Investigation of Metallobetalactamase (blaIMP & blaVIM) and Carbapenemase (blaKPC & blaGES) Genes in Gram Negative Rods Isolated from Cancer Patients

Document Type : Original Research

Authors
1 Department of Immunology & Microbiology, Arak University of Medical Sciences, Arak, Iran
2 Infectious Research Center, Arak University of Medical Sciences, Arak, Iran
3 Vice Chancellor for Research of IDRC Arak University of Medical Sciences, Iran.
4 Assistant professor, IDRC research center Arak University of Medical Sciences.
Abstract
Backgrounds: Bacterial infections are the most common complication in cancer patients. Infection with multi-drug resistant bacteria has recently become a worrying phenomenon in cancer patients.

This study focused on Gram-negative bacteria isolated from clinical samples of cancer patients. The purpose of this study was to evaluate the presence and prevalence of drug resistance genes, including metallobetalactamase (blaIMP and blaVIM) and carbapenemase (blaKPC and blaGES) genes, in the main bacteria agents of nosocomial infections in cancer patients, such as Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli.

Materials & Methods: Common biochemical methods were used to identify bacterial isolates. Antimicrobial susceptibility testing was performed according to the standard method recommended by the Clinical and Laboratory Standards Institute (2019).

Polymerase chain reaction (PCR) method was also used to check the presence and prevalence of resistance genes.

Findings: During six months, from May to November 2020, 250 clinical samples were collected from cancer patients in Ayatollah Khansari hospital in Arak city, Iran. From which 80 Gram-negative bacilli were isolated, including 33 (41.2%) E. coli, 15 (18.7%) A. baumannii complex, 12 (15%) P. aeruginosa, eight (10%) K. pneumoniae, seven (8.7%) Citrobacter freundii, and five (6.2%) Enterobacter aerogenes isolates. The frequency of blaKPC, blaGES, blaIMP, and blaVIM genes was 39.95, 21.25, 16.25, and 17.45%, respectively.

Conclusion: The present study emphasizes the importance of identifying Gram negative rods and their resistance genes (metallobetalactamase and carbapenemase genes) in cancer patients, carrying out preventive instructions to prevent the transmission of resistance genes, and reducing mortality in these patients.

