Coexistence of aminoglycoside resistance genes in CTX-M-producing isolates of Klebsiella pneumoniae in Bushehr province, Iran
Abstract
Background and Objectives: Increasing the rate of extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae has given rise to a major healthcare issue in clinical settings over the past few years. Treatment of these strains is hardly effective since the plasmid encoding ESBL may also carry other resistance genes including aminoglycosides. The current study aimed to evaluate the prevalence of ESBL-producing K. pneumoniae and investigate the coexistence of Cefoxitamase-Munich (blaCTX‑M) with aminoglycoside-modifying enzyme (AME) genes, aac(3)IIa as well as aac(6′)Ib, in CTX-M-producing K. pneumoniae isolated from patients in Bushehr province, Iran.
Materials and Methods: A total of 212 K. pneumoniae isolates were collected and confirmed using polymerase chain reaction (PCR) of the malate dehydrogenase gene. Isolates were screened for production of ESBL. Phenotypic confirmatory test was performed using combined disk test. The genes encoding CTX-M groups and AME genes, aac(3)IIa and aac(6′)Ib, were investigated by PCR.
Results: The ESBL phenotype was detected in 56 (26.4%) K. pneumoniae isolates. Moreover, 83.9% of ESBL-producing isolates carried the genes for CTX-M type β-lactamases, which were distributed into the two genetic groups of CTX-M-1 (97.8%)- and CTX-M-2 (2.1%)-related enzymes. Notably, among K. pneumoniae isolates containing the blaCTX-M gene, 68.08% of isolates harbored AME genes. In addition, the coexistence of blaCTX-M with aac(3)-IIa and aac(6’)-Ib was observed in 46.8% of CTX-M-producing K. pneumoniae isolates.
Conclusion: This study provides evidence of a high prevalence of AME genes in CTX-M- producing K. pneumoniae isolates; therefore, in the initial empirical treatment of infections caused by ESBL-KP in regions with such antibiotic resistance patterns, aminoglycoside combination therapy should be undertaken carefully.
1. Afzali H, Firoozeh F, Amiri A, Moniri R, Zibaei M. Characterization of CTX-M-type extend-spectrum β-lactamase producing Klebsiella spp. in Kashan, Iran. Jundishapur J Microbiol 2015;8(10):e27967.
2. Fernández-Martínez M, Del Castillo BR, Lecea-Cuello MJ, Rodríguez-Baño J, Pascual Á, Martínez-Martínez L, et al. Prevalence of aminoglycoside-modifying enzymes in Escherichia coli and Klebsiella pneumoniae producing extended spectrum β-lactamases collected in two multicenter studies in Spain. Microb Drug Resist 2018;24:367-376.
3. Rossolini G, D'andrea M, Mugnaioli C. The spread of CTX-M-type extended-spectrum β-lactamases. Clin Microbiol Infect 2008; 14 Suppl 1:33-41.
4. Adler A, Katz DE, Marchaim D. The continuing plague of extended-spectrum β-lactamase–producing Enterobacteriaceae infections. Infect Dis Clin North Am 2016;30: 347-375.
5. Cantón R, González-Alba JM, Galán JC. CTX-M enzymes: origin and diffusion. Front Microbiol 2012;3:110.
6. Bonnet R. Growing group of extended-spectrum β-lactamases: the CTX-M enzymes. Antimicrob Agents Chemother 2004; 48: 1-14.
7. Canton R, Coque TM. The CTX-M beta-lactamase pandemic. Curr Opin Microbiol 2006;9:466-475.
8. Roschanski N, Fischer J, Guerra B, Roesler U. Development of a multiplex real-time PCR for the rapid detection of the predominant beta-lactamase genes CTX-M, SHV, TEM and CIT-type AmpCs in Enterobacteriaceae. PLoS One 2014;9(7): e100956.
