Streptococcus pneumoniae has been recognised as a major cause of
pneumonia since the time of Sir William Osler.
Drug-resistant S. pneumoniae (DRSP), which have gradually become resistant to
penicillins as well as more recently developed
macrolides and
fluoroquinolones, have emerged as a consequence of indiscriminate use of antibacterials coupled with the ability of the pneumococcus to adapt to a changing antibacterial milieu. Pneumococci use cell wall
choline components to bind
platelet-activating factor receptors, colonise mucosal surfaces and evade innate immune defenses. Numerous
virulence factors that include
hyaluronidase,
neuraminidase,
iron-binding proteins,
pneumolysin and
autolysin then facilitate cytolysis of host cells and allow tissue invasion and bloodstream dissemination. Changes in pneumococcal cell wall
penicillin-binding proteins account for resistance to
penicillins, mutations in the ermB gene cause high-level
macrolide resistance and mutations in
topoisomerase IV genes coupled with GyrA gene mutations alter
DNA gyrase and lead to high-level
fluoroquinolone resistance. Risk factors for lower
respiratory tract infections in the elderly include age-associated changes in oral clearance, mucociliary clearance and immune function. Other risks for developing
pneumonia include poor nutrition, hypoalbuminaemia, bedridden status, aspiration, recent
viral infection, the presence of chronic organ dysfunction syndromes including parenchymal
lung disease and recent antibacterial
therapy. Although the incidence of
infections caused by DRSP is rising, the effect of an increase in the prevalence of resistant pneumococci on mortality is not clear. When
respiratory infections occur, rapid diagnosis and prompt, empirical administration of appropriate antibacterial
therapy that ensures adequate coverage of DRSP is likely to increase the probability of a successful outcome when treating community-acquired
pneumonia in elderly patients, particularly those with multiple risk factors for DRSP. A chest x-ray is recommended for all patients, but other testing such as obtaining a sputum Gram's smear is not necessary and should not prolong the time gap between clinical suspicion of
pneumonia and antibacterial administration. The selection of antibacterials should be based upon local resistance patterns of suspected organisms and the bactericidal efficacy of the chosen drugs. If time-dependent agents are chosen and DRSP are possible pathogens, dosing should keep
drug concentrations above the minimal inhibitory concentration that is effective for DRSP. Treatment guidelines and recent studies suggest that combination
therapy with a
beta-lactam and
macrolide may be associated with a better outcome in hospitalised patients, and overuse of
fluoroquinolones as a single agent may promote
quinolone resistance. The
ketolides represent a new class of
macrolide-like antibacterials that are highly effective in vitro against
macrolide- and azalide-resistant pneumococci. Pneumococcal vaccination with the currently available
polysaccharide vaccine is thought to confer some preventive benefit (preventing invasive
pneumococcal disease), but more effective
vaccines, such as nonconjugate
protein vaccines, need to be developed that provide broad protection against
pneumococcal infection.