Therapeutic Options for CRAB

Summary

CRAB infections in ICUs are on the rise, leading to higher morbidity, mortality, and healthcare costs due to resistance to most antibiotics, including carbapenems. The main resistance mechanisms include carbapenemases, efflux pumps, and changes in the bacterial cell wall. Current treatments include polymyxins (Colistin, Polymyxin B), which are effective but can lead to resistance, aminoglycosides (Amikacin, Gentamicin), which are limited by resistance, and tetracyclines (Tigecycline, Eravacycline), which are effective against CRAB. Fosfomycin is effective in combination treatments, and combination therapy (e.g., colistin with sulbactam, fosfomycin, or eravacycline) can enhance outcomes. Previous research shows promise for combination therapies, improving treatment efficacy and reducing mortality. New regimens are being studied to find optimal combinations. Individualized dosing is crucial, considering patient-specific factors like age, weight, and renal function. Adjustments depend on the infection site and comorbidities. Strict infection control and antimicrobial stewardship programs (ASPs) are essential. ASPs focus on optimizing antibiotic use and reducing resistance through education and surveillance. Future directions include continued research for new drugs or combinations and strategies to overcome resistance and improve treatment efficacy. Study goals include achieving negative samples after 10 days of therapy, 30-day survival, discharge rates, reduced SOFA scores, and improved clinical and radiological findings. A randomized study will compare colistin combined with fosfomycin, ampicillin/sulbactam, and eravacycline. In summary, treating CRAB infections is complex, requiring combination therapy, individualized dosing, and strict infection control measures.

