Bacteraemic pneumococcal pneumonia: current therapeutic options

Streptococcus pneumoniae is the major bacterial cause of pneumonia, meningitis and otitis media, and continues to be associated with significant morbidity and mortality in individuals both in the developed and developing world. Management of these infections is potentially complicated by the emergence of resistance of this pathogen to many of the commonly used first-line antimicrobial agents. A number of significant risk factors exist that predispose to the occurrence of pneumococcal pneumonia, including lifestyle factors, such as exposure to cigarette smoke, as well as underlying medical conditions, such as HIV infection. Several of these predisposing factors also enhance the risk of bacteraemia. The initial step in the pathogenesis of pneumococcal infections is the occurrence of nasopharyngeal colonization, which may be followed by invasive disease. The pneumococcus has a myriad of virulence factors that contribute to these processes, including a polysaccharide capsule, various cell surface structures, toxins and adhesins, and the microorganism is also an effective producer of biofilm. Antibacterial resistance is emerging in this microorganism and affects all the various classes of drugs, including the β-lactams, the macrolides and the fluoroquinolones. Even multidrug resistance is occurring. Pharmacokinetic/pharmacodynamic parameters allow us to understand the relationship between the presence of antibacterial resistance in the pneumococcus and the outcome of pneumococcal infections treated with the different antibacterial classes. Furthermore, these parameters also allow us to predict which antibacterials are most likely to be effective in the management of pneumococcal infections and the correct dosages to use. Most guidelines for the management of community-acquired pneumonia recommend the use of either a β-lactam/macrolide combination or fluoroquinolone monotherapy for the empirical therapy of more severe hospitalized cases with pneumonia, including the subset of cases with pneumococcal bacteraemia. There are a number of adjunctive therapies that have been studied for use in combination with standard antibacterial therapy, in an attempt to decrease the high mortality, of which macrolides in particular, corticosteroids and cyclic adenosine monophosphate-elevating agents appear potentially most useful.