9. Ghotaslou R, Yeganeh Sefidan F, Akhi MT, Asgharzadeh M, Mohammadzadeh Asl Y. Dissemination of genes encoding aminoglycoside-modifying enzymes and armA among Enterobacteriaceae isolates in northwest Iran. Microb Drug Resist 2017;23:826-832.
10. Poole K. Aminoglycoside resistance in Pseudomonas aeruginosa. Antimicrob Agents Chemother 2005;49:479-487.
11. Azimi L, Nordmann P, Lari AR, Bonnin RA. First report of OXA-48-producing Klebsiella pneumoniae strains in Iran. GMS Hyg Infect Control 2014;9:Doc07.
12. Han SB, Lee SC, Lee SY, Jeong DC, Kang JH. Aminoglycoside therapy for childhood urinary tract infection due to extended-spectrum β-lactamase-producing Escherichia coli or Klebsiella pneumoniae. BMC Infect Dis 2015; 15: 414.
13. Peerayeh SN, Rostami E, Siadat SD, Derakhshan S. High rate of aminoglycoside resistance in CTX-M-15 producing Klebsiella pneumoniae isolates in Tehran, Iran. Lab Med 2014;45:231-237.
14. Ramirez MS, Tolmasky ME. Aminoglycoside modifying enzymes. Drug Resist Updat 2010; 13: 151-171.
15. Barati A, Ghaderpour A, Chew L, Bong C, Thong K, Chong V, et al. Isolation and characterization of aquatic-borne Klebsiella pneumoniae from tropical estuaries in Malaysia. Int J Environ Res Public Health 2016; 13: 426.
16. Wayne PA. Clinical and Laboratory Standards Institute, Performance Standards for Antimicrobial Susceptibility Testing 2018;M100, 28th ed.
17. Ghafourian S, Bin Sekawi Z, Sadeghifard N, Mohebi R, Kumari Neela V, Maleki A, et al. The prevalence of ESBLs producing Klebsiella pneumoniae isolates in some major hospitals, Iran. Open Microbiol J 2011; 5: 91-95.
18. Jeong S, Bae I, Kwon S, Lee J, Song J, Jung H, et al. Dissemination of transferable CTX‐M‐type extended‐spectrum β‐lactamase‐producing Escherichia coli in Korea. J Appl Microbiol 2005; 98: 921-927.
19. Liu Z, Li W, Wang J, Pan J, Sun S, Yu Y, et al. Identification and characterization of the first Escherichia coli strain carrying NDM-1 gene in China. PLoS One 2013;8(6):e66666.
20. Arpin C, Dubois V, Coulange L, André C, Fischer I, Noury P, et al. Extended-spectrum β-lactamase-producing Enterobacteriaceae in community and private health care centers. Antimicrob Agents Chemother 2003;47:3506-3514.
21. Park CH, Robicsek A, Jacoby GA, Sahm D, Hooper DC. Prevalence in the United States of aac(6′)-Ib-cr encoding a ciprofloxacin-modifying enzyme. Antimicrob Agents Chemother 2006;50:3953-3955.
22. Aghamohammad S, Badmasti F, Solgi H, Aminzadeh Z, Khodabandelo Z, Shahcheraghi F. First report of extended-spectrum betalactamase-producing Klebsiella pneumoniae among fecal carriage in Iran: high diversity of clonal relatedness and virulence factor profiles. Microb Drug Resist 2020;26:261-269.
23. Shoja S, Ansari M, Faridi F, Azad M, Davoodian P, Javadpour S, et al. Identification of carbapenem-resistant Klebsiella pneumoniae with emphasis on New Delhi metallo-beta-lactamase-1 (blaNDM-1) in Bandar Abbas, South of Iran. Microb Drug Resist 2018;24:447-454.
24. Hosseinzadeh Z, Ebrahim-Saraie HS, Sarvari J, Mardaneh J, Dehghani B, Rokni-Hosseini SMH, et al. Emerge of blaNDM-1 and blaOXA-48-like harboring carbapenem-resistant Klebsiella pneumoniae isolates from hospitalized patients in southwestern Iran. J Chin Med Assoc 2018; 81: 536-540.
