MRSA Still Got Nothin’ on Pneumococcus in Pneumonia

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has grabbed the attention of physicians, particularly emergency physicians, with its emergence as the predominant cause of increasing numbers of ED patients seen with skin and soft tissue infections. (N Engl J Med 2006;355 [7]:666; Ann Emerg Med 2008;51[3]:291.) Previously healthy children and young adults with community-associated pneumonia (CAP) have also succumbed to this pathogen. (Ann Emerg Med 2009;53[3]:358.) Recent seasonal influenza vaccine inadequacies and the H1N1 pandemic have stoked fears of CA-MRSA superinfection and a bacterial Armageddon played out in EDs. Increasingly, emergency physicians caring for acutely ill patients with pneumonia are considering adding vancomycin or linezolid to empirical CAP therapies to cover for this putative superbug. We may have our eye on the wrong coccus, however. Pneumococus, not staphylococcus, is the killer in CAP. Lost in the CA-MRSA superbug hype is recent evidence that Streptococcus pneumoniae remains the most common and deadly cause of CAP, including in H1N1 deaths, and pneumococcal strains resistant to standard CAP antimicrobials are emerging around existing pneumococcal vaccine coverage. Traditionally, S. pneumoniae has been the most commonly identified CAP pathogen. (Clin Infect Dis 1992; 14[Suppl 2]:S233.) But it is underappreciated that the sicker a CAP patient is, the more likely he is to be infected with pneumococcus. The prevalence of pneumococcus increases from nine percent in outpatients, for example, to 15 percent in general admitted patients to 33 percent in those going to the ICU. (Medicine 1990;69[5]:307; Eur J Clin Microbiol 1986;5[4]:446.) Among hospitalized patients with pneumococcal pneumonia, approximately 20 percent to 30 percent are also bacteremic with an associated mortality of approximately 20 percent to 30 percent. S. pneumoniae causes about 50 percent of CAP deaths, and 40,000 people die annually of this infection in the United States. (Chest 1994;105[5]:1487.) With the broad application of the 7-valent protein-polysaccharide conjugate vaccine in infants (Prevnar) since its introduction in 2000, rates of invasive pneumococcal infections due to vaccine strains have declined, most dramatically in children but also in adults. (N Engl J Med 2003;348[18]:1737.) The rate of disease caused by strains that were not susceptible to penicillin also generally decreased following Prevnar's introduction. Although young children have the highest risk of invasive disease, most cases of pneumococcal disease and nearly all deaths from pneumococcal disease occur in adults. Despite Prevnar and the increased emphasis of adult vaccination with the 23-valent polysaccharide pneumococcal vaccine (Pneumovax), rates of infections due to pneumococcal strains not included in existing vaccines have become increasingly common. (Clin Infect Dis 2009;48[3]:e23.) Among native Alaskan children, increased rates of invasive disease due to non-Prevnar strains almost have offset the decreased rates due to vaccine strains. (JAMA 2007;297[16]:1784.) Studies from University Hospitals Case Medical Center in 2008 revealed that of 171 pneumococcal isolates, eight were vaccine and 163 were nonvaccine (82 vaccine-related and 81 other) types. (Jacobs MR, et al. Continued emergence of nonvaccine serotypes of Streptococcus pneumoniae in Cleveland. 2009 ICAAC Poster G1-1536.) Twenty (11.7%) were from invasive sources, 17 in adults and three in children; none were vaccine types. Pneumococcal strain 19A, which accounts for one-third of isolates, is particularly worrisome because it is multidrug-resistant, including to advanced generation cephalosporins such as the ED workhorse, ceftriaxone. Rates of ceftriaxone resistance among 19A isolates based on levels needed was about 40 percent for nonmeningeal infections and about 93 percent for meningeal infections. With the existence of pneumococcal vaccines and the dramatic emergence of CA-MRSA, it is not surprising that doctors have refocused their empirical antibiotic crosshairs on CA-MRSA. A series of cases of patients with staphylococcal pneumonia referred to the Centers for Disease Control and Prevention between Nov. 1, 2006, and April 30, 2007, reported that 79 percent had MRSA infections. (Ann Emerg Med 2009;53[3]:358.) The median age of the study group was 16 years, 47 percent had an associated viral infection, and one-third had documented influenza. The mortality rate among MRSA-infected patients was 51 percent. The most recent CAP guidelines from the Infectious Diseases Society of America and the American Thoracic Society, published in 2007, state, “If CA-MRSA is a consideration, add vancomycin or linezolid.” (Clin Infect Dis 2007;44[Suppl 2]:S27.) With the arrival of the H1N1 pandemic, practitioners have increasingly expanded empirical coverage for patients with either etiology (e.g., prodromal influenza-like illness) or outcome risk (e.g., ICU admission). Recent observations continue to demonstrate the predominance of pneumococcal etiology for CAP. The Sept. 29, 2009, edition of Mortality and Morbidity Weekly Report reported that 22 (29%) of 77 U.S. H1N1 deaths had autopsy evidence of concurrent bacterial pneumonia; 10 cases were due to pneumococcus and seven to staphylococcus (4 MRSA). (MMWR 2009;58[38]:1.) Recent clinical trials of new antimicrobials for CAP continue to demonstrate that S. pneumoniae accounts for about half of the cases in which a pathogen is identified, three to four times more common than S. aureus. (Eckburg P, et al. FOCUS 1 and randomized, double-blinded, multicenter phase 3 trials of the efficacy and safety of ceftaroline vs ceftriaxone in community-acquired pneumonia. 2009 ICAAC Poster L1-345A; Nicholson SC, et al. Efficacy of ceftobiprole compared to ceftriaxone +/− linezolid for the treatment of hospitalized community-acquired pneumonia. ATS 2008, Toronto International Conference Poster #C16.) That is not to say that staphylococcal pneumonia is not also important, and rates from community-presenting patients have increased. U.S. National Hospital Discharge Survey data of more than 100,000 cases during 2001 and 2006 revealed S. aureus had overtaken S. pneumoniae (25.8% vs. 21.5%, respectively) as the most common identified pathogen. (Attridge RT, et al. Increasing incidence of Staphylococcus aureus pneumonia among patients admitted to United States hospitals from community settings. 2009 ICAAC Poster L1-994.) This has been most apparent in patients with health care-associated pneumonia presenting from nursing homes, on dialysis, or with recent hospitalizations. Rates of CA-MRSA as a cause of CAP in otherwise healthy persons appear to be low, but further study is needed, and empirical coverage would be reasonable in severely ill patients, particularly associated with an influenza-like illness. (Ann Emerg Med 2009;53[3]:366.) Pneumococcus is still the king of pneumonia, but just like staphylococcus, more resistant strains are emerging. New vaccines are being developed that incorporate additional pneumococcal strains. In the meantime, more careful monitoring of local pneumococcal susceptibility patterns will be necessary to guide empirical antibiotic therapy in the ED, and additional Gram-positive coverage, for MRSA and multidrug resistant S. pneumoniae, may be necessary for selected patients presenting with pneumonia.Figure: Dr. Talan is a professor of medicine at the UCLA School of Medicine and the chairman of emergency medicine and faculty in infectious diseases at Olive View-UCLA Medical Center.

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