Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

In vitro analysis of synergistic combination of polymyxin B with 12 other antibiotics against MDR Acinetobacter baumannii isolated from a Chinese tertiary hospital

The Journal of Antibiotics volume 76, pages 20–26 (2023)Cite this article

Subjects

Abstract

In clinical practice, polymyxins are suggested to be used in combination with other antibiotics for improving their antibacterial efficacy and preventing the emergency of antibiotic-resistant strains. However, even though synergistic combination of polymyxin B with many antibiotics have been confirmed in various studies with different bacterial species and analyzing methods, which antibiotic is the best option for combination therapy of polymyxin B against MDR A. baumannii remains uncertain. In this study, we systematically analyzed the synergistic combination of polymyxin B with 12 other antibiotics against MDR A. baumannii isolated from a Chinese tertiary hospital using the checkerboard assay. The results suggest that, for polymyxin B-based combination therapy against MDR A. baumannii as characterized in this hospital, cefperazone-sulbactam may be the best partner, since it has the highest synergistic rate and the best synergistic effect with polymyxin B. Minocycline, imipenem, meropenem, ceftazidime, cefepime, amikacin and sulfamethoxazole also have some synergistic effects with polymyxin B, but piperacillin-tazobactam, ciprofloxacin, levofloxacin and tobramycin show no synergism. None of these 12 antibiotics has an antagonistic effect when combined with polymyxin B.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

References

  1. Xie R, Zhang XD, Zhao Q, Peng B, Zheng J. Analysis of global prevalence of antibiotic resistance in Acinetobacter baumannii infections disclosed a faster increase in OECD countries. Emerg Microbes Infect. 2018;7:31.

    Article  Google Scholar 

  2. Zhang X, Gu B, Mei Y, Wen Y, Xia W. Increasing resistance rate to carbapenem among blood culture isolates of Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa in a university-affiliated hospital in China, 2004-2011. J Antibiot. 2015;68:115–20.

    Article  CAS  Google Scholar 

  3. Vázquez-López R, Solano-Gálvez SG, Juárez Vignon-Whaley JJ, Abello Vaamonde JA, Padró Alonzo LA, Rivera Reséndiz A, et al. Acinetobacter baumannii resistance: a real challenge for clinicians. Antibiotics. 2020;9:205

    Article  Google Scholar 

  4. Ibrahim S, Al-Saryi N, Al-Kadmy IMS, Aziz SN. Multidrug-resistant Acinetobacter baumannii as an emerging concern in hospitals. Mol Biol Rep. 2021;48:6987–98.

    Article  CAS  Google Scholar 

  5. Chang HL, Tang CH, Hsu YM, Wan L, Chang YF, Lin CT, et al. Nosocomial outbreak of infection with multidrug-resistant Acinetobacter baumannii in a medical center in Taiwan. Infect Control Hosp Epidemiol. 2009;30:34–8.

    Article  Google Scholar 

  6. Mosqueda N, Espinal P, Cosgaya C, Viota S, Plasensia V, Alvarez-Lerma F, Montero M, Gómez J, Horcajada JP, Vila J, Roca I. Globally expanding carbapenemase finally appears in Spain: nosocomial outbreak of Acinetobacter baumannii producing plasmid-encoded OXA-23 in Barcelona, Spain. Antimicrob Agents Chemother. 2013;57:5155–7.

    Article  CAS  Google Scholar 

  7. Satlin MJ, Lewis JS,II, Weinstein MP, Patel J, Humphries RM, Kahlmeter G, et al. Clinical and Laboratory Standards Institute and European Committee on antimicrobial susceptibility testing position statements on polymyxin B and colistin clinical breakpoints. Clin Infect Dis. 2020;71:e523–e529.

    CAS  Google Scholar 

  8. Garonzik SM, Li J, Thamlikitkul V, Paterson DL, Shoham S, Jacob J, et al. Population pharmacokinetics of colistin methanesulfonate and formed colistin in critically ill patients from a multicenter study provide dosing suggestions for various categories of patients. Antimicrob Agents Chemother. 2011;55:3284–94.

    Article  CAS  Google Scholar 

  9. Sandri AM, Landersdorfer CB, Jacob J, Boniatti MM, Dalarosa MG, Falci DR, et al. Population pharmacokinetics of intravenous polymyxin B in critically ill patients: implications for selection of dosage regimens. Clin Infect Dis. 2013;57:524–31.

    Article  CAS  Google Scholar 

  10. Manchandani P, Zhou J, Babic JT, Ledesma KR, Truong LD, Tam VH. Role of renal drug exposure in polymyxin B-induced nephrotoxicity. Antimicrob Agents Chemother. 2017;61:e02391–16.

