High prevalence of multidrug-resistant non-fermentative Gram-negative bacilli harboring blaIMP-1 and blaVIM-1 metallo-beta-lactamase genes in Birjand, south-east Iran
Background and Objectives: Non-fermentative Gram-negative Bacilli (NFGNB) is known as a major cause of healthcare-associated infections with high levels of antibiotic resistance. The aim of this study was to investigate the antibiotic resistance profiles and molecular characteristics of metallo-beta-lactamase (MBL)-producing NFGNB.
Materials and Methods: In this cross-sectional study, the antibiotic resistance profile of 122 clinical NFGNB isolates was determined by the Kirby-Bauer disk diffusion and microdilution broth methods. Bacterial isolates were investigated for the detection of MBLs production using the combination disk diffusion Test (CDDT). The existence of blaIMP, blaVIM, and blaNDM genes in all carbapenem-resistant isolates was determined employing polymerase chain reaction (PCR) assays.
Results: High resistance in Pseudomonas aeruginosa was reported to cefotaxime and minocycline, whereas Acinetobacter baumannii isolates were highly resistant to all antibiotics except colistin. Multidrug resistance (MDR)-NFGNB (66% vs. 12.5%, P=0.0004) and extensively drug resistant (XDR)-NFGNB (55.7% vs. 12.5%, P=0.001) isolates were significantly more common in hospitalized patients than in outpatients. The production of MBL was seen in 40% of P. aeruginosa and 93.3% of A. baumannii isolates. It was found that 33.3% and 46.7% of carbapenem-resistant P. aeruginosa isolates, and 13.3% and 28.9% of carbapenem-resistant A. baumannii isolates were harboring blaIMP-1 and blaVIM-1 genes, respectively. The incidence of MDR (98.2% vs. 28.3%, P<0.001) and XDR (96.4% vs. 11.7%, P<0.001) in MBL-producing NFGNB isolates was significantly higher than non-MBL-producing isolates.
Conclusion: This study demonstrated a higher rate of resistance among NFGNB isolates with an additional burden of MBL production within them, warranting a need for robust microbiological surveillance and accurate detection of MBL producers among the NFGNB.
2. Gupta R, Malik A, Rizvi M, Ahmed M. Presence of metallo-beta-lactamases (MBL), extended-spectrum beta-lactamase (ESBL) & AmpC positive non-fermenting Gram-negative bacilli among intensive care unit patients with special reference to molecular detection of blaCTX-M & blaAmpC genes. Indian J Med Res 2016; 144: 271-275.
3. Usha Rani P, Vijayalakshmi P. Detection of metallo-beta-lactamase production in rare carbapenem-resistant non-fermentative gram-negative bacilli isolated in a tertiary care hospital, Visakhapatnam, India. J Med Microbiol Infect Dis 2016; 4: 31-36.
4. Gupta V. Metallo beta lactamases in Pseudomonas aeruginosa and Acinetobacter species. Expert Opin Investig Drugs 2008; 17: 131-143.
5. Yadav SK, Bhujel R, Mishra SK, Sharma S, Sherchand JB. Emergence of multidrug-resistant non-fermentative gram negative bacterial infection in hospitalized patients in a tertiary care center of Nepal. BMC Res Notes 2020; 13: 319.
6. Farhan SM, Ibrahim RA, Mahran KM, Hetta HF, Abd El-Baky RM. Antimicrobial resistance pattern and molecular genetic distribution of metallo-β-lactamases producing Pseudomonas aeruginosa isolated from hospitals in Minia, Egypt. Infect Drug Resist 2019; 12: 2125-2133.
7. Tarashi S, Goudarzi H, Erfanimanesh S, Pormohammad A, Hashemi A. Phenotypic and molecular detection of metallo-beta-lactamase genes among imipenem resistant Pseudomonas aeruginosa and Acinetobacter baumannii strains isolated from patients with burn injuries. Arch Clin Infect Dis 2016; 11(4): e39036.
8. Kaur A, Gupta V, Chhina D. Prevalence of metalo-β-lactamase-producing (MBL) Acinetobacter species in a tertiary care hospital. Iran J Microbiol 2014; 6: 22-25.
9. Esther J, Edwin DH, Uma. Prevalence of carbapenem resistant non-fermenting gram negative bacterial infection and identification of carbapenemase producing NFGNB isolates by simple phenotypic tests. J Clin Diagn Res 2017; 11: DC10-DC13.
10. Chaudhary AK, Bhandari D, Amatya J, Chaudhary P, Acharya B. Metallo-Beta-Lactamase producing gram-negative bacteria among patients visiting shahid Gangalal national heart centre. Austin J Microbiol 2016; 2: 1010.
11. 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. ISRN Microbiol 2014; 2014: 941507.
12. Gupta V, Sidhu S, Chander J. Metallo-β-lactamase producing nonfermentative gram-negative bacteria: an increasing clinical threat among hospitalized patients. Asian Pac J Trop Med 2012; 5: 718-721.
13. Acharya M, Joshi PR, Thapa K, Aryal R, Kakshapati T, Sharma S. Detection of metallo-β-lactamases-encoding genes among clinical isolates of Pseudomonas aeruginosa in a tertiary care hospital, Kathmandu, Nepal. BMC Res Notes 2017; 10: 718.
