Abstract
Due to the recent appearance of organisms that are resistant to several drugs (multidrug-resistant) like Enterobacteriaceae that produce extended-spectrum ?-lactamase (ESBL, concerns have remarkably increased regarding the suitable treatment of infections. The present study was an investigation into ESBL molecular characteristics among clinical isolates of Klebsiella pneumoniae and Escherichia coli resulting in UTIs and their pattern of antimicrobial resistance in order to come up with helpful information on the epidemiology of these infections and risk factors accompanied with them. In order to conduct the study, 20 K. pneumoniae and 48 E. coli were isolated and retrieved from thalassemia center in Erbil, Iraq during July 2016 and September 2016. The collected strains were analyzed and the profile of their antimicrobial susceptibility was specified. In order to spot ?-lactamase genes (i.e. blaTEM, blaSHV, and blaCTX-M), polymerase chain reaction was conducted. The results obtained from multiplex PCR assay showed that out of the collected strains of ESBL-producing E. coli, 37 had 81% blaTEM, 16.2% blaSHV, and 32.4% blaCTX-M genes. Similarly, 64.7% blaTEM, 35.2% blaSHV, and 41.1% blaCTX-M genes existed in the isolates of K. pneumoniae. It was found that antibiotic resistance pattern of E. coli and K. pneumoniae isolates to 20 antibiotics varied widely. It was also concluded that the majority of the K. pneumoniae and E. coli isolates were multi-drug resistant (MDR). Moreover, 75% and 87.5% of respectively K. pneumoniae and E. coli isolates showed the MDR phenotypes. TEM prevalence was high among other types of ESBLs. Over all, the most active antimicrobial agents in vitro remained to be the carbapenems.
References
Gaynes R, Edwards JR; National Nosocomial Infections Surveillance System.Overview of nosocomial infections caused by gram-negative bacilli.Clin Infect Dis. 2005 ;41(6):848-54https://doi.org/10.1086/432803PMid:161079852.Ojdana D, Sacha P, Wieczorek P,Czaban S, Michalska A, Jaworowska J.The Occurrence of blaCTX-M, blaSHV, and blaTEM Genes in Extended-Spectrum ?-Lactamase-Positive Strains of Klebsiella pneumoniae, Escherichia coli, and Proteus mirabilis in Poland.Intern J Antibi Volume 2014, Article ID 935842, 7 pageshttps://doi.org/10.1155/2014/9358423.Paterson DL, Bonomo RA.Extended-spectrum beta-lactamases: a clinical update.Clin Microbiol Rev. 2005 ;18(4):657-86.https://doi.org/10.1128/CMR.18.4.657-686.2005PMid:16223952 PMCid:PMC12659084.Liao K, Chen Y, Wang M, Guo P, Yang Q, Ni Y, Yu Y, Hu B, Sun Z, Huang W.Molecular characteristics of extended-spectrum ?-lactamase-producing Escherichia coli and Klebsiella pneumoniae causing intra-abdominal infections from 9 tertiary hospitals in China.Diagn Microbiol Infect Dis. 2017;87(1):45-48https://doi.org/10.1016/j.diagmicrobio.2016.10.007PMid:27773544 5.Malloy AM, Campos JM.Extended-spectrum beta-lactamases: a brief clinical update.Pediatr Infect Dis J. 2011;30(12):1092-3.https://doi.org/10.1097/INF.0b013e31823c0e9dPMid:22105419 6.Akpaka PE, Legall B, Padman J. Molecular detection and epidemiology of extended-spectrum beta-lactamase genes prevalent in clinical isolates of Klebsiella pneumoniae and E coli from Trinidad and Tobago. West Indian Med J. 2010;59(6):591-6 7.Fraser A, Paul M, Almanasreh N, Tacconelli E, Frank U, Cauda R, Borok S, Cohen M, Andreassen S, Nielsen AD, Leibovici L; TREAT Study Group. Benefit of appropriate empirical antibiotic treatment: thirty-day mortality andduration of hospital stay. Am J Med. 2006;119(11):970-6.https://doi.org/10.1016/j.amjmed.2006.03.034PMid:170711668.Livermore DM, Paterson DL. Pocket Guide to Extended-spectrum [beta]-lactamases in Resistance. Current Medicine Group, London, UK. 2006 9.Sharma J, Sharma M, Ray P. Detection of TEM & SHV genes in Escherichia coli & Klebsiella pneumoniae isolates in a tertiary care hospital from India. Indian J Med Res. 2010;132:332-6.10.Collee JG, Miles RS , WB. Tests for the identification of bacteria In: Collee JG, Fraser AG, Marmion BP and S. A (eds.), Mackie & McCartney practical medical microbiology. Churchill Livingstone, Edinburgh. 