The molecular characterization of colistin-resistant isolates of Acinetobacter baumannii from patients at intensive care units
-
Safar Farajnia
,
Fariba Lotfi
,
Alireza Dehnad
,
Maryam Shojaie
,
Roya Raisi
,
Leila Rahbarnia
,
Ahad Bazmani
,
Behrooz Naghili
,
Samaneh Shiry
Abstract
Background and Objectives: The objective of this study was to determine molecular characterization and genetic diversity of colistin-resistant A. baumannii clinical isolates in Intensive Care Unit hospitalized patients.
Materials and Methods: A total of 127 A. baumannii clinical isolates were evaluated for antimicrobial susceptibility. PCR reaction and sequencing were performed for the detection of mutations in pmrAB and lpx ACD genes.
Results: Based on antimicrobial susceptibility testing, 40.94% and 33.85% of the isolates were MDR and XDR respectively whereas 3.93% of them were found to be PDR. Results of agar dilution MIC and E-test indicated that 76% of the isolates were sensitive to colistin. All of the isolates were positive for blaOXA-51 and 50% of them were positive for both blaOXA-23-like and blaOXA-143-like genes while only 25% of the isolates were positive for blaOXA-72. None of them were positive for the blaOXA-58-like gene. There is no mutation in pmrA. The V162A substitution for pmrB gene was repeated in two isolates, and E394 D and Y292H substitutions in lpxA were observed in two isolates; also, C120R and F165L substitutions in lpxC gene was repeated in two isolates. Analysis of phylogenetic tree based on alterations in lpxACD and pmrB genes indicated the appearance of new isolates compared to the reference strain ATCC17978 A. baumannii isolates.
Conclusion: The present study indicated the prevalence of MDR and XDR A. baumannii isolates and the emergence of PDR isolates in the northwest portion of Iran. The appearance of colistin-resistant isolates with new mutations in pmrB, lpxACD genes indicates new resistance mechanisms.
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2. Pogue JM, Mann T, Barber KE, Kaye KS. Carbapenem-resistant Acinetobacter baumannii: epidemiology, surveillance and management. Expert Rev Anti Infect Ther 2013; 11: 383-393.
3. Ghavghani FR, Rahbarnia L, Naghili B, Dehnad A, Bazmani A, Varshochi M, et al. Nasal and extra nasal MRSA colonization in hemodialysis patients of north-west of Iran. BMC Res Notes 2019; 12: 260.
4. Rahbarnia L, Farajnia S, Khaneshi H, Farajnia H, Naghili B, Tanomand A. Detection of blaOXA-23 and blaNDM-1 carbapenemase among clinical isolates of A. baumannii in Tabriz, north-west of Iran. Gene Rep 2020; 18: 100555.
5. Shi J, Sun T, Cui Y, Wang C, Wang F, Zhou Y, et al. Multidrug resistant and extensively drug resistant Acinetobacter baumannii hospital infection associated with high mortality: a retrospective study in the pediatric intensive care unit. BMC Infect Dis 2020; 20: 597.
6. Freire MP, de Oliveira Garcia D, Garcia CP, Campagnari Bueno MF, Camargo CH, Kono Magri ASG, et al. Bloodstream infection caused by extensively drug-resistant Acinetobacter baumannii in cancer patients: high mortality associated with delayed treatment rather than with the degree of neutropenia. Clin Microbiol Infect 2016; 22: 352-358.
7. Ahmed SS, Alp E, Hopman J, Voss A. Global epidemiology on colistin resistant Acinetobacter baumannii. J Infect Dis Ther 2016; 4: 10.4172/2332-0877.1000287.
8. Bassetti M, Righi E, Esposito S, Petrosillo N, Nicolini L. Drug treatment for multidrug-resistant Acinetobacter baumannii infections. Future Microbiol 2008; 3: 649-660.
9. Biswas S, Brunel JM, Dubus JC, Reynaud-Gaubert M, Rolain JM. Colistin: an update on the antibiotic of the 21st century. Expert Rev Anti Infect ther 2012; 10: 917-934.
