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Enhanced bacterial killing with a combination of sulbactam/minocycline against dual carbapenemase-producing Acinetobacter baumannii

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Abstract

Carbapenem-resistant Acinetobacter baumannii (CRAB) is often difficult to treat. Considering the current circumstances, there is an unquestionable need for new therapeutic options to treat CRAB infections. In the present study, the synergistic activity of sulbactam-based combination was determined against genetically characterized CRAB isolates. Non-duplicate CRAB isolates (n = 150) recovered from blood culture and endotracheal aspirates were included in this study. The minimum inhibitory concentrations (MICs) of tetracyclines (minocycline, tigecycline, eravacycline) and their comparators (meropenem, sulbactam, cefoperazone/sulbactam, ceftazidime/avibactam, and colistin) were determined using the microbroth dilution method. Six isolates were tested for the synergistic activity of various sulbactam-based combinations using time-kill experiments. Tigecycline and minocycline showed a wide spread of MICs with most isolates in the range of 1 to 16 mg/L. The MIC90 of eravacycline (0.5 mg/L) was four dilutions lower than that of tigecycline (8 mg/L). Minocycline with sulbactam was the most active dual combination against OXA-23 like (n = 2) and NDM with OXA-23 like producers (n = 1), which resulted in ≥ 2 log10 kill. The combination of ceftazidime-avibactam with sulbactam showed ≥ 3 log10 kill against all the three tested OXA-23 like producing CRAB isolates, but showed no activity against dual carbapenemase producers. Sulbactam with meropenem showed ≥ 2 log10 kill against one OXA-23 like producing CRAB isolate. The findings suggest that sulbactam-based combination may confer therapeutic benefits against CRAB infections.

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The research data associated with a paper is available in the manuscript or will be available on request to the corresponding author.

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Acknowledgements

All authors would like to thank the Indian Council of Medical Research (No.3/2/Dec-2020/PG-Thesis-HRD) for funding this study. The authors would also like to thank the Institutional Review Board (IRB Min No: 13584, dated 25.11.2020) Christian Medical College, Vellore, and the Tamil Nadu Dr. M.G.R. Medical University, Chennai.

Funding

The study is funded by the Indian Council of Medical Research (No.3/2/Dec-2020/PG-Thesis-HRD).

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Authors and Affiliations

  1. Department of Clinical Microbiology, Christian Medical College, Vellore, 632004, India

    Suriya Chandran, Yuvasri Manokaran, Saranya Vijayakumar, Baby Abirami Shankar, Yamuna Devi Bakthavatchalam, Binesh Lal Yesudason & Balaji Veeraraghavan

  2. Department of Orthopedics, Christian Medical College, Vellore, India

    Hariharan Triplicane Dwarakanathan

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  1. Suriya Chandran
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  2. Yuvasri Manokaran
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  8. Balaji Veeraraghavan
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Contributions

All the authors contributed to the study conception and design. Material preparation and data collection and analysis were performed by Suriya Chandran, Yuvasri Manokaran, Saranya Vijayakumar, Baby Abirami Shankar, and Yamuna Devi Bakthavatchalam. The first draft of the manuscript was written by Suriya Chandran and all the authors commented on previous versions of the manuscript. All the authors read and approved the final manuscript.

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Correspondence to Balaji Veeraraghavan.

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Chandran, S., Manokaran, Y., Vijayakumar, S. et al. Enhanced bacterial killing with a combination of sulbactam/minocycline against dual carbapenemase-producing Acinetobacter baumannii. Eur J Clin Microbiol Infect Dis 42, 645–651 (2023). https://doi.org/10.1007/s10096-023-04583-z

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