199611.Wayne P. Clinical and laboratory standards institute. Performance standards for antimicrobial susceptibility testing. 201112.Paterson DL, Hujer KM, Hujer AM, Yeiser B, Bonomo MD, Rice LB, Bonomo RA; International Klebsiella Study Group. Extended-spectrum ?-lactamases in Klebsiella pneumoniae bloodstream isolates from seven countries: Dominance and widespread prevalence of SHV-and CTX-M-type ?-lactamases. Antimicrob Agents Chemother. 2003;47(11):3554-60.https://doi.org/10.1128/AAC.47.11.3554-3560.2003PMid:14576117 PMCid:PMC25377113.Monstein HJ, Ostholm-Balkhed A, Nilsson MV, Nilsson M, Dornbusch K, Nilsson LE.Multiplex PCR amplification assay for the detection of blaSHV, blaTEMand blaCTX?M genes in Enterobacteriaceae. APMIS. 2007;115(12):1400-8.https://doi.org/10.1111/j.1600-0463.2007.00722.xPMid:1818441114.Akova M. Epidemiology of antimicrobial resistance in bloodstream infections. Virulence, 2016;7:252-266.https://doi.org/10.1080/21505594.2016.1159366PMid:26984779 PMCid:PMC487163415.Bora A, Hazarika NK, Shukla SK, Prasad KN, Sarma JB, Ahmed G. Prevalence of blaTEM, blaSHV and blaCTX-M genes in clinical isolates of Escherichia coli and Klebsiella pneumoniae from Northeast India. Indian J Pathol Microbiol. 2014;57(2):249-54.https://doi.org/10.4103/0377-4929.134698PMid:2494375816.Tabar MM, Mirkalantari S, Amoli RI.Detection of ctx-M gene in ESBL-producing E. coli strains isolated from urinary tract infection in Semnan, Iran.Electron Physician. 2016;8(7):2686-90https://doi.org/10.19082/2686PMid:27648198 PMCid:PMC501451017.Pitout JD. The latest threat in the war on antimicrobial resistance. The Lancet Infectious Diseases, 2010;10:578-579.https://doi.org/10.1016/S1473-3099(10)70168-718.Paterson DL, Ko WC, Von Gottberg A, Casellas JM, Mulazimoglu L, Klugman KP, Bonomo RA, Rice LB, McCormack JG, Yu VL. Outcome of cephalosporin treatment for serious infections due to apparently susceptible organisms producing extended-spectrum ?-lactamases: implications for the clinical microbiology laboratory. J Clin Microbiol. 2001;39(6):2206-12.https://doi.org/10.1128/JCM.39.6.2206-2212.2001PMid:11376058 PMCid:PMC8811219.Wong-Beringer A. Therapeutic challenges associated with extended-spectrum, beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae. Pharmacotherapy. 2001;21(5):583-92.https://doi.org/10.1592/phco.21.6.583.34537PMid:1134974720.Babypadmini S, Appalaraju B. Extended spectrum-lactamases in urinary isolates of Escherichia coli and Klebsiella pneumoniae-prevalence and susceptibility pattern in a tertiary care hospital. Indian J Med Microbiol. 2004;22(3):172-4.21.Bradford PA.Extended-spectrum ?-lactamases in the 21st century: characterization, epidemiology, and detection of this important resistance threat. Clin MicrobiolRev. 2001;14(4):933-51https://doi.org/10.1128/CMR.14.4.933-951.2001PMid:11585791 PMCid:PMC8900922.Modi D, Patel D., Patel S., Jain M., Bhatt S, Vegad M. Comparison of various methods for the detection of extended spectrum beta lactamase in Klebsiella pneumoniae isolated from neonatal Intensive Care Unit, Ahmedabad. Natl J Med Res. 2012; 2(3): 348-35323.Khan MK, Thukral SS, Gaind R. Evaluation of a modified double-disc synergy test for detection of extended spectrum ?-lactamases in AMPC ?