Acinetobacter baumannii has emerged as an important nosocomial pathogen due to its ability to survive in hospital settings and its antimicrobial resistance. It is one of the key pathogens in ventilator-associated pneumonia (VAP). The aim of this study was to characterize the mechanisms of quinolone resistance among A. baumannii isolates causing VAP and to investigate the presence of the novel abaQ gene among them. Quinolone-resistant A. baumannii isolates causing VAP were collected over a period of 4 months. Mutations within gyrA and parC were analyzed and the presence of qnrA, qnrB, qnrS, and abaQ was investigated genotypically. Twenty-one A. baumannii isolates were collected, most of them (76.2%) were extensively drug-resistant (XDR) and only one isolate (4.8%) was pandrug-resistant (PDR). All isolates showed high level of resistance to ciprofloxacin, while qnrA, qnrB and qnrS were absent among our isolates. This is the first report of A. baumannii isolates co-harboring Ser81Leu in gyrA and Ser84Leu in parC together with the novel abaQ gene. Interestingly, a new mutation in gyrA quinolone resistance-determining region Arg89Cys was detected among two of our isolates. The emergence of XDR and PDR isolates among A. baumannii causing VAP is an alarming threat.
Deccache, Y., Irenge, L. M., Savov, E., Ariciuc, M., Macovei, A., Trifonova, A., Gergova, I., Ambroise, J., Vanhoof, R., Gala, J. L.: Development of a pyrosequencing assay for rapid assessment of quinolone resistance in Acinetobacter baumannii isolates. J Microbiol Methods 86, 115–118 (2011).
Erdem, H., Cag, Y., Gencer, S., Uysal, S., Karakurt, Z., Harman, R., Aslan, E., Mutlu-Yilmaz, E., Karabay, O., Uygun, Y., Ulug, M., Tosun, S., Dogru, A., Sener, A., Dogan, M., Hasbun, R., Durmus, G., Turan, H., Batirel, A., Duygu, F., Inan, A., Akkoyunlu, Y., Celebi, G., Ersoz, G., Guven, T., Dagli, O., Guler, S., Meric-Koc, M., Oncu, S., Rello, J.: Treatment of ventilator-associated pneumonia (VAP) caused by Acinetobacter: Results of prospective and multicenter ID-IRI study. Eur J Clin Microbiol Infect Dis (2019).
Cherkaoui, A., Emonet, S., Renzi, G., Schrenzel, J.: Characteristics of multidrug-resistant Acinetobacter baumannii strains isolated in Geneva during colonization or infection. Ann Clin Microbiol Antimicrob 14, 42 (2015).
Kalil, A. C., Metersky, M. L., Klompas, M., Muscedere, J., Sweeney, D. A., Palmer, L. B., Napolitano, L. M., O’Grady, N. P., Bartlett, J. G., Carratala, J., El Solh, A. A., Ewig, S., Fey, P. D., File, T. M., Jr., Restrepo, M. I., Roberts, J. A., Waterer, G. W., Cruse, P., Knight, S. L., Brozek, J. L.: Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis 63, e61–e111 (2016).
Nowak, J., Zander, E., Stefanik, D., Higgins, P. G., Roca, I., Vila, J., McConnell, M. J., Cisneros, J. M., Seifert, H., MagicBullet Working Group, W. P.: High incidence of pandrug-resistant Acinetobacter baumannii isolates collected from patients with ventilator-associated pneumonia in Greece, Italy and Spain as part of the MagicBullet clinical trial. J Antimicrob Chemother 72, 3277–3282 (2017).
Huang, Y., Zhou, Q., Wang, W., Huang, Q., Liao, J., Li, J., Long, L., Ju, T., Zhang, Q., Wang, H., Xu, H., Tu, M.: Acinetobacter baumannii ventilator-associated pneumonia: Clinical efficacy of combined antimicrobial therapy and in vitro drug sensitivity test results. Front Pharmacol 10, 92 (2019).
Hooper, D. C., Jacoby, G. A.: Mechanisms of drug resistance: Quinolone resistance. Ann N Y Acad Sci 1354, 12–31 (2015).
