Drug Treatment of Pneumococcal Pneumonia in the Elderly

Abstract

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 polysaccharid...

DAMPs and influenza virus infection in ageing

“…Streptococcus pneumoniae gradually becomes resistant to diverse classes of drugs such as β-lactams, penicillin, macrolides and fluoroquinolones (Neralla and Meyer, 2004;Feldman and Anderson, 2011;Deng, 2013). Several viral factors play a critical role for the development of secondary bacterial pneumonia.…”

Antibiotic therapy in elderly patients with acute exacerbation of chronic bronchitis

“…Bronchiectasis has been increasingly associated with COPD. One study reported that 50% of COPD patients with a mean forced expiratory volume in 1 s (FEV 1 ) of 0.96 l demonstrated high-resolution chest computed tomography evidence of bronchiectasis, and that these patients had more severe COPD exacerbations [18]. It is estimated that at least 110,000 individuals have significant noncystic fibrosis bronchiectasis in the USA, with a prevalence of 4.2 out of 100,000 population in the 18-34 age group, and 272 out of 100,000 among those greater than 75 years of age [17].…”

“…Several potential triggers for AECB have been identified, including bacterial, viral and atypical pathogens, environmental conditions (e.g., air pollution and tobacco smoke), lack of compliance with COPD therapies, and worsening congestive heat failure or pulmonary embolism [7,18,19]. However, infections are likely to cause more than 80% of AECBs.…”

“…The three major bacterial causes of AECB in mild COPD exacerbations include nontypeable Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae [5,18]. In one study, patients undergoing mechanical ventilation for their AECB/COPD exacerbations were frequently found to have Pseudomonas aeruginosa and Stenotrophomonas spp.…”

Antibacterial resistance patterns in Streptococcus pneumoniae isolated from elderly patients: PROTEKT years 1–5 (1999–2004)

“…Both the overall incidence of communityacquired RTIs and their associated rates of morbidity and mortality are higher among the elderly than the general adult population [2,3]. In CAP, factors that contribute to this increased incidence include changes in oral and mucociliary clearance and immune dysfunction [4]. Increasing age may also influence disease aetiology; for example, one recent study found that the incidence of pneumococcal pneumonia was highest among patients ≥75 years of age [2].…”