Abstract
The global emergence of antibacterial resistance among common and atypical respiratory pathogens in the last decade necessitates the strategic application of antibacterial agents. The use of bactericidal rather than bacteriostatic agents as first-line therapy is recommended because the eradication of microorganisms serves to curtail, although not avoid, the development of bacterial resistance. Bactericidal activity is achieved with specific classes of antimicrobial agents as well as by combination therapy. Newer classes of antibacterial agents, such as the fluoroquinolones and certain members of the macrolide/lincosamine/streptogramin class have increased bactericidal activity compared with traditional agents. More recently, the ketolides (novel, semisynthetic, erythromycin-A derivatives) have demonstrated potent bactericidal activity against key respiratory pathogens, including Streptococcus pneumoniae, Haemophilus influenzae, Chlamydia pneumoniae, and Moraxella catarrhalis. Moreover, the ketolides are associated with a low potential for inducing resistance, making them promising first-line agents for respiratory tract infections.
Highlights
The global emergence of antibacterial resistance among common and atypical respiratory pathogens in the last decade necessitates the strategic application of antibacterial agents
Methicillin-resistant Staphylococcus aureus strains have recently appeared in community-acquired infections [8], and Streptococcus pneumoniae strains resistant to both penicillins
Whereas 10.4% of all S. pneumoniae isolates were resistant to penicillin and 16.5% resistant to macrolides in 1996, these proportions rose to 14.1% and 21.9%, respectively, in 1997 [9]
Summary
All of the effects of antimicrobial agents against microbes, including the delineation of microbial resistance, are based upon the results of in vitro susceptibility testing. Subsequent exposure of the microorganism to a specific agent may select the mutant, leading to the emergence of resistance Some resistance mechanisms, such as bacterial production of beta-lactamase, are inducible or can be derepressed [35], requiring either upregulation or mutation of genetic material. Microorganisms inhibited by a bacteriostatic agent or exposed to an insufficient concentration of a bactericidal agent remain alive and, ipso facto, retain the potential to become resistant or promulgate any resistance selected by the exposure to the antimicrobial agent An example of this principle can be seen with the upper respiratory tract pathogen, Streptococcus pyogenes, which to date has not developed resistance to penicillin, a bactericidal agent, but has developed resistance to erythromycin, a bacteriostatic agent [36,37,38]. If a bactericidal agent kills a pathogen such as Klebsiella before mutation of the porin gene, resistance is less likely to develop These two examples illustrate the desirability of achieving bactericidal activity to curtail the emergence of resistance
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