Mortality associated with third-generation cephalosporin resistance in Enterobacterales bloodstream infections at eight sub-Saharan African hospitals (MBIRA): a prospective cohort study.

BACKGROUND: Bacteria of the order Enterobacterales are common pathogens causing bloodstream infections in sub-Saharan Africa and are frequently resistant to third-generation cephalosporin antibiotics. Although third-generation cephalosporin resistance is believed to lead to adverse outcomes, this relationship is difficult to quantify and has rarely been studied in this region. We aimed to measure the effects associated with resistance to third-generation cephalosporins in hospitalised patients with Enterobacterales bloodstream infection in Africa. METHODS: We conducted a prospective, matched, parallel cohort study at eight hospitals across sub-Saharan Africa. We recruited consecutive patients of all age groups with laboratory-confirmed Enterobacterales bloodstream infection and matched them to at least one patient without bloodstream infection on the basis of age group, hospital ward, and admission date. Date of infection onset (and enrolment) was defined as the day of blood sample collection for culturing. Patients infected with bacteria with a cefotaxime minimum inhibitory concentration of 1 mg/L or lower were included in the third-generation cephalosporin-susceptible (3GC-S) cohort, and the remainder were included in the third-generation cephalosporin-resistant (3GC-R) cohort. The primary outcomes were in-hospital death and death within 30 days of enrolment. We used adjusted multivariable regression models to first compare patients with bloodstream infection against matched patients within the 3GC-S and 3GC-R cohorts, then compared estimates between cohorts. FINDINGS: Between Nov 1, 2020, and Jan 31, 2022, we recruited 878 patients with Enterobacterales bloodstream infection (221 [25·2%] to the 3GC-S cohort and 657 [74·8%] to the 3GC-R cohort) and 1634 matched patients (420 [25·7%] and 1214 [74·3%], respectively). 502 (57·2%) bloodstream infections occurred in neonates and infants (age 0-364 days). Klebsiella pneumoniae (393 [44·8%] infections) and Escherichia coli (224 [25·5%] infections) were the most common Enterobacterales species identified. The proportion of patients who died in hospital was higher in patients with bloodstream infection than in matched controls in the 3GC-S cohort (62 [28·1%] of 221 vs 22 [5·2%] of 420; cause-specific hazard ratio 6·79 [95% CI 4·06-11·37] from Cox model) and the 3GC-R cohort (244 [37·1%] of 657 vs 115 [9·5%] of 1214; 5·01 [3·96-6·32]). The ratio of these cause-specific hazard ratios showed no significant difference in risk of in-hospital death in the 3GC-R cohort versus the 3GC-S cohort (0·74 [0·42-1·30]). The ratio of relative risk of death within 30 days (0·82 [95% CI 0·53-1·27]) also indicated no difference between the cohorts. INTERPRETATION: Patients with bloodstream infections with Enterobacterales bacteria either resistant or susceptible to third-generation cephalosporins had increased mortality compared with uninfected matched patients, with no differential effect related to third-generation cephalosporin-resistance status. However, this finding does not account for time to appropriate antibiotic treatment, which remains clinically important to optimise. Measures to prevent transmission of Enterobacterales could reduce bloodstream infection-associated mortality from both drug-resistant and drug-susceptible bacterial strains in Africa. FUNDING: Bill & Melinda Gates Foundation.

A mini- national surveillance study of resistance profiles of Staphylococcus Aureus isolated from clinical specimens across hospitals in Nigeria.

BACKGROUND: Infections with Staphylococcus aureus cause significant morbidity and mortality worldwide. Resistant strains of S. aureus to commonly used antibiotics are being increasingly encountered in clinical practice, necessitating the need to determine the resistance pattern in Nigeria. METHODS: Antibiotic susceptibility testing was performed on 360 S. aureus isolates from clinical specimen from seven hospitals across the six geo-political regions of Nigeria using Kirby Bauer disc diffusion technique, and E-test for vancomycin. Cefoxitin 30 µg disc was used to determine methicillin resistance, and D-test for inducible clindamycin resistance. RESULTS: Methicillin-resistant S. aureus was confirmed in 176 (48.9%) of the isolates, 346 (96%) for penicillin G and 311 (86.4%) for trimethoprim. 175 (99.4%) of the 176 resistant to methicillin were susceptible to vancomycin. Linezolid, tigecycline, chloramphenicol and clindamycin had susceptibilities of 341 (94.7%), 332 (92.2%), 298 (82.8%) and 290 (80.6%) respectively. Inducible clindamycin resistance was elucidated in 25 (29.1%) of the 86 isolates. Generally, MRSA isolates were more resistant than methicillin-sensitive S. aureus (MSSA) to all antibiotics tested. CONCLUSION: Staphylococcus aureus rates of resistance are high and call for urgent action such as antibiotic stewardship programmes and periodic surveillance to enhance clinical outcomes. While targeted therapy is preferred, options for empiric treatment include chloramphenicol, clindamycin, linezolid or vancomycin.