SAN DIEGO (FRONTLINE MEDICAL NEWS) Children exposed to antibiotics are at a significantly heightened risk to develop extended-spectrum cephalosporin-resistant (ESC-R) and carbapenem-resistant (CR) Enterobacteriaceae infections within 30 days of said exposure, according to a prospective, case-controlled study.

Dr. Matthew P. Kronman, a pediatric infectious disease specialist at Seattle Children’s Hospital, and several coinvestigators examined data on 1,263 children from four hospital centers in the United States – Seattle Children’s Hospital; Washington University, St. Louis; Children’s Mercy Hospital, Kansas City, Mo.; and Children’s Hospital of Philadelphia – from Oct. 1, 2009, through Sept. 30, 2013.

“The CDC [Centers for Disease Control and Prevention] estimates that 2 million Americans get multidrug resistant organism [MDRO] infections each year, and 23,000 die,” said Dr. Kronman, adding that while it’s known that prior exposure to antibiotics is a key risk factor for colonization and development of an infection in adults, similar data among children with respect to ampC and extended-spectrum beta-lactamase (ESBL) are conflicting.

The study population included 95 subjects with ampC infections, 213 with ESBL infections, and 955 controls, for a total of 1,263 children. Prior exposure to antibiotics within the previous month or 3 months before infection was associated with infection of either ESC-R or CR Enterobacteriaceae (P < .01). A cumulative effect was noted, with increased exposure to antibiotics increasing the likelihood of developing an MDRO infection within 3 months (odds ratio 1.28 per month, P < .01), Dr. Kronman reported at the annual meeting of the Pediatric Academic Societies.

Those with ESBL infections were more likely to have any antibiotic exposure in the 30 days prior to their infection than were their control counterparts (OR > 2), but a similar, statistically significant relationship among those with ampC infections was not observed. When the researchers looked at broad-spectrum antibiotic exposures – defined as “carbapenems, beta-lactams, beta-lactase inhibitors, tetracyclines, and so on” – those with ESBL infections were more likely to have broad-spectrum antibiotic exposures in the month prior to their infection, which was not the case for those with ampC infections.

Both ESBL and ampC subjects were more likely to have been exposed to extended-spectrum cephalosporin use in the month prior to infection than controls. “When we looked just the use of antibiotics with anaerobic activity only, neither ESBL nor ampC infections were more likely than their control counterparts to have had exposure to anaerobic antibiotics in the month prior to infection,” Dr. Kronman said.

Patients had Escherichia coli and Klebsiella pneumoniae isolates collected from normally sterile sites; 91% were isolated from urine, and 46% were found to be associated with “community onset infection.” Samples were phenotypically resistant to extended spectrum cephalosporins, but were genotyped at Seattle Children’s Hospital to determine if the resistant strain was ampC or an ESBL. E. coli cases dominated the study population (85%), compared with cases of K. pneumoniae (15%). Results were adjusted for age, gender, prior hospitalization, underlying medical conditions, immunosuppression, and presence of indwelling devices. Median age of subjects was 5 years.

Those with resistant infections were more likely to have a “significant past medical history” of urologic conditions or malignancies; to have had hospitalization within the previous year; to be on immunosuppression at the time of the infection; or to have an indwelling device at the time of the infection. Resistant infections were less likely to originate in the community and were more commonly health care associated.

Dr. Kronman did not report any relevant financial disclosures.


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