Abstract
Carbapenem-resistant Acinetobacter baumannii (CRAB) has been a common pathogen of nosocomial infections and severely threatened the public health for decades. Tigecycline is a new type of antibacterial glycylcycline and minocycline derivative and has been used to treat CRAB in clinical practice. However, the synergistic effects of tigecycline in combination with other antibiotics including colistin or amikacin remain unclear. A total of 216 CRAB isolates were collected from multiple body parts of different patients. The gene types of these isolates were analyzed and their resistance to carbapenems was determined by Etest. Broth microdilution method was utilized to evaluate the minimum inhibitory concentration (MIC) of each sample. Checkerboard screening technique was performed to demonstrate the synergistic effects of antibiotics and fractional inhibitory concentration index (FICI) was established. Therefore, the joint treatment of tigecycline and colistin (1:1) could effectively improve the sensitivity of AB to antibiotics. OXA-24-like isolates were more sensitive to the combination of tigecycline and amikacin. On the other hand, OXA-23-like isolates were more sensitive to the combination of tigecycline and colistin. Tigecycline exhibited synergistic effects with amikacin and colistin to inhibit CRAB.
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References
Ahmadi, A., & Salimizand, H. (2017). Delayed identification of Acinetobacter baumannii during an outbreak owing to disrupted blaOXA-51-like by ISAba19. International Journal of Antimicrobial Agents, 50, 119–122.
Alfouzan, W., Dhar, R., Abdo, N. M., Alali, W. Q., & Rabaan, A. A. (2021). Epidemiology and microbiological profile of common healthcare associated infections among patients in the intensive care unit of a general hospital in Kuwait: A retrospective observational study. Journal of Epidemiology and Global Health. https://doi.org/10.2991/jegh.k.210524.001
Antunes, L. C., Visca, P., & Towner, K. J. (2014). Acinetobacter baumannii: Evolution of a global pathogen. Pathogens and Disease, 71, 292–301.
Ayibieke, A., Kobayashi, A., Suzuki, M., Sato, W., Mahazu, S., Prah, I., Mizoguchi, M., Moriya, K., Hayashi, T., Suzuki, T., Iwanaga, S., Ablordey, A., & Saito, R. (2020). Prevalence and characterization of carbapenem-hydrolyzing class D beta-lactamase-producing Acinetobacter isolates from Ghana. Frontiers in Microbiology, 11, 587398.
Baginska, N., Pichlak, A., Gorski, A., & Jonczyk-Matysiak, E. (2019). Specific and selective bacteriophages in the fight against multidrug-resistant Acinetobacter baumannii. Virologica Sinica, 34, 347–357.
Basatian-Tashkan, B., Niakan, M., Khaledi, M., Afkhami, H., Sameni, F., Bakhti, S., & Mirnejad, R. (2020). Antibiotic resistance assessment of Acinetobacter baumannii isolates from Tehran hospitals due to the presence of efflux pumps encoding genes (adeA and adeS genes) by molecular method. BMC Research Notes, 13, 543.
Bender, J. K., Cattoir, V., Hegstad, K., Sadowy, E., Coque, T. M., Westh, H., Hammerum, A. M., Schaffer, K., Burns, K., Murchan, S., Novais, C., Freitas, A. R., Peixe, L., Del Grosso, M., Pantosti, A., & Werner, G. (2018). Update on prevalence and mechanisms of resistance to linezolid, tigecycline and daptomycin in enterococci in Europe: Towards a common nomenclature. Drug Resistance Updates, 40, 25–39.
Bialvaei, A. Z., & Samadi Kafil, H. (2015). Colistin, mechanisms and prevalence of resistance. Current Medical Research and Opinion, 31, 707–721.
Broeker, A., Wicha, S. G., Dorn, C., Kratzer, A., Schleibinger, M., Kees, F., Heininger, A., Kees, M. G., & Haberle, H. (2018). Tigecycline in critically ill patients on continuous renal replacement therapy: A population pharmacokinetic study. Critical Care (London, England), 22, 341.
