Antibiotic Stewardship in Paediatric Inpatients and C. Difficile Associated Disease?

Clostridium difficile associated disease (CDI) in children has been linked to pervious antibiotic treatment. In one recent study, paediatric patients with Healthcare-onset CDI had significantly higher rates of death and longer length of stay in hospital compared with those with Community acquired-CDI and significantly worse outcomes compared with matched unexposed subjects (Sammons JS et al. Clin Infect Dis 2013; 57: 1–8). In another paediatric nested case control study, 95 patients≥1 year with CDI were compared with 238 controls. In multivariate analyses, predictors of CDI included solid organ transplant (odds ratio [OR], 8.09; 95% confidence interval [CI], 2.10–31.12), lack of prior hospitalization (OR, 8.43; 95% CI, 4.39–16.20), presence of gastrostomy or jejunostomy (G or J) tube (OR, 3.32; 95% CI 1.71–6.42), and receipt of fluoroquinolones (OR, 17.04; 95% CI, 5.86–49.54) or non-quinolone antibiotics (OR, 2.23; 95% CI, 1.18–4.20) in the past 4 weeks (Sandora TJ et al. Pediatr Infect Dis J. 2011; 30: 580–584.

The association of CDI with prior antibiotic treatment intuitively implicates the question, whether Antimicrobial Stewardship programs (ASPs, Hyun DY et al., JAMA Pediatr 2013; 167: 859–866) in paediatric inpatient care facilities impact on the epidemiology of CDI in children Feaezel et al. recently performed a systematic literature analysis on the effect of ASPs on CDI incidence but their analysis was restricted to studies performed in adult patient populations (Feazel LM et al. J Antimicrob Chemother 2014; 69: 1748–1754). The final dataset included 16 articles, which used quasi-experimental (interrupted time series or before-after) or observational (case-control) study designs. When the results of all studies were pooled in a random effects model, a significant protective effect (pooled risk ratio 0.48; 95% CI: 0.38–0.62) was observed between ASPs and CDI incidence. When stratified by intervention type, the authors found a significant effect for restrictive ASPs (complete removal of drug or prior approval requirement). Furthermore, ASPs were particularly effective in geriatric settings.

We performed a literature search to identify original articles (2000–2016) investigating any impact of ABS on CDI in children>1 year of age. Our starting point was a supplemental literature list of the Feazel publication, in which articles from the primary literature list were marked as being excluded because of including paediatric patients (n=37). In addition, we searched our literature database on CDI in children, which contains 441 citations, searched in PubMed/Medline (June 01, 2016) and manually checked recent publications (and their reference lists) detailing the benefits of ABS programs in paediatric inpatient care facilities (extensively reviewed in Smith MJ et al., J Pediatric Infect Dis Soc. 2015 4: e127–e135).

A single study abstract was identified, which showed a positive impact of paediatric ABS on the incidence of CDI in children. This study has not yet been published but has been discussed at the IDWeek 2015^TM (https://www.ucdmc.ucdavis.edu/publish/news/news room/10436). Researchers (including Jean Wiedeman and Natasha Nakra) compared rates of CDI and antibiotic-related costs at UC Davis Children’s Hospital between the pre-antibiotic stewardship era (2008–2010) and the antibiotic stewardship era (2011–2014). They found the rates of CDI decreased from 9.2 to 2.8 per 10 000 patient days after the ABS program was instituted, a greater than 3-fold reduction. Awaiting the full text publication of this study, we come to the conclusion that the impact of paediatric ABS programs on the incidence of CDI in paediatric inpatient care facilities is still an unresolved issue and should be included as a surrogate parameter in future studies detailing the benefits of paediatric ABS programs.