Intravenous Acyclovir for Suspected or Confirmed Neonatal Herpes Simplex Virus Infection.

OBJECTIVE: To describe the epidemiology of and risk factors associated with acute kidney injury (AKI) during acyclovir treatment in neonates and infants. STUDY DESIGN: We conducted a multicenter (n = 4), retrospective cohort study of all hospitalized infants age <60 days treated with intravenous acyclovir (≥1 dose) for suspected or confirmed neonatal herpes simplex virus disease from January 2011 to December 2015. Infants with serum creatinine measured both before acyclovir (baseline) and during treatment were included. We classified AKI based on changes in creatinine according to published neonatal AKI criteria and performed Cox regression analysis to evaluate risk factors for AKI during acyclovir treatment. RESULTS: We included 1017 infants. The majority received short courses of acyclovir (median, 5 doses). Fifty-seven infants (5.6%) developed AKI during acyclovir treatment, with an incidence rate of AKI at 11.6 per 1000 acyclovir days. Cox regression analysis identified having confirmed herpes simplex virus disease (OR, 4.35; P = .002), receipt of ≥2 concomitant nephrotoxic medications (OR, 3.07; P = .004), receipt of mechanical ventilation (OR, 5.97; P = .001), and admission to an intensive care unit (OR, 6.02; P = .006) as risk factors for AKI during acyclovir treatment. CONCLUSIONS: Among our cohort of infants exposed to acyclovir, the rate of AKI was low. Sicker infants and those exposed to additional nephrotoxic medications seem to be at greater risk for acyclovir-induced toxicity and warrant closer monitoring.

Feasibility of a Centralized, Pharmacy-Led Penicillin Allergy Delabeling Program.

BACKGROUND: Penicillin allergy labels are often inaccurate in children and removing unnecessary labels results in improved outcomes and lower health care costs. Although the hospital setting is a frequent point of contact for children, strategies to evaluate penicillin allergies in the hospital are lacking. METHODS: We performed a prospective pilot study to determine the feasibility of a centralized, pharmacy-led approach to penicillin allergy evaluation. Children with a reported history of penicillin allergy admitted to our children's hospital were risk-stratified and those stratified as low-risk underwent a single-dose oral challenge by a central pharmacist, regardless of the need for antibiotics. After the completion of each patient's delabeling process, surveys were distributed to health care personnel involved in the patient's care to collect perceptions on the acceptability, appropriateness, and feasibility of this intervention. Measures were scored by using a 5-point Likert scale. RESULTS: Of the 23 patients who screened as low-risk, 20 underwent a penicillin allergy evaluation and an oral challenge. Of these, the penicillin allergy label was removed in 19 (95%) patients (Fig 1). The median age was 7 years (range 11 months-18 years). Participants rated the risk stratification and delabeling favorably overall, with high ratings on all 3 implementation measures: acceptability (mean 4.55, ± standard deviation [STD] 0.65), appropriateness (mean 4.58, STD ± 0.6), and feasibility (mean 4.51, STD ± 0.73). Measures of acceptability, appropriateness, and feasibility remained high when stratified by health care worker type and provider type. CONCLUSIONS: Our findings provide support for systemic implementation of penicillin allergy delabeling strategies in hospitalized children.

Incidence of Nephrotoxicity Among Pediatric Patients Receiving Vancomycin With Either Piperacillin-Tazobactam or Cefepime: A Cohort Study.