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1. Brink AJ. Epidemiology of carbapenem-resistant Gram-negative infections globally. Curr Opin Infect Dis. 2019;32(6):609-16.
2. Trecarichi EM, Tumbarello M. Antimicrobial-resistant Gram-negative bacteria in febrile neutropenic patients with cancer: Current epidemiology and clinical impact. Curr Opin Infect Dis. 2014;27(2):200-10.
3. Nurain AM, Bilal NE, Ibrahim ME. The frequency and antimicrobial resistance patterns of nosocomial pathogens recovered from cancer patients and hospital environments. Asian Pac J Trop Biomed. 2015;5(12):1055-9.
4. Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis. 2011;52(4):e56-93.
5. Kurtaran B, Candevir A, Tasova Y, Kibar F, Yavuz S, Kara O, et al. Hospital-acquired bloodstream infections in cancer patients between 2005 and 2007 in a Turkish university hospital. Arch Clin Microbiol. 2010;1(2):1-5.
6. Baden LR, Bensinger W, Angarone M, Casper C, Dubberke ER, Freifeld AG, et al. Prevention and treatment of cancer-related infections. J Natl Compr Canc Netw. 2012;10(11):1412-45.
7. Galloway-Peña J, Brumlow C, Shelburne S. Impact of the microbiota on bacterial infections during cancer treatment. Trends Microbiol. 2017;25(12):992-1004.
8. Cai B, Echols R, Magee G, Arjona Ferreira JC, Morgan G, Ariyasu M, et al. Prevalence of carbapenem-resistant Gram-negative infections in the United States predominated by Acinetobacter baumannii and Pseudomonas aeruginosa. Open Forum Infect Dis. 2017;4(3):ofx176.
9. Moosavian M, Ahmadi K, Shoja S, Mardaneh J, Shahi F, Afzali M. Antimicrobial resistance patterns and their encoding genes among clinical isolates of Acinetobacter baumannii in Ahvaz, southwest Iran. MethodsX. 2020;7:101031.
10. Ebrahim-Saraie HS, Heidari H, Soltani B, Mardaneh J, Motamedifar M. Prevalence of antibiotic resistance and integrons, sul and Smqnr genes in clinical isolates of Stenotrophomonas maltophilia from a tertiary care hospital in southwest Iran. Iran J Basic Med Sci. 2019;22(8):872-7.
11. Razavi Nikoo H, Ardebili A, Mardaneh J. Systematic review of antimicrobial resistance of clinical Acinetobacter baumannii isolates in Iran: An update. Microb Drug Resist. 2017;23(6):744-56.
12. Bostanghadiri N, Ghalavand Z, Fallah F, Yadegar A, Ardebili A, Tarashi S, et al. Characterization of phenotypic and genotypic diversity of Stenotrophomonas maltophilia strains isolated from selected hospitals in Iran. Front Microbiol. 2019;10:1191.
13. Ahmed N, Ali Z, Riaz M, Zeshan B, Wattoo JI, Aslam MN. Evaluation of antibiotic resistance and virulence genes among clinical isolates of Pseudomonas aeruginosa from cancer patients. Asian Pac J Cancer Prev. 2020;21(5):1333-8.
14. Wasfi R, Rasslan F, Hassan SS, Ashour HM, El-Rahman A, Ola A. Co-existence of carbapenemase-encoding genes in Acinetobacter baumannii from cancer patients. Infect Dis Ther. 2021;10(1):291-305.
15. Rolston KV. Challenges in the treatment of infections caused by Ggram-positive and Ggram-negative bacteria in patients with cancer and neutropenia. Clinical Iinfectious Ddiseases. 2005;40(Suppl ement_4):S246-S52.
16. Zhao X, Li S, Sun X, Liu S, Duan F. Risk factors for hospital-acquired infection in cancer patients in a central Chinese hospital. Am J Infect Control. 2016;44(9):e163-5.
17. Amini A, Namvar AE. Antimicrobial resistance pattern and presence of beta-lactamase genes in Pseudomonas aeruginosa strains isolated from hospitalized patients, Babol-Iran. J Med Bacteriol. 2019;8(1-2):45-50.
18. Zare D, Fazeli H. First prevalence of metallo beta-lactamases producing Enterobacteriacea in Iranian cancer patients. Ann Ig. 2019;31:62-8.
19. Aghamiri S, Amirmozafari N, Fallah Mehrabadi J, Fouladtan B, Samadi Kafil H. Antibiotic resistance pattern and evaluation of metallo-beta lactamase genes including bla-IMP and bla-VIM types in Pseudomonas aeruginosa isolated from patients in Tehran hospitals. Int Sch Res Notices. 2014;2014.
20. Ghasemian A, Rizi KS, Vardanjani HR, Nojoomi F. Prevalence of clinically isolated metallo-beta-lactamase-producing Pseudomonas aeruginosa, coding genes, and possible risk factors in Iran. Iran J Pathol. 2018;13(1):1-9.
21. Nojoomi F, Ghasemian A. Resistance and virulence factor determinants of carbapenem-resistant Escherichia coli clinical isolates in three hospitals in Tehran, Iran. Infect Epidemiol Microbiol. 2017;3(4):107-11.