    Article  CAS  Google Scholar 

  11. Tsuji BT, Pogue JM, Zavascki AP, Paul M, Daikos GL, Forrest A, et al. International Consensus Guidelines for the Optimal Use of the Polymyxins: Endorsed by the American College of Clinical Pharmacy (ACCP), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of America (IDSA), International Society for Anti-infective Pharmacology (ISAP), Society of Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP). Pharmacotherapy. 2019;39:10–39.

    Article  Google Scholar 

  12. Sobieszczyk ME, Furuya EY, Hay CM, Pancholi P, Della-Latta P., Hammer SM, et al. Combination therapy with polymyxin B for the treatment of multidrug-resistant Gram-negative respiratory tract infections. J Antimicrob Chemother. 2004;54:566–9.

    Article  CAS  Google Scholar 

  13. Liu L, Yu J, Shen X, Cao X, Zhan Q, Guo Y, Yu F. Resveratrol enhances the antimicrobial effect of polymyxin B on Klebsiella pneumoniae and Escherichia coli isolates with polymyxin B resistance. BMC Microbiol. 2020;20:306.

    Article  Google Scholar 

  14. Drlica K, Zhao X. Mutant selection window hypothesis updated. Clin Infect Dis. 2007;44:681–8.

    Article  Google Scholar 

  15. Urban C, Mariano N, Rahal JJ. In vitro double and triple bactericidal activities of doripenem, polymyxin B, and rifampin against multidrug-resistant Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli. Antimicrob Agents Chemother. 2010;54:2732–4.

    Article  CAS  Google Scholar 

  16. Rao GG, Ly NS, Diep J, Forrest A, Bulitta JB, Holden PN, et al. Combinatorial pharmacodynamics of polymyxin B and tigecycline against heteroresistant Acinetobacter baumannii. Int J Antimicrob Agents. 2016:331–6.

  17. Jiang M, Zhang Z, Zhao S. Epidemiological characteristics and drug resistance analysis of multidrug-resistant Acinetobacter baumannii in a China hospital at a certain time. Pol J Microbiol. 2014;63:275–81.

    Article  Google Scholar 

  18. Jiang AM, Shi X, Liu N, Gao H, Ren MD, Zheng XQ, et al. Nosocomial infections due to multidrug-resistant bacteria in cancer patients: a six-year retrospective study of an oncology Center in Western China. BMC Infect Dis. 2020;20:452

    Article  CAS  Google Scholar 

  19. Yoon J, Urban C, Terzian C, Mariano N, Rahal JJ. In vitro double and triple synergistic activities of Polymyxin B, imipenem, and rifampin against multidrug-resistant Acinetobacter baumannii. Antimicrob Agents Chemother. 2004;48:753–7.

    Article  CAS  Google Scholar 

  20. Ozseven AG, Cetin ES, Aridogan BC, Ozseven L. In vitro synergistic activity of carbapenems in combination with other antimicrobial agents against multidrug-resistant Acinetobacter baumannii. Afr J Microbiol Res. 2012;6:2985–92.

    CAS  Google Scholar 

  21. Guelfi KC, Tognim MC, Cardoso CL, Gales AC, Carrara-Marrone FE, Garcia LB. In vitro evaluation of the antimicrobial activity of meropenem in combination with polymyxin B and gatifloxacin against Pseudomonas aeruginosa and Acinetobacter baumannii. J Chemother. 2008;20:180–5.

    Article  CAS  Google Scholar 

  22. Zhang Y, Chen F, Sun E, Ma R, Qu C, Ma L. In vitro antibacterial activity of combinations of fosfomycin, minocycline and polymyxin B on pan-drug-resistant Acinetobacter baumannii. Exp Ther Med. 2013;5:1737–9.

    Article  CAS  Google Scholar 

  23. Netto B, Vieira BJ, Hermes DM, Ribeiro VB, Zavascki AP. In vitro activity of non-bactericidal concentrations of polymyxin B in combination with other antimicrobials against OXA-23-producing carbapenem-resistant Acinetobacter baumannii. Braz J Infect Dis. 2013;17:502–4.

    Article  Google Scholar 

  24. Fu Y, Zhou J, Zhou H, Yang Q, Wei Z, Yu Y, et al. Wide dissemination of OXA-23-producing carbapenem-resistant Acinetobacter baumannii clonal complex 22 in multiple cities of China. J Antimicrob Chemother. 2010;65:644–50.

    Article  CAS  Google Scholar 

  25. Gozalan A, Unaldı O, Guldemir D, Aydogan S, Kuzucu C, Cakirlar FK, et al. Molecular characterization of carbapenem-resistant Acinetobacter baumannii blood culture isolates from three hospitals in Turkey. Jpn J Infect Dis. 2021;74:200–8.

