ABSTRACT
It has been reported that the risk of acute kidney injury (AKI) is higher during treatment with vancomycin and piperacillin/tazobactam compared to use of vancomycin and cefepim or meropenem. We investigated the risk of AKI in patients receiving vancomycin and piperacillin/tazobactam versus those receiving vancomycin and meropenem or doripenem. The subjects were patients over 18 years old who received either vancomycin and piperacillin/tazobactam (V+P/T therapy) or vancomycin and carbapenems (meropenem or doripenem) (V+C therapy) for at least 48 h between 1 May 2013 and 28 February 2019. The primary endpoint was the incidence of AKI in patients receiving V+P/T or V+C therapy, while the secondary outcome was the timing of AKI in each group. The incidence of AKI was 33.3% (9/27) in patients receiving V+P/T therapy versus 9.1% (5/55) in those receiving V+C therapy, and its incidence was significantly higher with the former regimen (χ2=5.90, p=0.015). Multiple logistic regression analysis confirmed that V+P/T therapy was associated with an increased risk of AKI compared to V+C therapy (adjusted odds ratio: 5.05, 95% confidence interval: 1.46-17.5, p=0.01). The time to onset of AKI after initiation of treatment was not significantly different between patients receiving V+T/P or V+C therapy [median (interquartile range): 4 d (2-6 d) versus 7 d (3-10 d); p=0.282]. V+P/T therapy was associated with a significantly higher incidence of AKI than alternative regimens, suggesting that it should be avoided. When broad spectrum antibacterial therapy is required, V+C therapy should be considered instead.
Subject(s)
Acute Kidney Injury/chemically induced , Anti-Bacterial Agents/adverse effects , Doripenem/adverse effects , Meropenem/adverse effects , Piperacillin, Tazobactam Drug Combination/adverse effects , Vancomycin/adverse effects , Acute Kidney Injury/epidemiology , Aged , Aged, 80 and over , Anti-Bacterial Agents/administration & dosage , Cohort Studies , Doripenem/administration & dosage , Drug Therapy, Combination , Female , Humans , Incidence , Logistic Models , Male , Meropenem/administration & dosage , Middle Aged , Piperacillin, Tazobactam Drug Combination/administration & dosage , Retrospective Studies , Risk , Vancomycin/administration & dosageABSTRACT
Febrile neutropenia is often observed in patients with hematologic malignancies, especially in those with acute leukemia. Meropenem has potent and broad antibacterial activity against gram-positive and gram-negative bacteria, and is recommended as first-line empiric therapy for febrile neutropenia. In contrast, the safety and efficacy of doripenem in patients with febrile neutropenia and hematologic malignancies is limited. In this randomized, prospective, cooperative, open-label trial, we compared doripenem (1.0 g every 8 h) to meropenem (1.0 g every 8 h) as first-line empiric antibacterial treatment of febrile neutropenia. To evaluate efficacy and safety, 133 hospitalized patients with acute leukemia or high-risk myelodysplastic syndrome, who developed febrile neutropenia during or after chemotherapy, were randomized to each drug. Resolution of fever within 3 to 5 days without treatment modification (i.e., the primary endpoint) did not significantly differ between the doripenem and meropenem groups (60.0% vs. 45.6%, respectively; P = 0.136). However, resolution of fever within 7 days of treatment was significantly higher in the doripenem group than in the meropenem group (78.4% vs. 60.2%, respectively; P = 0.037). Similar rates of adverse events (grades 1-2) were observed in both groups. Thus, we conclude that both drugs are safe and well-tolerated for the treatment of febrile neutropenia in patients with acute leukemia or high-risk myelodysplastic syndrome, and that the clinical efficacy of doripenem is noninferior to that of meropenem. UMIN Clinical Trial Registry number: 000006124.
