Antibiotic resistance pattern of Acinetobacter baumannii from burns patients: increase in prevalence of blaOXA-24-like and blaOXA-58-like genes
Background and Objectives: Notwithstanding the increased prevalence of Acinetobacter baumannii drug-resistant isolates, treatment options are progressively limiting. This study aims to provide a recent report on antibiotic susceptibility in burn wound isolates of A. baumannii, and the importance of OXA beta-lactamases in carbapenem resistance.
Materials and Methods: The susceptibility levels to different antimicrobial categories were determined among 84 A. baumannii isolates from burn wound infection between 2016 and 2018. Multiplex PCR was used to detect OXA beta-lactamases genes, including blaOXA-51, blaOXA-23, blaOXA-24 and blaOXA-58. ISAba-1 association with blaOXA-51, blaOXA-23 and blaOXA-58 was detected by PCR mapping.
Results: All the isolates were determined as multidrug-resistant (MDR) and 69% as extensively drug-resistant (XDR). Different carbapenems MIC ranges (MIC50 and MIC90) were observed among the isolates harboring blaOXA-like genes and isolates with the OXA-24-like enzyme showed higher carbapenems MIC ranges. The prevalence of blaOXA-51-like, blaOXA-23-like, blaOXA-24-like and blaOXA-58-like were 100%, 53.57%, 41.66% and 30.95%, respectively. ISAba-1 insertion sequence was found to be upstream to blaOXA-23-like and blaOXA-58-like genes in 23 out of 45 (71.1%) blaOXA-23-like-positive and 4 out of 23 (15.3) blaOXA-58-like-positive isolates, respectively.
Conclusion: Resistance to carbapenems as the last resort for treatment of A. baumannii infections is growing. This study, for the first time in Iran, has observed the increased frequency of blaOXA-24-like and blaOXA-58-like genes and found an association between ISAba-1 and blaOXA-58-like gene, which signifies the possible risk of increased diversity in OXA beta-lactamases and growth in carbapenem resistance.
2. Gutkind GO, Di Conza J, Power P, Radice M. β-Lactamase-mediated resistance: a biochemical, epidemiological and genetic overview. Curr Pharm Des 2013; 19:164-208.
3. Bush K, Jacoby GA. Updated functional classification of β-lactamases. Antimicrob Agents Chemother 2010; 54: 969-976.
4. Poirel L, Nordmann P. Carbapenem resistance in Acinetobacter baumannii: mechanisms and epidemiology. Clin Microbiol Infect 2006; 12: 826-836.
5. Turton JF, Woodford N, Glover J, Yarde S, Kaufmann ME, Pitt TL. Identification of Acinetobacter baumannii by detection of the blaOXA-51-like carbapenemase gene intrinsic to this species. J Clin Microbiol 2006; 44: 2974-2976.
6. Figueiredo S, Poirel L, Papa A, Koulourida V, Nordmann P. Overexpression of the naturally occurring blaOXA-51 gene in Acinetobacter baumannii mediated by novel insertion sequence ISAba9. Antimicrob Agents Chemother 2009; 53: 4045-4047.
7. Mugnier PD, Poirel L, Naas T, Nordmann P. World wide dissemination of the blaOXA-23 carbapenemase gene of Acinetobacter baumannii. Emerg Infect Dis 2010; 16: 35-40.
8. Feizabadi MM, Fathollahzadeh B, Taherikalani M, Rasoolinejad M, Sadeghifard N, Aligholi M, et al. Antimicrobial susceptibility patterns and distribution of blaOXA genes among Acinetobacter spp. Isolated from patients at Tehran hospitals. Jpn J Infect Dis 2008; 61: 274-278.
9. Kooti S, Motamedifar M, Sarvari J. Antibiotic resistance profile and distribution of oxacillinase genes among clinical isolates of Acinetobacter baumannii in Shiraz teaching hospitals, 2012-2013. Jundishapur J Microbiol 2015; 8(8):e20215.
10. Rezaei A, Fazeli H, Moghadampour M, Halaji M, Faghri J. Determination of antibiotic resistance pattern and prevalence of OXA-type carbapenemases among Acinetobacter baumannii clinical isolates from inpatients in Isfahan, central Iran. Infez Med 2018; 26: 61-66.
11. Taherikalani M, Fatolahzadeh B, Emaneini M, Soroush S, Feizabadi MM. Distribution of different carbapenem resistant clones of Acinetobacter baumannii in Tehran hospitals. New Microbiol 2009; 32: 265-271.
12. Ganjo Aryann R, Maghdid Delshad M, Mansoor Isam Y, Kok Dik J, Severin Juliette A, Verbrugh Henri A, et al. OXA-carbapenemases present in cClinical Acinetobacter baumannii-calcoaceticus complex isolates from patients in Kurdistan region, Iraq. Microb Drug Resist 2016; 22: 627-637.