Asif, M., Alvi, I. A., Rehman, S. U.: Insight into Acinetobacter baumannii: Pathogenesis, global resistance, mechanisms of resistance, treatment options, and alternative modalities. Infect Drug Resist 11, 1249–1260 (2018).
Perez-Varela, M., Corral, J., Aranda, J., Barbe, J.: Functional Characterization of AbaQ, a novel efflux pump mediating quinolone resistance in Acinetobacter baumannii. Antimicrob Agents Chemother 62, e00906–e00918 (2018).
Clinical and Laboratory Standards Institute: Performance Standards for Antimicrobial Susceptibility Testing, 28th ed. CLSI supplement M100. Clinical and Laboratory Standards Institute, Wayne, PA, 2018.
Turton, J. F., Woodford, N., Glover, J., Yarde, S., Kaufmann, M. E., Pitt, T. L.: Identification of Acinetobacter baumannii by detection of the blaOXA-51-like carbapenemase gene intrinsic to this species. J Clin Microbiol 44, 2974–2976 (2006).
Srinivasan, V. B., Rajamohan, G., Pancholi, P., Stevenson, K., Tadesse, D., Patchanee, P., Marcon, M., Gebreyes, W. A.: Genetic relatedness and molecular characterization of multidrug resistant Acinetobacter baumannii isolated in central Ohio, USA. Ann Clin Microbiol Antimicrob 8, 21 (2009).
Magiorakos, A. P., Srinivasan, A., Carey, R. B., Carmeli, Y., Falagas, M. E., Giske, C. G., Harbarth, S., Hindler, J. F., Kahlmeter, G., Olsson-Liljequist, B., Paterson, D. L., Rice, L. B., Stelling, J., Struelens, M. J., Vatopoulos, A., Weber, J. T., Monnet, D. L.: Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 18, 268–281 (2012).
Ciginskiene, A., Dambrauskiene, A., Rello, J., Adukauskiene, D.: Ventilator-associated pneumonia due to drug-resistant Acinetobacter baumannii: Risk factors and mortality relation with resistance profiles, and independent predictors of in-hospital mortality. Medicina (Kaunas) 55, E49 (2019).
Ostrer, L., Khodursky, R. F., Johnson, J. R., Hiasa, H., Khodursky, A.: Analysis of mutational patterns in quinolone resistance-determining regions of GyrA and ParC of clinical isolates. Int J Antimicrob Agents 53, 318–324 (2019).
Akter, F., Amin, M. R., Osman, K. T., Anwar, M. N., Karim, M. M., Hossain, M. A.: Ciprofloxacin-resistant Escherichia coli in hospital wastewater of Bangladesh and prediction of its mechanism of resistance. World J Microbiol Biotechnol 28, 827–834 (2012).
Conrad, S., Oethinger, M., Kaifel, K., Klotz, G., Marre, R., Kern, W. V.: gyrA Mutations in high-level fluoroquinolone-resistant clinical isolates of Escherichia coli. J Antimicrob Chemother 38, 443–455 (1996).
Lehn, N., Stower-Hoffmann, J., Kott, T., Strassner, C., Wagner, H., Kronke, M., Schneider-Brachert, W.: Characterization of clinical isolates of Escherichia coli showing high levels of fluoroquinolone resistance. J Clin Microbiol 34, 597–602 (1996).
Higuchi, S., Shikata, M., Chiba, M., Hoshino, K., Gotoh, N.: Characteristics of antibiotic resistance and sequence type of Acinetobacter baumannii clinical isolates in Japan and the antibacterial activity of DS-8587. J Infect Chemother 20, 256–261 (2014).
Bakour, S., Touati, A., Sahli, F., Ameur, A. A., Haouchine, D., Rolain, J. M.: Antibiotic resistance determinants of multidrug-resistant Acinetobacter baumannii clinical isolates in Algeria. Diagn Microbiol Infect Dis 76, 529–531 (2013).
Hamed, S. M., Elkhatib, W. F., El-Mahallawy, H. A., Helmy, M. M., Ashour, M. S., Aboshanab, K. M. A.: Multiple mechanisms contributing to ciprofloxacin resistance among Gram negative bacteria causing infections to cancer patients. Sci Rep 8, 12268 (2018).