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Published in: Antimicrobial Resistance & Infection Control 1/2018

Open Access 01-12-2018 | Research

Molecular characterization of extended spectrum β -lactamases enterobacteriaceae causing lower urinary tract infection among pediatric population

Authors: Nahla O. Eltai, Asmaa A. Al Thani, Khalid Al-Ansari, Anand S. Deshmukh, Eman Wehedy, Sara H. Al-Hadidi, Hadi M. Yassine

Published in: Antimicrobial Resistance & Infection Control | Issue 1/2018

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Abstract

Background

The β-lactam antibiotics have traditionally been the main treatment of Enterobacteriaceae infections, nonetheless, the emergence of species producing β- Lactamases has rendered this class of antibiotics largely ineffective. There are no published data on etiology of urinary tract infections (UTI) and antimicrobial resistance profile of uropathogens among children in Qatar. The aim of this study is to determine the phenotypic and genotypic profiles of antimicrobial resistant Enterobacteriaceae among children with UTI in Qatar.

Methods

Bacteria were isolated from 727 urine positive cultures, collected from children with UTI between February and June 2017 at the Pediatric Emergency Center, Doha, Qatar. Isolated bacteria were tested for antibiotic susceptibility against sixteen clinically relevant antibiotics using phoenix and Double Disc Synergy Test (DDST) for confirmation of extended-spectrum beta-lactamase (ESBL) production. Existence of genes encoding ESBL production were identified using polymerase chain reaction (PCR). Statistical analysis was done using non-parametric Kappa statistics, Pearson chi-square test and Jacquard’s coefficient.

Results

201 (31.7%) of samples were confirmed as Extended Spectrum β -Lactamases (ESBL) Producing Enterobacteriaceae. The most dominant pathogen was E. coli 166 (83%) followed by K. pneumoniae 22 (11%). Resistance was mostly encoded by bla CTX-M (59%) genes, primarily bla CTX-MG1 (89.2%) followed by bla CTX-MG9 (7.7%). 37% of isolated bacteria were harboring multiple bla genes (2 genes or more). E. coli isolates were categorized into 11 clusters, while K. pneoumoniae were grouped into five clonal clusters according to the presence and absence of seven genes namely bla TEM, bla SHV, bla CTX-MG1, bla CTX-MG2, bla CTX-MG8 bla CTX-MG9, bla CTX-MG25.

