Critical Priority Pathogen Carbapenem Resistant Acinetobacter Baumanii Complex (CRAB): Antibiotic Susceptibility to Salvage Antimicrobial Agents

OBJECTIVES: Carbapenem resistant Acinetobacter baumanii complex (CRAB) continues to be listed as a critical priority pathogen in the World health Organization (WHO) priority pathogen list released in 2024. This list highlights the urgent need for identifying additional antimicrobial agents for CRAB, which is an important nosocomial pathogen in India often associated with device associated infections. According to the data published by the Indian Healthcare Associated Infection (HAI) Network, CRAB is the primary cause of Ventilator associated pneumonia (VAP) (30%) and the second most common cause of Central Line associated Blood Stream Infections (CLABSI) (21%) in India. Resistance to Carbapenems is seen in 77% to 98% of these Acinetobacter baumanii isolates. Mortality associated with CRAB HAI was 57.6% versus non CRAB HAIs (39%), warranting an urgent need for identifying additional options for therapy to better manage these patients. The objective of this study was to determine the drug susceptibility (DST) of CRAB isolates to salvage therapy agents like Polymyxins, Minocycline, Ceftriaxone/Sulbactum/EDTA and Tigecycline, which are currently readily available for use in India. MATERIALS AND METHODS: The study received approval from the Research Advisory Board and Ethics Commiittee of Breach Candy Medical Research Center (BCMRC). CRAB isolated from various clinical specimens over two years (2022 to 2024) were included in this study. The isolates were identified and drug susceptibility testing (DST) was performed on Vitek 2 Compact (Bioemeriuex, Marcy l Etiole, France). Clinical Laboratory Standards Institute (CLSI), USA M100 guidelines were used for interpretation of the DST. All isolates were tested in triplicates. Tier II (CLSI) salvage agents like Colistin, Polymyxin B, Tigecycline and an indigenously developed agent Ceftriaxone/Sulbactum/disodium Ethylenediaminetetraacetic acid (EDTA) called ELORES were tested using the gold standard manual Broth Micro Dilution test (BMD). For Ceftriaxone/Sulbactum/EDTA, the susceptible break point was considered as that for Ceftriaxone (<8 μg/ml) and Sulbactum (< 4 μg/ml). Sulbactum and EDTA concentrations remained constant at 4 μg/ml and 4740 μg/ml respectively. For Tigecycline only MICs were noted, as neither CLSI, nor US FDA nor European Committee for Antimicrobial Susceptibility Testing (EUCAST) have provided breakpoints. RESULTS: 76 CRAB isolates were included in the study. Ceftriaxone/Sulbactum/EDTA showed 100% susceptibility, Polymyxins 97.3%, and Minocycline 22%. 77.4% of CRAB isolates had Tigecycline MICs below 2 mg/L. The MIC distribution for Ceftriaxone/Sulbactum/EDTA was as follows: 0.06 mg/L (18.5%),0.12 mg/L (10.5%),0.25 mg/L (36.8%), 0.5 mg/L (10.5%),1 mg/L (5.3%), 2 mg/L (2.6%) and 4 mg/L (15.8%). In 50% of the CRAB isolates Polymyxin B had one dilution MIC lower than Colistin. CONCLUSION: The results of this study indicate that Polymyxins, Ceftriaxone/Sulbactum/EDTA and Tigecycline may be options for multidrug salvage therapy in serious infections caused by CRAB, a critical priority pathogen.