10. Vila J, Pachón J. Therapeutic options for Acinetobacter baumannii infections: an update. Expert Opin Pharmacother 2012; 13: 2319-2336.
11. Da Silva GJ, Domingues S. Interplay between colistin resistance, virulence and fitness in Acinetobacter baumannii. Antibiotics (Basel) 2017; 6: 28.
12. Dahdouh E, Gómez-Gil R, Sanz S, González-Zorn B, Daoud Z, Mingorance J, et al. A novel mutation in pmrB mediates colistin resistance during therapy of Acinetobacter baumannii. Int J Antimicrob Agents 2017; 49: 727-733.
13. Park YK, Ko KS. Effect of carbonyl cyanide 3-chlorophenylhydrazone (CCCP) on killing Acinetobacter baumannii by colistin. J Microbiol 2015; 53: 53-59.
14. Thi Khanh Nhu N, Riordan DW, Do Hoang Nhu T, Thanh DP, Thwaites G, Huong Lan NP, et al. The induction and identification of novel Colistin resistance mutations in Acinetobacter baumannii and their implications. Sci Rep 2016; 6: 28291.
15. Moffatt J, Harper M, Harrison P, Hale JD, Vinogradov E, Seemann T, et al. Colistin resistance in Acinetobacter baumannii is mediated by complete loss of lipopolysaccharide production. Antimicrob Agents Chemother 2010; 54: 4971-4977.
16. Moffatt JH, Harper M, Adler B, Nation RL, Li J, Boyce JD. Insertion sequence IS Aba11 is involved in colistin resistance and loss of lipopolysaccharide in Acinetobacter baumannii. Antimicrob Agents Chemother 2011; 55: 3022-3024.
17. 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.
18. Sahu C, Jain V, Mishra P, Prasad KN. Clinical and laboratory standards institute versus European committee for antimicrobial susceptibility testing guidelines for interpretation of carbapenem antimicrobial susceptibility results for Escherichia coli in urinary tract infection (UTI). J Lab Physicians 2018; 10: 289-293.
19. Ranjbar R, Farahani A. Study of genetic diversity, biofilm formation, and detection of Carbapenemase, MBL, ESBL, and tetracycline resistance genes in multidrug-resistant Acinetobacter baumannii isolated from burn wound infections in Iran. Antimicrob Resist Infect Control 2019; 8: 172.
20. Peleg AY, Seifert H, Paterson DL. Acinetobacter baumannii: emergence of a successful pathogen. Clin Microbiol Rev 2008; 21: 538-582.
21. Mirshekar M, Shahcheraghi F, Azizi O, Solgi H, Badmasti F. Diversity of class 1 integrons, and disruption of carO and dacD by insertion sequences among Acinetobacter baumannii isolates in Tehran, Iran. Microb Drug Resist 2018; 24: 359-366.
22. Tenover FC, Emery SL, Spiegel CA, Bradford PA, Eells S, Endimiani A, et al. Identification of plasmid-mediated AmpC beta-lactamases in Escherichia coli, Klebsiella spp., and proteus species can potentially improve reporting of cephalosporin susceptibility testing results. J Clin Microbiol 2009; 47: 294-299.
23. Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, 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.
24. Ghanem S, El Shafey HM, Manzoor N. Antimicrobial resistance pattern of Acinetobacter spp. isolated from clinical samples in a tertiary care hospital at Madinah, Saudi Arabia. African J Microbiol Res 2018; 12: 723-729.
25. Sepahvand V, Davarpanah MA, Hejazi SH. Epidemiology of colistin-resistant Acinetobacter baumannii in Shiraz, Iran. J Appl Environ Biol Sci 2015; 5: 45-48.
26. Mirzaei B, Bazgir ZN, Goli HR, Iranpour F, Mohammadi F, Babaei R. Prevalence of multi-drug resistant (MDR) and extensively drug-resistant (XDR) phenotypes of Pseudomonas aeruginosa and Acinetobacter baumannii isolated in clinical samples from northeast of Iran. BMC Res Notes 2020; 13: 380.