-lactamase-producing Proteus mirabilis. Indian J Med Microbiol. 2008;26(1):58-61.https://doi.org/10.4103/0255-0857.38860PMid:1822760024.Kaur J, Chopra S, Sheevani, Mahajan G. Modified double disc synergy test to detect ESBL production in urinary isolates of Escherichia coli and Klebsiella pneumoniae. J Clin Diagn Res. 2013;7(2):229-33https://doi.org/10.7860/JCDR/2013/4619.2734PMid:23543257 PMCid:PMC359228025.Nüesch-Inderbinen MT, Hächler H, Kayser FH. Detection of genes coding for extended-spectrum SHV beta-lactamases in clinical isolates by a molecular genetic method, and comparison with the E test. Eur J Clin Microbiol Infect Dis. 1996;15(5):398-402.https://doi.org/10.1007/BF01690097PMid:879339926.Navon-Venezia S, Hammer-Munz O, Schwartz D, Turner D, Kuzmenko
www.mjhid.orgMediterr J Hematol Infect Dis 2019; 11; e2019041Pag. 7/7B, Carmeli Y. Occurrence and phenotypic characteristics of extended-spectrum ?-lactamases among members of the family Enterobacteriaceae at the Tel-Aviv Medical Center (Israel) and evaluation of diagnostic tests. J Clin Microbiol. 2003;41(1):155-8.https://doi.org/10.1128/JCM.41.1.155-158.2003PMid:12517841 PMCid:PMC14963627.Grover SS, Sharma M, Chattopadhya D, Kapoor H, Pasha ST, Singh G.Phenotypic and genotypic detection of ESBL mediated cephalosporin resistance in Klebsiella pneumoniae: emergence of high resistance against cefepime, the fourth generation cephalosporin. J Infect. 2006 ;53(4):279-88.https://doi.org/10.1016/j.jinf.2005.12.001PMid:1648847628.Jorgensen JH, McElmeel ML, Fulcher LC, Zimmer BL. Detection of CTX-M-type extended-spectrum beta-lactamase (ESBLs) by testing with MicroScan overnight and ESBL confirmation panels. J Clin Microbiol. 2010;48(1):120-3.https://doi.org/10.1128/JCM.01507-09PMid:19889896 PMCid:PMC281226829.Manoharan A, Premalatha K, Chatterjee S, Mathai D; SARI Study Group. Correlation of TEM, SHV and CTX-M extended-spectrum beta lactamases among Enterobacteriaceae with their in vitro antimicrobial susceptibility. Indian J Med Microbiol. 2011;29(2):161-4.https://doi.org/10.4103/0255-0857.81799PMid:2165411230.Moghnieh RA, Kanafani ZA, Tabaja HZ, Sharara SL, Awad LS, Kanj SS.Epidemiology of common resistant bacterial pathogens in the countries of the Arab League.Lancet Infect Dis. 2018;18(12):e379-e394https://doi.org/10.1016/S1473-3099(18)30414-631.Khalaf EA, Al-Ouqaili MTS.Molecular detection and sequencing of SHV gene encoding for extended-spectrum ?-lactamases produced by multidrug resistance some of the Gram-negative bacteria.Intern J Green Pharm 2018; 12 (4): S918https://doi.org/10.22377/ijgp.v12i04.227432.Teawtrakul N, Jetsrisuparb A, Sirijerachai C, Chansung K, Wanitpongpun C.Severe bacterial infections in patients with non-transfusion-dependent thalassemia: prevalence and clinical risk factors.Int J Infect Dis. 2015 ;39:53-6https://doi.org/10.1016/j.ijid.2015.09.001PMid:2635885533.Ricciardi W, Giubbini G, Laurenti P.Surveillance and Control of Antibiotic Resistance in the Mediterranean Region.Mediterr J Hematol Infect Dis. 2016;8(1):e2016036https://doi.org/10.4084/mjhid.2016.036PMid:27413528 PMCid:PMC492853734.Devrim F, Serdaro?lu E, Ça?lar ?, Oruç Y, Demiray N, Bayram N, A??n H, Çalkavur S, Sorguç Y, Dinçel N, Ayhan Y, Y?lmaz E, Devrim I.The Emerging Resistance in Nosocomial Urinary Tract Infections: From the Pediatrics Perspective.Mediterr J Hematol Infect Dis. 2018 Sep 1;10(1):e2018055.https://doi.org/10.4084/mjhid.2018.055PMid:30210748 PMCid:PMC613110035.Girmenia C, Serrao A, Canichella M.Epidemiology of Carbapenem Resistant Klebsiella pneumoniae Infections in Mediterranean Countries.Mediterr J Hematol Infect Dis. 2016 ;8(1):e2016032.https://doi.org/10.4084/mjhid.2016.032PMid:27441063 PMCid:PMC494306