Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine · 2026
Indian Society of Critical Care Medicine Guidelines on Evidence-based Recommendations for the Treatment of Carbapenem-resistant Enterobacterales, Carbapenem-resistant Acinetobacter baumannii, and Carbapenem-resistant Pseudomonas aeruginosa in Critically Ill Patients: A GRADE-guided Approach.
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Todi Subhash K, Jagiasi Bharat G, Juneja Deven, Gopaldas Justin A, Soni Kapil D, Karanth Sunil, Singh Ritu, Kharbanda Mohit, Bhardwaj Ashutosh, Sahoo Tapas K, Bhosale Shilpushp, Sinha Sharmili, Bharti Manish, Clerk Anuj M, Kumar Amit, Rochwerg Bram, Singh Vinod K, Bhattacharya Pradip K
Аннотация
BACKGROUND: Carbapenem-resistant Enterobacterales (CRE), Acinetobacter baumannii (CRAB), and Pseudomonas aeruginosa (CRPA) are major antimicrobial resistance (AMR) threats in Indian intensive care units, with mortality rates often exceeding 40-70%. Despite the clinical burden, there is a lack of standardized treatment guidelines. This study aimed to develop Grading of Recommendations Assessment, Development and Evaluation (GRADE)-based recommendations for managing carbapenem-resistant gram-negative (CRGN) infections in critically ill patients.
METHODOLOGY: A systematic review was conducted following the GRADE framework. PubMed was searched through October 2024 for studies comparing polymyxin B/colistin with alternative regimens for CRE, CRAB, and CRPA, and sulbactam-based therapy vs comparators for CRAB. Meta-analyses were performed using RevMan. Evidence of certainty was graded, and recommendations were formulated through structured expert consensus. Outcomes included clinical cure, microbiological eradication, mortality, and adverse events (AEs).
RESULTS: Fifty-two studies were included: 36 evaluating polymyxin/colistin and 16 evaluating sulbactam. For CRE, β-lactam/β-lactamase inhibitor (BL/BLI) combinations achieved higher cure rates (58.7 vs 48.9%), fewer AEs (10.3 vs 13.3%), and trends toward reduced mortality compared with polymyxin-based regimens, leading to a strong recommendation for non-polymyxin therapy (very low certainty). For CRAB, sulbactam-based regimens, particularly sulbactam-durlobactam, showed superior cure rates (61.9 vs 39.7%) and reduced nephrotoxicity (13 vs 38%), supporting a strong recommendation (very low certainty). For CRPA, efficacy appeared comparable, but polymyxin therapy caused higher toxicity (42.1 vs 17.9%), resulting in a weak recommendation for non-polymyxin options (very low certainty).
CONCLUSION: These findings provide GRADE-based treatment recommendations for carbapenem-resistant infections in Indian ICUs. Non-polymyxin regimens are preferred for CRE and CRPA, while sulbactam-based therapy is favored for CRAB. This shift away from polymyxin use may improve outcomes and reduce toxicity, though robust randomized trials are urgently needed.
METHODOLOGY: A systematic review was conducted following the GRADE framework. PubMed was searched through October 2024 for studies comparing polymyxin B/colistin with alternative regimens for CRE, CRAB, and CRPA, and sulbactam-based therapy vs comparators for CRAB. Meta-analyses were performed using RevMan. Evidence of certainty was graded, and recommendations were formulated through structured expert consensus. Outcomes included clinical cure, microbiological eradication, mortality, and adverse events (AEs).
RESULTS: Fifty-two studies were included: 36 evaluating polymyxin/colistin and 16 evaluating sulbactam. For CRE, β-lactam/β-lactamase inhibitor (BL/BLI) combinations achieved higher cure rates (58.7 vs 48.9%), fewer AEs (10.3 vs 13.3%), and trends toward reduced mortality compared with polymyxin-based regimens, leading to a strong recommendation for non-polymyxin therapy (very low certainty). For CRAB, sulbactam-based regimens, particularly sulbactam-durlobactam, showed superior cure rates (61.9 vs 39.7%) and reduced nephrotoxicity (13 vs 38%), supporting a strong recommendation (very low certainty). For CRPA, efficacy appeared comparable, but polymyxin therapy caused higher toxicity (42.1 vs 17.9%), resulting in a weak recommendation for non-polymyxin options (very low certainty).
CONCLUSION: These findings provide GRADE-based treatment recommendations for carbapenem-resistant infections in Indian ICUs. Non-polymyxin regimens are preferred for CRE and CRPA, while sulbactam-based therapy is favored for CRAB. This shift away from polymyxin use may improve outcomes and reduce toxicity, though robust randomized trials are urgently needed.