Nonsteroidal Anti-Inflammatory Drug without Antibiotics for Acute Viral Infection Increases the Empyema Risk in Children: A Matched Case-Control Study

J Pediatr. 2016 Aug;175:47-53.e3. doi: 10.1016/j.jpeds.2016.05.025. Epub 2016 Jun 20.


Objective: To investigate the risk factors of empyema after acute viral infection and to clarify the hypothesized association(s) between empyema and some viruses and/or the use of nonsteroidal anti-inflammatory drugs (NSAIDs).

Study design: A case-control study was conducted in 15 centers. Cases and controls were enrolled for a source population of children 3-15 years of age with acute viral infections between 2006 and 2009.

Results: Among 215 empyemas, 83 cases (children with empyema and acute viral infection within the 15 preceding days) were included, and 83 controls (children with acute viral infection) were matched to cases. Considering the intake of any drug within 72 hours after acute viral infection onset and at least 6 consecutive days of antibiotic use and at least 1 day of NSAIDs exposure, the multivariable analysis retained an increased risk of empyema associated with NSAIDs exposure (aOR 2.79, 95% CI 1.4-5.58, P = .004), and a decreased risk associated with antibiotic use (aOR 0.32, 95% CI 0.11-0.97, P = .04). The risk of empyema associated with NSAIDs exposure was greater for children not prescribed an antibiotic and antibiotic intake diminished that risk for children given NSAIDs.

Conclusions: NSAIDs use during acute viral infection is associated with an increased risk of empyema in children, and antibiotics are associated with a decreased risk. The presence of antibiotic-NSAIDs interaction with this risk is suggested. These findings suggest that NSAIDs should not be recommended as a first-line antipyretic treatment during acute viral infections in children.

Keywords: NSAIDs; children; empyema.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adolescent
  • Anti-Bacterial Agents / therapeutic use*
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Drug Therapy, Combination
  • Empyema, Pleural / diagnosis
  • Empyema, Pleural / etiology*
  • Female
  • Humans
  • Infant
  • Logistic Models
  • Male
  • Multivariate Analysis
  • Risk Factors
  • Virus Diseases / complications
  • Virus Diseases / diagnosis
  • Virus Diseases / drug therapy*


  • Anti-Bacterial Agents
  • Anti-Inflammatory Agents, Non-Steroidal