27. Deylam Salehi M, Ferdosi-Shahandashti E, Yahyapour Y, Khafri S, Pournajaf A, Rajabnia R. Integron-mediated antibiotic resistance in Acinetobacter baumannii isolated from intensive care unit patients, Babol, north of Iran. Biomed Res Int 2017; 2017: 7157923.
28. Sobouti B, Mirshekar M, Fallah S, Tabaei A, Mehrabadi JF, Darbandi A. Pan drug-resistant Acinetobacter baumannii causing nosocomial infections among burnt children. Med J Islam Repub Iran 2020; 34: 24.
29. Tavares LCB, Vasconcellos FMd, Sousa WVd, Rocchetti TT, Mondelli AL, Ferreira AM, et al. Emergence and persistence of high-risk clones among MDR and XDR Acinetobacter baumannii at a Brazilian teaching hospital. Front Microbiol 2019; 9: 2898.
30. Huang H, Zhang Y, Li S, Wang J, Chen J, Pan Z, et al. Rifampicin resistance and multidrug-resistant tuberculosis detection using Xpert MTB/RIF in Wuhan, China: A retrospective study. Microb Drug Resist 2018; 24: 675-679.
31. Park YK, Choi JY, Shin D, Ko KS. Correlation between overexpression and amino acid substitution of the PmrAB locus and colistin resistance in Acinetobacter baumannii. Int J Antimicrob Agents 2011; 37: 525-530.
32. Beceiro A, Llobet E, Aranda J, Bengoechea JA, Doumith M, Hornsey M, et al. Phosphoethanolamine modification of lipid A in colistin-resistant variants of Acinetobacter baumannii mediated by the pmrAB two-component regulatory system. Antimicrob Agents Chemother 2011; 55: 3370-3379.
33. Adams MD, Nickel GC, Bajaksouzian S, Lavender H, Murthy AR, Jacobs MR, et al. Resistance to colistin in Acinetobacter baumannii associated with mutations in the PmrAB two-component system. Antimicrob Agents Chemother 2009; 53: 3628-3634.
34. Haeili M, Kafshdouz M, Feizabadi MM. Molecular mechanisms of colistin resistance among pandrug-resistant isolates of Acinetobacter baumannii with high case-fatality rate in intensive care unit patients. Microb Drug Resist 2018; 24: 1271-1276.
35. Nurtop E, Bilman FB, Menekse S, Azap OK, Gönen M, Ergonul O, et al. Promoters of colistin resistance in Acinetobacter baumannii infections. Microb Drug Resist 2019; 25: 997-1002.
2. Pogue JM, Mann T, Barber KE, Kaye KS. Carbapenem-resistant Acinetobacter baumannii: epidemiology, surveillance and management. Expert Rev Anti Infect Ther 2013; 11: 383-393.
3. Ghavghani FR, Rahbarnia L, Naghili B, Dehnad A, Bazmani A, Varshochi M, et al. Nasal and extra nasal MRSA colonization in hemodialysis patients of north-west of Iran. BMC Res Notes 2019; 12: 260.
4. Rahbarnia L, Farajnia S, Khaneshi H, Farajnia H, Naghili B, Tanomand A. Detection of blaOXA-23 and blaNDM-1 carbapenemase among clinical isolates of A. baumannii in Tabriz, north-west of Iran. Gene Rep 2020; 18: 100555.
5. Shi J, Sun T, Cui Y, Wang C, Wang F, Zhou Y, et al. Multidrug resistant and extensively drug resistant Acinetobacter baumannii hospital infection associated with high mortality: a retrospective study in the pediatric intensive care unit. BMC Infect Dis 2020; 20: 597.
6. Freire MP, de Oliveira Garcia D, Garcia CP, Campagnari Bueno MF, Camargo CH, Kono Magri ASG, et al. Bloodstream infection caused by extensively drug-resistant Acinetobacter baumannii in cancer patients: high mortality associated with delayed treatment rather than with the degree of neutropenia. Clin Microbiol Infect 2016; 22: 352-358.
