Adverse Drug Reactions including Clostridium difficile

Tamma PD, Avdic E, Li Dx, Dzintars K, Cosgrove SE. Association of Adverse Events With Antibiotic Use in Hospitalized Patients. JAMA Intern Med. 2017 Sep 1; 177(9):1308-1315

Shehab N, Patel PR, Srinivasan A, Budnitz DS. Emergency department visits for antibiotic-associated adverse events. Clin Infect Dis. 2008 Sep 15;47(6):735-43.

  • Antibiotics were implicated in 19% of all ED visits for drug-related adverse events. It was estimated that antibiotic-related adverse events led to nearly 150,000 ED visits per year.
  • Most ED visits for antibiotic-associated adverse events were for allergic reactions (79% of visits).
  • Lovegrove MC, Geller AI, Fleming-Dutra KE, Shehab N, Sapiano MRP, Budnitz DS. US Emergency Department Visits for Adverse Drug Events From Antibiotics in Children, 2011-2015. J Pediatric Infect Dis Soc. 2018 Aug 23.
  • Almost half of all ED visits for adverse drug events in children 19 years and younger are due to antibiotics.
  • 40% of ED visits for adverse drug events occur in children 2 years and less.

Lovegrove MC et al. US Emergency Department Visits for Adverse Drug Events From Antibiotics in Children, 2011–2015. J Pediatric Infect Dis Soc. 2018 Aug 23.

  • Between 2011-2015, an estimated 69,464 ED visits per year were made among children with adverse drug events, accounting for 46.2% of ED visits for adverse drug events from systemic medication.
  • Two-fifths (40.7%) of ED visits for antibiotic ADEs involved a child aged ≤2 years, and 86.1% involved an allergic reaction.
  • Between 2011-2015, an estimated 69,464 ED visits per year were made among children with adverse drug events.
  • Almost half of all ED visits for adverse drug events in children 19 years and younger are due to antibiotics. 40% of ED visits for adverse drug events occur in children 2 years and less.

Goldman JL, Jackson MA, Herigon JC, Hersh AL, Shapiro DJ, Leeder JS. Trends in adverse reactions to trimethoprim-sulfamethoxazole. Pediatrics. 2013 Jan;131(1):e103-8.

  • At a single institution, Goldman et al (Pediatrics 2013) found that the incidence in children of adverse drug reactions due to TMP-SMX was 13 cases/100,000 admissions in 2005-2006. This was an increase from 5 cases/100,000 admissions in the 2000-2004 time period. The majority of these patients were prescribed TMP-SMX for a skin and soft tissue infection.

Antibiotic Exposure Increases the Risk of CDI

Previous antibiotic exposure is recognized as the single most important risk factor for CDI in adults and children, and nearly all antibiotics have been associated with C difficile disease (Owens RC Jr, Donskey CJ, Gaynes RP, Loo VG, Muto CA. Antibiotic-associated risk factors for Clostridium difficile infectionClin Infect Dis. 2008;46:(suppl 1 S19-S31)

Current Incidence of CDI in Children

Lesse et al (NEJM 2015) used active population and laboratory-based surveillance across 10 geographic areas in 2011 to identify the burden of CDI in the United States. Among children 1-17 years, the incidence of CDI was 24.2 per 100,000 persons; with community-associated CDI incidence of 17.9 per 100,000 persons and healthcare associated CDI incidence of 6.3 per 100,000 persons. (Lessa FC, Mu Y, Bamberg WM, Beldavs ZG, Dumyati GK, Dunn JR, et al. Burden of Clostridium difficile infection in the United States. N Engl J Med. 2015 Feb 26;372(9):825-34)

Increasing Incidence of CDI in Children

Several studies have noted a rise in CDI-related hospitalizations.

CDI Associated with Increased Mortality, Prolonged Hospitalization

Sammons et al (CID 2013) found that when matched to children without CDI, children with CDI had increased mortality (OR 6.73, 95% CI 3.77-12.02), longer length of hospital stay, and higher hospital costs. (Sammons JS, Localio R, Xiao R, Coffin SE, Zaoutis T. Clostridium difficile infection is associated with increased risk of death and prolonged hospitalization in children. Clin Infect Dis. 2013 Jul;57(1):1-8.)