Ceftazidime-avibactam and Aztreonam susceptibility of Carbapenem Resistant Enterobacterales and Pseudomonas aeruginosa isolates at Chris Hani Baragwanath Academic Hospital

Abstract

Background: The rising resistance of multidrug resistant organisms (MDROs) to currently available last resort antibiotics accompanied by increased mortality, has led to organisms such as Carbapenem Resistant Enterobacterales (CRE) and drug resistant P. aeruginosa becoming a global threat. New antibiotics such as Ceftazidime-Avibactam (CZA) and its use in combination with Aztreonam (ATM), has presented a glimmer of hope to this threat. There is a lack of susceptibility data of these MDROs to CZA and ATM in low to middle income countries such as South Africa. Finding out such information, may assist in motivating for acquisition and usage of these lifesaving antibiotics. Objectives: The aim of the study was to determine the in vitro susceptibility data of CZA and ATM against CRE, Drug resistant P. aeruginosa at Chris Hani Baragwaneth Academic Hospital (CHBAH). Secondarily, we aimed to investigate the invitro synergism of combined CZA and ATM to the CRE and P. aeruginosa isolates that were both CZA and ATM resistant. Methods: This was a prospective laboratory-based study conducted at the National Health Laboratory Services (NHLS), Department of Microbiology, CHBAH. We tested 101 CRE isolates and 32 drug-resistant P. aeruginosa isolates, including multidrug-resistant (MDR) and extremely drug resistant (XDR) strains, against CZA and ATM. Those that were resistant to both CZA and ATM were then tested for synergy using the combination of CZA and ATM. Results: Majority of the CRE isolates were Klebsiella species (84%) with OXA-48 & its variants being the predominant carbapenemase gene detected (67%). The P. aeruginosa isolates were predominantly carbapenem-resistant (88%), with 53% harbouring metallo-β- lactamases (VIM and NDM), and 78% classified as XDR. The overall CZA in vitro susceptibility amongst the serine active (OXA-48 positive) CRE in the study was 100%. The ATM susceptibility was 6% for all the CRE isolates tested. Synergism was seen in 96% of the CRE isolates that were resistant to both CZA and ATM. The activity of CZA and ATM against P. aeruginosa was 34% and 44% respective. Furthermore, the synergistic effect of combined CZA and ATM was seen in only 64 % of the P. aeruginosa isolates qualifying for testing. Conclusion: Local evaluation of CZA and CZA-ATM synergy is important in this era of antimicrobial resistance where there is great need of new treatment options. The high number v of CZA susceptible organisms amongst the OXA-48 isolates is encouraging. Synergistic activity of CZA and ATM presents as a good alternative for the MBL producers. More rigorous studies are needed to determine the clinical impact of usage of these antimicrobials.