PREVALENCE AND MOLECULAR CHARACTERIZATION OF EXTENDED SPECTRUM Î²-LACTAMASES IN KLEBSIELLA PNEUMONIAE ISOLATES FROM CANCER PATIENTS AND OTHERS
Keywords:Antimicrobial resistance, Egypt, ESBL, Klebsiella pneumoniae
AbstractObjective: Klebsiella pneumoniae is highly prevalent in hospitals and causes many nosocomial infections. The study sought to determine prevalence rates of extended spectrum Î²-lactamases (ESBLs) in clinical isolates of K. pneumoniae from Cairo, Egypt and to detect the ESBL-encoding genes in the isolates.
Methods: K. pneumoniae isolates were collected through two-year period (2011-2012). Identification of K. pneumoniae was carried out using automated Microscan and standard biochemical tests. ESBL pattern and minimum inhibitory concentrations (MICs) were detected using Clinical and Laboratory Standards Institute guidelines and confirmatory tests. Multiplex polymerase chain reaction for ESBL-encoding genes and plasmid profiling were performed.
Results: In the present work; 112 isolates, 75 of them from cancer patients, were characterized. High proportion (52 of 112, 46 %â€) of ESBLs among the isolates were detected. Highest prevalence of ESBLs was seen among cancer patients, 39 isolates of 75 (52%). Plasmid profile for ESBL-producing K. pneumoniae isolates showed different sizes and numbers of plasmids in all isolates. MICs for all ESBL-producing isolates revealed high resistance rates with tetracycline (100%), cefepime (96%), gentamycin (90%) and ciprofloxacin (79%). Whereas, only two isolates (4%) were resistant to both carbapenem drugs tested, imipenem and meropenem. blaTEM, blaSHV, and bla CTX-M were performed for all ESBL-producing isolates. Five patterns of ESBL-encoding genes were detected. The most prevalent ESBL-encoding gene was blaTEM;alone in 40% and with other ESBL-encoding gene(s) in 48% of the isolates.
Conclusion: High prevalence of ESBL (46%) in our isolates suggesting the need for continuous monitoring of emergence of this pattern in our region.
CurelloJ, MacDougall C. Beyond susceptible and resistant, part II: Treatment of infections due to Gram-negative organisms producing extended-spectrum Î²-lactamases. J Pediatr Pharmacol Ther 2014;19:156â€“64.
Coque TM, Baquero F, Canton R. Increasing prevalence of ESBL-producing Enterobacteriaceae in Europe. Euro surveillance 2008;13:pii=19044.
Fennell J, Vellinga A, Hanahoe B, Morris D, Boyle F, Higgins F, et al. Increasing prevalence of ESBL production among Irish clinical Enterobacteriaceae from 2004 to 2008: an observational study. BMC Infect Dis 2012;12:116.
Sankar S, Narayanan H, Kuppanan S, Nandagopal B. Frequency of extended spectrum Î²-lactamase (ESBL)-producing Gram-negative bacilli in a 200-bed multi-specialty hospital in Vellore district, Tamil Nadu, India. Infection 2012;40:425â€“9.
Bradford PA. Extended-spectrum Î²-lactamases in the 21st century: characterization, epidemiology, and detection of this important resistance threat. Clin Microbiol Rev 2001;14:933-51.
Tofteland S, Dahl KH, AasnÃ¦s B, Sundsfjord A, Naseer U. A nationwide study of mechanisms conferring reduced susceptibility to extended-spectrum cephalosporins in clinical Escherichia coli and Klebsiella spp. isolates. Scand J Infect Dis 2012;44:927-33.
Kang CI, Kim SH, Kim DM, Park WB, Lee KD, Kim HB, et al. Risk factors for ciprofloxacin resistance in bloodstream infections due to extended-spectrum Î²-lactamase producing Escherichia coli and Klebsiella pneumoniae. Microb Drug Resist 2004;10:71â€“6.
Yu WL, Jones RN, Hollis RJ, Messer SA, Biedenbach DJ, Deshpande LM, et al. Molecular epidemiology of extended spectrum Î²-lactamase-producing, fluoroquinolone-resistant isolates of Klebsiella pneumoniae in Taiwan. J Clin Microbiol 2002;40:4666â€“9.
Tansarli GS, Poulikakos B, Kapaskelis A, Falagas ME. Proportion of extended-spectrum Î²-lactamase (ESBL)-producingisolates among Enterobacteriaceae in Africa: evaluation of the evidenceâ€”systematic review. J Antimicrob Chemother 2014;69:1177â€“84.
Livermore DM. Current epidemiology and growing resistance of gram-negative pathogens. Korean J Intern Med 2012;27:128-42.
Clinical and Laboratory Standards Institute (CLSI). Performance standards for antimicrobial susceptibility testing. 23rd. informational supplement M100-S23. Wayne, PA: CLSI; 2013.
Catlin BW. Iodometric detection of Haemophilus influenzae beta-lactamase: rapid presumptive test for ampicillin resistance. Antimicrob Agents Chemother 1975;7:265-70.