7. Ahmed SS, Alp E, Hopman J, Voss A. Global epidemiology on colistin resistant Acinetobacter baumannii. J Infect Dis Ther 2016; 4: 10.4172/2332-0877.1000287.
8. Bassetti M, Righi E, Esposito S, Petrosillo N, Nicolini L. Drug treatment for multidrug-resistant Acinetobacter baumannii infections. Future Microbiol 2008; 3: 649-660.
9. Biswas S, Brunel JM, Dubus JC, Reynaud-Gaubert M, Rolain JM. Colistin: an update on the antibiotic of the 21st century. Expert Rev Anti Infect ther 2012; 10: 917-934.
10. Vila J, Pachón J. Therapeutic options for Acinetobacter baumannii infections: an update. Expert Opin Pharmacother 2012; 13: 2319-2336.
11. Da Silva GJ, Domingues S. Interplay between colistin resistance, virulence and fitness in Acinetobacter baumannii. Antibiotics (Basel) 2017; 6: 28.
12. Dahdouh E, Gómez-Gil R, Sanz S, González-Zorn B, Daoud Z, Mingorance J, et al. A novel mutation in pmrB mediates colistin resistance during therapy of Acinetobacter baumannii. Int J Antimicrob Agents 2017; 49: 727-733.
13. Park YK, Ko KS. Effect of carbonyl cyanide 3-chlorophenylhydrazone (CCCP) on killing Acinetobacter baumannii by colistin. J Microbiol 2015; 53: 53-59.
14. Thi Khanh Nhu N, Riordan DW, Do Hoang Nhu T, Thanh DP, Thwaites G, Huong Lan NP, et al. The induction and identification of novel Colistin resistance mutations in Acinetobacter baumannii and their implications. Sci Rep 2016; 6: 28291.
15. Moffatt J, Harper M, Harrison P, Hale JD, Vinogradov E, Seemann T, et al. Colistin resistance in Acinetobacter baumannii is mediated by complete loss of lipopolysaccharide production. Antimicrob Agents Chemother 2010; 54: 4971-4977.
16. Moffatt JH, Harper M, Adler B, Nation RL, Li J, Boyce JD. Insertion sequence IS Aba11 is involved in colistin resistance and loss of lipopolysaccharide in Acinetobacter baumannii. Antimicrob Agents Chemother 2011; 55: 3022-3024.
17. 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.
18. Sahu C, Jain V, Mishra P, Prasad KN. Clinical and laboratory standards institute versus European committee for antimicrobial susceptibility testing guidelines for interpretation of carbapenem antimicrobial susceptibility results for Escherichia coli in urinary tract infection (UTI). J Lab Physicians 2018; 10: 289-293.
19. Ranjbar R, Farahani A. Study of genetic diversity, biofilm formation, and detection of Carbapenemase, MBL, ESBL, and tetracycline resistance genes in multidrug-resistant Acinetobacter baumannii isolated from burn wound infections in Iran. Antimicrob Resist Infect Control 2019; 8: 172.
20. Peleg AY, Seifert H, Paterson DL. Acinetobacter baumannii: emergence of a successful pathogen. Clin Microbiol Rev 2008; 21: 538-582.
21. Mirshekar M, Shahcheraghi F, Azizi O, Solgi H, Badmasti F. Diversity of class 1 integrons, and disruption of carO and dacD by insertion sequences among Acinetobacter baumannii isolates in Tehran, Iran. Microb Drug Resist 2018; 24: 359-366.
22. Tenover FC, Emery SL, Spiegel CA, Bradford PA, Eells S, Endimiani A, et al. Identification of plasmid-mediated AmpC beta-lactamases in Escherichia coli, Klebsiella spp., and proteus species can potentially improve reporting of cephalosporin susceptibility testing results. J Clin Microbiol 2009; 47: 294-299.
23. Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, 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.