Conclusions

Our data indicates an escalated problem of ESBL in pediatrics with UTI, which mandates implementation of regulatory programs to reduce the spread of ESBL producing Enterobacteriaceae in the community. The use of cephalosporins, aminoglycosides (gentamicin) and trimethoprim/sulfamethoxazole is compromised in Qatar among pediatric population with UTI, leaving carbapenems and amikacin as the therapeutic option for severe infections caused by ESBL producers.
Literature
1.
go back to reference Talbot GH, Bradley J, Edwards Jr JE, Gilbert D, Scheld M, Bartlett JG: Bad bugs need drugs: an update on the development pipeline from the antimicrobial availability task force of the Infectious Diseases Society of America. Clin Infect Dis 2006, 42(5):657–668. Talbot GH, Bradley J, Edwards Jr JE, Gilbert D, Scheld M, Bartlett JG: Bad bugs need drugs: an update on the development pipeline from the antimicrobial availability task force of the Infectious Diseases Society of America. Clin Infect Dis 2006, 42(5):657–668.
2.
go back to reference Goyal A, Prasad K, Prasad A, Gupta S, Ghoshal U, Ayyagari A: Extended spectrum beta-lactamases in Escherichia coli & Klebsiella pneumoniae & associated risk factors. 2009. Goyal A, Prasad K, Prasad A, Gupta S, Ghoshal U, Ayyagari A: Extended spectrum beta-lactamases in Escherichia coli & Klebsiella pneumoniae & associated risk factors. 2009.
3.
go back to reference Sharma M, Pathak S, SrivaStava P. Prevalence and antibiogram of extended Spectrum β-lactamase (ESBL) producing gram negative bacilli and further molecular characterization of ESBL producing Escherichia coli and Klebsiella spp. J Clin Diagn Res. 2013;7(10):2173.PubMedPubMedCentral Sharma M, Pathak S, SrivaStava P. Prevalence and antibiogram of extended Spectrum β-lactamase (ESBL) producing gram negative bacilli and further molecular characterization of ESBL producing Escherichia coli and Klebsiella spp. J Clin Diagn Res. 2013;7(10):2173.PubMedPubMedCentral
4.
go back to reference Nakamura T, Komatsu M, Yamasaki K, Fukuda S, Miyamoto Y, Higuchi T, Ono T, Nishio H, Sueyoshi N, Kida K. Epidemiology of Escherichia coli, Klebsiella species, and Proteus mirabilis strains producing extended-spectrum β-lactamases from clinical samples in the Kinki region of Japan. Am J Clin Pathol. 2012;137(4):620–6.CrossRefPubMed Nakamura T, Komatsu M, Yamasaki K, Fukuda S, Miyamoto Y, Higuchi T, Ono T, Nishio H, Sueyoshi N, Kida K. Epidemiology of Escherichia coli, Klebsiella species, and Proteus mirabilis strains producing extended-spectrum β-lactamases from clinical samples in the Kinki region of Japan. Am J Clin Pathol. 2012;137(4):620–6.CrossRefPubMed
5.
go back to reference Birgy A, Mariani-Kurkdjian P, Bidet P, Doit C, Genel N, Courroux C, Arlet G, Bingen E. Characterization of extended-spectrum-beta-lactamase-producing Escherichia coli strains involved in maternal-fetal colonization: prevalence of E. Coli ST131. J Clin Microbiol. 2013;51(6):1727–32.CrossRefPubMedPubMedCentral Birgy A, Mariani-Kurkdjian P, Bidet P, Doit C, Genel N, Courroux C, Arlet G, Bingen E. Characterization of extended-spectrum-beta-lactamase-producing Escherichia coli strains involved in maternal-fetal colonization: prevalence of E. Coli ST131. J Clin Microbiol. 2013;51(6):1727–32.CrossRefPubMedPubMedCentral
6.
go back to reference Lukac PJ, Bonomo RA, Logan LK. Extended-Spectrum β-lactamase–producing Enterobacteriaceae in children: old foe, emerging threat. Clin Infect Dis: Offic Public Infect Dis Soc Am. 2015;60(9):1389–97. Lukac PJ, Bonomo RA, Logan LK. Extended-Spectrum β-lactamase–producing Enterobacteriaceae in children: old foe, emerging threat. Clin Infect Dis: Offic Public Infect Dis Soc Am. 2015;60(9):1389–97.