Jarlier V, Nicolas MH, Fournier G, Philippon A. Extended broad-spectrum beta-lactamases conferring transferable resistance to newer beta-lactam agents in Enterobacteriaceae: hospital prevalence and susceptibility patterns. Rev Infect Dis 1988;10:867-78.
Johnson AP, Burns L, Woodford N, Threlfall EJ, Naidoo J, Cooke EM, et al. Gentamicin resistance in clinical isolates of Escherichia coli encoded by genes of veterinary origin. J Med Microbiol 1994;40:221-6.
Monstein HJ, Ostholm-Balkhed A, Nilsson MV, Nilsson M, Dornbusch K, Nilsson LE. Multiplex PCR amplification assay for the detection of blaSHV, blaTEM and blaCTX-M genes in Enterobacteriaceae. Apmis 2007;115:1400-8.
Saied T, Elkholy A, Hafez SF, Basim H, Wasfy MO, El-Shoubary W, et al. Antimicrobial resistance in pathogens causing nosocomial bloodstream infections in university hospitals in Egypt. Am J Infect Control 2011;39:e61â€“5.
Messai Y, Iabadene H, Benhassine T, Alouache S, Tazir M, Gautier V, et al. Prevalence and characterization of extended-spectrum beta-lactamases in Klebsiella pneumoniae in Algiers hospitals (Algeria). Pathol Biol 2008;56:319-25.
Nijssen S, Florijn A, Bonten MJ, Schmitz FJ, Verhoef J, Fluit AC. Beta-lactam susceptibilities and prevalence of ESBL-producing isolates among more than 5000 European Enterobacteriaceae isolates. Int J Antimicrob Agents 2004;24:585-91.
Tumbarello M, Spanu T, Sanguinetti M, Citton R, Montuori E, Leone F, et al. Bloodstream infections caused by extended-spectrum Î²-lactamaseâ€“producing Klebsiella pneumoniae: risk factors, molecular epidemiology, and clinical outcome. Antimicrob Agents Chemother 2006;50:498-504.
Daoud Z, Hakime N. Prevalence and susceptibility patterns of extended spectrum beta-lactamaseâ€“producing Escherichia coli and Klebsiella pneumoniae in a general university hospital in Beirut, Lebanon. Rev Esp Quimioter 2003;16:233-8.
Reinert RR, Low DE, Rossi F, Zhang X, Wattal C, Dowzicky MJ. Antimicrobial susceptibility among organisms from the Asia/Pacific Rim, Europe and Latin and North America collected as part of TEST and the in vitro activity of tigecycline. J Antimicrob Chemother 2007;60:1018â€“29.
Kawamura I, Ohmagari N, Tsukahara M, Kudo T, Kurai H. Surveillance of extended-spectrum Î²-lactamase-producing Escherichia coli and Klebsiella pneumoniae at a comprehensive cancer center in Japan, 2009-2013. Am J Infect Control 2015;43:185-7.
Winokur PL, Canton R, Casellas JM, Legakis N. Variations in the prevalence of strains expressing an extended-spectrum beta-lactamase phenotype and characterization of isolates from Europe, the Americas, and the Western Pacific region. Clin Infect Dis 2001;32 Suppl 2:S94-103.
Mac AogÃ¡in M, Mooij MJ, Adams C, Clair J, O'Gara F. Emergence of extended-spectrum beta-lactamase and fluoroquinolone resistance genes among Irish multidrug-resistant isolates. Diagn Microbiol Infect Dis 2010;67:106-9.
Sabate M, Tarrago R, Navarro F, MirÃ³ E, VergÃ©s C, BarbÃ© J, et al. Cloning and sequence of the gene encoding a novel cefotaxime-hydrolyzing beta-lactamase (CTX-M-9) from Escherichia coli in Spain. Antimicrob Agents Chemother 2000;44:1970-3.
Al-Agamy MH. Phenotypic and molecular characterization of extended-spectrum Î²-lactamases and AmpC Î²-lactamases in Klebsiella pneumoniae. Pak J Pharm Sci 2013;26:291-8.
Abdallah HM, Wintermans BB, Reuland EA, Koek A, al Naiemi N, Ammar AM, et al. Extended-spectrum Î²-Lactamase-and carbapenemase-producing Enterobacteriaceae isolated from egyptian patients with suspected blood stream infection. PLoS One 2015;10:e0128120.
Metwally L, Gomaa N, Attallah M, Kamel N. High prevalence of Klebsiella pneumonia carbapenemase-mediated resistance in K. pneumoniae isolates from Egypt. East Mediterr Health J 2013;19:947-52.
Ashour HM, El-Sharif A. Species distribution and antimicrobial susceptibility of gram-negative aerobic bacteria in hospitalized cancer patients. J Trans Med 2009;7:1-14.30.
El Kholy A, Baseem H, Hall G, Procop W, Longworth L. Antimicrobial resistance in Cairo, Egypt 1999-2000: a survey of five hospitals. J Antimicrob Chemother 2003;51:625-30.