Antimicrobial Resistance in Gram-negative bacteria from Urinary Specimens: a study of prevalence, risk factors and molecular mechanisms of resistance (ARGUS) in Zimbabwe - a study protocol.

Ioana D Olaru,Heidi Hopkins,Shungu Munyati,David Mabey,Katharina Kranzer,Kudzai P.E Masunda,Richard Stabler,John Bradley,Shunmay Yeung,Prosper Chonzi,Rashida A Ferrand

doi:10.12688/wellcomeopenres.15977.1

Abstract

Antimicrobial resistance (AMR) is compromising our ability to successfully treat infections. There are few data on gram-negative AMR prevalence in sub-Saharan Africa especially from the outpatient setting. This study aims to investigate the prevalence of and underlying molecular mechanisms for AMR in gram-negative bacilli causing urinary tract infections (UTIs) in Zimbabwe. Risk factors for AMR and how AMR impacts on clinical outcomes will also be investigated. Adults presenting with UTI symptoms at primary health clinics in Harare will be included. A questionnaire will be administered, and urine samples will be collected for culture. Participants with positive urine cultures will be followed up at 7-14 days post-enrolment. All participants will also be followed by telephone at 28 days to determine clinical outcomes. Bacterial identification and antibiotic susceptibility testing will be performed on positive cultures. The results from this study will be used to inform policy and development of treatment recommendations. Whole genome sequencing results will provide a better understanding of the prevalent resistance genes in Zimbabwe, of the spread of successful clones, and potentially will contribute to developing strategies to tackle AMR.

Highlights

Antimicrobials have revolutionized modern medicine leading to important reductions in mortality, morbidity and disability
This may be due to various causes such as antimicrobial use prior to sample collection, low bacterial load, delayed sample inoculation leading to overgrowth of contaminants or depletion of pathogen, or symptoms due to sexually transmitted infections rather than urinary tract infections (UTIs)
Preliminary data from this study have shown that the prevalence of Antimicrobial resistance (AMR) in UTI isolates is 83%

Summary

Introduction

Antimicrobials have revolutionized modern medicine leading to important reductions in mortality, morbidity and disability. Their discovery and use in medical practice was, accompanied by the rapid development of resistance. Antimicrobial resistance (AMR) can reverse the benefits brought by these drugs, leading to increased patient deaths and healthcare costs. Considering the current trends of increasing AMR, it is estimated that by 2050, 10 million deaths per year globally will be caused by antimicrobial resistant infections, exceeding the number of deaths due to cancer. Resistance genes are mobilized and can disseminate to other commensal and pathogenic organisms. Resistance genes are mobilized and can disseminate to other commensal and pathogenic organisms6 This in turn may lead to increased carriage of resistant organisms in the population and an increase in use of second-line antimicrobial drugs. Other risk factors for infections due to resistant organisms are underlying co-morbid conditions and healthcare contact

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