25. Mansouri S, Neyestanaki DK, Shokoohi M, Halimi S, Beigverdi R, Rezagholezadeh F, et al. Characterization of AmpC, CTX-M and MBLs types of β-lactamases in clinical isolates of Klebsiella pneumoniae and Escherichia coli producing extended spectrum β-lactamases in Kerman, Iran. Jundishapur J Microbiol 2014; 7(2):e8756.
26. Bialvaei AZ, Kafil HS, Asgharzadeh M, Aghazadeh M, Yousefi M. CTX-M extended-spectrum β-lactamase-producing Klebsiella spp, Salmonella spp, Shigella spp and Escherichia coli isolates in Iranian hospitals. Braz J Microbiol 2016; 47: 706-711.
27. Vading M, Nauclér P, Kalin M, Giske C. Invasive infection caused by Klebsiella pneumoniae is a disease affecting patients with high comorbidity and associated with high long-term mortality. PLoS One 2018;13(4):e0195258.
28. Karlowsky JA, Adam HJ, Baxter MR, Lagacé-Wiens PR, Walkty AJ, Hoban DJ, et al. In vitro activity of ceftaroline-avibactam against Gram-negative and Gram-positive pathogens isolated from patients in Canadian hospitals from 2010 to 2012: results from the CANWARD surveillance study. Antimicrob Agents Chemother 2013;57:5600-5611.
29. Cubero M, Grau I, Tubau F, Pallarés R, Domínguez MÁ, Linares J, et al. Molecular epidemiology of Klebsiella pneumoniae strains causing bloodstream infections in adults. Microb Drug Resist 2018;24:949-957.
30. Lai C-C, Lee K, Xiao Y, Ahmad N, Veeraraghavan B, Thamlikitkul V, et al. High burden of antimicrobial drug resistance in Asia. J Glob Antimicrob Resist 2014; 2: 141-147.
31. Derakhshan S, Peerayeh SN, Fallah F, Bakhshi B, Rahbar M, Ashrafi A. Detection of class 1, 2, and 3 integrons among Klebsiella pneumoniae isolated from children in Tehran hospitals. Arch Pediatr Infect Dis 2014;2:164-168.
32. Saeidi S, Alavi-Naini R, Shayan S. Antimicrobial susceptibility and distribution of tem and ctx-m genes among esbl-producing Klebsiella pneumoniae and Pseudomonas aeruginosa causing urinary tract infections. Zahedan J Res Med Sci 2013;16:1-5.
33. Mohammed AS. Molecular detection of CTX-M genes in Klebsiella pneumoniae isolated from different clinical samples in Baghdad city. Med J Babylon 2015;12:152-160.
34. Bindayna KM, Murtadha M. High prevalence of blaCTX–M in Enterobacteriaceae isolates from the Kingdom of Bahrain. Asian Pac J Trop Med 2011; 4: 937-940.
35. Al Sweih N, Salama M, Jamal W, Al Hashem G, Rotimi V. An outbreak of CTX-M-15-producing Klebsiella pneumoniae isolates in an intensive care unit of a teaching hospital in Kuwait. Indian J Med Microbiol 2011; 29: 130-135.
36. Erum K, Schneiders T, Afia Z, Erum A, Asra P, Rumina H. Emergence of CTX-M Group 1-ESBL producing Klebsiella pneumonia from a tertiary care centre in Karachi, Pakistan. J Infect Dev Ctries 2010;4:472-476.
37. Kiratisin P, Apisarnthanarak A, Laesripa C, Saifon P. Molecular characterization and epidemiology of extended-spectrum-β-lactamase-producing Escherichia coli and Klebsiella pneumoniae isolates causing health care-associated infection in Thailand, where the CTX-M family is endemic. Antimicrob Agents Chemother 2008;52:2818-2824.
