Bloodstream infections (BSI) caused by antimicrobial-resistant (AMR) Gram-negative bacteria (GNB) are a significant cause of morbidity and mortality. Third-generation cephalosporins (3GCs) have been used as empiric treatment for BSI and other invasive infections for years; however, their overuse could promote the emergence of extended-spectrum beta-lactamases (ESBLs). Thus, this study aimed to determine the epidemiological, clinical and microbiological features and the effects of antimicrobial resistance on the outcomes of BSIs at a referral hospital in Lusaka, Zambia. This was a six-month prospective facility-based study undertaken at a referral hospital in Lusaka, Zambia. As part of the routine diagnosis and patient care, blood samples for bacteriological culture were collected from patients presenting with fever and processed for pathogen identification and antimicrobial susceptibility testing using the VITEK 2 Compact instrument. ESBLs and plasmid-mediated quinolone resistance (PMQR) associated genes were determined using the polymerase chain reaction method. Patient information was collected using a structured data collection sheet and entered in CSpro 7.6. Data were analysed in WHOnet and STATA version 14. A total of 88 GNB were isolated, of which 76% were Enterobacterales, 14% Acinetobacter baumannii and 8% Pseudomonas aeruginosa. Resistance to third and fourth-generation cephalosporins was 75% and 32%, respectively. Noteworthy was the high prevalence (68%) of inappropriate empirical treatment, carbapenem resistance (7%), multi-drug resistance (83%) and ESBL-producers (76%). In comparison to E. coli as a causative agent of BSI, the odds of death were significantly higher among patients infected with Acinetobacter baumannii (OR = 3.8). The odds of death were also higher in patients that received 3GCs as empiric treatment than in those that received 4GCs or other (none cephalosporin) treatment options. Structured surveillance, yearly antibiogram updates, improved infection control and a well functional antimicrobial stewardship (AMS) program, are of utmost importance in improving appropriate antimicrobial treatment selection and favourable patient outcomes.

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