Cao, Y., Wu, H., Zhai, W., Wang, Y., Li, M., Li, M., Yang, L., Tian, Y., Song, Y., Li, J., Wang, Y., Ding, Q., Zhang, L., Cai, M., & Chang, Z. (2020). A safety consideration of mesenchymal stem cell therapy on COVID-19. Stem Cell Research, 49, 102066.
Chen, Y., Yang, Y., Liu, L., Qiu, G., Han, X., Tian, S., Zhao, J., Chen, F., Grundmann, H., Li, H., Sun, J., & Han, L. (2018). High prevalence and clonal dissemination of OXA-72-producing Acinetobacter baumannii in a Chinese hospital: A cross sectional study. BMC Infectious Diseases, 18, 491.
Falghoush, A., Beyenal, H., & Call, D. R. (2020). Sequential hypertonic-hypotonic treatment enhances efficacy of antibiotic against Acinetobacter baumannii biofilm communities. Antibiotics (Basel), 9.
Gehrlein, M., Leying, H., Cullmann, W., Wendt, S., & Opferkuch, W. (1991). Imipenem resistance in Acinetobacter baumannii is due to altered penicillin-binding proteins. Chemotherapy, 37, 405–412.
Hakeam, H. A., & Al Duhailib, Z. (2020). Tigecycline-induced coagulopathy: A literature review. International Journal of Clinical Pharmacy, 42, 846–847.
Harding, C. M., Hennon, S. W., & Feldman, M. F. (2018). Uncovering the mechanisms of Acinetobacter baumannii virulence. Nature Reviews: Microbiology, 16, 91–102.
Hujer, A. M., Hujer, K. M., Leonard, D. A., Powers, R. A., Wallar, B. J., Mack, A. R., Taracila, M. A., Rather, P. N., Higgins, P. G., Prati, F., Caselli, E., Marshall, S. H., Clarke, T., Greco, C., Venepally, P., Brinkac, L., Kreiswirth, B. N., Fouts, D. E., Bonomo, R. A., & Antibacterial Resistance Leadership, G. (2020). A comprehensive and contemporary “snapshot” of beta-lactamases in carbapenem resistant Acinetobacter baumannii. Diagnostic Microbiology and Infectious Disease, 99, 115242.
Karvouniaris, M., Pontikis, K., Nitsotolis, T., & Poulakou, G. (2020). New perspectives in the antibiotic treatment of mechanically ventilated patients with infections from Gram-negatives. Expert Review of Anti-Infective Therapy.
Lai, C. C., Chen, C. C., Lu, Y. C., Chuang, Y. C., & Tang, H. J. (2019). In vitro activity of cefoperazone and cefoperazone-sulbactam against carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa. Infection and Drug Resistance, 12, 25–29.
Lee, C. R., Lee, J. H., Park, M., Park, K. S., Bae, I. K., Kim, Y. B., Cha, C. J., Jeong, B. C., & Lee, S. H. (2017). Biology of Acinetobacter baumannii: Pathogenesis, antibiotic resistance mechanisms, and prospective treatment options. Frontiers in Cellular and Infection Microbiology, 7, 55.
Leelasupasri, S., Santimaleeworagun, W., & Jitwasinkul, T. (2018). Antimicrobial susceptibility among colistin, sulbactam, and fosfomycin and a synergism study of colistin in combination with sulbactam or fosfomycin against clinical isolates of carbapenem-resistant Acinetobacter baumannii. Journal of Pathology, 2018, 3893492.
Nasr, P. (2020). Genetics, epidemiology, and clinical manifestations of multidrug-resistant Acinetobacter baumannii. Journal of Hospital Infection, 104, 4–11.
Neidhofer, C., Buechler, C., Neidhofer, G., Bierbaum, G., Hannet, I., Hoerauf, A., & Parcina, M. (2021). Global distribution patterns of carbapenemase-encoding bacteria in a new light: Clues on a role for ethnicity. Frontiers in Cellular and Infection Microbiology, 11, 659753.
Oh, D. H., Kim, Y. C., Kim, E. J., Jung, I. Y., Jeong, S. J., Kim, S. Y., Park, M. S., Kim, A., Lee, J. G., & Paik, H. C. (2019). Multidrug-resistant Acinetobacter baumannii infection in lung transplant recipients: Risk factors and prognosis. Infectious Diseases (Lond), 51, 493–501.
