Role of Ceftazidime-Avibactam in Urinary Tract Infections Caused by Carbapenem-Resistant Enterobacterales

Introduction Urinary tract infections (UTIs) are one of the most common bacterial infections encountered in community and healthcare settings. Increasing antimicrobial resistance patterns worldwide have limited the treatment options available. Overuse of carbapenems which were considered as the last resort for multi-drug resistant UTIs over the past decade has led to the emergence of carbapenem-resistant Enterobacterales (CRE). Ceftazidime-avibactam is a novel beta-lactam inhibitor combination drug indicated for the treatment of complicated UTIs caused by CRE. Materials and methods This was a prospective, observational study conducted in the Department of Microbiology at Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow from January 1, 2022, to June 30, 2022. A total of 1716 urine samples were processed for identification and antimicrobial susceptibility testing. This research was approved by the Institutional Ethics Committee (IEC) of Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India, under IEC number 140/20. Isolates belonging to Enterobacterales and showing resistance to carbapenems were selected for further processing. Epidemiological details and the antimicrobial susceptibility profile of all patients with CRE uropathogens were compared. These isolates were then tested for susceptibility to ceftazidime-avibactam (30/20 μg) disc using the Kirby-Bauer disc diffusion method. A subset (n= 20) of CRE isolates were chosen for gene detection using multiplex polymerase chain reaction followed by synergy testing using ceftazidime-avibactam and aztreonam gradient strip-based susceptibility testing. Results In the 1716 samples processed, only 28.1% samples had significant growth out of which 15.3% isolates belonged to Enterobacterales and showed in-vitro resistance to imipenem/meropenem. CRE were approximately two times more common in men as compared to women in the age group of 41-60 years (31.1%). The majority were inpatient samples (72%). The antimicrobial susceptibility profile of the CRE uropathogens showed maximum susceptibility to fosfomycin (66.7%), nitrofurantoin (30.7%), and aminoglycosides (13.5%) and maximum resistance to norfloxacin (100%), cefazolin (98.7%), and netilmicin (98.7%). Ceftazidime-avibactam had an in vitro resistance of 91.9%. The most common gene detected was NDM followed by KPC. The isolates that were resistant to ceftazidime-avibactam and positive for NDM gene (n=20) on being tested for phenotypic synergy using ceftazidime-avibactam and aztreonam E strips showed 100% susceptibility. Conclusion Carbapenem-resistant gram-negative pathogens have become a major healthcare burden. They limit the treatment options available thereby increasing the morbidity and mortality in patients. Carbapenems which were at one time considered as the last line of treatment are deemed ineffective by these superbugs. CRE are among the most dreaded infectious agents. Ceftazidime-avibactam has been suggested as a therapeutic option for the management of CRE but in our study ceftazidime-avibactam alone had a high in-vitro resistance. Nonetheless, the combination of ceftazidime-avibactam and aztreonam showed good in-vitro susceptibility. Synergistic combination of these two antimicrobials can be considered as a treatment option, especially in regions where NDM is prevalent. Research is still limited regarding the clinical efficacy of this combination.