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Incidence and Risk Factors for Acute Kidney Injury during the Treatment of Methicillin-Sensitive Staphylococcus aureus Infections with Cloxacillin Based Antibiotic Regimens: A French Retrospective Study.

ABSTRACT:

Background

Cloxacillin has been associated with the occurrence of acute kidney injury (AKI). The incidence of this complication in the literature is low (2.5-3.5%) and probably underestimated, since most studies were done by selecting the presence of AKI in discharge codes.

Objectives

The primary goal was to define the incidence of AKI in patients with a methicillin-sensitive Staphylococcus aureus infection treated with cloxacillin based antibiotic regimens. The secondary goals were to identify the risk factors associated with this complication and to describe the characteristics of AKI.

Patients and methods

We carried out a retrospective study. The inclusion criteria were adult patients hospitalized in a medical department at the Le Mans Hospital between 1 July 2012 and 1 July 2019 with a diagnosis of methicillin-sensitive Staphylococcus aureus infection treated with cloxacillin.

Results

One hundred twenty-three patients were included in the study. Forty-two patients (34.2%) developed AKI. In the multivariate analysis, age, the use of diuretics and the presence of endocarditis were independently associated with AKI. Age was associated with an OR of 4.38 (p = 0.002) for patients older than 75, being treated with diuretics was associated with an OR of 2.94 (p = 0.036) for loop diuretics and an OR of 3.05 (p = 0.027) for non-loop diuretics; type of infection was associated with an OR of 3.42 (p = 0.012) for endocarditis.

Conclusions

The occurrence of AKI is frequent during cloxacillin based antibiotic regimens for methicillin-sensitive Staphylococcus aureus infections. Being older than 75, being treated with diuretics and the presence of endocarditis were the main risk factors for AKI in our population.

SUBMITTER: Crochette R

PROVIDER: S-EPMC8231553 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Treatment failure occurs in about 25% of patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. We assessed whether cloxacillin plus fosfomycin achieves better treatment success than cloxacillin alone in hospitalized adults with MSSA bacteremia. We conducted a multicenter, open-label, phase III-IV superiority randomized clinical trial. We randomly assigned patients (1:1) to receive 2 g of intravenous cloxacillin alone every 4 h or with 3 g of intravenous fosfomycin every 6 h for the initial 7 days. The primary endpoint was treatment success at day 7, a composite endpoint with the following criteria: patient alive, stable or with improved quick Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA, adjudicated by an independent committee blinded to treatment allocation. We randomized 215 patients, of whom 105 received cloxacillin plus fosfomycin and 110 received cloxacillin alone. We analyzed the primary endpoint with the intention-to-treat approach in 214 patients who received at least 1 day of treatment. Treatment success at day 7 after randomization was achieved in 83 (79.8%) of 104 patients receiving combination treatment versus 82 (74.5%) of 110 patients receiving monotherapy (risk difference 5.3%; 95% confidence interval (CI), -5.95-16.48). Secondary endpoints, including mortality and adverse events, were similar in the two groups except for persistent bacteremia at day 3, which was less common in the combination arm. In a prespecified interim analysis, the independent committee recommended stopping recruitment for futility prior to meeting the planned randomization of 366 patients. Cloxacillin plus fosfomycin did not achieve better treatment success at day 7 of therapy than cloxacillin alone in MSSA bacteremia. Further trials should consider the intrinsic heterogeneity of the infection by using a more personalized approach. ClinicalTrials.gov registration: NCT03959345 .