Bacterial Co-infection in H1N1 Influenza
By Carol A. Kemper, MD, FACP, Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases, Santa Clara Valley Medical Center. Dr. Kemper conducts research for GSK Pharmaceuticals, Abbott Laboratories, and Merck. This brief was originally published in the December issue of Infectious Disease Alert. At that time it was reviewed by Connie Price, MD, Assistant Professor, University of Colorado School of Medicine. Dr. Price reports no financial relationship to this field of study.
Source: CDC. Bacterial coinfections in lung tissue specimens from fatal cases of 2009 pandemic influenza A (H1N1) United States, May-August 2009. MMWR 2009;58:1071-1074.
Data early on in the pandemic influenza outbreak suggested that most severely ill patients with influenza A were not suffering from bacterial co-infection. An initial MMWR report found no evidence of bacterial super-infection in 30 patients hospitalized in April-May 2009 with confirmed H1N1 in California, although 15 of 25 (60%) with chest radiographs had pulmonary infiltrates. Two-thirds had multilobar infiltrates and four patients required mechanical ventilation. A second report in MMWR this summer described an additional 10 patients with H1N1 influenza requiring critical care in Michigan lacking evidence of bacterial pneumonia.
These reports may have been misleading, insomuch as causative agents of pneumonia are difficult to identify, even under optimal circumstances. Newer data, based on autopsy specimens, suggest that nearly one-third of patients with fatal H1N1 illness have evidence of super-infecting bacterial pneumonia. Respiratory specimens (lung, trachea, and large-airway specimens) collected at autopsy from 77 patients with laboratory-confirmed fatal H1N1 infection were evaluated for evidence of bacterial infection. This included tissues stains, immuno-histochemical antibody testing for various bacterial pathogens (including antibodies to S. pneumoniae, S. pyogenes, S. aureus, H. influenza, but not Legionella spp.), and PCR-based assays to further characterize streptococcal and pneumococcal infection. H1N1 infection was confirmed in 41 of the patients before death and identified in 36 patients post-mortem.
Of the 77 fatal cases of H1N1 infection submitted for analysis, 22 (29%) had histopathological, immunohistochemical, and molecular evidence of bacterial pneumonia.
Streptococcus pneumoniae was the most frequently identified pathogen, occurring in 10 persons (13%), followed by S. aureus (9.1%), S. pyogenes (7.8%), S. mitis (2.6%), and H. influenza (1.3%). Multiple bacterial pathogens were found in four patients (5%). The mean age at death was 31 (range, 2 months to 56 years), and half were male. The median duration of illness, available for 17 of the patients, was 6 days (range, 1-25 days). Fourteen had received some kind of medical care, at least seven had received antibiotics, and eight had been hospitalized. In 21 patients for whom this kind of information was available, 16 had significant underlying medical conditions known to increase the risk for severe influenza infection (five were described as obese, two with diabetes, asthma, and Down syndrome, and one with HIV infection).
The presence of bacterial pneumonia in nearly one-third of patients with fatal H1N1 infection should be viewed as a minimum estimate of the risk of bacterial super-infection in such patients. Even with the best techniques, super-infecting bacterial pneumonia in patients with viral pneumonia or ARDS may be difficult to confirm. Based on these data, empirical antibacterial therapy should be considered for critically ill patients with influenza, at least until their respiratory status has stabilized or improved. An agent with activity against MRSA should be considered, especially in persons at risk.