Abstract:
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 which 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 bacteremia. 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. Antibiotic resistance is emerging in this microorganism and effects all the
various classes of drugs, including the beta-lactams, the macrolides, and the
fluoroquinolones. Even multidrug resistance is occurring. PK/PD parameters allow us to understand the relationship between the presence of antibiotic resistance in the
pneumococcus and the outcome of pneumococcal infections treated with the different
antibiotic classes. Furthermore, these parameters also allow us to predict which
antibiotics are most likely to be effective in the management of pneumococcal
infections and the correct dosages to use. Most guidelines for the management of CAP
recommend the use of either a beta-lactam/macrolide combination or fluoroquinolone
monotherapy for the empiric therapy of more severe hospitalized cases with
pneumonia, including the subset of cases with pneumococcal bacteremia. There are a
number of adjunctive therapies that have been studied for use in combination with
standard antibiotic therapy, in an attempt to decrease the high mortality, of which
macrolides in particular, corticosteroids and cyclic AMP-elevating agents appear
potentially most useful.
