Double Trouble: Influenza and S aureus Co-infection

Abstract

Nguyen T, Kyle UG, Jaimon N, et al. Co-infection with Staphylococcus aureus increases risk of severe coagulopathy in critically ill children with influenza A (H1N1) virus infection. Crit Care Med. 2012; 40(12): 3246– 3250; doi: 10.1097/CCM.0b013e318260c7f8Investigators from Baylor College of Medicine conducted an observational study of pediatric patients admitted to the PICU from 2009 to 2010 with either confirmed or suspected influenza infection to assess the effect of bacterial co-infection on morbidity and mortality. Confirmed influenza infection was defined as any positive laboratory test for influenza A or B virus infection. Confirmed cases were further subtyped using PCR for H1N1, but this was incomplete since the study began prior to the introduction of PCR primers specific for H1N1. A clinically relevant bacterial co-infection was defined as: (1) empiric treatment of a clinical diagnosis of bacterial pneumonia, (2) bacterial super-infection within 72 hours of the initial PICU admission from a sterile site (respiratory secretions or blood), or (3) a bacterial pathogen identified in the patient’s respiratory secretions. Comorbidities and treatment with regular- and high-dose oseltamivir were recorded. The following outcomes were compared between patients with and without methicillin-sensitive or -resistant S aureus (MSSA/MRSA) co-infection: severity of illness within the first 24 hours of admission using the Pediatric Risk of Mortality III acute physiology (PRISM) score,1 receipt of vasoactive medications, duration of PICU care, survival at day 90, and disseminated intravascular coagulation (DIC).Of the 66 children enrolled, 59% were males and the mean age was 5.9 years. A total of 64% had H1N1 and 36% were influenza A-positive but not subtyped. Bacterial co-infections were present in 52% of patients, with 35% of these being MSSA/MRSA. Fifty-five percent of patients had comorbidities, most commonly asthma (14%), chronic lung disease (11%), and developmental delay (14%). Fifty-nine percent of patients were treated with high-dose oseltamivir and 20% with regular-dose oseltamivir.Compared to those without co-infection, children with MSSA/ MRSA had a significantly greater severity of illness (median PRISM III score 14 vs 6), receipt of vasoactive medications (58% vs 22%), and duration of PICU care (median 11.0 vs 5.5 days). Survival at day 90 was not significantly different between those with MSSA/MRSA co-infection and no co-infection (83% vs 91%). Patients with MSSA/ MRSA co-infection were significantly more likely to have DIC than those without co-infection.The authors conclude that among children admitted to the PICU with influenza A or H1N1, those with a higher level of severity of illness are at increased risk of MSSA/MRSA and DIC.H1N1 influenza emerged as a novel strain of the influenza virus during 2009 and 2010 leading to a global pandemic. Unlike most influenza A strains, H1N1 has a predilection to cause disease in children and young adults, and young age was a risk factor for H1N1-associated deaths.2 The Centers for Disease Control and Prevention (CDC) identified 338 influenza-associated pediatric deaths during the outbreak, a fourfold increase in annual influenza-related deaths. Ninety-two percent of fatal cases were attributed to H1N1.3 Among fatal cases, co-infection with bacteria was approximately twice as common in children compared to adults.4 Secondary infections complicating influenza infection include bloodstream infections (BSI) due to S pneumoniae, S pyogenes and S aureus. BSI increased during the H1N1 epidemic, with the greatest increase for pneumococcal bacteremia among children <5 years old.5Several mechanisms are proposed for this viral-bacterial virulence, including viral-induced airway changes favoring bacterial growth and viral-induced defects in immune responses.5 The current study suggests another pathological process for increased virulence associated with MSSA/MRSA: increased risk of DIC. DIC and inadequate initial antimicrobial treatment are both associated with increased risk of death.6Approximately 15% of hospitalized pediatric H1N1 patients required intensive care.7 A previous multicenter US report of children with H1N1 treated in an ICU found that 70% had 1 or more chronic conditions. The majority developed respiratory failure treated with mechanical ventilation (67%) and 19% received vasoactive medications. Mortality was 9%, and among previously well children, MRSA co-infection was associated with an eightfold increased risk of death.8Both primary and hospital-based care providers can improve pediatric health by strictly adhering to influenza vaccination recommendations. All children ≥6 months old should be vaccinated against influenza every year. As this study reminds us, influenza causes significant mortality and morbidity in children and the best treatment is prevention.