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Mortality Associated with 3 rd Generation Cephalosporin Resistance in Enterobacterales Bloodstream Infections at Eight Sub-Saharan African Hospitals, a Prospective Cohort Study (MBIRA)
25 Pages Posted: 14 Feb 2023
More...Abstract
Background: Enterobacterales are common pathogens causing bloodstream infection (BSI) in sub-Saharan Africa and are frequently resistant to 3rd generation cephalosporin (3GC) antibiotics. Although 3GC-resistance is believed to lead to adverse outcomes, this relationship is difficult to quantify and has rarely been studied in this region.
Methods: We conducted a prospective matched parallel cohort study of 3GC-resistance impacts in Enterobacterales BSI at eight hospitals across sub-Saharan Africa. We included all age-groups and matched each BSI patient to ≥1 uninfected patients. We analyzed impacts using multivariable regression models, first comparing BSI against matches within the 3GC-resistant and 3GC-susceptible cohorts. Estimates were then compared between cohorts.
Findings: Between November 2020 and January 2022, we recruited 878 Enterobacterales BSI patients and 1,634 uninfected matches. Amongst these BSIs, 75% were phenotypically 3GC-resistant and over half occurred in neonates and infants. Klebsiella pneumoniae and Escherichia coli were the most common Enterobacterales identified. In multivariable Cox regression, we found a mortality impact over uninfected matches for both 3GC-resistant (cause-specific Hazard Ratio [csHR] 5·01; 95%CI 3·96-6·32) and 3GC-susceptible (csHR 6·79; 95%CI 4·06-11·37) BSI. The ratio of these ratios was not significantly different (csHR 0·74; 95%CI 0·42-1·30, p=0·29).
Interpretation: In this multi-site African study, both 3GC-resistant and 3GC-susceptible Enterobacterales BSI were associated with substantial mortality impacts over uninfected matches. However, no differential impact was found due to 3GC-R status. Measures to prevent transmission of Enterobacterales would reduce BSI-associated mortality from both resistant and susceptible strains in Africa – these are likely to be the most useful future priorities.
Funding: Bill & Melinda Gates Foundation.
Declaration of Interest: All authors state that they have no competing interests to declare.
Ethical Approval: Ethical approval for this study was granted by the London School of Hygiene and Tropical Medicine Ethics committee and relevant institutional bodies at all participating sites. Individual patients (or their relatives/guardians) gave informed consent to participate in the study.
Participating hospitals in Kenya, Malawi and Ethiopia obtained consent at time of blood culture
collection rather than after culture results became available.
Keywords: Mortality, bloodstream infection, Enterobacterales, extended-spectrum β-lactamase, antibiotic resistance, sub-Saharan Africa
Suggested Citation: Suggested Citation