Antibiotic resistance profiles and population structure of disease-associated Staphylococcus aureus infecting patients in Fort Portal Regional Referral Hospital, Western Uganda.

Tackling antimicrobial resistance (AMR) is particularly challenging in low-resource settings such as Fort Portal Regional Referral Hospital (FPRRH) in Western Uganda. Specific knowledge of local AMR epidemiology is required to inform evidence-based improvement of antibiotic stewardship measures in the hospital. To address this, we combined existing antimicrobial susceptibility testing (AST) from FPRRH, with whole genome sequencing (WGS) of 41 Staphylococcus aureus isolates (2017-2019). AST revealed 73 % (30 of 41) of isolates were resistant to one or more antibiotics and 29 % (12 of 41) were multi-drug resistant (MDR). Resistance phenotypes were largely explained by the presence of antibiotic resistance genes in WGS data. Five isolates were methicillin-resistant S. aureus (MRSA) and MDR. Although all isolates were susceptible to clindamycin, a 24 % carriage of erm genes suggests potential for rapid development of resistance. We inferred a population structure for the S. aureus isolates by comparing their core genomes. Twenty isolates formed a tight cluster corresponding to multilocus sequence typing clonal complex (CC) 152, a CC found to be particularly prevalent in northern Africa. The frequency of genes associated with methicillin, chloramphenicol and ciprofloxacin resistance were significantly lower among CC152 strains than non-CC152 strains; thus, in keeping with previous work, we find that CC152 is almost exclusively methicillin-sensitive S. aureus (MSSA). Also, in agreement with other studies, we observed that the occurrence of Panton-Valentine leukocidin toxin-encoding genes was significantly higher among CC152 strains than non-CC152 strains. However, we also observed that the coagulase gene was over-represented in this CC, further defining the virulence strategy of this important pathogen. By generating detailed information about the epidemiology of circulating S. aureus and their antibiotic susceptibility, our study has provided, for the first time, data on which evidence-based infection and AMR interventions at FPRRH can be based.

Characterization of Antibiotic Resistance in Select Tertiary Hospitals in Uganda: An Evaluation of 2020 to 2023 Routine Surveillance Data.

Antimicrobial resistance (AMR) is a public health concern in Uganda. We sought to conduct an extended profiling of AMR burden at selected Ugandan tertiary hospitals. We analyzed routine surveillance data collected between October 2020 and March 2023 from 10 tertiary hospitals. The analysis was stratified according to the hospital unit, age, gender, specimen type, and time. Up to 2754 isolates were recovered, primarily from pus: 1443 (52.4%); urine: 1035 (37.6%); and blood: 245 (8.9%). Most pathogens were Staphylococcus aureus, 1020 (37%), Escherichia coli, 808 (29.3%), and Klebsiella spp., 200 (7.3%). Only 28% of Escherichia coli and 42% of the other Enterobacterales were susceptible to ceftriaxone, while only 44% of Staphylococcus aureus were susceptible to methicillin (56% were MRSA). Enterococcus spp. susceptibility to vancomycin was 72%. The 5-24-year-old had 8% lower ampicillin susceptibility than the >65-year-old, while the 25-44-year-old had 8% lower ciprofloxacin susceptibility than the >65-year-old. The 0-4-year-old had 8% higher ciprofloxacin susceptibility. Only erythromycin susceptibility varied by sex, being higher in males. Escherichia coli ciprofloxacin susceptibility in blood (57%) was higher than in urine (39%) or pus (28%), as was ceftriaxone susceptibility in blood (44%) versus urine (34%) or pus (14%). Klebsiella spp. susceptibility to ciprofloxacin and meropenem decreased by 55% and 47%, respectively, during the evaluation period. During the same period, Escherichia coli ciprofloxacin susceptibility decreased by 40%, while Staphylococcus aureus gentamicin susceptibility decreased by 37%. Resistance was high across the Access and Watch antibiotic categories, varying with time, age, sex, specimen type, and hospital unit. Effective antimicrobial stewardship targeted at the critical AMR drivers is urgently needed.

The Joint Mobile Emerging Disease Clinical Capability (JMEDICC) laboratory approach: Capabilities for high-consequence pathogen clinical research.

Following the 2013-2016 Ebola virus outbreak in West Africa, numerous groups advocated for the importance of executing clinical trials in outbreak settings. The difficulties associated with obtaining reliable data to support regulatory approval of investigational vaccines and therapeutics during that outbreak were a disappointment on a research and product development level, as well as on a humanitarian level. In response to lessons learned from the outbreak, the United States Department of Defense established a multi-institute project called the Joint Mobile Emerging Disease Intervention Clinical Capability (JMEDICC). JMEDICC's primary objective is to establish the technical capability in western Uganda to execute clinical trials during outbreaks of high-consequence pathogens such as the Ebola virus. A critical component of clinical trial execution is the establishment of laboratory operations. Technical, logistical, and political challenges complicate laboratory operations, and these challenges have been mitigated by JMEDICC to enable readiness for laboratory outbreak response operations.