Antibacterial Activity of Ceftazidime-avibactam against carbapenem-resistant non-fermenters Gram-negative bacteria: a cross-sectional study from a tertiary care hospital

Abstract

Introduction

Ceftazidime-avibactam (CAZ-AVI) is an innovative combination of the non-ß-lactam ß-lactamase inhibitor avibactam and the extended-spectrum ceftazidime. This combination is effective in treating infections resulted frommultidrug resistant (MDR) Gram-negative bacteria. Therefore, the present study was done to determine the efficacy of CAZ-AVI in carbapenem-resistant against non-fermenters Gram-negative bacteria.

Materials and Methods

The present study was done at a tertiary care hospital in Lahore, Pakistan over the period of 2 years. Different clinical samples were processed according to standard microbiological techniques. Confirmation of bacterial isolates was done by different biochemical tests. Antimicrobial sensitivity testing was done onVitek 2® automated system. CAZ-AVI sensitivity testing was performed for carbapenem-resistant isolates on Meuller Hamilton (MH) agar according to Clinical and Laboratory Standard institute (CLSI) guidelines.

Results

CAZ-AVI was 100% sensitive in carbapenem sensitive isolates. Among non-fermenters, highest resistance against CAZ-AVI was found in Acinetobacterspp. (90.8%) while 75% resistance was observed in P. aeruginosa isolates. Maximum number of isolates were collected from wound (35%) followed by pus (16.8%).

Discussion

In our study, 66.7% resistance was observed against CAZ-AVI among the isolates of carbapenem resistant P. aeruginosa while only 33.3% isolates were found to be susceptible. Similar to our results, reduced susceptibility rate of P. aeruginosa was also reported from several other countries. Lowest susceptibility rates were observed in Romania which was22.2%, 23.1% in Latvia/Lituania and 39.4% susceptibility rate was reported from Ukraine[19]. These results were in accordance with our findings. Contradiction to our results, a study conducted in 2018, reported only 2.9% resistance against CAZ-AVI among P. aeruginosa isolates but the isolates were carbapenem sensitive[20].However, several other studies reported higher resistance rates of 50.9% and 48.2% especially when the isolates were extensively drug resistant or resistant to carbapenems respectively[21]. Moreover, it was also found that MBL-positive isolates also showed >95% resistance rate against ceftazidime-avibactam[22, 23].

Our study reported 74.7% resistance in A. baumanii against CAZ-AVI, consistent to our results, a study conducted by Sader et al in 2015 reported 68.8% resistance of CAZ-AVI in Acinetobacter isolates. Higher resistance was observed in isolates collected from intensive care units (ICUs) which was 73.6%[24].Moreover, MDR and blaOXA-51 gene carrying isolates were found to be completely resistant against CAZ- AVI[25]. Another study conducted on cancer patients reported 57.1% resistance of Acinetobacter spp. against CAZ-AVI. Likewise, several other antimicrobial agents were found to be of moderate to poor efficacy against Acinetobacter spp[26].

Conclusion

CAZ-AVI was considered a good option for the treatment of infections caused by XDR and MDR Gram negative rods. However, its effectiveness against non-fermenters is less as compared to othermembers of Gram-negative bacteria. Moreover, the increasing resistance rate against CAZ-AVI associated with CR needs to be noted.