In Vitro Activity of Ceftolozane-Tazobactam against Escherichia coli , Klebsiella pneumoniae and Pseudomonas aeruginosa Obtained from Blood Cultures from Sentinel Public Hospitals in South Africa.

Multidrug-resistant (MDR) Gram-negative bacteria are responsible for the majority of healthcare-associated infections and pose a serious threat as they complicate and prolong clinical care. A novel cephalosporin-β-lactamase-inhibitor combination, ceftolozane-tazobactam (C/T) was introduced in 2014, which improved the treatment of MDR pathogens. This study aimed to evaluate the activity of C/T against (n = 100), (n = 100), and (n = 100) blood culture isolates in South Africa (SA). Isolates were sequentially selected (2010 to 2020) from the Group for Enteric, Respiratory, and Meningeal Diseases Surveillance (GERMS) programme in SA. Organism identification was performed using the matrix-assisted laser desorption/ionisation-time of flight mass spectrometry (MALDI-TOF MS) instrument (Microflex, Bruker Daltonics, Bremen, Germany), and antibiotic susceptibility was performed using the Sensititre instrument (Trek Diagnostic Systems, East Grinstead, UK). C/T resistance was reported in 16 , 28 and 13 isolates. Fifty percent of the C/T resistant isolates were subjected to whole-genome sequencing (WGS). According to the whole genome multilocus sequence typing (MLST) analysis, the isolates (n = 8) belonged to sequence type (ST)10, ST131, ST405, and ST410, the isolates (n = 14) belonged to ST1, ST37, ST73, ST101, ST231, ST307, ST336 and ST6065 (novel ST), and the isolates (n = 7) belonged to ST111, ST233, ST273, and ST815. The WGS data also showed that all the isolates harboured aminoglycoside ( (3'')-Ib, (6)-Id), macrolide (A, A), and sulphonamide (2) antibiotic resistance genes, all the isolates harboured β-lactam (), and sulphonamide (2) antibiotic resistance genes, and all the isolates harboured aminoglycoside ( (3')-IIb), β-lactam (), fosfomycin (A), phenicol (B7), quinolone (P), and disinfectant (E) antibiotic resistance genes. It is evident that , and can adapt pre-existing resistance mechanisms to resist newer β-lactam molecules and inhibitors, since these isolates were not exposed to ceftolozane-tazobactam previously.