7.
go back to reference Bush K. Alarming β-lactamase-mediated resistance in multidrug-resistant Enterobacteriaceae. Curr Opin Microbiol. 2010;13(5):558–64.CrossRefPubMed Bush K. Alarming β-lactamase-mediated resistance in multidrug-resistant Enterobacteriaceae. Curr Opin Microbiol. 2010;13(5):558–64.CrossRefPubMed
9.
go back to reference Pitout JD, Laupland KB. Extended-spectrum β-lactamase-producing Enterobacteriaceae: an emerging public-health concern. Lancet Infect Dis. 2008;8(3):159–66.CrossRefPubMed Pitout JD, Laupland KB. Extended-spectrum β-lactamase-producing Enterobacteriaceae: an emerging public-health concern. Lancet Infect Dis. 2008;8(3):159–66.CrossRefPubMed
10.
go back to reference Stedt J, Bonnedahl J, Hernandez J, Waldenström J, McMahon BJ, Tolf C, Olsen B, Drobni M. Carriage of CTX-M type extended spectrum β-lactamases (ESBLs) in gulls across Europe. Acta Vet Scand. 2015;57(1):74.CrossRefPubMedPubMedCentral Stedt J, Bonnedahl J, Hernandez J, Waldenström J, McMahon BJ, Tolf C, Olsen B, Drobni M. Carriage of CTX-M type extended spectrum β-lactamases (ESBLs) in gulls across Europe. Acta Vet Scand. 2015;57(1):74.CrossRefPubMedPubMedCentral
11.
go back to reference Lahlaoui H, Khalifa A, Haj B, Moussa MB. Epidemiology of Enterobacteriaceae producing CTX-M type extended spectrum β-lactamase (ESBL). Medecine et maladies infectieuses. 2014;44(9):400–4.CrossRefPubMed Lahlaoui H, Khalifa A, Haj B, Moussa MB. Epidemiology of Enterobacteriaceae producing CTX-M type extended spectrum β-lactamase (ESBL). Medecine et maladies infectieuses. 2014;44(9):400–4.CrossRefPubMed
12.
go back to reference Malloy AM, Campos JM. Extended-spectrum beta-lactamases: a brief clinical update. Pediatr Infect Dis J. 2011;30(12):1092–3.CrossRefPubMed Malloy AM, Campos JM. Extended-spectrum beta-lactamases: a brief clinical update. Pediatr Infect Dis J. 2011;30(12):1092–3.CrossRefPubMed
13.
go back to reference Bakshi R, Walia G, Shikha J. Prevalence of extended spectrum β-lactamases in multidrug resistant strains of gram negative bacilli. J Acad Indus Res. 2013;1:558–60. Bakshi R, Walia G, Shikha J. Prevalence of extended spectrum β-lactamases in multidrug resistant strains of gram negative bacilli. J Acad Indus Res. 2013;1:558–60.
14.
go back to reference CDC. Antibiotic resistance threats in the United States, 2013. In: Centers for disease control and prevention USA; 2013. CDC. Antibiotic resistance threats in the United States, 2013. In: Centers for disease control and prevention USA; 2013.
15.
go back to reference Zowawi HM, Balkhy HH, Walsh TR, Paterson DL. β-Lactamase production in key gram-negative pathogen isolates from the Arabian peninsula. Clin Microbiol Rev. 2013;26(3):361–80.CrossRefPubMedPubMedCentral Zowawi HM, Balkhy HH, Walsh TR, Paterson DL. β-Lactamase production in key gram-negative pathogen isolates from the Arabian peninsula. Clin Microbiol Rev. 2013;26(3):361–80.CrossRefPubMedPubMedCentral
16.
go back to reference Chandramohan L, Revell PA. Prevalence and molecular characterization of extended-spectrum-β-lactamase-producing Enterobacteriaceae in a pediatric patient population. Antimicrob Agents Chemother. 2012;56(9):4765–70.CrossRefPubMedPubMedCentral Chandramohan L, Revell PA. Prevalence and molecular characterization of extended-spectrum-β-lactamase-producing Enterobacteriaceae in a pediatric patient population. Antimicrob Agents Chemother. 2012;56(9):4765–70.CrossRefPubMedPubMedCentral
17.
