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

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.

Figure 1.

Clinical course and outcomes of critically ill children with influenza virus–methicillin-resistant Staphylococcus aureus (N = 30) compared to influenza with other bacteria identified (N = 61) and influenza with no bacteria identified (N = 79). Abbreviations: ECMO, extracorporeal membrane oxygenation; MRSA, methicillin-resistant Staphylococcus aureus.*P ≤ .05, **P ≤ .001, ***P < .0001. Comparisons were made using Mann-Whitney U test with the ends of the bars showing the groups compared.

Figure 2.

White blood cell (WBC) counts of children with influenza virus infection within first 24 hours of pediatric intensive care unit admission. WBC counts were available for all 30 influenza–methicillin-resistant Staphylococcus aureus patients, 56/61 influenza–other bacteria patients, and 78/79 influenza–no bacteria patients. Abbreviation: MRSA, methicillin-resistant Staphylococcus aureus. *P ≤ .05, **P ≤ .001, ***P < .0001. Comparisons were made using Mann-Whitney U test with the ends of the bars identifying the groups compared.

Figure 3.

Comparison of vancomycin only to vancomycin with additional anti-methicillin-resistant Staphylococcus aureus agent(s) within the first 24 hours of pediatric intensive care unit admission stratified by survival The relative risk (RR) of mortality in the vancomycin only group was 5.54 (95% confidence interval, 1.4–21.3). Abbreviation: MRSA, methicillin-resistant Staphylococcus aureus.

Figure 4.

(A) Initial vancomycin trough levels (prior to the fourth dose) of methicillin-resistant Staphylococcus aureus patients (78.5% of initial trough levels were less than 10 µg/mL). (B) Vancomycin dosing and initial trough level. Initial trough levels were not associated with initial vancomycin dose (Spearman’s correlation, P = .6). Abbreviation: PICU, pediatric intensive care unit.