The Clinical and Molecular Epidemiology of CTX-M-9 Group Producing Enterobacteriaceae Infections in Children

Abstract

Introduction The pandemic of extended-spectrum beta-lactamase-(ESBL)-producing Enterobacteriaceae (Ent) is strongly linked to the dissemination of CTX-M-type-ESBL-Ent. We sought to define the epidemiology of infections in children due to an emerging resistance type, CTX-M-9-group-producing-Ent (CTX-M-9-grp-Ent). Methods A retrospective matched case-control analysis of children with CTX-M-9-grp-Ent infections who received medical care at three Chicago area hospitals was performed. Cases were defined as children possessing extended-spectrum cephalosporin-resistant (ESC-R) infections due to bla CTX-M-9 . PCR and DNA analysis assessed beta-lactamase ( bla ) genes, multi-locus sequence types (MLST) and phylogenetic grouping of E. coli . Controls were children with ESC-susceptible (ESC-S)-Ent infections matched one case to three controls by age, source, and hospital. The clinical-epidemiologic predictors of CTX-M-9-grp-Ent infection were assessed. Results Of 356 ESC-R-Ent isolates from children (median age 4.1 years), the CTX-M-9-group was the solely detected bla gene in 44 (12.4%). The predominant species was E. coli (91%) of virulent phylogroups D (60%) and B2 (40%). MLST revealed multiple strain types. On multivariable analysis, CTX-M-9-grp-Ent occurred more often in E. coli than other Ent genera (OR 7.4, 95% CI 2.4, 27.2), children of non-Black-White-Hispanic race (OR 7.4, 95% CI 2.4, 28.2), and outpatients (OR 4.5, 95% CI 1.7, 12.3), which was a very unexpected finding for infections due to antibiotic-resistant bacteria. Residents of South Chicago had a 6.7 times higher odds of having CTX-M-9-grp-Ent infections than those in the reference region (West), while residence in Northwestern Chicago was associated with an 81% decreased odds of infection. Other demographic, comorbidity, invasive-device, and antibiotic use differences were not found. Conclusion CTX-M-9-grp-Ent infection may be associated with patient residence and is occurring in children without traditional in-patient exposure risk factors. This suggests that among children, the community environment may be a key contributor in the spread of these resistant pathogens.

A Pilot Study of Chicago Waterways as Reservoirs of Multidrug-Resistant Enterobacteriaceae (MDR-Ent) in a High-Risk Region for Community-Acquired MDR-Ent Infection in Children

“…1), we discovered that compared to living in a reference region (West Chicago, region 4), residence in South and Southwest Chicago (regions 5 and 6) was associated with a 5-times-higher MDR-Ent infection risk. Conversely, residence in Central and Northwest Chicago (regions 1 and 2) was linked to a Ͼ80% decreased infection risk (9,10). We also found that the majority of the highest-risk zip codes for MDR-Ent infection within the high-risk regions were in close proximity to area waterways (Fig.…”

“…Mcr-1 (colistin) was found in A2 to A4, and QnrS, OqxA/B (quinolone), and bla OXA /bla AmpC (beta-lactam) were found in A1 to A4. Through culture-based methods (Table 1), 15 viable E. coli, Klebsiella pneumoniae, and Enterobacter cloacae isolates from A2 to A4 were found to harbor transmissible ARGs that were also detected in clinical isolates recovered from children residing in the high-risk region, including bla CTX-M-9grp , bla CTX-M-1grp , bla SHV-ESBL , and bla CMY-AmpCs , along with additional aminoglycoside and quinolone ARGs (7,9,10). Sixty percent of culture isolates were resistant to three or more antibiotic classes.…”

“…Additionally, antibiotic exposure has been associated with communityacquired ESBL-Ent in adults in Chicago (18). However, among children in Chicago, traditional health care exposures, including antibiotic exposure, were not found to be risk factors for community-acquired MDR-Ent, and the community environment appears to represent a key contributor in the spread of these resistant pathogens (9,10).…”

“…In contrast, in our studies of MDR-Ent infections in children cared for at six centers in the Chicagoland area, we found that genetic determinants of beta-lactam and fluoroquinolone resistance in strains infecting children are diverse and that certain transmissible resistance mechanisms (including several novel strain types) differ from known circulating genotypes in adults (5,7,8). Additionally, when comparing children with MDR-Ent infections (median patient age, 4 years) to children with antibiotic-sensitive Enterobacteriaceae infections, we found that for both plasmid-mediated fluoroquinolone-resistant (PMFQR) Enterobacteriaceae and CTX-M-9 group Enterobacteriaceae infections, there was a 4 to 34 times greater chance that these infections were community-acquired (9,10).…”

The composition of the microbial community associated with Macrobrachium rosenbergii zoeae varies throughout larval development

“…Most bacterial species within the Enterobacter genus are commonly found in human and animal intestines. Only a few Enterobacter species have been identified as conditional pathogens and have been described to cause extra‐intestinal and invasive infections in humans (Logan et al, ; Logan, Renschler, Sumanth, Weinstein, & Ramanan, ; Lukac, Bonomo, & Logan, ; Mogle, Beccari, Steele, Fazili, & Kufel, ). In aquaculture, the pathogenicity of Enterobacter has been reported relatively infrequently.…”