go back to reference Eltai NO, Abdfarag EA, Al-Romaihi H, Wehedy E, Mahmoud MH, Alawad OK, Al-Hajri MM, Al Thani AA, Yassine HM. Antibiotic resistance profile of commensal Escherichia coli isolated from broiler chickens in Qatar. J Food Prot. 2017;81(2):302–7.CrossRef Eltai NO, Abdfarag EA, Al-Romaihi H, Wehedy E, Mahmoud MH, Alawad OK, Al-Hajri MM, Al Thani AA, Yassine HM. Antibiotic resistance profile of commensal Escherichia coli isolated from broiler chickens in Qatar. J Food Prot. 2017;81(2):302–7.CrossRef
18.
go back to reference CLSI. Clinical and laboratory standards institute. Performance standards for antimicrobial susceptibility testing. M100S. 2016;26:1–129. CLSI. Clinical and laboratory standards institute. Performance standards for antimicrobial susceptibility testing. M100S. 2016;26:1–129.
19.
go back to reference Woodford N, Fagan EJ, Ellington MJ. Multiplex PCR for rapid detection of genes encoding CTX-M extended-spectrum β-lactamases. J Antimicrob Chemother. 2005;57(1):154–5.CrossRefPubMed Woodford N, Fagan EJ, Ellington MJ. Multiplex PCR for rapid detection of genes encoding CTX-M extended-spectrum β-lactamases. J Antimicrob Chemother. 2005;57(1):154–5.CrossRefPubMed
20.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
21.
go back to reference Ahmed SF, Ali MMM, Mohamed ZK, Moussa TA, Klena JD. Fecal carriage of extended-spectrum β-lactamases and AmpC-producing Escherichia coli in a Libyan community. Ann Clin Microbiol Antimicrob. 2014;13(1):22.CrossRefPubMedPubMedCentral Ahmed SF, Ali MMM, Mohamed ZK, Moussa TA, Klena JD. Fecal carriage of extended-spectrum β-lactamases and AmpC-producing Escherichia coli in a Libyan community. Ann Clin Microbiol Antimicrob. 2014;13(1):22.CrossRefPubMedPubMedCentral
22.
go back to reference Kamatchi C, Magesh H, Sekhar U, Vaidyanathan R. Identification of clonal clusters of Klebsiella pneumoniae isolates from Chennai by extended spectrum beta lactamase genotyping and antibiotic resistance phenotyping analysis. Am J Infect Dis. 2009;5(2):74–82.CrossRef Kamatchi C, Magesh H, Sekhar U, Vaidyanathan R. Identification of clonal clusters of Klebsiella pneumoniae isolates from Chennai by extended spectrum beta lactamase genotyping and antibiotic resistance phenotyping analysis. Am J Infect Dis. 2009;5(2):74–82.CrossRef
23.
go back to reference Chapman TA, Wu X-Y, Barchia I, Bettelheim KA, Driesen S, Trott D, Wilson M, Chin JJ-C. Comparison of virulence gene profiles of Escherichia coli strains isolated from healthy and diarrheic swine. Appl Environ Microbiol. 2006;72(7):4782–95.CrossRefPubMedPubMedCentral Chapman TA, Wu X-Y, Barchia I, Bettelheim KA, Driesen S, Trott D, Wilson M, Chin JJ-C. Comparison of virulence gene profiles of Escherichia coli strains isolated from healthy and diarrheic swine. Appl Environ Microbiol. 2006;72(7):4782–95.CrossRefPubMedPubMedCentral
24.
go back to reference Hammer Ø, Harper D, Ryan P. Paleontological Statistics Software Package for Education and Data Analysis. Palaeontol Electron. 2001;4:9. Hammer Ø, Harper D, Ryan P. Paleontological Statistics Software Package for Education and Data Analysis. Palaeontol Electron. 2001;4:9.
25.
go back to reference Fernando M, Luke W, Miththinda J, Wickramasinghe R, Sebastiampillai B, Gunathilake M, Silva F, Premaratna R. Extended spectrum beta lactamase producing organisms causing urinary tract infections in Sri Lanka and their antibiotic susceptibility pattern–a hospital based cross sectional study. BMC Infect Dis. 2017;17(1):138.CrossRefPubMedPubMedCentral Fernando M, Luke W, Miththinda J, Wickramasinghe R, Sebastiampillai B, Gunathilake M, Silva F, Premaratna R. Extended spectrum beta lactamase producing organisms causing urinary tract infections in Sri Lanka and their antibiotic susceptibility pattern–a hospital based cross sectional study. BMC Infect Dis. 2017;17(1):138.CrossRefPubMedPubMedCentral
