Vancomycin Monotherapy May Be Insufficient to Treat Methicillin-resistant Staphylococcus aureus Coinfection in Children With Influenza-related Critical Illness

Clin Infect Dis. 2019 Jan 18;68(3):365-372. doi: 10.1093/cid/ciy495.

Abstract

Background: Coinfection with influenza virus and methicillin-resistant Staphylococcus aureus (MRSA) causes life-threatening necrotizing pneumonia in children. Sporadic incidence precludes evaluation of antimicrobial efficacy. We assessed the clinical characteristics and outcomes of critically ill children with influenza-MRSA pneumonia and evaluated antibiotic use.

Methods: We enrolled children (<18 years) with influenza infection and respiratory failure across 34 pediatric intensive care units 11/2008-5/2016. We compared baseline characteristics, clinical courses, and therapies in children with MRSA coinfection, non-MRSA bacterial coinfection, and no bacterial coinfection.

Results: We enrolled 170 children (127 influenza A, 43 influenza B). Children with influenza-MRSA pneumonia (N = 30, 87% previously healthy) were older than those with non-MRSA (N = 61) or no (N = 79) bacterial coinfections. Influenza-MRSA was associated with increased leukopenia, acute lung injury, vasopressor use, extracorporeal life support, and mortality than either group (P ≤ .0001). Influenza-related mortality was 40% with MRSA compared to 4.3% without (relative risk [RR], 9.3; 95% confidence interval [CI], 3.8-22.9). Of 29/30 children with MRSA who received vancomycin within the first 24 hours of hospitalization, mortality was 12.5% (N = 2/16) if treatment also included a second anti-MRSA antibiotic compared to 69.2% (N = 9/13) with vancomycin monotherapy (RR, 5.5; 95% CI, 1.4, 21.3; P = .003). Vancomycin dosing did not influence initial trough levels; 78% were <10 µg/mL.

Conclusions: Influenza-MRSA coinfection is associated with high fatality in critically ill children. These data support early addition of a second anti-MRSA antibiotic to vancomycin in suspected severe cases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Anti-Bacterial Agents / therapeutic use*
  • Child
  • Child, Preschool
  • Coinfection / drug therapy*
  • Coinfection / microbiology
  • Coinfection / mortality
  • Coinfection / pathology
  • Critical Illness*
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Influenza, Human / complications*
  • Influenza, Human / mortality
  • Influenza, Human / pathology
  • Male
  • Methicillin-Resistant Staphylococcus aureus / isolation & purification*
  • Pneumonia, Staphylococcal / drug therapy*
  • Pneumonia, Staphylococcal / microbiology
  • Pneumonia, Staphylococcal / mortality
  • Pneumonia, Staphylococcal / pathology
  • Prospective Studies
  • Survival Analysis
  • Treatment Outcome
  • Vancomycin / therapeutic use*

Substances

  • Anti-Bacterial Agents
  • Vancomycin