24. Ghanem S, El Shafey HM, Manzoor N. Antimicrobial resistance pattern of Acinetobacter spp. isolated from clinical samples in a tertiary care hospital at Madinah, Saudi Arabia. African J Microbiol Res 2018; 12: 723-729.
25. Sepahvand V, Davarpanah MA, Hejazi SH. Epidemiology of colistin-resistant Acinetobacter baumannii in Shiraz, Iran. J Appl Environ Biol Sci 2015; 5: 45-48.
26. Mirzaei B, Bazgir ZN, Goli HR, Iranpour F, Mohammadi F, Babaei R. Prevalence of multi-drug resistant (MDR) and extensively drug-resistant (XDR) phenotypes of Pseudomonas aeruginosa and Acinetobacter baumannii isolated in clinical samples from northeast of Iran. BMC Res Notes 2020; 13: 380.
27. Deylam Salehi M, Ferdosi-Shahandashti E, Yahyapour Y, Khafri S, Pournajaf A, Rajabnia R. Integron-mediated antibiotic resistance in Acinetobacter baumannii isolated from intensive care unit patients, Babol, north of Iran. Biomed Res Int 2017; 2017: 7157923.
28. Sobouti B, Mirshekar M, Fallah S, Tabaei A, Mehrabadi JF, Darbandi A. Pan drug-resistant Acinetobacter baumannii causing nosocomial infections among burnt children. Med J Islam Repub Iran 2020; 34: 24.
29. Tavares LCB, Vasconcellos FMd, Sousa WVd, Rocchetti TT, Mondelli AL, Ferreira AM, et al. Emergence and persistence of high-risk clones among MDR and XDR Acinetobacter baumannii at a Brazilian teaching hospital. Front Microbiol 2019; 9: 2898.
30. Huang H, Zhang Y, Li S, Wang J, Chen J, Pan Z, et al. Rifampicin resistance and multidrug-resistant tuberculosis detection using Xpert MTB/RIF in Wuhan, China: A retrospective study. Microb Drug Resist 2018; 24: 675-679.
31. Park YK, Choi JY, Shin D, Ko KS. Correlation between overexpression and amino acid substitution of the PmrAB locus and colistin resistance in Acinetobacter baumannii. Int J Antimicrob Agents 2011; 37: 525-530.
32. Beceiro A, Llobet E, Aranda J, Bengoechea JA, Doumith M, Hornsey M, et al. Phosphoethanolamine modification of lipid A in colistin-resistant variants of Acinetobacter baumannii mediated by the pmrAB two-component regulatory system. Antimicrob Agents Chemother 2011; 55: 3370-3379.
33. Adams MD, Nickel GC, Bajaksouzian S, Lavender H, Murthy AR, Jacobs MR, et al. Resistance to colistin in Acinetobacter baumannii associated with mutations in the PmrAB two-component system. Antimicrob Agents Chemother 2009; 53: 3628-3634.
34. Haeili M, Kafshdouz M, Feizabadi MM. Molecular mechanisms of colistin resistance among pandrug-resistant isolates of Acinetobacter baumannii with high case-fatality rate in intensive care unit patients. Microb Drug Resist 2018; 24: 1271-1276.
35. Nurtop E, Bilman FB, Menekse S, Azap OK, Gönen M, Ergonul O, et al. Promoters of colistin resistance in Acinetobacter baumannii infections. Microb Drug Resist 2019; 25: 997-1002.
| Files | ||
| Issue | Vol 14 No 3 (2022) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v14i3.9768 | |
| Keywords | ||
| Acinetobacter baumannii; Beta-lactamase OXA-23; Beta-lactamase OXA-143; OXA-72 carbapenemase; Beta-lactamase OXA-58; Colistin | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Farajnia S, Lotfi F, Dehnad A, Shojaie M, Raisi R, Rahbarnia L, Bazmani A, Naghili B, Shiry S. The molecular characterization of colistin-resistant isolates of Acinetobacter baumannii from patients at intensive care units. Iran J Microbiol. 2022;14(3):319-327.
