180 respiratory tract isolates of Streptococcus pneumoniae were collected from 18 medical centers in 9 of the 10 Canadian provinces. Penicillin-intermediate and -resistant isolates occurred at rates of 14.8 and 6.4%, respectively, and these rates varied considerably by geographic region. Trimethoprim-sulfamethoxazole, tetracycline, and macrolide rates of nonsusceptibility were 12.2, 10.6, and 8.0 to 9.3%, respectively. The most potent agents studied were newer fluoroquinolones.
Recent surveillance studies suggest that the incidence of resistance to macrolide antibiotics in common community-acquired respiratory tract pathogens, particularly Streptococcus pneumoniae and Streptococcus pyogenes, is increasing and limiting the usefulness of these drugs. The ketolides, of which telithromycin is the first to be available for clinical use (but not yet in the United States), represent a new class of antibacterials developed specifically to combat respiratory tract pathogens that have acquired resistance to macrolides. The ketolides possess innovative structural modifications, a 3-keto group and a large N-substituted C11, C12-carbamate side chain. This novel structure allows ketolides, which are inhibitors of protein synthesis, to exert a more effective interaction with domain II of the 23S rRNA, enhancing binding to bacterial ribosomes and allowing binding to macrolide-lincosamide-streptogramin B-resistant ribosomes. This novel chemical structure also promotes greater stability of telithromycin in acid conditions, providing the potential for greater stability in gastric fluid and at cellular/tissue levels. Early clinical trials support the bacteriologic and clinical efficacy of telithromycin in the treatment of upper respiratory tract infections (RTIs) such as streptococcal pharyngitis and acute sinusitis, including infections caused by macrolide-resistant S. pneumoniae and S. pyogenes. Common adverse side effects associated with telithromycin are predominantly gastrointestinal, usually of mild to moderate severity, and rarely involve withdrawal of the drug. Telithromycin represents an attractive option for the empiric treatment of upper RTIs, especially as resistance to macrolides is likely to continue to increase.
The oxazolidinones represent a new class of antimicrobials with a unique mechanism of action. They have excellent activity against susceptible and resistant Gram-positive organisms such as MRSA, methicillin-susceptible S epidermidis, VRE and PRSP, and a good adverse effect profile; they can be administered both intravenously and orally. Their potential use in Canada may be as an intravenous and oral alternative to glycopeptides and streptogramins.
Gemifloxacin, a new fluoroquinolone with enhanced activity against gram-positive aerobes, was compared to ciprofloxacin, levofloxacin and ofloxacin against 21,464 recent isolates from 16 European countries. Gemifloxacin was the most potent fluoroquinolone against streptococci including penicillin-, macrolide- and ciprofloxacin-resistant Streptococcus pneumoniae, Staphylococcus aureus, coagulase-negative staphylococci, Acinetobacter spp., Haemophilus spp. and Moraxella catarrhalis. This drug was more potent than or comparable to ciprofloxacin against members of the family Enterobacteriaceae, Burkholderia cepacia, Pseudomonas aeruginosa and Stenotrophomonas maltophilia. Gemifloxacin is a promising fluoroquinolone with potent in vitro activity.
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