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Clin Infect Dis. 2018 Jun 9. doi: 10.1093/cid/ciy495. [Epub ahead of print]
Vancomycin Monotherapy May Be Insufficient to Treat Methicillin-resistant Staphylococcus aureus Coinfection in Children with Influenza-Related Critical Illness.
Randolph AG1,2,3, Xu R1, Novak T1, Newhams MM1, Bubeck Wardenburg J4, Weiss SL5, Sanders RC6, Thomas NJ7, Hall MW8, Tarquinio KM9, Cvijanovich N10, Gedeit RG11, Truemper EJ12, Markovitz B13, Hartman ME4, Ackerman KG14, Giuliano JS Jr15, Shein SL16, Moffitt K3,17; Pediatric Intensive Care Influenza (PICFLU) Investigators from the Pediatric Acute Lung Injury and Sepsis Investigator?s (PALISI) Network.
Author information
Abstract
Background:
Respiratory 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 respiratory coinfection and evaluated antibiotic use.
Methods:
We prospectively enrolled children (<18 years) with influenza infection and acute respiratory failure across 34 pediatric intensive care units Nov 2008 to May 2016. We compared baseline characteristics, clinical courses and therapies in children with 1.) MRSA coinfection, 2.) non-MRSA bacterial coinfection, and 3.) 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 other bacterial coinfections (N=61) or no bacterial coinfection (N=79). Influenza-MRSA was associated with more frequent leukopenia, acute lung injury, vasopressor use, extracorporeal life support and mortality compared to either non-MRSA group (all P≤0.0001). Influenza-related mortality was 40% with MRSA compared to 4.3% without MRSA (RR 9.3, 95% CI, 3.8-22.9). Of 29/30 children with MRSA receiving vancomycin within the first 24 hours of hospitalization, mortality was 12.5% (N=2/16) if treatment included a second anti-MRSA antibiotic in the first 24 hours compared to 69.2% (N=9/13) with vancomycin monotherapy (RR 5.5, 95% CI 1.4, 21.3; P=0.003). Vancomycin dosing did not influence trough levels; 78% of initial troughs were <10 mcg/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.
PMID: 29893805 DOI: 10.1093/cid/ciy495
Vancomycin Monotherapy May Be Insufficient to Treat Methicillin-resistant Staphylococcus aureus Coinfection in Children with Influenza-Related Critical Illness.
Randolph AG1,2,3, Xu R1, Novak T1, Newhams MM1, Bubeck Wardenburg J4, Weiss SL5, Sanders RC6, Thomas NJ7, Hall MW8, Tarquinio KM9, Cvijanovich N10, Gedeit RG11, Truemper EJ12, Markovitz B13, Hartman ME4, Ackerman KG14, Giuliano JS Jr15, Shein SL16, Moffitt K3,17; Pediatric Intensive Care Influenza (PICFLU) Investigators from the Pediatric Acute Lung Injury and Sepsis Investigator?s (PALISI) Network.
Author information
Abstract
Background:
Respiratory 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 respiratory coinfection and evaluated antibiotic use.
Methods:
We prospectively enrolled children (<18 years) with influenza infection and acute respiratory failure across 34 pediatric intensive care units Nov 2008 to May 2016. We compared baseline characteristics, clinical courses and therapies in children with 1.) MRSA coinfection, 2.) non-MRSA bacterial coinfection, and 3.) 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 other bacterial coinfections (N=61) or no bacterial coinfection (N=79). Influenza-MRSA was associated with more frequent leukopenia, acute lung injury, vasopressor use, extracorporeal life support and mortality compared to either non-MRSA group (all P≤0.0001). Influenza-related mortality was 40% with MRSA compared to 4.3% without MRSA (RR 9.3, 95% CI, 3.8-22.9). Of 29/30 children with MRSA receiving vancomycin within the first 24 hours of hospitalization, mortality was 12.5% (N=2/16) if treatment included a second anti-MRSA antibiotic in the first 24 hours compared to 69.2% (N=9/13) with vancomycin monotherapy (RR 5.5, 95% CI 1.4, 21.3; P=0.003). Vancomycin dosing did not influence trough levels; 78% of initial troughs were <10 mcg/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.
PMID: 29893805 DOI: 10.1093/cid/ciy495