    Article  CAS  Google Scholar 

  26. Cho HH, Kwon KC, Sung JY, Koo SH. Spread and genetic characterization of ST137 and ST138 multidrug-resistant Acinetobacter baumannii isolated from a tertiary hospital in Korea. Ann Clin Lab Sci. 2013;43:145–50.

    CAS  Google Scholar 

  27. Azevedo FKSF, Dutra V, Nakazato L, Mello CM, Pepato MA, de Sousa ATHI, et al. Molecular epidemiology of multidrug-resistant Acinetobacter baumannii infection in two hospitals in Central Brazil: the role of ST730 and ST162 in clinical outcomes. J Med Microbiol. 2019;68:31–40.

    Article  Google Scholar 

  28. Cetin ES, Tekeli A, Ozseven AG, Us E, Aridogan BC. Determination of in vitro activities of polymyxin B and rifampin in combination with ampicillin/sulbactam or cefoperazone/sulbactam against multidrug-resistant Acinetobacter baumannii by the E-test and checkerboard methods. Jpn J Infect Dis. 2013;66:463–8.

    Article  Google Scholar 

  29. Meliani S, Toumi S, Djahoudi H, Deghdegh K, Amoura K, Djahoudi A. Synergistic combination of colistin with imipenem, amikacineor ciprofloxacin against Acinetobacter baumannii and Pseudomonas aeruginosa carbapenem-resistant isolated in Annaba hospital Algeria. Biocell. 2020;44:175–82.

    Article  CAS  Google Scholar 

  30. 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;45:8–18.

    Article  CAS  Google Scholar 

  31. Ruan Z, Chen Y, Jiang Y, Zhou H, Zhou Z, Fu Y, Wang H, Wang Y, Yu Y. Wide distribution of CC92 carbapenem-resistant and OXA-23-producing Acinetobacter baumannii in multiple provinces of China. Int J Antimicrob Agents. 2013;42:322–8.

    Article  CAS  Google Scholar 

  32. Kumar S, Patil PP, Singhal L, Ray P, Patil PB, Gautam V. Molecular epidemiology of carbapenem-resistant Acinetobacter baumannii isolates reveals the emergence of blaOXA-23 and blaNDM-1 encoding international clones in India. Infect Genet Evol. 2019;75:103986.

    Article  CAS  Google Scholar 

  33. Mayanskiy N, Chebotar I, Alyabieva N, Kryzhanovskaya O, Savinova T, Turenok A, et al. Emergence of the Uncommon Clone ST944/ST78 Carrying blaOXA-40-like and blaCTX-M-like Genes Among Carbapenem-Nonsusceptible Acinetobacter baumannii in Moscow, Russia. Micro Drug Resist. 2017;23:864–70.

    Article  CAS  Google Scholar 

  34. McKay SL, Vlachos N, Daniels JB, Albrecht VS, Stevens VA, Rasheed JK, et al. Molecular epidemiology of carbapenem-resistant Acinetobacter baumannii in the United States, 2013-2017. Micro Drug Resist. 2022;28:645–53.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors are grateful to the Shiyan Renmin Hospital of Hubei University of Medicine and the Jinzhou Medical University.

Funding

This work was supported by the Science Foundation of Hubei Health Commission in Hubei province (Grant No: WJ2021F040).

Author information

Author notes

  1. These authors contributed equally: Hui Liu, Dan Hu

Authors and Affiliations

  1. Department of Clinical Laboratory, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, PR China

    Hui Liu, Dan Hu, Dongxin Wang, Han Wu, Yunjun Pan, Xin Chen, Lin Qi, Lian Li & Rongxin Liang

  2. Department of Clinical Laboratory, Jinzhou Medical University Graduate Training Base, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, PR China

    Lin Qi & Lian Li

Authors
  1. Hui Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dan Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dongxin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Han Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yunjun Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xin Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lin Qi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Lian Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Rongxin Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

HL, DH, LL and RX designed the study. HL and DH were in charge of this study and performed the majority of those experiments. RX drafted the manuscript and revised it critically for important intellectual content. DX, HW, YJ, XC and LQ participated in the collection and identification of MDR A.baumannii isolates.

Corresponding author

Correspondence to Rongxin Liang.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Liu, H., Hu, D., Wang, D. et al. In vitro analysis of synergistic combination of polymyxin B with 12 other antibiotics against MDR Acinetobacter baumannii isolated from a Chinese tertiary hospital. J Antibiot 76, 20–26 (2023). https://doi.org/10.1038/s41429-022-00573-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41429-022-00573-z

Search

Advanced search

Quick links