Differences in the Molecular Epidemiology and Antibiotic Susceptibility of Clostridium difficile Isolates in Pediatric and Adult Patients

Abstract

fThe rising incidence of Clostridium difficile infections (CDIs) in adults is partly related to the global spread of fluoroquinoloneresistant strains, namely, BI/NAP1/027. Although CDIs are also increasingly diagnosed in children, BI/NAP1/027 is relatively uncommon in children. Little is known about the antibiotic susceptibility of pediatric CDI isolates. C. difficile was cultured from tcdB-positive stools collected from children diagnosed with CDI between December 2012 and December 2013 at an academic children's hospital. CDI isolates were grouped by restriction endonuclease analysis (REA). MICs were measured by agar dilution method for 7 antibiotics. Susceptibility breakpoints were based on guidelines from CLSI and/or the European Committee on Antimicrobial Susceptibility Testing (EUCAST). MICs and REA groupings of C. difficile isolates from 74 adult patients (29 isolates underwent REA) from a temporally and geographically similar adult cohort were compared to those of pediatric isolates. Among 122 pediatric and 74 adult isolates, respectively, the rates of resistance were as follows: metronidazole, 0% and 0%; vancomycin, 0% and 8% (P ‫؍‬ 0.003); rifaximin, 1.6% and 6.7% (P ‫؍‬ 0.11); clindamycin, 18.9% and 25.3% (P ‫؍‬ 0.29); and moxifloxacin, 2.5% and 36% (P ‫؍‬ <0.0001). Only 1 of 122 (0.8%) BI/NAP1/027 isolates was identified among the children, compared to 9 of 29 (31%) isolates identified among the adults (P ‫؍‬ <0.0001). The 3 moxifloxacin-resistant pediatric isolates were of REA groups BI and CF and a nonspecific group. The 2 rifaximin-resistant pediatric isolates were of REA groups DH and Y. The 21 clindamycin-resistant pediatric isolates were distributed among 9 REA groups (groups A, CF, DH, G, L, M, and Y and 2 unique nonspecific REA groups). These data suggest that a diverse array of relatively antibiotic-susceptible C. difficile strains predominate in a cohort of children with CDI compared to adults. T he increased frequency, morbidity, and mortality of Clostridium difficile infections (CDI) in adults over the past 2 decades are primarily attributable to the emergence and global spread of a fluoroquinolone-resistant strain known as BI/NAP1/027 (1, 2). CDI is now the most frequently encountered health care-associated infection in the United States (3), causing nearly 500,000 infections and 30,000 deaths each year (4). These troubling trends in the clinical and molecular epidemiology of CDI recently prompted the Centers for Disease Control and Prevention (CDC) to classify CDI among the most serious immediate antibiotic-resistant diseases representing "public health threats that require urgent and aggressive action" (5).The molecular epidemiology (6-8) and antibiotic resistance (7-9) patterns of CDI in adults over the past 3 decades have been well described. Although the prevalence of BI/NAP1/027 is declining, recent data from the United States (4) and the United Kingdom (10) indicate that BI/NAP1/027 is still an important cause of CDI in adults. Limited investigation of the molecular epidemiology of...

A multicenter study to define the epidemiology and outcomes of Clostridioides difficile infection in pediatric hematopoietic cell and solid organ transplant recipients

“…29,30 The differential effects of various broad spectrum antibiotics on rates of CDI may reflect variable effects on gut anaerobes and possibly, a direct inhibitor effect of quinolones against C difficile. 31 We also found a higher risk of developing CDI among HCT recipients who had a history of CDI in the 12 months before the current transplant. The increased risk in recipients with a history of prior CDI may reflect increased C difficile colonization or absence of antibodies to the toxin.…”

“…Recent studies examining the use of levofloxacin prophylaxis in leukemia and HCT patients reported reduced positive C difficile test results when compared to placebo or other prophylactic regimens . The differential effects of various broad spectrum antibiotics on rates of CDI may reflect variable effects on gut anaerobes and possibly, a direct inhibitor effect of quinolones against C difficile …”

Comparative genomics analysis of Clostridium difficile epidemic strain DH/NAP11/106

“…Antibiotic susceptibility data were derived from a previous study [14]. Mean inhibitory concentrations (MIC) of the following antibiotics were measured at the Loyola University Chicago Stritch School of Medicine: metronidazole, vancomycin, rifaximin, fidaxomicin, surotomycin, clindamycin, and moxifloxacin (i.e., high-level fluoroquinolone resistance).…”

Barriers and facilitators and the need for a clinical guideline for microbiological diagnostic testing in the hospital: a qualitative and quantitative study

“…The division between medical specialists versus residents was made to depict differences in professional experience. The division between the paediatrics department versus non-paediatrics departments was made to depict epidemiological, clinical and microbiological differences in infectious diseases and because separate diagnostic and treatment guidelines exist for the two [ 21 – 25 ].…”