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Community Origins and Regional Differences Highlight Risk of Plasmid-mediated Fluoroquinolone Resistant Enterobacteriaceae Infections in Children

Logan, Latania K., MD, MSPH*,†,‡,§; Medernach, Rachel L., MD*,¶; Rispens, Jared R., MD*,¶; Marshall, Steven H., MS; Hujer, Andrea M., BS†,‖; Domitrovic, T. Nicholas, MS†,‖; Rudin, Susan D., BS†,‖; Zheng, Xiaotian, MD, PhD**,††; Qureshi, Nadia K., MD‡‡; Konda, Sreenivas, PhD; Hayden, Mary K., MD; Weinstein, Robert A., MD§,¶; Bonomo, Robert A., MD†,‖,§§

The Pediatric Infectious Disease Journal: June 2019 - Volume 38 - Issue 6 - p 595–599
doi: 10.1097/INF.0000000000002205
Antimicrobial Reports

Background: Fluoroquinolones are uncommonly prescribed in children, yet pediatric multidrug resistant (MDR) enterobacteriaceae (Ent) infections often reveal fluoroquinolone resistance (FQR). We sought to define the molecular epidemiology of FQR and MDR-Ent in children.

Methods: A case–control analysis of children with MDR-Ent infections at 3 Chicago hospitals was performed. Cases were children with third-generation cephalosporin-resistant and/or carbapenem-resistant Ent infections. Polymerase chain reaction and DNA analysis assessed bla and plasmid-mediated FQR (PMFQR) genes. Controls were children with third-generation cephalosporin, fluoroquinolone, and carbapenem-susceptible Ent infections matched by age, source and hospital. We assessed clinical-epidemiologic predictors of PMFQR Ent infection.

Results: Of 169 third-generation cephalosporin-resistant and/or carbapenem-resistant Ent isolates from children (median age, 4.8 years), 85 were FQR; 56 (66%) contained PMFQR genes. The predominant organism was Escherichia coli, and most common bla gene blaCTX-M-1 group. In FQR isolates, PMFQR gene mutations included aac6’1bcr, oqxA/B, qepA and qnrA/B/D/S in 83%, 15%, 13% and 11% of isolates, respectively. FQR E. coli was often associated with phylogroup B2, ST43/ST131. On multivariable analysis, PMFQR Ent infections occurred mostly in outpatients (odds ratio, 33.1) of non–black-white-Hispanic race (odds ratio, 6.5). Residents of Southwest Chicago were >5 times more likely to have PMFQR Ent infections than those in the reference region, while residence in Central Chicago was associated with a 97% decreased risk. Other demographic, comorbidity, invasive-device, antibiotic use or healthcare differences were not found.

Conclusions: The strong association of infection with MDR organisms showing FQR with patient residence rather than with traditional risk factors suggests that the community environment is a major contributor to spread of these pathogens in children.

From the *Pediatrics, Rush University Medical Center, Chicago, Illinois

Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio

University of Illinois at Chicago

§Cook County Health and Hospital Systems

Medicine, Rush University Medical Center, Chicago, Illinois

Department of Pharmacology, Molecular Biology, Microbiology and Medicine, Case Western Reserve School of Medicine, Cleveland, Ohio

**Microbiology, Ann & Robert H. Lurie Children’s Hospital of Chicago

††Pathology, Northwestern Feinberg School of Medicine, Chicago, Illinois

‡‡Pediatrics, Loyola University Medical Center, Maywood, Illinois

§§Pharmacology, Molecular Biology, and Microbiology, Case Western Reserve School of Medicine, Cleveland, Ohio.

Accepted for publication August 28, 2018.

Supported by National Institutes of Health - National Institute of Allergy and Infectious Diseases grant K08AI112506 (L.K.L.) and grants R01AI072219, R01AI063517 and R01AI100560 (R.A.B.). Also supported by the Department of Veterans Affairs Research and Development under award number I01BX001974, VISN 10 Geriatrics Research, Education and Clinical Center (R.A.B.).

The authors have no conflicts of interest to disclose.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Department of Veterans Affairs.

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Address for correspondence: Latania K. Logan, Rush University Medical Center 1620 W. Harrison, Suite 951 Jelke, Chicago, IL 60612. E-mail:

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