Earlier generations of fluoroquinolones (e.g., ofloxacin) had limited activity against some respiratory pathogens, such as S. pneumoniae. However, recent fluoroquinolone agents (so-called third-generation agents, or the “respiratory fluoroquinolones”) are active against a broad spectrum of gram-positive and gram-negative bacteria, including atypical organisms. Therefore, they are highly effective in RTIs.
Author: Brian Holtry
Gatifloxacin (Gatiflo, Tequin and Zymar)
Gatifloxacin has a broad spectrum of activity similar to activity observed in other third-generation fiuoroquinolones. The agent is well absorbed following oral administration (almost 100% bioavailability), and its pharmacodynamic and pharmacokinetic properties (e.g., high volume of distribution, long elimination half-life) allow once-daily administration.
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The widespread use of tetracyclines has resulted in a steady increase in the prevalence of resistance to these agents. Therefore, empiric use of tetracycline is usually restricted to regions where resistance levels remain low or to cases where other appropriate antibiotics are contraindicated. Although some tetracyclines have very low activity against S. pneumoniae, doxycycline maintains good antipneumococcal activity and is the tetracycline most commonly used for treatment of bacterial community-acquired pneumonia.
Aminoglycosides
Aminoglycosides are the preferred agents for treating serious infections caused by aerobic gram-negative bacilli. Aminoglycosides play only a minor role in the treatment of community-acquired pneumonia; their use is typically limited to hospitalized patients with severe or complicated community-acquired pneumonia in which gram-negative infections (particularly P. aeruginosa) are suspected.
Glycopeptides – Bactericidal Antibiotics
Glycopeptides are bactericidal antibiotics used principally for treatment of severe gram-positive infections in patients who cannot receive or who have failed to respond to penicillins and cephalosporins. They may also be used in patients suspected of having pathogens resistant to β-lactams and other anti-infectives.
Oxazolidinones
Oxazolidinones are bacteriostatic against staphylococci and enterococci and may be slowly bactericidal against other gram-positive bacteria.
Community-Acquired Pneumonia: Pathophysiology
Host defenses such as anatomic, functional, and mechanical barriers serve to protect the intact bronchial tree from invading organisms. Some key factors in the pathophysiology of community-acquired pneumonia are alterations in host defense mechanisms, invasion by virulent microorganisms, and the quantity (i.e., inoculum) of the invading microbes. community-acquired pneumonia is usually acquired by inhalation or aspiration of pulmonary pathogenic organisms into a lung segment or lobe. Much less commonly, community-acquired pneumonia may result from a secondary bacteremia from a distant source — for example, community-acquired pneumonia secondary to Escherichia coli urinary tract infection and/or bacteremia.
Pneumonia Risk Factors
Several risk factors are associated with increasing susceptibility to pneumonia. Smoking increases the risk of acquiring pneumonia by destroying both the ciliated cells and alveoli.
Antimicrobial Resistance
The prevalence in the community of bacterial resistance to common antibiotic classes has risen dramatically over the past two to three decades. Pathogens can develop antibiotic resistance through many mechanisms. These mechanisms include production of enzymes that degrade the antibiotic (e.g., β-lactamases), modification of drug targets (e.g., modified penicillin-binding proteins and ribosomes that limit the activity of penicillins and macrolides, respectively), and expression of membrane proteins that pump the antibiotic out of the bacteria.
Community-Acquired Pneumonia: Etiology
The upper respiratory tract is colonized by several bacterial species that make up the normal flora. Although these commensal organisms can cause disease in certain situations (e.g., in immunocompromised persons), they generally serve a protective function by limiting the growth of other pathogenic bacteria in the respiratory tract. In the lower respiratory tract (LRT), macrophages that can clear foreign particles reside within the alveoli and serve as the final defense against infection.