Olaru, I; (2023) Understanding gram-negative infections and antimicrobial resistance in Zimbabwe. PhD thesis, London School of Hygiene & Tropical Medicine. DOI: https://doi.org/10.17037/PUBS.04670825
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Abstract
Data on the burden of antimicrobial resistance (AMR) from sub-Saharan Africa are scarce. Although many countries have enrolled into the WHO Global Antimicrobial Resistance Use and Surveillance System (GLASS), less than 1% of contributing sites are from sub-Saharan Africa. In addition, data from both published research studies and surveillance may not be representative as reporting sites are usually large hospitals or referral laboratories. Patients encounter difficulties in accessing care and testing due to financial constraints while laboratories can be affected by stock outs of consumables, insufficient training, long turnaround times, and suboptimal quality of testing. The lack of diagnostics, safety netting for patients, and the high costs of care result in frequent overprescribing of antibiotics which leads in turn to further development of AMR. This PhD explores some of these issues related to Gram-negative AMR and laboratory testing with a focus on Zimbabwe. I conducted a systematic review to determine the prevalence of AMR in sub-Saharan Africa in key Gram-negatives and a review investigating the association between HIV infection and AMR. I then conducted the ARGUS (Antimicrobial Resistance in Gram-negatives from Urinary Specimens) study, which recruited patients with suspected urinary tract infections from primary care clinics. Within the ARGUS study I aimed to i) determine the prevalence of resistance in community-acquired urinary tract infections ii) investigate the association between HIV infection and AMR; iii) identify mechanisms of resistance in Escherichia coli through sequencing; iv) assess the effect of AMR on patient outcomes; v) explore antibiotic prescribing and use in the outpatient setting; and vi) evaluate novel culture media. This PhD showed that resistance to antibiotics recommended for the treatment of urinary tract infections by the national guidelines was common and patients who received ineffective antibiotics experienced less favourable outcomes. Patients with HIV infection were twice as likely to have infections with third-generation cephalosporin resistant E. coli. There was a large diversity of sequence types in E. coli and isolates frequently had resistance genes to multiple antibiotic classes. Around one in five patients had antibiotic exposure prior to accessing healthcare. Primary care providers acknowledged the problem of antibiotic overprescribing and the need for training on AMR. Novel chromogenic media evaluated in patients with urinary tract infections and neonatal sepsis had a good performance and may be considered for surveillance in low-resource settings. This work has highlighted the need for representative setting- and population- specific AMR data to inform treatment guidelines and improve patient care. Given the challenges in conducting laboratory testing, novel strategies for expanding use of laboratory diagnostics should be considered. However, sustained efforts are needed to acquire AMR data using high quality testing and to use these data for informing treatment decisions. Reducing antibiotic use is challenging in this setting due to the economic situation, high burden of infections, diagnostic uncertainties and the need to provide care
Item Type | Thesis |
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Thesis Type | Doctoral |
Thesis Name | PhD |
Contributors | Kranzer, K; Ferrand, R and Yeung, S |
Faculty and Department | Faculty of Infectious and Tropical Diseases > Dept of Clinical Research |
Funder Name | Wellcome Trust |
Copyright Holders | Ioana Diana Olaru |
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Filename: 2022_ITD_PhD_Olaru_ID.pdf
Licence: Creative Commons: Attribution-Noncommercial-No Derivative Works 4.0
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