13. Hasan B, Perveen K, Olsen B, Zahra R. Emergence of carbapenem-resistant Acinetobacter baumannii in hospitals in Pakistan. J Med Microbiol 2014; 63: 50-55.
14. Zanganeh Z, Eftekhar, F. Correlation of oxacillinase gene carriage with the genetic fingerprints of imipenem-resistant clinical isolates of Acinetobacter baumannii. Jundishapur J Microbiol 2015; 8(9): e26545.
15. Ahmed SS, Alp E, Ulu-Kilic A, Dinc G, Aktas Z, Ada B, et al. Spread of carbapenem-resistant international clones of Acinetobacter baumannii in Turkey and Azerbaijan: a collaborative study. Eur J Clin Microbiol Infect Dis 2016; 35: 1463-1468.
16. Poirel L, Naas T, Nordmann P. Diversity, epidemiology, and genetics of class D beta-lactamases. Antimicrob Agents Chemother 2010; 54: 24-38.
17. Segal H, Garny S, Elisha BG. Is ISAba-1 customized for Acinetobacter? FEMS Microbiol Lett 2005;243: 425-429.
18. Turton JF1, Ward ME, Woodford N, Kaufmann ME, Pike R, Livermore DM, et al. The role of ISAba1 in expression of OXA carbapenemase genes in Acinetobacter baumannii. FEMS Microbiol Lett 2006; 258: 72-77.
19. Peymani A, Higgins PG, Nahaei MR, Farajnia S, Seifert H. Characterisation and clonal dissemination of OXA-23-producing Acinetobacter baumannii in Tabriz, northwest Iran. Int J Antimicrob Agents 2012; 39: 526-528.
20. Farshadzadeh Z, Hashemi FB, Rahimi S, Pourakbari B, Esmaeili D, Haghighi MA, et al. Wide distribution of carbapenem resistant Acinetobacter baumannii in burns patients in Iran. Front Microbiol 2015; 6: 1146.
21. Forbes, B.A., Sahm, D.F. and Weissfeld, A. Bailey and Scott’s Diagnostic Microbiology. 12th Edition, Mosby Elsevier, St Louis, Missouri; 2007. 334-339.
22. Woodford N, Ellington MJ, Coelho JM, Turton JF, Ward ME, Brown S, et al. Multiplex PCR for genes encoding prevalent OXA carbapenemases in Acinetobacter spp. Int J Antimicrob Agents 2006; 27: 351-353.
23. Clinical and Laboratory Standards. Institute Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Fourth Informational Supplement 2017; M100-S27.CLSI.
24. Magiorakos AP, Srinivasan A, Carey R, Carmeli Y, Falagas M, Giske C, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 2012; 18: 268-281.
25. Afzal-Shah M, Woodford N, Livermore DM. Characterization of OXA-25, OXA-26, and OXA-27, molecular class D β-lactamases associated with carbapenem resistance in clinical isolates of Acinetobacter baumannii. Antimicrob Agents Chemother 2001; 45: 583-588.
26. Karmostaji A, Peerayeh SN, Salmanian AH. Distribution of OXA-type class D β-lactamase genes among nosocomial multi drug resistant Acinetobacter baumannii isolated in Tehran hospitals. Jundishapur J Microbiol 2013; 6(5): e8219.
27. Shoja S, Moosavian M, Peymani A, Tabatabaiefar MA, Rostami S, Ebrahimi N. Genotyping of carbapenem resistant Acinetobacter baumannii isolated from tracheal tube discharge of hospitalized patients in intensive care units, Ahvaz, Iran. Iran J Microbiol 2013; 5: 315-322.
28. Bagheri Josheghani S, Moniri R, Firoozeh F, Sehat M, Dasteh Goli Y. Susceptibility pattern and distribution of oxacillinases and blaPER-1 genes among multidrug resistant Acinetobacter baumannii in a teaching hospital in Iran. J Pathog 2015; 2015: 957259.
29. Zavascki AP, Goldani LZ, Li J, Nation RL. Polymyxin B for the treatment of multidrug-resistant pathogens: a critical review. J Antimicrob Chemother 2007; 60: 1206-1215.
30. Livermore DM, Mushtaq S, Warner M, Zhang J, Maharjan S, Doumith M, et al. Activities of NXL104 combinations with ceftazidime and aztreonam against carbapenemase-producing Enterobacteriaceae. Antimicrob Agents Chemother 2011; 55: 390-394.
31. Zowawi HM, Sartor AL, Sidjabat HE, Balkhy HH, Walsh TR, Al Johani SM, et al. Molecular epidemiology of carbapenem-resistant Acinetobacter baumannii isolates in the gulf cooperation Council States: Dominance of OXA-23-type producers. J Clin Microbiol 2015; 53: 896-903.
32. Wang TH, Leu YS, Wang NY, Liu CP, Yan TR. Prevalence of different carbapenemase genes among carbapenem-resistant Acinetobacter baumannii blood isolates in Taiwan. Antimicrob Resist Infect Control 2018; 7:123.