Fatal Flu Cluster in Maryland Highlights Dangerous
Complications of MRSA
By Amesh A. Adalja, MD, FACP, March 16, 2012
Recently, a cluster of 3 deaths and 1 case of severe pneumonia were reported in a single family in Calvert County, Maryland.1 Diagnostic testing confirmed influenza H3N2 in all 4 patients and methicillin-resistant Staphylococcus aureus (MRSA) in at least 2. While it is unusual to see such a dramatic cluster of severe disease in one family, death from H3N2 influenza complicated by secondary MRSA pneumonia is not surprising. S. aureus, including MRSA, is well known to complicate influenza. During the 1968 H3N2 influenza pandemic, S. aureus pneumonia was a lethal cofactor in many cases.2
Less than 10% of Cases
S. aureus accounts for less than 10% community acquired bacterial pneumonia cases in the U.S.3 Infection with Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, or Chlamydophila pneumoniae is most common. This is reflected in current treatment guidelines, which recommend doxycycline, azithromycin, the beta-lactams and fluoroquinolones as first line drugs. Coverage for other pathogens is based on specific risk factors and severity of presentation.4
ca-MRSA: Fulminant and Deadly
Pneumonia caused by ca-MRSA often manifests as hemorrhagic pneumonitis and septic shock, and it can be fatal in up to 60% of cases.3 One of the hallmarks of pneumonia caused by S. aureus, including MRSA, is that it can produce a fulminant clinical picture characterized by necrotizing damage to the lung and rapid progression. This damage is thought to be caused by the elaboration of bacterial toxins. Particular attention has focused on the Panton-Valentine Leukocidin (PVL), which is often secreted by community acquired MRSA (ca-MRSA) strains and has been associated with severe disease. Both methicillin- sensitive and hospital-acquired MRSA strains are also capable of producing PVL but do so much less often.3 However, research indicates that PVL may only be a marker for virulence and that phenol solubule modulins (PSMs) are the true mechanism of pathogenicity.5
Influenza and MRSA: Fatal Synergy
While ca-MRSA pneumonia can occur on its own, it also has been associated with antecedent influenza A infection. It is thought that in a person colonized with ca-MRSA, influenza creates an environment in which invasive ca-MRSA disease is favored. Influenza A creates this environment in a variety of ways, including impairment of S. aureus phagocytosis via an interferon gamma pathway, suppression of Th17 T-cell function, and suppression of natural killer (NK) cell function.6,7,8
Appropriate Antimicrobial Therapy Is Key
In cases of influenza complicated by secondary bacterial pneumonia, prompt initiation of antiviral and antibacterial therapy is critical. When bacterial pneumonia is suspected in a patient with influenza, S. aureus as a pathogen and the presence of MRSA should be considered and ruled out promptly. Given the emergence of ca-MRSA, all those with secondary bacterial pneumonia should be treated empirically for MRSA. Moreover, as mortality is likely correlated with delay of appropriate antimicrobial therapy, prompt initiation of anti-MRSA medications (linezolid, vancomycin, etc.) is essential.9
- CIDRAP News. Maryland tests confirm MRSA in fatal flu cases. http://www.cidrap.umn.edu/cidrap/content/influenza/general/
news/mar0912mrsa.html. Accessed March 13, 2012.
- Schwarzmann SW, Adler JL, Sullivan RJ, Marine WM. Bacterial pneumonia during the Hong Kong influenza epidemic of 1968–1969. Arch Intern Med 1971;127:1037–41.
- Que YA, Moreillon P. Staphylococcus aureus (Including Staphylococcal Toxic Shock). In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, PA: Churchill Livingstone; 2010.
- Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007;44:S27–72
- Wang R, Braughton KR, Kretschmer D, et al. Identification of novel cytolytic peptides as key virulence determinants for community-associated MRSA. Nat Med 2007;13:1510–1514.
- Hang do TT, Choi EJ, Song JY, et al. Differential effect of prior influenza infection on alveolar macrophage phagocytosis of Staphylococcus aureus and Escherichia coli: involvement of interferon-gamma production. Microbiol Immunol 2011;55:751–759.
- Kudva A, Scheller EV, Robinson KM, et al. Influenza A inhibits Th17-mediated host defense against bacterial pneumonia in mice. J Immunol 2011;186:1666–1674.
- Small CL, Shaler CR, McCormick S, et al. Influenza infection leads to increased susceptibility to subsequent bacterial superinfection by impairing NK cell responses in the lungs. J Immunol 2010;2048–2056.
- Rubinstein E, Kollef MH, Nathwani D. Pneumonia caused by methicillin-resistant Staphylococcus aureus. Clin Infect Dis 2008;46:S378–385.