Timeline

Start

2025-01-30

Primary completion

2026-12

Completion

2027-02

Publications

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• Background Dalfino L, Stufano M, Bavaro DF, Diella L, Belati A, Stolfa S, Romanelli F, Ronga L, Di Mussi R, Murgolo F, Loconsole D, Chironna M, Mosca A, Montagna MT, Saracino A, Grasso S. Effectiveness of First-Line Therapy with Old and Novel Antibiotics in Ventilator-Associated Pneumonia Caused by Carbapenem-Resistant Acinetobacter baumannii: A Real Life, Prospective, Observational, Single-Center Study. Antibiotics (Basel). 2023 Jun 14;12(6):1048. doi: 10.3390/antibiotics12061048.
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• Background Rodrigues RD, Garcia RCL, Bittencourt GA, Waichel VB, Garcia ECL, Rigatto MH. Antimicrobial Therapy Duration for Bloodstream Infections Caused by Pseudomonas aeruginosa or Acinetobacter baumannii-calcoaceticus complex: A Retrospective Cohort Study. Antibiotics (Basel). 2023 Mar 8;12(3):538. doi: 10.3390/antibiotics12030538.
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• Background Nartey YA, Donkor AB, Siaw ADJ, Ekor OE, Jimah BB. Carbapenem-Resistant Acinetobacter baumannii Bloodstream Infection in a Ghanaian Patient with Unilateral Diaphragmatic Eventration and HIV Type 1 Infection. Case Rep Infect Dis. 2023 Oct 12;2023:9930291. doi: 10.1155/2023/9930291. eCollection 2023.
• Background Kim SH, Wi YM, Peck KR. Clinical Effectiveness of Tetracycline-Class Agents Based Regimens in Patients With Carbapenem-Resistant Acinetobacter baumannii Bacteremia: A Single-Center Retrospective Cohort Study. J Korean Med Sci. 2023 Aug 28;38(34):e263. doi: 10.3346/jkms.2023.38.e263.
• Background Jung SY, Lee SH, Lee SY, Yang S, Noh H, Chung EK, Lee JI. Antimicrobials for the treatment of drug-resistant Acinetobacter baumannii pneumonia in critically ill patients: a systemic review and Bayesian network meta-analysis. Crit Care. 2017 Dec 20;21(1):319. doi: 10.1186/s13054-017-1916-6.
• Background Pogue JM, Zhou Y, Kanakamedala H, Cai B. Burden of illness in carbapenem-resistant Acinetobacter baumannii infections in US hospitals between 2014 and 2019. BMC Infect Dis. 2022 Jan 6;22(1):36. doi: 10.1186/s12879-021-07024-4.
• Background Seok H, Choi WS, Lee S, Moon C, Park DW, Song JY, Cheong HJ, Kim J, Kim JY, Park MN, Kim YR, Lee HJ, Kim B, Pai H, Jo YM, Kim JH, Sohn JW. What is the optimal antibiotic treatment strategy for carbapenem-resistant Acinetobacter baumannii (CRAB)? A multicentre study in Korea. J Glob Antimicrob Resist. 2021 Mar;24:429-439. doi: 10.1016/j.jgar.2021.01.018. Epub 2021 Feb 8.
• Background Gatti M, Viaggi B, Rossolini GM, Pea F, Viale P. An Evidence-Based Multidisciplinary Approach Focused on Creating Algorithms for Targeted Therapy of Infection-Related Ventilator-Associated Complications (IVACs) Caused by Pseudomonas aeruginosa and Acinetobacter baumannii in Critically Ill Adult Patients. Antibiotics (Basel). 2021 Dec 28;11(1):33. doi: 10.3390/antibiotics11010033.
• Background Ozger HS, Cuhadar T, Yildiz SS, Demirbas Gulmez Z, Dizbay M, Guzel Tunccan O, Kalkanci A, Simsek H, Unaldi O. In vitro activity of eravacycline in combination with colistin against carbapenem-resistant A. baumannii isolates. J Antibiot (Tokyo). 2019 Aug;72(8):600-604. doi: 10.1038/s41429-019-0188-6. Epub 2019 Apr 26.
• Background Abdallah M, Olafisoye O, Cortes C, Urban C, Landman D, Quale J. Activity of eravacycline against Enterobacteriaceae and Acinetobacter baumannii, including multidrug-resistant isolates, from New York City. Antimicrob Agents Chemother. 2015 Mar;59(3):1802-5. doi: 10.1128/AAC.04809-14. Epub 2014 Dec 22.
• Background Monogue ML, Thabit AK, Hamada Y, Nicolau DP. Antibacterial Efficacy of Eravacycline In Vivo against Gram-Positive and Gram-Negative Organisms. Antimicrob Agents Chemother. 2016 Jul 22;60(8):5001-5. doi: 10.1128/AAC.00366-16. Print 2016 Aug.
• Background Zhanel GG, Baxter MR, Adam HJ, Sutcliffe J, Karlowsky JA. In vitro activity of eravacycline against 2213 Gram-negative and 2424 Gram-positive bacterial pathogens isolated in Canadian hospital laboratories: CANWARD surveillance study 2014-2015. Diagn Microbiol Infect Dis. 2018 May;91(1):55-62. doi: 10.1016/j.diagmicrobio.2017.12.013. Epub 2017 Dec 22.
• Background Ni W, Shao X, Di X, Cui J, Wang R, Liu Y. In vitro synergy of polymyxins with other antibiotics for Acinetobacter baumannii: a systematic review and meta-analysis. Int J Antimicrob Agents. 2015 Jan;45(1):8-18. doi: 10.1016/j.ijantimicag.2014.10.002. Epub 2014 Oct 24.
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• Background Assimakopoulos SF, Karamouzos V, Eleftheriotis G, Lagadinou M, Bartzavali C, Kolonitsiou F, Paliogianni F, Fligou F, Marangos M. Efficacy of Fosfomycin-Containing Regimens for Treatment of Bacteremia Due to Pan-Drug Resistant Acinetobacter baumannii in Critically Ill Patients: A Case Series Study. Pathogens. 2023 Feb 9;12(2):286. doi: 10.3390/pathogens12020286.
• Background Nwabor OF, Terbtothakun P, Voravuthikunchai SP, Chusri S. Evaluation of the Synergistic Antibacterial Effects of Fosfomycin in Combination with Selected Antibiotics against Carbapenem-Resistant Acinetobacter baumannii. Pharmaceuticals (Basel). 2021 Feb 25;14(3):185. doi: 10.3390/ph14030185.
• Background Mohd Sazlly Lim S, Heffernan A, Naicker S, Wallis S, Roberts JA, Sime FB. Evaluation of Fosfomycin-Sulbactam Combination Therapy against Carbapenem-Resistant Acinetobacter baumannii Isolates in a Hollow-Fibre Infection Model. Antibiotics (Basel). 2022 Nov 9;11(11):1578. doi: 10.3390/antibiotics11111578.
• Background Warrier AR, Sneha R, Wilson A, Prakash S. 654. Clinical efficacy and safety of high dose Ampicillin sulbactam among patients with CRAB infections: A case series. Open Forum Infect Dis [Internet]. 2022 Dec 15 [cited 2024 Apr 30];9(Supplement_2). Available from: https://dx.doi.org/10.1093/ofid/ofac492.706
• Background Saelim W, Changpradub D, Thunyaharn S, Juntanawiwat P, Nulsopapon P, Santimaleeworagun W. Colistin plus Sulbactam or Fosfomycin against Carbapenem-Resistant Acinetobacter baumannii: Improved Efficacy or Decreased Risk of Nephrotoxicity? Infect Chemother. 2021 Mar;53(1):128-140. doi: 10.3947/ic.2021.0007.
• Background Cunha BA. Optimal therapy for multidrug-resistant Acinetobacter baumannii. Emerg Infect Dis. 2010 Jan;16(1):170; author reply 170-1. doi: 10.3201/eid1601.091467. No abstract available.
• Background Bartal C, Rolston KVI, Nesher L. Carbapenem-resistant Acinetobacter baumannii: Colonization, Infection and Current Treatment Options. Infect Dis Ther. 2022 Apr;11(2):683-694. doi: 10.1007/s40121-022-00597-w. Epub 2022 Feb 17.

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