Original Article

The linkage between prevalence of integron I and reduced susceptibility to biocides in MDR Klebsiella pneumoniae isolated from neonates


Background and Objectives: Klebsiella pneumoniae causes challenging nosocomial fatal infections including neonatal sepsis. Our study aims at clarifying the contribution of integrons in the observed reduced susceptibility of multidrug-resistant (MDR) K. pneumoniae isolated from septicemic neonates to the clinically used antimicrobial agents and biocides.
Materials and Methods: Eighty-six K. pneumoniae isolates were collected from Mansoura University Children’s Hospital from septicemic neonates. Isolates were subjected to antibiotic and biocide susceptibility using disk diffusion and the agar dilution method, respectively. The distribution of different classes of integrons was screened in the isolates by PCR. Detected inegron I was sequenced in selected isolates.
Results: Fifty-seven isolates (66.27%) were MDR. In the MDR isolates, class I integron was detected in 23 (40.3%), integron III was detected in 20 (35%), whereas integron II could not be detected. Sequencing results of integron I from MDR K. pneumoniae isolates revealed that only aminoglycoside and folate synthesis inhibitors gene cassettes were detected, while the rest of the resistance genes were not associated with integron I.
Conclusion: The presence of integron I in MDR K. pneumoniae tested isolates may contribute only to some biocide resistance, however, it does not seem to be the only contributor in multiple drug resistance.

