What is optimal antimicrobial therapy for bacteremic pneumococcal pneumonia?

Streptococcus pneumoniae is the leading cause of community-acquired pneumonia (CAP) and accounts for approximately two-thirds of cases of CAP associated with mortality [1]. The mortality rate associated with bacteremic pneumococcal pneumonia is 6%–20% [2]. Thus, bacteremic pneumococcal pneumonia has significant clinical importance, and any new information that may lead to better outcomes is welcomed. In this issue of Clinical Infectious Diseases, Martínez et al. [3] report a study that examined the effect of initial antimicrobial treatment (before the results of blood cultures were known) of bacter-emic pneumococcal pneumonia and concluded that not adding a macrolide is an independent predictor of in-hospital mortality [3]. This observation has significant therapeutic implications and, therefore, requires close scrutiny and analysis. Currently, both major CAP guidelines from the United States (Infectious Diseases Society of America [IDSA] and American Thoracic Society [ATS]) and the Canadian guidelines (Canadian Infectious Disease Society–Canadian Thoracic Society [CIDS-CTS]) recommend the combination of a macrolide and a b-lactam as one of the preferred options for empirical therapy for CAP requiring hospitalization in a medical ward [4–6]. This recommendation is based, in part, on the results of several observational studies, which indicated that use of a macrolide with a ceph-alosporin as part of an initial empirical regimen for such patients was associated with a shorter length of hospital stay and lower mortality rate than was treatment with a cephalosporin alone [7–10]. The IDSA, ATS, and CIDS-CTS documents also suggest administration of combination therapy for patients who require admission to an intensive care unit. Even if Pseudomonas aeruginosa infection is not a consideration, all 3 guidelines recommend use of a b-lactam plus either a macrolide or a fluoroquinolone. The reason for such a recommendation was the paucity of data regarding use of a respiratory fluoroquin-olone as monotherapy for severe CAP and concerns about possible infection due to a resistant bacterial pathogen or an atyp-ical pathogen. In hospitalized patients, the etiology of CAP is generally unknown, but a possible explanation for the findings of the observational studies is the role of " atypical " pathogens. The study by Martínez et al. [3] suggests that the benefit of combination therapy including a macrolide applies not only to CAP in general but also to CAP specifically associated with S. pneumoniae bacter-emia—even if the isolate is susceptible to the b-lactam. This supports the findings of 2 prior studies, which found that dual-antimicrobial therapy including a macro-lide reduced mortality …