Activity of temafloxacin against respiratory pathogens

Abstract

The activity of the quinolone temafloxacin against respiratory pathogens was compared with those of ciprofloxacin and ofloxacin. MICs for 90% of strains tested indicated that temafloxacin was at least two-to fourfold more potent than the other two quinolones against Staphylococcus aureus, Streptococcus pneumoniae, and Legionella pneumophila. Temafloxacin had potency equal to that of ciprofloxacin and was twofold more active than ofloxacin against Streptococcus pyogenes, Moraxella catarrhalis, and Bordetella pertussis. Against Haemophilus influenzae and Klebsiella pneumoniae, temafloxacin was four-and twofold less potent than ciprofloxacin, respectively. When administered orally in mouse protection tests against S. aureus, S. pneumoniae, and S. pyogenes, temafloxacin was at least eight times more potent than ciprofloxacin and was two to four times more active than ofloxacin. Against H. influenzae, temafloxacin was as active as ofloxacin and was two times less active than ciprofloxacin following oral administration in mice. In treating L. pneumophila in guinea pigs and H. influenzae otitis media in gerbils, temafloxacin and ofloxacin were more effective than ciprofloxacin. Against S. pneumoniae otitis media in gerbils, temafloxacin and ciprofloxacin were more active than ofloxacin. Following subcutaneous administration in mice, temafloxacin achieved higher lung levels than ciprofloxacin or ofloxacin did.Temafloxacin is a new fluoroquinolone with broad-spectrum potency and favorable pharmacokinetics. Previously, it has been reported that temafloxacin is active against a wide range of bacteria and that it is effective in treating both gram-positive and gram-negative infections in mice (2,4,8,13,18,19). Temafloxacin also is well absorbed in humans, with a mean peak level in serum of 3.3 ,ug/ml and a serum elimination half-life of 6.8 h following a single oral dose of 400 mg (17).Like most of the new fluoroquinolones, temafloxacin has substantial activity against many of the classic respiratory pathogens, including Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae, Staphylococcus aureus, and Legionella pneumophila. Current clinical data indicate that the new quinolones can be successfully used to treat acute exacerbations of chronic bronchitis and other lower respiratory tract infections caused by these bacteria. In treating these conditions, the rates of cure or improvement for ciprofloxacin, ofloxacin, enoxacin, and pefloxacin range from 70 to 100% (23)(24)(25). However, the use of these new quinolones in treating bronchopulmonary infections appears to be limited by their reduced in vitro activity against Streptococcus pneumoniae, one of the most frequently isolated bacteria from community-acquired respiratory tract infections. Clinical and bacteriological relapses in S. pneumoniae-infected patients receiving quinolones have been reported; and in one study the rate of persistence, recurrence, or reinfection because of pneumococcus in quinolonetreated patients was 67% (5, 24). Temafloxacin is repor...

Quinolones: a class of antimicrobial agents

“…Temafloxacin is more potent than either ciprofloxacin or ofloxacin against staphylococci and streptococci, but not against Haemophylus influenzae. Improved oral activity of temafloxacin is a function of both improved potency and better oral bioavailability (Swanson et al, 1991). The MIC of danofloxacin against 90% of the field isolates of Pasteurella haemolytica, Pasteurella multocida, and Haemophylus somnus was found to be < 0.125 µ/ml (Jackson et al, 1990), and the range of MICs against Mycoplasma species was 0.008-0.5 µg/ml .…”

Efficacies of ABT-719 and related 2-pyridones, members of a new class of antibacterial agents, against experimental bacterial infections

“…Streptococcus pyogenes was tested in brain heart infusion broth (BBL, Cockeysville, Md. ), and S. pneumoniae was tested in Mueller-Hinton broth (BBL) supplemented with 3% lysed horse blood (18). Serial twofold dilutions were used for all determinations of MICs, and both 100 and 128 dilution scales were utilized.…”

“…Plasma samples were obtained as pools from mice at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, and 6 h after dosing. Concentrations of ABT-719 were determined by a microbiological assay using Klebsiella pneumoniae as the detector organism (18).…”

In vitro and in vivo evaluations of A-80556, a new fluoroquinolone

“…Streptococcus pyogenes was tested in brain heart infusion broth (BBL, Cockeysville, Md. ), and S. pneumoniae was tested in Mueller-Hinton broth (BBL) supplemented with 3% lysed horse blood (15). Serum effects were determined with media containing 50% heat-inactivated serum, and pH effects were determined with media adjusted to various pHs with NaOH or HCl.…”

“…The susceptibility of Legionella spp. was determined on buffered charcoal-yeast extract agar (15). Minimum bactericidal activity was determined essentially as described previously (2).…”