1. Saleem AF, Qamar FN, Shahzad H, Qadir M, Zaidi AK. Trends in antibiotic susceptibility and incidence of late-onset Klebsiella pneumoniae neonatal sepsis over a six-year period in a neonatal intensive care unit in karachi, pakistan. Int J Infect Dis 2013; 17(11): e961-5.
2. Firoozeh F, Mahluji Z, Khorshidi A, Zibaei M. Molecular characterization of class 1, 2 and 3 integrons in clinical multi-drug resistant Klebsiella pneumoniae isolates. Antimicrob Resist Infect Control 2019; 8: 59.
3. Lawn JE, Cousens S, Zupan J, Lancet Neonatal Survival Steering Team. 4 million neonatal deaths: When? Where? Why? Lancet 2005; 365: 891-900.
4. Sands K, Carvalho MJ, Portal E, Thomson K, Dyer C, Akpulu C, et al. Characterization of antimicrobial-resistant gram-negative bacteria that cause neonatal sepsis in seven low-and middle-income countries. Nat Microbiol 2021; 6: 512-523.
5. Gajul SV, Mohite ST, Mangalgi SS, Wavare SM, Kakade SV. Klebsiella pneumoniae in septicemic neonates with special reference to extended spectrum β-lactamase, ampc, metallo β-lactamase production and multiple drug resistance in tertiary care hospital. J Lab Physicians 2015; 7: 32-37.
6. Vijayakumar R, Sandle T, Al-Aboody MS, AlFonaisan MK, Alturaiki W, Mickymaray S. et al. Distribution of biocide resistant genes and biocides susceptibility in multidrug-resistant Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii—a first report from the kingdom of saudi arabia. J Infect Public Health 2018; 11: 812-816.
7. Odumosu BT, Adeniyi BA, Chandra R. Analysis of integrons and associated gene cassettes in clinical isolates of multidrug resistant Pseudomonas aeruginosa from southwest nigeria. Ann Clin Microbiol Antimicrob 2013; 12: 29.
8. Magiorakos A-P, 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.
9. Mazel D. Integrons: Agents of bacterial evolution. Nat Rev Microbiol 2006; 4: 608-620.
10. Roy Chowdhury P, Ingold A, Vanegas N, Martínez E, Merlino J, Merkier AK, et al. Dissemination of multiple drug resistance genes by class 1 integrons in Klebsiella pneumoniae isolates from four countries: A comparative study. Antimicrob Agents Chemother 2011; 55: 3140-3149.
11. Kadry AA, Serry FM, El-Ganiny AM, El-Baz AM. Integron occurrence is linked to reduced biocide susceptibility in multidrug resistant Pseudomonas aeruginosa. Br J Biomed Sci 2017; 74: 78-84.
12. Malek MM, Amer FA, Allam AA, El-Sokkary RH, Gheith T, Arafa M. Occurrence of classes i and ii integrons in Enterobacteriaceae collected from zagazig university hospitals, egypt. Front Microbiol 2015; 6: 601.
13. Sehmi SK, Allan E, MacRobert AJ, Parkin I. The bactericidal activity of glutaraldehyde-impregnated polyurethane. Microbiologyopen 2016; 5: 891-897.
14. Lukabwe H, Kajabwangu R, Mugisha D, Mayengo H, Munyanderu B, Baluku A, et al. Effectiveness of preoperative bath using chloroxylenol antiseptic soap on the incidence of post emergency cesarean section surgical site infection at Mbarara Regional Referral hospital, Uganda: a randomized controlled trial. Pan Afr Med J 2022; 41: 92.
15. Durani P, Leaper D. Povidone-iodine: Use in hand disinfection, skin preparation and antiseptic irrigation. Int Wound J 2008; 5: 376-387.
16. Yao H, Liu J, Jiang X, Chen F, Lu X, Zhang J. Analysis of the clinical effect of combined drug susceptibility to guide medication for carbapenem-resistant Klebsiella pneumoniae patients based on the Kirby-Bauer disk diffusion method. Infect Drug Resist 2021; 14: 79-87.
17. (CLSI), Performance standards for antimicrobial susceptibility Tests. Clinical and laboratory standards institute, Wayne, PA 2019, In 29th edition document M100.
18. Kawamura-Sato K, Wachino J-I, Kondo T, Ito H, Arakawa Y. Correlation between reduced susceptibility to disinfectants and multidrug resistance among clinical isolates of Acinetobacter species. J Antimicrob Chemother 2010; 65: 1975-1983.
19. Marinho SA, Teixeira AB, Santos OS, Cazanova RF, Ferreira CAS, Cherubini K, et al. Identification of Candida spp. By phenotypic tests and PCR. Braz J Microbiol 2010; 41: 286-294.
20. White PA, McIver CJ, Deng Y, Rawlinson WD. Characterisation of two new gene cassettes, aada5 and dfra17. FEMS Microbiol Lett 2000; 182: 265-269.
21. Ploy M-C, Denis F, Courvalin P, Lambert T. Molecular characterization of integrons in Acinetobacter baumannii: Description of a hybrid class 2 integron. Antimicrob Agents Chemother 2000; 44: 2684-2688.
22. Du Q, Pan F, Wang C, Yu F, Shi Y, Liu W, et al. Nosocomial dissemination of hypervirulent Klebsiella pneumoniae with high-risk clones among children in shanghai. Front Cell Infect Microbiol 2022; 12: 984180.
23. Wang J, Lv Y, Yang W, Zhao P, Yin C. Epidemiology and clinical characteristics of infection/colonization due to carbapenemase-producing enterobacterales in neonatal patients. BMC Microbiol 2022; 22: 177.
24. Ballot DE, Bandini R, Nana T, Bosman N, Thomas T, Davies VA, et al. A review of -multidrug-resistant Enterobacteriaceae in a neonatal unit in johannesburg, south africa. BMC Pediatr 2019; 19: 320.
25. Albasha AM, Osman EH, Abd-Alhalim S, Alshaib EF, Al-Hassan L, Altayb HN. Detection of several carbapenems resistant and virulence genes in classical and hyper-virulent strains of Klebsiella pneumoniae isolated from hospitalized neonates and adults in khartoum. BMC Res Notes 2020; 13: 312.
26. Jahanbin F, Marashifard M, Jamshidi S, Zamanzadeh M, Dehshiri M, Malek Hosseini SAA, et al. Investigation of integron-associated resistance gene cassettes in urinary isolates of Klebsiella pneumoniae in yasuj, southwestern iran during 2015–16. Avicenna J Med Biotechnol 2020; 12: 124-131.
27. Hassuna NA, AbdelAziz RA, Zakaria A, Abdelhakeem M. Extensively-drug resistant Klebsiella pneumoniae recovered from neonatal sepsis cases from a major nicu in egypt. Front Microbiol 2020; 11: 1375.
28. Heidary M, Goudarzi H, Hashemi A, Eslami G, Goudarzi M, Salimi Chirani A, et al. Prevalence of quinolone resistance genes in Klebsiella pneumoniae strains isolated from hospitalized patients during 2013-2014. Arch Pediatr Infect Dis 2016; 5(4): e38343.
29. Su J, Shi L, Yang L, Xiao Z, Li X, Yamasaki S. Analysis of integrons in clinical isolates of Escherichia coli in china during the last six years. FEMS Microbiol Lett 2006; 254: 75-80.
30. Derakhshan S, Najar Peerayeh S, 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.
31. Xu X, Li X, Luo M, Liu P, Su K, Qing Y, et al. Molecular characterisations of integrons in clinical isolates of Klebsiella pneumoniae in a chinese tertiary hospital. Microb Pathog 2017; 104: 164-170.
32. Fluit AC, Schmitz F-J. Resistance integrons and super-integrons. Clin Microbiol Infect 2004; 10: 272-288.
33. Zeighami H, Haghi F, Hajiahmadi F. Molecular characterization of integrons in clinical isolates of betalactamase-producing Escherichia coli and Klebsiella pneumoniae in iran. J Chemother 2015; 27: 145-151.
34. Mobarak-Qamsari M, Ashayeri-Panah M, Eftekhar F, Feizabadi MM. Integron mediated multidrug resistance in extended spectrum beta-lactamase producing clinical isolates of Klebsiella pneumoniae. Braz J Microbiol 2014; 44: 849-854.
35. Liao W, Li D, Liu F, Du F-L, Long D, Zhang W, et al. Distribution of integrons and phylogenetic groups among highly virulent serotypes of Klebsiella pneumoniae in a chinese tertiary hospital. J Glob Antimicrob Resist 2020; 21: 278-284.
36. Poirel L, Naas T, Nordmann P. Diversity, epidemiology, and genetics of class d beta-lactamases. Antimicrob Agents Chemother 2010; 54: 24-38.
37. Pal C, Bengtsson-Palme J, Kristiansson E, Larsson DGJ. Co-occurrence of resistance genes to antibiotics, biocides and metals reveals novel insights into their co-selection potential. BMC Genomics 2015; 16: 964.
IssueVol 15 No 1 (2023) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijm.v15i1.11915
Klebsiella pneumoniae; Integrons; Disinfectants; Drug resistance; Newborn

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How to Cite
Samir P, Mohamed El-Baz A, Ibrahim Kenawy H. The linkage between prevalence of integron I and reduced susceptibility to biocides in MDR Klebsiella pneumoniae isolated from neonates. Iran J Microbiol. 2023;15(1):27-37.