Efficiency and safety of 12 antimicrobial drug regimens against multidrug-resistant gram-negative bacterial infections: a network meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

HUANG Benrun ¹ , OUYANG Ronglan ² , ZHENG Lingzhao ³ ,  OUYANG Hua ⁴ , GUO Xiaodan ¹ ,  DAI Li ¹

1. Department of Pharmacy, The 910th Hospital of the Joint Logistics Support Force of the People's Liberation Army of China, Quanzhou 362000, P. R. China;
2. Department of Burn and Plastic Surgery, The 910th Hospital of the Joint Logistics Support Force of the People's Liberation Army of China, Quanzhou 362000, P. R. China;
3. Department of Science and Education, Fujian Medical University-Affiliated Union Hospital, Fuzhou 350001, P. R. China;
4. Department of Pharmacy, Zhongshan Hospital Affiliated to Xiamen University, Xiamen 361004, P. R. China;

Corresponding author：

DAI Li, Email: dailyjia@163.com

Keywords：

Multidrug-resistant gram-negative infections; Carbapenems; Network meta-analysis; Randomised controlled trials; Cohort study

DOI：

10.7507/1672-2531.202405139

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Objective To systematically review the efficacy and safety of 12 antimicrobial drug regimens for the treatment of multidrug-resistant Gram-negative bacterial (MDR-GNB) infections. Methods The PubMed, Cochrane Library, Web of Science, Clinical Trials, CNKI, WanFang Data, and Chinese Medical Journal Full-text Database were electronically searched to collect studies related to objectives form inception to February 2023. Two researchers independently screened the literature, extracted data, and assessed the risk of bias in the included studies. Stata software was then used to perform a network meta-analysis. Results A total of 64 articles were included. The network meta-analysis results indicated that combination regimens based on carbapenems, β-lactam/combination agents, or tigecycline showed higher clinical antibacterial effectiveness and bacterial clearance rates for resistant bacterial infections. Among all regimens, tigecycline + β-lactam/combination agent, polymyxin + β-lactam/combination agent, and triple-therapy regimens exhibited superior antibacterial effects. Moreover, most combination regimens containing carbapenems had lower mortality risks, with carbapenems combined with aminoglycosides, β-lactam/combination agents, or polymyxins ranking high in clinical or bacteriological efficacy. Conclusion Current evidence suggests that combination regimens based on β-lactam/combination agents, carbapenems, and tigecycline may be beneficial for improving the clinical and bacteriological efficacy of treating resistant bacterial infections. Due to the limited quantity and quality of the included studies, more high-quality studies are needed to verify the above conclusion.

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1. WHO. Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics. 2017.
2. Lodise TP, Bassetti M, Ferrer R, et al. All-cause mortality rates in adults with carbapenem-resistant Gram-negative bacterial infections: a comprehensive review of pathogen-focused, prospective, randomized, interventional clinical studies. Expert Rev Anti Infect Ther, 2022, 20(5): 707-719.
3. Bassetti M, Echols R, Matsunaga Y, et al. Efficacy and safety of cefiderocol or best available therapy for the treatment of serious infections caused by carbapenem-resistant Gram-negative bacteria (CREDIBLE-CR): a randomised, open-label, multicentre, pathogen-focused, descriptive, phase 3 trial. Lancet Infect Dis, 2021, 21(2): 226-240.
4. Kengkla K, Kongpakwattana K, Saokaew S, et al. Comparative efficacy and safety of treatment options for MDR and XDR Acinetobacter baumannii infections: a systematic review and network meta-analysis. J Antimicrob Chemother, 2018, 73(1): 22-32.
5. Hutton B, Salanti G, Caldwell DM, et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med, 2015, 162(11): 777-784.
6. Paul M, Daikos GL, Durante-Mangoni E, et al. Colistin alone versus colistin plus meropenem for treatment of severe infections caused by carbapenem-resistant Gram-negative bacteria: an open-label, randomised controlled trial. Lancet Infect Dis, 2018, 18(4): 391-400.
7. Khalili H, Shojaei L, Mohammadi M, et al. Meropenem/colistin versus meropenem/ampicillin-sulbactam in the treatment of carbapenem-resistant pneumonia. J Comp Eff Res, 2018, 7(9): 901-911.
8. Wunderink RG, Matsunaga Y, Ariyasu M, et al. Cefiderocol versus high-dose, extended-infusion meropenem for the treatment of Gram-negative nosocomial pneumonia (APEKS-NP): a randomised, double-blind, phase 3, non-inferiority trial. Lancet Infect Dis, 2021, 21(2): 213-225.
9. Sirijatuphat R, Thamlikitkul V. Preliminary study of colistin versus colistin plus fosfomycin for treatment of carbapenem-resistant Acinetobacter baumannii infections. Antimicrob Agents Chemother, 2014, 58(9): 5598-5601.
10. Durante-Mangoni E, Signoriello G, Andini R, et al. Colistin and rifampicin compared with colistin alone for the treatment of serious infections due to extensively drug-resistant Acinetobacter baumannii: a multicenter, randomized clinical trial. Clin Infect Dis, 2013, 57(3): 349-358.
11. Aydemir H, Akduman D, Piskin N, et al. Colistin vs. the combination of colistin and rifampicin for the treatment of carbapenem-resistant Acinetobacter baumannii ventilator-associated pneumonia. Epidemiol Infect, 2013, 141(6): 1214-1222.
12. Cisneros JM, Rosso-Fernández CM, Roca-Oporto C, et al. Colistin versus meropenem in the empirical treatment of ventilator-associated pneumonia (Magic Bullet study): an investigator-driven, open-label, randomized, noninferiority controlled trial. Crit Care, 2019, 23(1): 383.
13. Amat T, Gutiérrez-Pizarraya A, Machuca I, et al. The combined use of tigecycline with high-dose colistin might not be associated with higher survival in critically ill patients with bacteraemia due to carbapenem-resistant Acinetobacter baumannii. Clin Microbiol Infect, 2018, 24(6): 630-634.
14. Batirel A, Balkan II, Karabay O, et al. Comparison of colistin-carbapenem, colistin-sulbactam, and colistin plus other antibacterial agents for the treatment of extremely drug-resistant Acinetobacter baumannii bloodstream infections. Eur J Clin Microbiol Infect Dis, 2014, 33(8): 1311-1322.
15. Katip W, Uitrakul S, Oberdorfer P. The effectiveness and nephrotoxicity of loading dose colistin combined with or without meropenem for the treatment of carbapenem-resistant A. baumannii. Int J Infect Dis, 2020, 97: 391-395.
16. Falagas ME, Rafailidis PI, Ioannidou E, et al. Colistin therapy for microbiologically documented multidrug-resistant Gram-negative bacterial infections: a retrospective cohort study of 258 patients. Int J Antimicrob Agents, 2010, 35(2): 194-199.
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Latest ArticlesEfficiency and safety of 12 antimicrobial drug regimens against multidrug-resistant gram-negative bacterial infections: a network meta-analysis

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