Effect of concomitant vancomycin and piperacillin-tazobactam on frequency of acute kidney injury in pediatric patients.

PURPOSE: Results of a study of rates of acute kidney injury (AKI) in pediatric patients treated with vancomycin plus piperacillin-tazobactam or vancomycin plus alternative antipseudomonal ß-lactams (APBLs) are reported. METHODS: A retrospective, single-center cohort study was performed. Pediatric patients were included in the study cohort if they received combination therapy for at least 48 hours, had documented baseline and follow-up serum creatinine levels, and had a documented serum vancomycin trough concentration. The primary outcome was the frequency of AKI, defined as a 50% or greater increase in serum creatinine concentration from baseline or an increase of at least 0.5 mg/dL from baseline. The secondary outcome was time to AKI onset. RESULTS: A total of 474 patients were included. Among 100 patients who received vancomycin plus piperacillin-tazobactam, the rate of AKI was higher than the rate in the group treated with vancomycin plus alternative APBLs (27% versus 7%, p < 0.0001). The median time to AKI onset was shorter in the piperacillin-tazobactam group versus the alternative APBL group (3.8 versus 7.9 days, p = 0.0065). Patients who were administered piperacillin-tazobactam were almost 6 times as likely to develop AKI (odds ratio [OR], 5.955; 95% confidence interval [CI], 2.774-12.784), and patients who had a maximum vancomycin trough concentration greater than 20 mg/L were 7.5 times as likely to develop AKI (OR, 7.552; 95% CI, 3.625-15.734). CONCLUSION: Pediatric patients treated with concomitant vancomycin and piperacillin-tazobactam had a higher rate of AKI, with faster AKI onset, than those who received vancomycin in combination with other APBLs.

Adverse effects of pegaspargase in pediatric patients receiving doses greater than 3,750 IU.

BACKGROUND: Increased toxicities have been identified with higher doses of pegaspargase (PEG-ASP) in adults. This has led to routine use of a dose cap of 3,750 IU for adult acute lymphoblastic leukemia (ALL) patients in most institutions. In pediatric ALL patients, PEG-ASP is not capped. There is concern at our institution that larger doses may result in increased rates of adverse effects and that increased monitoring may be warranted in pediatric patients receiving doses greater than 3,750 IU. The objective of this study is to quantify the difference in the rates of PEG-ASP-associated adverse events between pediatric patients who received doses greater than 3,750 IU and less than or equal to 3,750 IU. METHODS: Retrospective chart review of patients 1-21 years old with pre-B-cell ALL who received PEG-ASP between 2007 and 2014 at an academic medical center. RESULTS: Of 183 patients included in the analysis, 24 received PEG-ASP doses higher than 3,750 IU and 159 received doses less than or equal to 3,750 IU. The incidence of venous thromboembolism (VTE) was significantly higher for patients in the group that received more than 3,750 IU compared with those who received 3,750 IU or less (20.8 vs. 1.89%, respectively; P = 0.0011). The incidence of pancreatitis (P = 0.0306) and hyperglycemia (P = 0.0089) were also higher in the group that received more than 3,750 IU. CONCLUSIONS: PEG-ASP doses higher than 3,750 IU are associated with higher rates of VTE, pancreatitis, and hyperglycemia in pediatric patients with pre-B-cell ALL. Patients receiving more than 3,750 IU should have increased monitoring, and larger, multicenter trials are needed to determine if monitoring, VTE prophylaxis, and potential dose capping recommendations should be added to clinical trial protocols.

Vincristine toxicity with co-administration of fluconazole during induction therapy for pediatric acute lymphoblastic leukemia.

BACKGROUND: Antifungal prophylaxis is recommended for patients with acute lymphoblastic leukemia (ALL) during high-risk periods such as induction; however, increased vincristine toxicities have been reported with the co-administration of triazole antifungals. We sought to determine whether vincristine-associated toxicities are higher among children with ALL concurrently given fluconazole prophylaxis compared to no prophylaxis. PROCEDURE: Using a retrospective cohort design, we reviewed records of pediatric patients treated for newly diagnosed ALL from 2003 to 2013. Patients were classified by fluconazole exposure during induction. The development of vincristine-associated toxicity and vincristine dose adjustment were the primary outcomes evaluated. The adjusted risk difference (RD) for vincristine-related toxicity associated with triazole exposure was determined. RESULTS: We identified 197 patients meeting inclusion criteria for evaluation, 160 (81%) of whom received fluconazole prophylaxis. Among patients receiving fluconazole, 36/160 (22%) developed vincristine toxicity compared to 7/37 (19%) among those not receiving prophylaxis (RD: 3%, 95% confidence interval [CI] -11 to 18%). Adjusting for patient age and race, no statistically significant increased risk for vincristine-associated toxicity with fluconazole exposure was observed (RD 5%, 95% CI -8 to 17%). An increased risk for vincristine-associated toxicity was independently associated with age 10 years or older (RD 19%, 95% CI 4-34%). CONCLUSION: Co-administration of fluconazole during induction therapy for pediatric ALL does not significantly increase the risk for vincristine-associated toxicities; however, patients 10 years or older are at an increased risk for toxicity independent of fluconazole exposure. Prophylaxis with fluconazole during induction therapy for pediatric ALL, if warranted, appears to be a safe clinical practice.