38. Lotfollahi L, Samadi N, Hosainzadegan H, Qomi MA. Prevalence of aac(3’)-IIa and aac(6’)-Ib genes incidence involved in aminoglycoside resistance in Klebsiella pneumoniae isolated from clinical samples in Urmia Hospitals, Iran. Am J Pharm Tech Res 2015;5:326-334.
39. Eftekhar F. Prevalence of qnr and aac(6’)-Ib-cr Genes in clinical isolates of Klebsiella pneumoniae from Imam Hussein Hospital in Tehran. Iran J Med Sci 2015; 40: 515-521.
40. Nasiri G, Peymani A, Farivar TN, Hosseini P. Molecular epidemiology of aminoglycoside resistance in clinical isolates of Klebsiella pneumoniae collected from Qazvin and Tehran provinces, Iran. Infect Genet Evol 2018;64:219-224.
2. Fernández-Martínez M, Del Castillo BR, Lecea-Cuello MJ, Rodríguez-Baño J, Pascual Á, Martínez-Martínez L, et al. Prevalence of aminoglycoside-modifying enzymes in Escherichia coli and Klebsiella pneumoniae producing extended spectrum β-lactamases collected in two multicenter studies in Spain. Microb Drug Resist 2018;24:367-376.
3. Rossolini G, D'andrea M, Mugnaioli C. The spread of CTX-M-type extended-spectrum β-lactamases. Clin Microbiol Infect 2008; 14 Suppl 1:33-41.
4. Adler A, Katz DE, Marchaim D. The continuing plague of extended-spectrum β-lactamase–producing Enterobacteriaceae infections. Infect Dis Clin North Am 2016;30: 347-375.
5. Cantón R, González-Alba JM, Galán JC. CTX-M enzymes: origin and diffusion. Front Microbiol 2012;3:110.
6. Bonnet R. Growing group of extended-spectrum β-lactamases: the CTX-M enzymes. Antimicrob Agents Chemother 2004; 48: 1-14.
7. Canton R, Coque TM. The CTX-M beta-lactamase pandemic. Curr Opin Microbiol 2006;9:466-475.
8. Roschanski N, Fischer J, Guerra B, Roesler U. Development of a multiplex real-time PCR for the rapid detection of the predominant beta-lactamase genes CTX-M, SHV, TEM and CIT-type AmpCs in Enterobacteriaceae. PLoS One 2014;9(7): e100956.
9. Ghotaslou R, Yeganeh Sefidan F, Akhi MT, Asgharzadeh M, Mohammadzadeh Asl Y. Dissemination of genes encoding aminoglycoside-modifying enzymes and armA among Enterobacteriaceae isolates in northwest Iran. Microb Drug Resist 2017;23:826-832.
10. Poole K. Aminoglycoside resistance in Pseudomonas aeruginosa. Antimicrob Agents Chemother 2005;49:479-487.
11. Azimi L, Nordmann P, Lari AR, Bonnin RA. First report of OXA-48-producing Klebsiella pneumoniae strains in Iran. GMS Hyg Infect Control 2014;9:Doc07.
12. Han SB, Lee SC, Lee SY, Jeong DC, Kang JH. Aminoglycoside therapy for childhood urinary tract infection due to extended-spectrum β-lactamase-producing Escherichia coli or Klebsiella pneumoniae. BMC Infect Dis 2015; 15: 414.
13. Peerayeh SN, Rostami E, Siadat SD, Derakhshan S. High rate of aminoglycoside resistance in CTX-M-15 producing Klebsiella pneumoniae isolates in Tehran, Iran. Lab Med 2014;45:231-237.
14. Ramirez MS, Tolmasky ME. Aminoglycoside modifying enzymes. Drug Resist Updat 2010; 13: 151-171.
15. Barati A, Ghaderpour A, Chew L, Bong C, Thong K, Chong V, et al. Isolation and characterization of aquatic-borne Klebsiella pneumoniae from tropical estuaries in Malaysia. Int J Environ Res Public Health 2016; 13: 426.
