The in vitro activity of BAY 12-8039, a new fluoroquinolone, was studied in comparison with those of ciprofloxacin, trovafloxacin (CP 99,219), cefpodoxime, and amoxicillin-clavulanate against gram-negative, grampositive, and anaerobic bacteria. Its activity against mycobacteria and chlamydia was also investigated. BAY 12-8039 was active against members of the family Enterobacteriaceae (MIC at which 90% of strains tested were inhibited [MIC 90 s] <1 g/ml, except for Serratia spp. MIC 90 2 g/ml), Neisseria spp. (MIC 90 s, 0.015 g/ml), Haemophilus influenzae (MIC 90 , 0.03 g/ml), and Moraxella catarrhalis (MIC 90 , 0.12 g/ml), and these results were comparable to those obtained for ciprofloxacin and trovafloxacin. Against Pseudomonas aeruginosa, the quinolones were more active than the ␤-lactam agents but BAY-12-8039 was less active than ciprofloxacin. Strains of Stenotrophomonas maltophilia were fourfold more susceptible to BAY 12-8039 and trovafloxacin (MIC 90 s, 2 g/ml) than to ciprofloxacin. BAY 12-8039 was as active as trovafloxacin but more active than ciprofloxacin against Streptococcus pneumoniae (MIC 90 , 0.25 g/ml) and methicillin-susceptible Staphylococcus aureus (MIC 90 s, 0.12 g/ml). The activity of BAY 12-8039 against methicillin-resistant S. aureus (MIC 90 , 2 g/ ml) was lower than that against methicillin-susceptible strains. BAY 12-8039 was active against anaerobes (MIC 90 s < 2 g/ml), being three-to fourfold more active against Bacteroides fragilis, Prevotella spp., and Clostridium difficile than was ciprofloxacin. Against Mycobacterium tuberculosis, BAY 12-8039 exhibited activity comparable to that of rifampin (MICs < 0.5 g/ml). Against Chlamydia trachomatis and Chlamydia pneumoniae BAY 12-8039 was more active (MICs < 0.12 g/ml) than either ciprofloxacin or erythromycin and exhibited a greater lethal effect than either of these two agents. The protein binding of BAY 12-8039 was determined at 1 and 5 g/ml as 30 and 26.4%, respectively. The presence of human serum (at 20 or 70%) had no marked effect on the in vitro activity of BAY 12-8039.

The in-vitro activity of linezolid, a novel oxazolidinone, was investigated in comparison with those of amoxycillin, cefuroxime, quinupristin/dalfopristin, trovafloxacin and vancomycin against 420 recent Gram-positive and anaerobic clinical isolates. Linezolid was equally active (MIC90 1 mg/L) against methicillin-susceptible and -resistant Staphylococcus aureus. It demonstrated uniform activity against streptococci and enterococci and no cross-resistance with other agents. The time-kill kinetic data demonstrated that the in-vitro activity of linezolid was predominantly bacteriostatic; slow bactericidal activity was only observed at the higher concentration with streptococci. An increase in inoculum from 10(4) to 10(6) cfu on selected strains had little effect on the MICs (MIC90 within one dilution step) of linezolid and an increase in inoculum from 10(5) to 10(7) cfu/mL had no notable effect on the in-vitro bactericidal activity. A tentative linezolid breakpoint of 2 mg/L was chosen after analysis of distribution of susceptibilities.

The time-kill kinetics and post-antibiotic effect (PAE) of moxifloxacin were studied for strains of Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, Staphylococcus aureus and Escherichia coli. Moxifloxacin had a bactericidal effect against all strains tested, with the least rapid bactericidal effect being against S. pyogenes and the most rapid effect against S. aureus and E. coli. The PAE of moxifloxacin was similar to that of other fluoroquinolones and increased with increasing concentration. No association was found between the bactericidal effect of moxifloxacin and the duration of PAE. Gram-positive and gram-negative organisms were also exposed to concentrations of moxifloxacin, sparfloxacin and amoxycillin that simulated the drug concentrations obtained in human serum after standard oral dosing schedules. Simulation of moxifloxacin concentrations in human serum reduced viable counts more effectively and more rapidly than shown in time-kill experiments; in contrast, sparfloxacin and amoxycillin were less effective than when constant concentrations of these antibacterials were used.

The in-vitro activity of CG 5501 against a wide range of recent clinical isolates was compared with that of three fluoroquinolones. CG 5501 inhibited 90% of the species of the family Enterobacteriaceae at 0.5 mg/L or less, exceptions being Enterobacter spp. (MIC90 2 mg/L) and Serratia spp. (MIC90 4 mg/L). Ninety per cent of Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Acinetobacter spp. were inhibited by 16, 4 and 1 mg/L respectively. CG 5501 had high activity against Gram-positive cocci, 90% of staphylococci being inhibited at 2 mg/L. Methicillin-resistant Staphylococcus aureus strains were generally ciprofloxacin-resistant yet were all susceptible to 4 mg/L or less of CG 5501. Isolates of Streptococcus pneumoniae were eight-fold more susceptible to CG 5501 (MIC90 0.5 mg/L) than to ciprofloxacin (MIC90 4 mg/L) and the former had a similar activity to that of trovafloxacin and sparfloxacin. Enterococcus faecalis was generally two- to four-fold more susceptible to CG 5501 or trovafloxacin than to ciprofloxacin. CG 5501 and trovafloxacin had high activity against Bacteroides fragilis (MIC90 0.25 mg/L). Five strains of Chlamydia spp. were inhibited by < or =0.12 mg/L of CG 5501; sensitive and multiresistant strains of Mycobacterium tuberculosis were inhibited by < or =0.5 mg/L of CG 5501. The high activity and breadth of its antibacterial spectrum suggests that CG 5501 should be useful in a wide range of clinical infections.

The pharmacodynamic properties of a novel ketolide (a new class of macrolide), HMR 3647, were investigated by studying time-kill kinetics and postantibiotic effect (PAE). The time-kill kinetics were studied at two inocula against three strains each of Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, Streptococcus pyogenes, Enterococcus faecalis, Enterococcus faecium and Bacteroides fragilis. The PAEs of HMR 3647 were also investigated on these organisms at concentrations equivalent to 1, 4 and 10 x MIC. The time-kill kinetic data demonstrated that HMR 3647 is predominantly bacteriostatic and only slowly bactericidal at higher concentrations. HMR 3647 exhibited a significant PAE with all strains studied, ranging from 1.2 h to 8.2 h at 10 x MIC. The bacteriostatic activity and significant PAE demonstrated by HMR 3647 are similar to those previously obtained with other macrolides.