BACKGROUND: Recent studies in adults have found an incidence of acute kidney injury (AKI) in patients treated with a combination of vancomycin and piperacillin-tazobactam (TZP) that is greater than that expected with either medication alone. The purpose of this study was to determine whether combination therapy with vancomycin and TZP is associated with an incidence of AKI in pediatric patients higher than that in those on combination therapy with vancomycin and cefepime. METHODS: We performed a retrospective single-center matched-cohort study of pediatric patients who received vancomycin in combination with TZP or cefepime between January 2015 and June 2016. The patients were matched according to chronic disease, age, sex, and number of concomitant nephrotoxic medications at the time of combination antibiotic therapy. The primary outcome was incidence of AKI. Secondary outcomes included differences between groups in time to AKI, resolution of AKI, and effect of vancomycin trough levels on the incidence of nephrotoxicity. Conditional logistic regression was used to compare categorical and continuous variables between treatment groups. Conditional Poisson regression was used to assess the association between AKI and treatment groups. Stratified log-rank tests and Cox proportional hazards models with shared frailty were used to compare the times to AKI according to treatment group. RESULTS: Two hundred twenty-eight matched patients were included. AKI developed in 9 (7.9%) of 114 and 33 (28.9%) of 114 patients in the cefepime and TZP groups, respectively (P < .001). Type of combination therapy remained a significant predictor for AKI in multivariate conditional Poisson analysis in which adjustments were made for age, sex, use of concomitant nephrotoxins, and vancomycin dose (relative risk, 2.5 [95% confidence interval, 1.1-5.8]; P = .03). AKI developed almost 3 times sooner in the TZP group than in the cefepime group (hazard ratio, 2.9 [95% confidence interval, 1.3-6.1]; P = .006). Sensitivity analyses in which adjustment was made for antibiotic indication in addition to the aforementioned variables and excluding those with gastrointestinal infection revealed similar results. CONCLUSION: Among hospitalized children at our institution, combination therapy with vancomycin and TZP was associated with an incidence of AKI higher than that associated with vancomycin and cefepime.

Off-label use of intravenous antimicrobials for inhalation in patients with cystic fibrosis.

Management of infections in patients with cystic fibrosis (CF) presents challenges for healthcare providers, including the eradication of initial acquisition, treatment of acute exacerbations, and chronic infection with suppressive therapy. Inhaled antimicrobial therapy for infections in patients with CF has been used in these capacities, often in an effort to achieve optimal concentrations in sputum for antimicrobial efficacy while mitigating potential toxicities associated with systemic therapy. Unfortunately, there are few commercially available products formulated for inhalation, resulting in the off-label use of other formulations, such as intravenous products, administered via nebulization. This review aims to examine the evidence supporting the efficacy of these off-label formulations for management of acute and chronic infections associated with CF, as well as adverse effects associated with their use.

Analysis of 72-hour sterility of common pediatric continuous intravenous infusions.

OBJECTIVES: Patient morbidity and mortality associated with contaminated and improperly prepared sterile products has captured national attention. In response, both the United States Pharmacopeia (USP) and Centers for Disease Control (CDC) have published recommendations in an effort to minimize the risk of infection. While the CDC recommends that administration sets are not changed more frequently than every 72 hours, the USP recommends a maximum beyond use date of 48 hours. Neither organization provides specific guidance on expiration dating once the intravenous drug is dispensed. Likewise, neither addresses the length of time that a bag containing medication for continuous infusion may hang once administration to the patient has begun. We evaluated the sterility of medications that are commonly administered by continuous infusion to pediatric patients. Because frequent manipulation of infusion and administration sets may predispose the patient to adverse events, we evaluated sterility for extended beyond use dating up to 72 hours. METHODS: Thirty-five common intravenous (IV) continuous infusions using 94 standard concentrations and diluents were identified. IV solutions were mixed using sterile technique in the laminar flow hood in accordance with USP guidelines. Medications were excluded for short stability, short durations of use or high cost. A sample from each solution was tested for contamination or bacterial growth at 72 hours. Any visible discoloration suggesting physical instability was also evaluated. RESULTS: None of the syringes or chambers resulted in contamination, bacterial growth or discoloration after 72 hours. CONCLUSIONS: This study provides sufficient data that these compounded sterile products may be stored using a beyond use date up to 72 hours for a number of commonly used continuous IV infusions in pediatric patients. In our institution, this allows for a more convenient and consistent change of both administration sets and continuous infusions at 72 hours to potentially minimize adverse events, workload and cost.

Enhancing Computerized Provider Order Entry (CPOE) for neonatal intensive care.

The authors describe design, implementation, and use of a new order entry system module for neonatal intensive care. WizOrder is a Computerized Provider Order Entry (CPOE) system developed at Vanderbilt University Medical Center. Since WizOrder's introduction in 1995, it has been continually refined and enhanced; especially when new hospital units and specialties are implemented. Recently, in March 2003, WizOrder was updated and implemented in the Neonatal Intensive Care Unit (NICU).