14. Farajzadeh Sheikh A, Shahin M, Shokoohizadeh L, Ghanbari F, Solgi H, Shahcheraghi F. Emerge of NDM-1-producing multidrug-resistant Pseudomonas aeruginosa and co-harboring of carbapenemase genes in South of Iran. Iran J Public Health 2020; 49: 959-967.
15. Wayne PA (2019). Clinical and Laboratory Standards Institute (CLSI). performance standards for antimicrobial susceptibility testing. 29th ed. CLSI supplement M100S.
16. 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.
17. Peleg AY, Franklin C, Bell JM, Spelman DW. Dissemination of the metallo-β-lactamase gene bla IMP-4 among gram-negative pathogens in a clinical setting in Australia. Clin Infect Dis 2005; 41: 1549-1556.
18. Poirel L, Walsh TR, Cuvillier V, Nordmann P. Multiplex PCR for detection of acquired carbapenemase genes. Diagn Microbiol Infect Dis 2011; 70: 119-123.
19. Sedighi M, Halajzadeh M, Ramazanzadeh R, Amirmozafari N, Heidary M, Pirouzi S. Molecular detection of β-lactamase and integron genes in clinical strains of Klebsiella pneumoniae by multiplex polymerase chain reaction. Rev Soc Bras Med Trop 2017; 50: 321-328.
20. Spilker T, Coenye T, Vandamme P, LiPuma JJ. PCR-based assay for differentiation of Pseudomonas aeruginosa from other Pseudomonas species recovered from cystic fibrosis patients. J Clin Microbiol 2004; 42: 2074-2079.
21. Porbaran M, Habibipour R. Relationship between biofilm regulating operons and various β-Lactamase enzymes: analysis of the clinical features of infections caused by non-fermentative gram-negative bacilli (NFGNB) from Iran. J Pure Appl Microbiol 2020; 14: 1723-1736.
22. 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.
23. Grewal US, Bakshi R, Walia G, Shah PR. Antibiotic susceptibility profiles of non-fermenting gram-negative bacilli at a tertiary care hospital in Patiala, India. Niger Postgrad Med J 2017; 24: 121-125.
24. Hu LF, Chen GS, Kong QX, Gao LP, Chen X, Ye Y, et al. Increase in the prevalence of resistance determinants to trimethoprim/sulfamethoxazole in clinical Stenotrophomonas maltophilia isolates in China. PLoS One 2016; 11(6): e0157693.
25. Chung HS, Kim K, Hong SS, Hong SG, Lee K, Chong Y. The sul1 gene in Stenotrophomonas maltophilia with high-level resistance to trimethoprim/sulfamethoxazole. Ann Lab Med 2015; 35: 246-249.
26. Alcaraz E, Garcia C, Papalia M, Vay C, Friedman L, Passerini de Rossi B. Stenotrophomonas maltophilia isolated from patients exposed to invasive devices in a university hospital in Argentina: molecular typing, susceptibility and detection of potential virulence factors. J Med Microbiol 2018; 67: 992-1002.
27. Gheorghe I, Czobor I, Chifiriuc MC, Borcan E, Ghiţă C, Banu O, et al. Molecular screening of carbapenemase-producing gram-negative strains in Romanian intensive care units during a one year survey. J Med Microbiol 2014; 63: 1303-1310.
28. El-Mahallawy HA, Hamid RMA, Hassan SS, Radwan S, Saber M. The increased frequency of carbapenem resistant non fermenting gram negative pathogens as causes of health care associated infections in adult cancer patients. J Cancer Ther 2015; 6: 881-888.
29. 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.
30. Tohamy ST, Aboshanab KM, El-Mahallawy HA, El-Ansary MR, Afifi SS. Prevalence of multidrug-resistant gram-negative pathogens isolated from febrile neutropenic cancer patients with bloodstream infections in Egypt and new synergistic antibiotic combinations. Infect Drug Resist 2018; 11: 791-803.
31. Gajdács M, Burián K, Terhes G. Resistance levels and epidemiology of non-fermenting gram-negative bacteria in urinary tract infections of inpatients and outpatients (RENFUTI): a 10-year epidemiological snapshot. Antibiotics (Basel) 2019; 8: 143.
32. Kaleem F, Usman J, Hassan A, Khan A. Frequency and susceptibility pattern of metallo-beta-lactamase producers in a hospital in Pakistan. J Infect Dev Ctries 2010; 4: 810-813.
33. Thapa P, Bhandari D, Shrestha D, Parajuli H, Chaudhary P, Amatya J, et al. A hospital based surveillance of metallo-beta-lactamase producing gram negative bacteria in Nepal by imipenem-EDTA disk method. BMC Res Notes 2017; 10: 322.
34. Lee K, Lee WG, Uh Y, Ha GY, Cho J, Chong Y, et al. VIM-and IMP-type metallo-beta-lactamase-producing Pseudomonas spp. and Acinetobacter spp. in Korean hospitals. Emerg Infect Dis 2003; 9: 868-871.
35. Choudhary V, Pal N, Hooja S. Prevalence and antibiotic resistance pattern of metallo-β-lactamase-producing Pseudomonas aeruginosa isolates from clinical specimens in a tertiary care hospital. J Mahatma Gandhi Inst Med Sci 2019; 24: 19-22.
|Issue||Vol 13 No 4 (2021)|
|Gram-negative bacteria; Carbapenems; Anti-bacterial agents; Metallo-beta-lactamase; Carbapenem resistance|
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