22. Van der Zwaluw K, de Haan A, Pluister GN, Bootsma HJ, de Neeling AJ, Schouls LM. The carbapenem inactivation method (CIM), a simple and low-cost alternative for the Carba NP test to assess phenotypic carbapenemase activity in Gram-negative rods. PloS One. 2015;10(3):e0123690.
23. Freire M, Pierrotti L, Ibrahim K, Magri A, Bonazzi P, Hajar L, et al. Infection with Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae in cancer patients. Eur J Clin Microbiol Infect Dis. 2015;34(2):277-86.
24. Shariati A, Azimi T, Ardebili A, Chirani A, Bahramian A, Pormohammad A, et al. Insertional inactivation of oprD in carbapenem-resistant Pseudomonas aeruginosa strains isolated from burn patients in Tehran, Iran. New Microbes New Infect. 2018;21:75-80.
25. Eyvazi S, Hakemi-Vala M, Hashemi A, Bagheri Bejestani F, Elahi N. Emergence of NDM-1-producing Escherichia coli in Iran. Arch Clin Infect Dis. 2018;13(4):e62029.
26. Nagaraj S, Chandran S, Shamanna P, Macaden R. Carbapenem resistance among Escherichia coli and Klebsiella pneumoniae in a tertiary care hospital in south India. Indian J Med Microbiol. 2012;30(1):93-5.
27. Österblad M, Kirveskari J, Hakanen AJ, Tissari P, Vaara M, Jalava J. Carbapenemase-producing Enterobacteriaceae in Finland: The first years (2008–11). J Antimicrob Chemother. 2012;67(12):2860-4.
28. Jácome PR, Alves LR, Jácome-Júnior AT, Silva MJ, Lima JL, Araújo PS, et al. Detection of blaSPM-1, blaKPC, blaTEM, and blaCTX-M genes in isolates of Pseudomonas aeruginosa, Acinetobacter spp. and Klebsiella spp. from cancer patients with healthcare-associated infections. J Med Microbiol. 2016;65(7):658-65.
29. Chaudhary M, Payasi A. Molecular characterization and in vitro susceptibilities of β-lactamase producing Escherichia coli, Klebsiella species, Acinetobacter baumannii, Pseudomonas aeruginosa, and Staphylococcus aureus to CSE1034 and other β-lactams. Asian Pac J Trop Med. 2014;7(Suppl 1):S217-23.
30. Robledo IE, Aquino EE, Santé MI, Santana JL, Otero DM, León CF, et al. Detection of KPC in Acinetobacter spp. in Puerto Rico. Antimicrob Agents Chemother. 2010;54(3):1354-7.
31. Khodaei H, Eftekhar F. Detection of kpc-type carbapenemases in clinical isolates of Acinetobacter baumannii. JKIMSU. 2017;6(4):64-70.
32. Robledo IE, Aquino EE, Vázquez GJ. Detection of the KPC gene in Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii during a PCR-based nosocomial surveillance study in Puerto Rico. Antimicrob Agents Chemother. 2011;55(6):2968-70.
33. Vala MH, Hallajzadeh M, Hashemi A, Goudarzi H, Tarhani M, Tabrizi MS, et al. Detection of Ambler class A, B, and D ß-lactamases among Pseudomonas aeruginosa and Acinetobacter baumannii clinical isolates from burn patients. Ann Burns Fire Disasters. 2014;27(1):8-13.
34. Azimi L, Talebi M, Pourshafie MR, Owlia P, Lari AR. Characterization of carbapenemases in extensively drug resistance Acinetobacter baumannii in a burn care center in Iran. Int J Mol Cell Med. 2015;4(1):46-53.
35. Bogaerts P, Naas T, El Garch F, Cuzon G, Deplano A, Delaire T, et al. GES extended-spectrum β-lactamases in Acinetobacter baumannii isolates in Belgium. Antimicrob Agents Chemother. 2010;54(11):4872-8.
36. Al-Agamy MH, Khalaf NG, Tawfick MM, Shibl AM, El Kholy A. Molecular characterization of carbapenem-insensitive Acinetobacter baumannii in Egypt. Int J Infect Dis. 2014;22:49-54.
37. Al-Agamy MH, Shibl AM, Ali MS, Khubnani H, Radwan HH, Livermore DM. Distribution of β-lactamases in carbapenem-non-susceptible Acinetobacter baumannii in Riyadh, Saudi Arabia. J Glob Antimicrob Resist. 2014;2(1):17-21.
38. Tawfick MM, Alshareef WA, Bendary HA, Elmahalawy H, Abdulall AK. The emergence of carbapenemase blaNDM genotype among carbapenem-resistant Enterobacteriaceae isolates from Egyptian cancer patients. Eur J Clin Microbiol Infect Dis. 2020;39(7):1251-9.
39. Morsi SS. Comparative evaluation of phenotypic and genotypic methods for detection of carbapenemases in clinically significant Klebsiella pneumoniae Isolates. Egypt J Med Microbiol (EJMM). 2016;25(1):109-16.
40. Soares C, Inácio CP, Silva MJ, Leal NC, Xavier DE, Magalhães V, et al. Epidemiological profile and detection of resistance genes in bloodstream infection in cancer patients: High occurrence of metallo-β-lactamases in Enterobacteriales. Res Sq. 2021.