Trends in Clostridium difficile infection and risk factors for hospital acquisition of Clostridium difficile among children with cancer

Abstract

Objectives: To study the trend of Clostridium difficile infection (CDI) and risk factors for hospital acquired CDI (HA-CDI) among children with cancer.

Study design: We analyzed 33 095 first pediatric hospitalizations for malignancy among 43 pediatric hospitals between 1999 and 2011. The effect of demographics, disease characteristics, and weekly drug exposure (antibiotics, antacids, and chemotherapy) on HA-CDI was assessed with multivariate Cox regression. CDI was defined by the combination of International Classification of Diseases, 9th edition-Clinical Modification (ICD-9CM), CDI diagnostic assay billing code, and concurrent administration of a CDI-active antibiotic. HA-CDI was defined as CDI with assay occurring after the sixth hospital day.

Results: A total of 1736 admissions with CDI were identified, of which 380 were HA-CDI. CDI incidence increased from 1999-2006 (P = .01); however, CDI testing frequency and disease decreased from 2006-2010 (P < .05). Admissions with HA-CDI had longer lengths of stay compared with those without HA-CDI (35 days vs 12 days, P < .01) and greater risk of inpatient mortality (relative risk 2.3, P < .01). Increased risk of HA-CDI (hazard ratio [95% CI]) was seen after exposure to the following drugs: aminoglycoside (1.357 [1.053-1.749]), third generation cephalosporin (1.518 [1.177-1.959]), cefepime (2.383 [1.839-3.089]), and proton pump inhibiting agent (1.398 [1.096-1.784]) in the prior week, and chemotherapy (1.942 [1.491-2.529]) in the 8-14 days prior to HA-CDI onset. Histamine-2 receptor antagonist exposure in the prior week was associated with decreased risk of HA-CDI (0.730 [0.584-0.912]).

Conclusions: Despite an apparent decrease in CDI incidence from 2006-2010, HA-CDI remains prevalent and morbid among children with cancer. Recent exposure to chemotherapy, proton pump inhibitor, and certain antibiotics were independent risk factors for HA-CDI.

Keywords: CDI; CNS; Central nervous system; Clostridium difficile infection; DOT; Days of antibiotic therapy; H2; HA-CDI; HR; Hazard ratio; Histamine-2; Hospital acquired CDI; ICD-9CM; International Classification of Diseases, 9th edition-Clinical Modification; PCR; PHIS; Pediatric Health Information System; Polymerase chain reaction.

Figure 1

Overall incidence of CDI and frequency of C. difficile toxin assay among children hospitalized for cancer in 43 children’s hospitals in the United States, 1999–2010.

Figure 2

Hazard ratios for exposure in the last week to individual agents used commonly for febrile neutropenia. Results are stratified by hospital site, clustered by patient, and adjusted for sex, race, age at admission, and year of admission.