16. Wayne PA. Clinical and Laboratory Standards Institute, Performance Standards for Antimicrobial Susceptibility Testing 2018;M100, 28th ed.
17. Ghafourian S, Bin Sekawi Z, Sadeghifard N, Mohebi R, Kumari Neela V, Maleki A, et al. The prevalence of ESBLs producing Klebsiella pneumoniae isolates in some major hospitals, Iran. Open Microbiol J 2011; 5: 91-95.
18. Jeong S, Bae I, Kwon S, Lee J, Song J, Jung H, et al. Dissemination of transferable CTX‐M‐type extended‐spectrum β‐lactamase‐producing Escherichia coli in Korea. J Appl Microbiol 2005; 98: 921-927.
19. Liu Z, Li W, Wang J, Pan J, Sun S, Yu Y, et al. Identification and characterization of the first Escherichia coli strain carrying NDM-1 gene in China. PLoS One 2013;8(6):e66666.
20. Arpin C, Dubois V, Coulange L, André C, Fischer I, Noury P, et al. Extended-spectrum β-lactamase-producing Enterobacteriaceae in community and private health care centers. Antimicrob Agents Chemother 2003;47:3506-3514.
21. Park CH, Robicsek A, Jacoby GA, Sahm D, Hooper DC. Prevalence in the United States of aac(6′)-Ib-cr encoding a ciprofloxacin-modifying enzyme. Antimicrob Agents Chemother 2006;50:3953-3955.
22. Aghamohammad S, Badmasti F, Solgi H, Aminzadeh Z, Khodabandelo Z, Shahcheraghi F. First report of extended-spectrum betalactamase-producing Klebsiella pneumoniae among fecal carriage in Iran: high diversity of clonal relatedness and virulence factor profiles. Microb Drug Resist 2020;26:261-269.
23. Shoja S, Ansari M, Faridi F, Azad M, Davoodian P, Javadpour S, et al. Identification of carbapenem-resistant Klebsiella pneumoniae with emphasis on New Delhi metallo-beta-lactamase-1 (blaNDM-1) in Bandar Abbas, South of Iran. Microb Drug Resist 2018;24:447-454.
24. Hosseinzadeh Z, Ebrahim-Saraie HS, Sarvari J, Mardaneh J, Dehghani B, Rokni-Hosseini SMH, et al. Emerge of blaNDM-1 and blaOXA-48-like harboring carbapenem-resistant Klebsiella pneumoniae isolates from hospitalized patients in southwestern Iran. J Chin Med Assoc 2018; 81: 536-540.
25. Mansouri S, Neyestanaki DK, Shokoohi M, Halimi S, Beigverdi R, Rezagholezadeh F, et al. Characterization of AmpC, CTX-M and MBLs types of β-lactamases in clinical isolates of Klebsiella pneumoniae and Escherichia coli producing extended spectrum β-lactamases in Kerman, Iran. Jundishapur J Microbiol 2014; 7(2):e8756.
26. Bialvaei AZ, Kafil HS, Asgharzadeh M, Aghazadeh M, Yousefi M. CTX-M extended-spectrum β-lactamase-producing Klebsiella spp, Salmonella spp, Shigella spp and Escherichia coli isolates in Iranian hospitals. Braz J Microbiol 2016; 47: 706-711.
27. Vading M, Nauclér P, Kalin M, Giske C. Invasive infection caused by Klebsiella pneumoniae is a disease affecting patients with high comorbidity and associated with high long-term mortality. PLoS One 2018;13(4):e0195258.
28. Karlowsky JA, Adam HJ, Baxter MR, Lagacé-Wiens PR, Walkty AJ, Hoban DJ, et al. In vitro activity of ceftaroline-avibactam against Gram-negative and Gram-positive pathogens isolated from patients in Canadian hospitals from 2010 to 2012: results from the CANWARD surveillance study. Antimicrob Agents Chemother 2013;57:5600-5611.
