A randomised controlled trial of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDITOF-MS) versus conventional microbiological methods for identifying pathogens: Impact on optimal antimicrobial therapy of invasive bacterial and fungal infections in Vietnam

Behzad Nadjm,Vu Quoc Dat,James I Campbell,Vu Tien Viet Dung,Alessandro Torre,Nguyen Thi Cam Tu,Ninh Thi Thanh Van,Dao Tuyet Trinh,Nguyen Phu Huong Lan,Nguyen Vu Trung,Nguyen Thi Thuy Hang,Le Thi Hoi,Stephen Baker,Marcel Wolbers,Nguyen Van Vinh Chau,Nguyen Van Kinh,Guy E Thwaites,H Rogier Van Doorn,Heiman F.L Wertheim

doi:10.1016/j.jinf.2019.03.010

Abstract

We assessed the impact of MALDITOF-MS on the timeliness of optimal antimicrobial therapy through a parallel-arm randomised controlled trial in two hospitals in Vietnam. We recruited patients with a pathogen (bacterial or fungal) cultured from a normally sterile sample. Samples were randomly assigned (1:1) to identification by MALDITOF-MS or conventional diagnostics. The primary outcome was the proportion on optimal antimicrobial therapy within 24 h of positive culture, determined by a blinded independent review committee. Trial registered at ClinicalTrials.gov (NCT02306330). Among 1005 randomised patients, pathogens were isolated from 628 (326 intervention, 302 control), with 377 excluded as likely contaminants or discharged/died before positive culture. Most isolates were cultured from blood (421/628, 67.0%). The proportion receiving optimal antimicrobial therapy within 24 h (the primary outcome) or 48 h of growth was not significantly different between MALDITOF-MS and control arms (135/326, 41.4% vs 120/302, 39.7%; Adjusted Odds ration (AOR) 1.17, p = 0.40 and 151/326, 46.3% vs 141/302, 46.7%; AOR 1.05 p = 0.79, respectively). MALDITOF-MS, in the absence of an antimicrobial stewardship programme, did not improve the proportion on optimal antimicrobial therapy at 24 or 48 h after first growth in a lower-middle income setting with high rates of antibiotic resistance.

Highlights

IntroductionInvestment in hospital laboratory infrastructure and capacity building in LMICs has attracted international attention.[3,4,5] Efficient use of limited available resources is needed to develop optimal laboratory capacity, avoid inappropriate use of antibiotics and improve patient outcomes.[6] Novel technologies have been developed to improve identification and susceptibility testing results, but many are expensive[1,7] and developed in and for high income countries[8] but are being introduced in LMIC laboratories
A parallel arm randomised controlled trial was conducted in 2 tertiary infectious diseases hospitals in Vietnam: the National Hospital for Tropical Diseases (NHTD) in Hanoi and the Hospital for Tropical Diseases (HTD) in Ho Chi Minh City
Optimal antimicrobial treatment was defined as treatment using any drug to which the isolate showed in vitro susceptibility and had known clinical susceptibility, but not including unnecessarily broad spectrum regimens

Summary

Introduction

Investment in hospital laboratory infrastructure and capacity building in LMICs has attracted international attention.[3,4,5] Efficient use of limited available resources is needed to develop optimal laboratory capacity, avoid inappropriate use of antibiotics and improve patient outcomes.[6] Novel technologies have been developed to improve identification and susceptibility testing results, but many are expensive[1,7] and developed in and for high income countries[8] but are being introduced in LMIC laboratories Systematic evaluation of these is important, especially in resource constrained settings, to show impact on clinical decision-making and patient care

Objectives

Methods

Results

Conclusion