Vancomycin-resistant enterococcal infection in a Thai university hospital: clinical characteristics, treatment outcomes, and synergistic effect
Received 11 April 2019
Accepted for publication 12 June 2019
Published 11 July 2019 Volume 2019:12 Pages 2049—2057
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Melinda Thomas
Peer reviewer comments 2
Editor who approved publication: Professor Suresh Antony
Jatapat Hemapanpairoa,1–3 Dhitiwat Changpradub,4 Sudaluck Thunyaharn,5 Wichai Santimaleeworagun3,6
1Department of Pharmacy Practice and Pharmaceutical Care, Faculty of Pharmaceutical Sciences, Burapha University, Chonburi 20131, Thailand; 2College of Pharmacotherapy Thailand, Nonthaburi 11000, Thailand; 3Pharmaceutical Initiative for Resistant Bacteria and Infectious Diseases Working Group, Nakorn Pathom 73000, Thailand; 4Division of Infectious Disease, Department of Medicine, Phramongkutklao Hospital, Bangkok 10400, Thailand; 5Faculty of Medical Technology, Nakhonratchasima College, Nakhon Ratchasima 30000, Thailand; 6Department of Pharmacy, Faculty of Pharmacy, Silpakorn University, Nakorn Pathom 73000, Thailand
Purpose: The incidence of infections with vancomycin-resistant enterococci (VRE) is increasing, with associated high mortality rates and limited therapeutic choices. We investigated the clinical characteristics and treatment outcomes of VRE infection and also determined the in vitro effect of monotherapy and combined antimicrobials against clinical VRE isolates.
Patients and methods: Clinical data and bacterial isolates obtained from patients with VRE infections between January 2014 and April 2018 at Phramongkutklao Hospital were reviewed. The clinical outcomes included in-hospital mortality, 30-day mortality, and microbiological eradication. Clonal relationships were assessed by random amplified polymorphic DNA analysis. In vitro activity of linezolid, tigecycline, fosfomycin, gentamicin, chloramphenicol, and ampicillin were determined by minimum inhibitory concentration (MIC) values. Tests of synergy of fosfomycin- or gentamicin-based combinations by the checkerboard method were reported with the fractional inhibitory concentration index or MIC reduction, respectively.
Results: Among 26 cases of VRE infection, nosocomial and gastrointestinal infections were the most common. There were various treatment regimens, but linezolid-containing regimens were generally used. In-hospital and 30-day mortality were 73.1% and 57.7%, respectively. Higher mortality was significantly associated with illness severity. The VRE isolates tested were universally susceptible to linezolid and tigecycline. A synergistic or additive effect was observed for fosfomycin combined with linezolid (100%) and with tigecycline (83.3%). Fourfold or greater MIC reduction was observed for linezolid or fosfomycin plus gentamicin at concentrations 1 (58.3%, 62.5%), 2 (83.3%, 62.5%), and 4 μg/mL (91.6%, 62.5%).
Conclusion: In-hospital mortality among patients with VRE infection was high. Linezolid remains a treatment of choice. However, combination therapy such as linezolid plus fosfomycin and linezolid plus gentamicin should be considered in cases of serious infection.
Keywords: clinical outcomes, vancomycin-resistant enterococci, minimum inhibitory concentration, synergism
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