29. Cubero M, Grau I, Tubau F, Pallarés R, Domínguez MÁ, Linares J, et al. Molecular epidemiology of Klebsiella pneumoniae strains causing bloodstream infections in adults. Microb Drug Resist 2018;24:949-957.
30. Lai C-C, Lee K, Xiao Y, Ahmad N, Veeraraghavan B, Thamlikitkul V, et al. High burden of antimicrobial drug resistance in Asia. J Glob Antimicrob Resist 2014; 2: 141-147.
31. Derakhshan S, Peerayeh SN, Fallah F, Bakhshi B, Rahbar M, Ashrafi A. Detection of class 1, 2, and 3 integrons among Klebsiella pneumoniae isolated from children in Tehran hospitals. Arch Pediatr Infect Dis 2014;2:164-168.
32. Saeidi S, Alavi-Naini R, Shayan S. Antimicrobial susceptibility and distribution of tem and ctx-m genes among esbl-producing Klebsiella pneumoniae and Pseudomonas aeruginosa causing urinary tract infections. Zahedan J Res Med Sci 2013;16:1-5.
33. Mohammed AS. Molecular detection of CTX-M genes in Klebsiella pneumoniae isolated from different clinical samples in Baghdad city. Med J Babylon 2015;12:152-160.
34. Bindayna KM, Murtadha M. High prevalence of blaCTX–M in Enterobacteriaceae isolates from the Kingdom of Bahrain. Asian Pac J Trop Med 2011; 4: 937-940.
35. Al Sweih N, Salama M, Jamal W, Al Hashem G, Rotimi V. An outbreak of CTX-M-15-producing Klebsiella pneumoniae isolates in an intensive care unit of a teaching hospital in Kuwait. Indian J Med Microbiol 2011; 29: 130-135.
36. Erum K, Schneiders T, Afia Z, Erum A, Asra P, Rumina H. Emergence of CTX-M Group 1-ESBL producing Klebsiella pneumonia from a tertiary care centre in Karachi, Pakistan. J Infect Dev Ctries 2010;4:472-476.
37. Kiratisin P, Apisarnthanarak A, Laesripa C, Saifon P. Molecular characterization and epidemiology of extended-spectrum-β-lactamase-producing Escherichia coli and Klebsiella pneumoniae isolates causing health care-associated infection in Thailand, where the CTX-M family is endemic. Antimicrob Agents Chemother 2008;52:2818-2824.
38. Lotfollahi L, Samadi N, Hosainzadegan H, Qomi MA. Prevalence of aac(3’)-IIa and aac(6’)-Ib genes incidence involved in aminoglycoside resistance in Klebsiella pneumoniae isolated from clinical samples in Urmia Hospitals, Iran. Am J Pharm Tech Res 2015;5:326-334.
39. Eftekhar F. Prevalence of qnr and aac(6’)-Ib-cr Genes in clinical isolates of Klebsiella pneumoniae from Imam Hussein Hospital in Tehran. Iran J Med Sci 2015; 40: 515-521.
40. Nasiri G, Peymani A, Farivar TN, Hosseini P. Molecular epidemiology of aminoglycoside resistance in clinical isolates of Klebsiella pneumoniae collected from Qazvin and Tehran provinces, Iran. Infect Genet Evol 2018;64:219-224.
| Files | ||
| Issue | Vol 13 No 2 (2021) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v13i2.5975 | |
| Keywords | ||
| Aminoglycoside-modifying enzymes; Cefotaximase-Munich; Klebsiella pneumoniae; Extended spectrum β-lactamases; Iran | ||
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How to Cite
1.
Latifi B, Tajbakhsh S, Ahadi L, Yousefi F. Coexistence of aminoglycoside resistance genes in CTX-M-producing isolates of Klebsiella pneumoniae in Bushehr province, Iran. Iran J Microbiol. 2021;13(2):161-170.
