Emergence of Camrsa as a Cause of Pneumonia in Otherwise Healthy Children

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The emergence of CA-MRSA as a cause of pneumonia in otherwise healthy children (and adults) has now been reported in many parts of the United States (Herold et al., 1998; Gorak et al., 1999; Buckingham et al., 2003; Buckingham et al., 2004; Alfaro et al., 2005; Gonzalez et al., 2005b), adolescents (Alfaro et al., 2005; Gonzalez et al., 2005b) and adults (Gorak et al., 1999; Francis et al., 2005). Pneumonia caused by CA-MRSA has been associated with severe local (pleural effusion, empyema, pneumatocele) and systemic (metastatic foci, toxic shock syndrome, necrotizing fasciiitis, sepsis, Waterhouse-Friedrichsen syndrome) complications. And, unlike the controversy regarding the effects of discordant therapy on the outcome of pneumonia caused by penicillin/cefotaxime-resistant pneumococci, there is no doubt that the available beta-lactam antibiotics (including cefotaxime and ceftriaxone) will fail to successfully treat pneumonia and other serious infections caused by CA-MRSA.

Thus the impact of CA-MRSA infections on the outcome of empiric cefotax-ime/ceftriaxone therapy of pediatric pneumonia in a particular geographic area can be predicted on the basis of local epidemiology. Once CA-MRSA are recognized as frequent causes of skin and soft tissue infections in a community, increased vigilance is necessary to determine whether CA-MRSA is also a cause of pneumonia in that community. Once pneumonia caused by CA-MRSA is documented in that area, empiric therapy of severe or complicated pneumonia should include an agent active against CA-MRSA (in addition to cefotaxime or ceftriaxone in most cases).

The optimal therapy of pneumonia caused by CA-MRSA is not known. The time-honored therapy for serious infections caused by MRSA is vancomycin, but many reports indicate that this agent is suboptimal for therapy of infections caused by either methicillin-susceptible or methicillin-resistant strains of S. aureus (Karchmer, 1991; Levine et al., 1991; Sakoulas et al., 2004). Recently, new agents such as linezolid have been reported to be at least as effective as (Stevens et al., 2002; Kaplan et al., 2003) and perhaps superior to (Wunderink et al., 2003; Kollef et al., 2004; Weigelt et al., 2005) vancomycin for treatment of certain MRSA infections, including ventilator-associated pneumonia caused by hospital-associated strains of MRSA (Wunderink et al., 2003; Kollef et al., 2004). Whether linezolid is equivalent to or superior to vancomycin or other agents in the treatment of pneumonia caused by CA-MRSA strains (in children or adults) is not known.

Published reports indicate that clindamycin is effective for the treatment of pneumonia and other infections caused by susceptible strains of CA-MRSA (Frank et al., 2002; Martinez-Aguilar et al., 2003; Alfaro et al., 2005). However, clinda-mycin must be used with caution in the treatment of serious CA-MRSA infections because MRSA (and MSSA) isolates may harbor either constitutive or inducible resistance to clindamycin. All MRSA isolates found to be susceptible to clindamycin but resistant to erythromycin on initial testing should be examined for the presence of inducible resistance to clindamycin by performance of the double-disk diffusion "D" test (Weisblum, 1995). Again, local epidemiology is critical: rates of clindamy-cin resistance amongst CA-MRSA isolates vary widely in different regions (Frank et al., 2002; Martinez-Aguilar et al., 2003; Buckingham et al., 2004; Alfaro et al., 2005; Kaplan et al., 2005; Braun et al., 2005; Chavez-Bueno et al., 2005) and may be increasing in some areas (Kaplan et al., 2005; Braun et al., 2005).

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