A randomized phase 2B trial of vancomycin versus daptomycin for the treatment of methicillin-resistant Staphylococcus aureus bacteremia due to isolates with high vancomycin minimum inhibitory concentrations - results of a prematurely terminated study
Author(s)
Type
Journal Article
Abstract
BACKGROUND: Studies have suggested the reduced effectiveness of vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections with high vancomycin minimum inhibitory concentrations. Alternative agents such as daptomycin may be considered. We conducted a randomized controlled study comparing daptomycin against vancomycin in the treatment of MRSA bloodstream infections with high vancomycin minimum inhibitory concentrations. METHODS: Patients were randomized to receive vancomycin or daptomycin for a minimum of 14 days. The primary end point was the rate of all-cause mortality at day 60. RESULTS: A total of 14 patients were randomized in this study, with 7 patients in each treatment arm. The study was terminated early due to slow patient accrual. At day 60, there was one death in the vancomycin arm and none in the daptomycin arm. The median time to microbiological clearance was 4 days in both arms (IQR 3-5 days in the vancomycin arm and 3-7 days in daptomycin arm). Only one patient in the vancomycin arm had recurrence of bacteremia. Rates of adverse events were similar in both arms. There was one case of musculoskeletal toxicity and one case of drug-related nephrotoxicity - both events occurred in the daptomycin arm. None of the patients in either treatment arm required cessation of study treatment or addition of a second anti-MRSA agent because of worsening infection. CONCLUSION: Based on the limited number of patients evaluated in this study, it remains unclear if alternative, more expensive agents such as daptomycin are superior to vancomycin in the treatment of high vancomycin minimum inhibitory concentration MRSA bloodstream infections. More studies are urgently needed but investigators may wish to consider employing novel, alternative trial methodologies to ensure a greater chance of success. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01975662 . Registered on 5 November 2013.
Date Issued
2018-06-01
Date Acceptance
2018-05-21
Citation
Trials, 2018, 19 (1)
ISSN
1745-6215
Publisher
BioMed Central
Journal / Book Title
Trials
Volume
19
Issue
1
Copyright Statement
© The Author(s). 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/29859132
PII: 10.1186/s13063-018-2702-8
Subjects
Bacteremia
Daptomycin
Methicillin-resistant Staphylococcus aureus
Minimum inhibitory concentration
Vancomycin
Aged
Anti-Bacterial Agents
Bacteremia
Cause of Death
Daptomycin
Drug Resistance, Bacterial
Early Termination of Clinical Trials
Female
Humans
Male
Methicillin-Resistant Staphylococcus aureus
Microbial Sensitivity Tests
Middle Aged
Predictive Value of Tests
Recurrence
Singapore
Staphylococcal Infections
Time Factors
Treatment Outcome
Vancomycin
Publication Status
Published
Coverage Spatial
England
Article Number
305