26.
go back to reference Hellerstein S. Urinary tract infections in children: why they occur and how to prevent them. Am Fam Physician. 1998;57(10):2440–6. 2452-2444PubMed Hellerstein S. Urinary tract infections in children: why they occur and how to prevent them. Am Fam Physician. 1998;57(10):2440–6. 2452-2444PubMed
27.
go back to reference Zeyaullah M, Kaul V. Prevalence of urinary tract infection and antibiotic resistance pattern in Saudi Arabia population. Global J Biol, Agricult Health Sci. 2015;4(1):206–14. Zeyaullah M, Kaul V. Prevalence of urinary tract infection and antibiotic resistance pattern in Saudi Arabia population. Global J Biol, Agricult Health Sci. 2015;4(1):206–14.
28.
go back to reference Zhao W-H, Hu Z-Q. Epidemiology and genetics of CTX-M extended-spectrum β-lactamases in gram-negative bacteria. Crit Rev Microbiol. 2013;39(1):79–101.CrossRefPubMed Zhao W-H, Hu Z-Q. Epidemiology and genetics of CTX-M extended-spectrum β-lactamases in gram-negative bacteria. Crit Rev Microbiol. 2013;39(1):79–101.CrossRefPubMed
29.
go back to reference Potz NA, Hope R, Warner M, Johnson AP, Livermore DM. Prevalence and mechanisms of cephalosporin resistance in Enterobacteriaceae in London and south-East England. J Antimicrob Chemother. 2006;58(2):320–6.CrossRefPubMed Potz NA, Hope R, Warner M, Johnson AP, Livermore DM. Prevalence and mechanisms of cephalosporin resistance in Enterobacteriaceae in London and south-East England. J Antimicrob Chemother. 2006;58(2):320–6.CrossRefPubMed
30.
go back to reference Hassan H, Abdalhamid B. Molecular characterization of extended-spectrum beta-lactamase producing Enterobacteriaceae in a Saudi Arabian tertiary hospital. J Infect Dev Countries. 2014;8(03):282–8.CrossRef Hassan H, Abdalhamid B. Molecular characterization of extended-spectrum beta-lactamase producing Enterobacteriaceae in a Saudi Arabian tertiary hospital. J Infect Dev Countries. 2014;8(03):282–8.CrossRef
31.
go back to reference Bindayna K, Khanfar HS, Senok AC, Botta GA. Predominance of CTX-M genotype among extended spectrum beta lactamase isolates in a tertiary hospital in Saudi Arabia. Saudi Med J. 2010;31(8):859–63.PubMed Bindayna K, Khanfar HS, Senok AC, Botta GA. Predominance of CTX-M genotype among extended spectrum beta lactamase isolates in a tertiary hospital in Saudi Arabia. Saudi Med J. 2010;31(8):859–63.PubMed
32.
go back to reference Mendonça N, Leitão J, Manageiro V, Ferreira E, Caniça M. Portugal ARSPi: spread of extended-spectrum β-lactamase CTX-M-producing Escherichia coli clinical isolates in community and nosocomial environments in Portugal. Antimicrob Agents Chemother. 2007;51(6):1946–55.CrossRefPubMedPubMedCentral Mendonça N, Leitão J, Manageiro V, Ferreira E, Caniça M. Portugal ARSPi: spread of extended-spectrum β-lactamase CTX-M-producing Escherichia coli clinical isolates in community and nosocomial environments in Portugal. Antimicrob Agents Chemother. 2007;51(6):1946–55.CrossRefPubMedPubMedCentral
33.
34.
go back to reference Livermore DM, Canton R, Gniadkowski M, Nordmann P, Rossolini GM, Arlet G, Ayala J, Coque TM, Kern-Zdanowicz I, Luzzaro F. CTX-M: changing the face of ESBLs in Europe. J Antimicrob Chemother. 2007;59(2):165–74.CrossRefPubMed Livermore DM, Canton R, Gniadkowski M, Nordmann P, Rossolini GM, Arlet G, Ayala J, Coque TM, Kern-Zdanowicz I, Luzzaro F. CTX-M: changing the face of ESBLs in Europe. J Antimicrob Chemother. 2007;59(2):165–74.CrossRefPubMed
35.
