1887

Abstract

Introduction. The last few years have seen the emergence of multi-drug resistant (MDR) Gram-negative infections, which are associated with high morbidity and mortality. The indiscriminate use of colistin has led to the development of resistance, which can be diagnosed effectively by broth microdilution. Studies from India are limited, and this study was conducted in order to determine the prevalence and risk factors associated with colistin resistance.

Methods. Urine samples from patients admitted with urinary tract infection (UTI), growing MDR Escherichia coli and Klebsiella pneumoniae , were tested for the minimum inhibitory concentration (MIC) of colistin by broth microdilution. Isolates with an MIC >2 µg ml (resistant) were subjected to polymerase chain reaction (PCR) for the mcr1, mcr2 and mgrB genes. A case–control study with 21 cases (resistant) and 42 matched controls (sensitive) was designed to evaluate risk factors and outcomes (recurrent UTI, readmission and hospital stay >2 weeks).

Results. Two hundred and fifty MDR isolates ( E. coli =142/2319 and K.pneumoniae=108/775) from 216 patients were selected from the 25 046 isolates screened. Twenty-five isolates (20 K.pneumoniae and 5 E. coli ) were resistant to colistin, with a prevalence of 3.52  % in E. coli and 18.5  % in K. pneumoniae among the MDR isolates. PCR for the mcr1 and mcr2 genes was negative. Multivariate regression showed that multiple episodes of hospitalization, hospital stay >2 weeks, exposure to >three antibiotic classes and abnormality/surgery of the lower urinary tract were the significant risk factors for colistin resistance. Previous use of colistin and colistin resistance had a significant effect on all outcomes.

Conclusions. K. pneumoniae show six times higher prevalence of colistin resistance than E. coli , and the emergence of resistant organisms has led to an increase in morbidity in infected patients.

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2019-05-14
2024-04-25
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References