Pei, G., Mao, Y., & Sun, Y. (2012). In vitro activity of minocycline alone and in combination with cefoperazone-sulbactam against carbapenem-resistant Acinetobacter baumannii. Microbial Drug Resistance, 18, 574–577.
Qureshi, Z. A., Hittle, L. E., O’Hara, J. A., Rivera, J. I., Syed, A., Shields, R. K., Pasculle, A. W., Ernst, R. K., & Doi, Y. (2015). Colistin-resistant Acinetobacter baumannii: Beyond carbapenem resistance. Clinical Infectious Diseases, 60, 1295–1303.
Ramirez, M. S., & Tolmasky, M. E. (2017). Amikacin: Uses, resistance, and prospects for inhibition. Molecules, 22.
Raro, O. H. F., Gallo, S. W., Ferreira, C. A. S., & Oliveira, S. D. (2017). Carbapenem-resistant Acinetobacter baumannii contamination in an intensive care unit. Revista da Sociedade Brasileira de Medicina Tropical, 50, 167–172.
Seifert, H., Stefanik, D., Olesky, M., & Higgins, P. G. (2020). In vitro activity of the novel fluorocycline TP-6076 against carbapenem-resistant Acinetobacter baumannii. International Journal of Antimicrobial Agents, 55, 105829.
Singkham-In, U., Higgins, P. G., Wannigama, D. L., Hongsing, P., & Chatsuwan, T. (2020). Rescued chlorhexidine activity by resveratrol against carbapenem-resistant Acinetobacter baumannii via down-regulation of AdeB efflux pump. PloS One, 15, e0243082.
Tooke, C. L., Hinchliffe, P., Bragginton, E. C., Colenso, C. K., Hirvonen, V. H. A., Takebayashi, Y., & Spencer, J. (2019). beta-Lactamases and beta-lactamase inhibitors in the 21st century. Journal of Molecular Biology, 431, 3472–3500.
Vahhabi, A., Hasani, A., Rezaee, M. A., Baradaran, B., Hasani, A., Samadi Kafil, H., Abbaszadeh, F., & Dehghani, L. (2020). A plethora of carbapenem resistance in Acinetobacter baumannii: No end to a long insidious genetic journey. Journal of Chemotherapy, 1–19.
VanPelt, J., Stoffel, S., Staude, M. W., Dempster, K., Rose, H. A., Graney, S., Graney, E., Braynard, S., Kovrigina, E., Leonard, D. A., & Peng, J. W. (2021). Arginine modulates carbapenem deactivation by OXA-24/40 in Acinetobacter baumannii. Journal of Molecular Biology, 167150.
Yamabe, K., Arakawa, Y., Shoji, M., Onda, M., Miyamoto, K., Tsuchiya, T., Akeda, Y., Terada, K., & Tomono, K. (2020). Direct anti-biofilm effects of macrolides on Acinetobacter baumannii: Comprehensive and comparative demonstration by a simple assay using microtiter plate combined with peg-lid. Biomedical Research (Tokyo, Japan), 41, 259–268.
Yuan, W. L., Shen, Y. J., & Deng, D. Y. (2018). Sex bias of Acinetobacter baumannii nosocomial infection. American Journal of Infection Control, 46, 957–958.
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The study was supported by the Science and Technology Project of Binhai New Area Health Bureau (2013BWKY022).
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Data curation, analysis: Hongbin Wu, Heqiang Feng, Lijie He, Heping Zhang, and Ping Xu; Drafting of the manuscript: Hongbin Wu and Heqiang Feng; Concept, design of the study: Hongbin Wu and Heqiang Feng. All authors approved the publication of the manuscript.
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Hongbin Wu and Heqiang Feng contributed equally to this paper.
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Wu, H., Feng, H., He, L. et al. In Vitro Activities of Tigecycline in Combination with Amikacin or Colistin Against Carbapenem-Resistant Acinetobacter baumannii. Appl Biochem Biotechnol 193, 3867–3876 (2021). https://doi.org/10.1007/s12010-021-03664-z
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DOI: https://doi.org/10.1007/s12010-021-03664-z