go back to reference Ahmed AMS, Sultan AA, Deshmukh A, Acharya A, Elmi AA, Bansal D, Ibrahim E, Hamid JM, Ahmed MAS, Bilal NE. Antimicrobial susceptibility and molecular epidemiology of extended-spectrum beta-lactamase-producing Enterobacteriaceae from intensive care units at Hamad Medical Corporation, Qatar. Antimicrob Resist Infect Control. 2016;5(1):4.CrossRef Ahmed AMS, Sultan AA, Deshmukh A, Acharya A, Elmi AA, Bansal D, Ibrahim E, Hamid JM, Ahmed MAS, Bilal NE. Antimicrobial susceptibility and molecular epidemiology of extended-spectrum beta-lactamase-producing Enterobacteriaceae from intensive care units at Hamad Medical Corporation, Qatar. Antimicrob Resist Infect Control. 2016;5(1):4.CrossRef
36.
go back to reference Balkhy HH, Assiri AM, Al Mousa H, Al-Abri SS, Al-Katheeri H, Alansari H, Abdulrazzaq NM, Aidara-Kane A, Pittet D, Erlacher-Vindel E. The strategic plan for combating antimicrobial resistance in gulf cooperation council states. J Infect Public Health. 2016;9(4):375–85.CrossRefPubMed Balkhy HH, Assiri AM, Al Mousa H, Al-Abri SS, Al-Katheeri H, Alansari H, Abdulrazzaq NM, Aidara-Kane A, Pittet D, Erlacher-Vindel E. The strategic plan for combating antimicrobial resistance in gulf cooperation council states. J Infect Public Health. 2016;9(4):375–85.CrossRefPubMed
37.
go back to reference Giamarellou H. Multidrug resistance in gram-negative bacteria that produce extended-spectrum β-lactamases (ESBLs). Clin Microbiol Infect. 2005;11(s4):1–16.CrossRefPubMed Giamarellou H. Multidrug resistance in gram-negative bacteria that produce extended-spectrum β-lactamases (ESBLs). Clin Microbiol Infect. 2005;11(s4):1–16.CrossRefPubMed
38.
go back to reference Jacoby GA, Walsh KE, Mills DM, Walker VJ, Oh H, Robicsek A, Hooper DC. qnrB, another plasmid-mediated gene for quinolone resistance. Antimicrob Agents Chemother. 2006;50(4):1178–82.CrossRefPubMedPubMedCentral Jacoby GA, Walsh KE, Mills DM, Walker VJ, Oh H, Robicsek A, Hooper DC. qnrB, another plasmid-mediated gene for quinolone resistance. Antimicrob Agents Chemother. 2006;50(4):1178–82.CrossRefPubMedPubMedCentral
39.
go back to reference Boyd DA, Tyler S, Christianson S, McGeer A, Muller MP, Willey BM, Bryce E, Gardam M, Nordmann P, Mulvey MR. Complete nucleotide sequence of a 92-kilobase plasmid harboring the CTX-M-15 extended-spectrum beta-lactamase involved in an outbreak in long-term-care facilities in Toronto, Canada. Antimicrob Agents Chemother. 2004;48(10):3758–64.CrossRefPubMedPubMedCentral Boyd DA, Tyler S, Christianson S, McGeer A, Muller MP, Willey BM, Bryce E, Gardam M, Nordmann P, Mulvey MR. Complete nucleotide sequence of a 92-kilobase plasmid harboring the CTX-M-15 extended-spectrum beta-lactamase involved in an outbreak in long-term-care facilities in Toronto, Canada. Antimicrob Agents Chemother. 2004;48(10):3758–64.CrossRefPubMedPubMedCentral
40.
go back to reference Heffernan H, Dyet K, Woodhouse R, Williamson D: Antimicrobial susceptibility and molecular epidemiology of extended-spectrum β-lactamase producing Enterobacteriaceae in New Zealand, 2013. 2014. Heffernan H, Dyet K, Woodhouse R, Williamson D: Antimicrobial susceptibility and molecular epidemiology of extended-spectrum β-lactamase producing Enterobacteriaceae in New Zealand, 2013. 2014.
Metadata
Title
Molecular characterization of extended spectrum β -lactamases enterobacteriaceae causing lower urinary tract infection among pediatric population
Authors
Nahla O. Eltai
Asmaa A. Al Thani
Khalid Al-Ansari
Anand S. Deshmukh
Eman Wehedy
Sara H. Al-Hadidi
Hadi M. Yassine
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Antimicrobial Resistance & Infection Control / Issue 1/2018
Electronic ISSN: 2047-2994
DOI
https://doi.org/10.1186/s13756-018-0381-6

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