  1. Exner M, Bhattacharya S, Christiansen B, Gebel J, Goroncy-Bermes P et al. Antibiotic resistance: what is so special about multidrug-resistant Gram-negative bacteria?. GMS Hyg Infect Control 2017; 12:Doc05 [View Article]
    [Google Scholar]
  2. Patolia S, Abate G, Patel N, Patolia S, Frey S. Risk factors and outcomes for multidrug-resistant Gram-negative bacilli bacteremia. Ther Adv Infect Dis 2018; 5:11–18 [View Article]
    [Google Scholar]
  3. Tenney J, Hudson N, Alnifaidy H, Li JTC, Fung KH. Risk factors for aquiring multidrug-resistant organisms in urinary tract infections: a systematic literature review. Saudi Pharm J 2018; 26:678–684 [View Article]
    [Google Scholar]
  4. Olaitan AO, Morand S, Rolain JM. Mechanisms of polymyxin resistance: acquired and intrinsic resistance in bacteria. Front Microbiol 2014; 5:643 [View Article]
    [Google Scholar]
  5. Taneja N, Kaur H. Insights into newer antimicrobial agents against Gram-negative bacteria. Microbiol Insights 2016; 9:9–19 [View Article]
    [Google Scholar]
  6. Nation RL, Li J. Colistin in the 21st century. Curr Opin Infect Dis 2009; 22:535–543 [View Article]
    [Google Scholar]
  7. Poirel L, Jayol A, Nordmann P. Polymyxins: antibacterial activity, susceptibility testing, and resistance mechanisms encoded by plasmids or chromosomes. Clin Microbiol Rev 2017; 30:557–596 [View Article]
    [Google Scholar]
  8. Liu YY, Wang Y, Walsh TR, Yi LX, Zhang R et al. Emergence of plasmid-mediated colistin resistance mechanism mcr-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis 2016; 16:161–168 [View Article]
    [Google Scholar]
  9. Xavier BB, Lammens C, Ruhal R, Kumar-Singh S, Butaye P et al. Identification of a novel plasmid-mediated colistin-resistance gene, mcr-2, in Escherichia coli, Belgium, June 2016. Euro Surveill 2016; 21: 07 Jul 2016 [View Article]
    [Google Scholar]
  10. Nordmann P, Poirel L. Plasmid-mediated colistin resistance: an additional antibiotic resistance menace. Clin Microbiol Infect 2016; 22:398–400 [View Article]
    [Google Scholar]
  11. Mathur P, Veeraraghavan B, Devanga Ragupathi NK, Inbanathan FY, Khurana S et al. First report on a cluster of colistin-resistant Klebsiella pneumoniae strains isolated from a tertiary care center in India: whole-genome shotgun sequencing. Genome Announc 2017; 5:e01466–16 [View Article]
    [Google Scholar]
  12. Kumar M, Saha S, Subudhi E. More furious than ever: Escherichia coli-acquired co-resistance toward colistin and carbapenems. Clin Infect Dis 2016; 63:1267–1268 [View Article]
    [Google Scholar]
  13. Lima Barbieri N, Nielsen DW, Wannemuehler Y, Cavender T, Hussein A et al. mcr-1 identified in avian pathogenic Escherichia coli (APEC). PLoS One 2017; 12:e0172997 [View Article]
    [Google Scholar]
  14. Haeili M, Javani A, Moradi J, Jafari Z, Feizabadi MM et al. MgrB alterations mediate colistin resistance in Klebsiella pneumoniae isolates from Iran. Front Microbiol 2017; 8:2470 [View Article]
    [Google Scholar]
  15. Cannatelli A, D'Andrea MM, Giani T, Di Pilato V, Arena F et al. Invivo emergence of colistin resistance in Klebsiella pneumoniae producing KPC-type carbapenemases mediated by insertional inactivation of the PhoQ/PhoP mgrB regulator. Antimicrob Agents Chemother 2013; 57:5521–5526 [View Article]
    [Google Scholar]
  16. Teo J, Ngan G, Balm M, Jureen R, Krishnan P et al. Molecular characterization of NDM-1 producing Enterobacteriaceae isolates in Singapore hospitals. Western Pac Surveill Response J 2012; 3:19–24 [View Article]
    [Google Scholar]
  17. Long SW, Olsen RJ, Eagar TN, Beres SB, Zhao P et al. Population genomic analysis of 1,777 extended-spectrum beta-lactamase-producing Klebsiella pneumoniae isolates, Houston, Texas: unexpected abundance of clonal group 307. MBio 2017; 8: [View Article]
    [Google Scholar]
  18. Principe L, Piazza A, Mauri C, Anesi A, Bracco S et al. Multicenter prospective study on the prevalence of colistin resistance in Escherichia coli: relevance of mcr-1-positive clinical isolates in Lombardy, Northern Italy. Infect Drug Resist 2018; 11:377–385 [View Article]
    [Google Scholar]
  19. Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME 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 [View Article]
    [Google Scholar]
  20. Gundogdu A, Ulu-Kilic A, Kilic H, Ozhan E, Altun D et al. Could frequent carbapenem use be a risk factor for colistin resistance?. Microb Drug Resist 2018; 24:774–781 [View Article]
    [Google Scholar]
  21. Richter SE, Miller L, Uslan DZ, Bell D, Watson K et al. Risk factors for colistin resistance among Gram-negative rods and Klebsiella pneumoniae isolates. J Clin Microbiol 2018; 56: [View Article]
    [Google Scholar]
  22. Drozdinsky G, Ben-Zvi H, Kushnir S, Leibovici L, Yahav D. Colistin exposure as a risk factor for infections caused by inherently colistin resistant Enterobacteriaceae—a case–control study. Clin Microbiol Infect 2018; 24:896–899 [View Article]
    [Google Scholar]
  23. Büchler AC, Gehringer C, Widmer AF, Egli A, Tschudin-Sutter S. Risk factors for colistin-resistant Enterobacteriaceae in a low-endemicity setting for carbapenem resistance–a matched case–control study. Euro Surveill 2018; 23: [View Article]
    [Google Scholar]
  24. Yilmaz GR, Dizbay M, Guven T, Pullukcu H, Tasbakan M et al. Risk factors for infection with colistin-resistant Gram-negative microorganisms: a multicenter study. Ann Saudi Med 2016; 36:216–222 [View Article]
    [Google Scholar]
  25. Wang Y, Tian GB, Zhang R, Shen Y, Tyrrell JM et al. Prevalence, risk factors, outcomes, and molecular epidemiology of mcr-1-positive Enterobacteriaceae in patients and healthy adults from China: an epidemiological and clinical study. Lancet Infect Dis 2017; 17:390–399 [View Article]
    [Google Scholar]
  26. Li J, Nation RL, Turnidge JD, Milne RW, Coulthard K et al. Colistin: the re-emerging antibiotic for multidrug-resistant Gram-negative bacterial infections. Lancet Infect Dis 2006; 6:589–601 [View Article]
    [Google Scholar]
  27. Oliva A, Mascellino MT, Cipolla A, D'Abramo A, De Rosa A et al. Therapeutic strategy for pandrug-resistant Klebsiella pneumoniae severe infections: short-course treatment with colistin increases the in vivo and in vitro activity of double carbapenem regimen. Int J Infect Dis 2015; 33:132–134 [View Article]
    [Google Scholar]
  28. Brust K, Evans A, Plemmons R. Tigecycline in treatment of multidrug-resistant Gram-negative Bacillus urinary tract infections: a systematic review. J Antimicrob Chemother 2014; 69:2606–2610 [View Article]
    [Google Scholar]
  29. Rojas LJ, Salim M, Cober E, Richter SS, Perez F et al. Colistin resistance in carbapenem-resistant Klebsiella pneumoniae: laboratory detection and impact on mortality. Clin Infect Dis 2017; 64:711–718 [View Article]
    [Google Scholar]
  30. Giancola SE, Mahoney MV, Hogan MD, Raux BR, McCoy C et al. Assessment of fosfomycin for complicated or multidrug-resistant urinary tract infections: patient characteristics and outcomes. Chemotherapy 2017; 62:100–104 [View Article]
    [Google Scholar]
  31. Falagas ME, Vouloumanou EK, Samonis G, Vardakas KZ. Fosfomycin. Clin Microbiol Rev 2016; 29:321–347 [View Article]
    [Google Scholar]
  32. MacNair CR, Stokes JM, Carfrae LA, Fiebig-Comyn AA, Coombes BK et al. Overcoming mcr-1 mediated colistin resistance with colistin in combination with other antibiotics. Nat Commun 2018; 9:458 [View Article]
    [Google Scholar]
  33. Luque S, Escaño C, Sorli L, Li J, Campillo N et al. Urinary concentrations of colistimethate and formed colistin after intravenous administration in patients with multidrug-resistant Gram-negative bacterial infections. Antimicrob Agents Chemother 2017; 61: 25 07 2017 [View Article]
    [Google Scholar]
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