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

Abstract

BackgroundThe 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.MethodsBacteria 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.Results201 (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.ConclusionsOur 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.

Antibiotic resistance and virulence patterns of pathogenic Escherichia coli strains associated with acute gastroenteritis among children in Qatar

“…Without any exception, all isolates harbored bla CTX-M gene (100%), primarily bla CTX-MG1 , which includes bla CTX-M-3 &15 (88.23%). This is in accordance with our previous study on E. coli ESBL producers isolated from children with urinary tract infection, where CTX-MG1 was present in more than 89% isolates [24]. That study did not investigate the type of E. coli causing the diseases and hence, we could not associate the present findings with our previous urinary tract study.…”

“…Isolates that were tested positive for third generation cephalosporin were consequently confirmed by Double Disc Synergy Test, (DDST) as previously described [21,23]. Molecular genotyping of isolates exhibiting ESBL was performed by characterization of the presence/absence of 10 genes namely, bla CTX-M-G (1, 2, 8, 9, &25) , bla TEM and bla SHV as described by [24]. Furthermore, in this study we targeted the presence of bla CTX-M − 14 and stratified the CTX-M-G1 to specify CTX-M-3 or CTX-M-15 type's resistant genes.…”

Urine Tests for Diagnosis of Infectious Diseases and Antibiotic-Resistant Pathogens

“…Enterobacteriaceae, the leading cause of UTIs, developed resistance to β-lactam antibiotics by producing β-Lactamases, rendering this class of antibiotic to a large extended ineffective [37]. As mentioned above, with the lack of new drug development and only few new drugs being in the production pipeline, UTIs with AMR are a major concern, and it is a leading cause of morbidity and a cause of significant financial loss in many countries.…”

“…Treatment of UTI is a good example of AMR impact on the medical field. Many of the antibiotics prescribed traditionally for the treatment of UTIs are now compromised and to a large extent are ineffective [37]. More alarming, recent years have recorded the emergence of bacterial strains that are resistant to even last resort antibiotics such as colistin, making the treatment of UTIs a global challenge [38].…”

Antimicrobial Susceptibility Profile of Extended Spectrum Beta- lactamases Producing Enterobacteriaceae isolated from clinical samples refereed to the National Bacteriology and Mycology Reference Laboratory, Ethiopia

“…ESBLs producing bacteria may also hydrolyze carbapenems drugs including impenem, meropenem and ertapenem. This is commonly true in ESBL positive organisms producing Klebsiella pneumoniae carbapenemase (KPC) when ESBL production is associated with chromosomal AmpC-type betalactamases [7]. Thus, Enterobacteriaceae harboring ESBLs are multidrug resistant for multiple antimicrobial classes with very limited treatment options available which significantly impact patient outcomes [8].…”