In-vitro activity of tosufloxacin, a new quinolone antibacterial agent.

The in-vitro activity of tosufloxacin (A-61827) was compared with that of temafloxacin, ciprofloxacin and selected members of other groups of antimicrobial agents, against 684 recent distinct clinical isolates and strains with known mechanisms of resistance. Against members of the Enterobacteriaceae, ciprofloxacin was slightly more active than tosufloxacin, which was more active than temafloxacin. The MIC90 of tosufloxacin for all species of Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp. was less than or equal to 1 mg/L. Tosufloxacin was slightly more active than temafloxacin, and four to eight fold more active than ciprofloxacin, against the Gram-positive species tested. The MIC90 of tosufloxacin for Staphylococcus aureus was 0.12 mg/L, and for Streptococcus pneumoniae was 0.5 mg/L. All strains of Neisseria spp., Haemophilus influenzae and Moraxella catarrhalis were inhibited by tosufloxacin at a concentration of less than or equal to 0.12 mg/L. Tosufloxacin was the most active quinolone against the anaerobic organisms tested. Cross resistance between quinolones was seen, but not between quinolones and other groups of antimicrobials. The protein binding of tosufloxacin across a range of concentrations averaged 60%. Human serum at a concentration of 70% decreased the bactericidal activity of tosufloxacin by about four-fold.     

In vitro activities of sparfloxacin, tosufloxacin, ciprofloxacin, and fleroxacin.

The in vitro activity of sparfloxacin was compared with those of tosufloxacin, ciprofloxacin, and fleroxacin against 730 bacterial isolates representing 49 different species. Sparfloxacin and ciprofloxacin had similar spectra of activity, but sparfloxacin was less active against Pseudomonas aeruginosa and more active against many gram-positive cocci and anaerobic bacteria. Tosufloxacin MICs were generally 8- to 16-fold lower than those for sparfloxacin or ciprofloxacin. All four fluoroquinolones were active against nalidixic acid-susceptible strains of the family Enterobacteriaceae (MIC for 90% of the isolates [MIC90], less than or equal to 0.25 micrograms/ml) but nalidixic acid-resistant strains were less susceptible (MIC90, greater than or equal to 4.0 micrograms/ml). Against Pseudomonas aeruginosa isolates, MIC90s were 1.0 micrograms/ml for tosufloxacin, 2.0 micrograms/ml for ciprofloxacin, and 4.0 micrograms/ml for sparfloxacin. Against Enterococcus faecalis, sparfloxacin and ciprofloxacin MIC90s were 1.0 and 2.0 micrograms/ml, respectively. MIC90s for ciprofloxacin-susceptible Staphylococcus aureus were 0.016 micrograms/ml for tosufloxacin, 0.06 micrograms/ml for sparfloxacin, and 0.5 micrograms/ml for both ciprofloxacin and fleroxacin. With four species of gram-negative bacilli, mutants resistant to two to four times the sparfloxacin MIC occurred spontaneously at frequencies of 10(-7) to 10(-9): single-step high-level resistance was not observed. In vitro-selected sparfloxacin-resistant mutants displayed cross-resistance to other quinolones, as did clinical isolates of ciprofloxacin-resistant S. aureus. Tosufloxacin MICs with broth microdilution methods were four- to eightfold greater than those obtained with agar dilution methods. The two procedures gave comparable results when sparfloxacin or ciprofloxacin was being tested.     

The in-vitro activity of tosufloxacin, a new fluorinated quinolone, compared with that of ciprofloxacin and temafloxacin.

Tosufloxacin was highly active in vitro against most isolates of Enterobacteriaceae. It was slightly less active than ciprofloxacin for most species but more active than temafloxacin. It was the most active agent against Acinetobacter spp., Xanthomonas maltophilia and some Pseudomonas spp. but was slightly less active than ciprofloxacin against the fluorescent pseudomonads. Tosufloxacin was highly active against strains of Haemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae and Campylobacter coli/jejuni. It was the most active of the fluoroquinolones tested against staphylococci (MICs 0.016-0.25 mg/L), streptococci (MICs 0.06-1 mg/L) and enterococci (MICs 0.12-4 mg/L). Tosufloxacin was also the most active quinolone tested against anaerobic bacteria and, with the exception of a few isolates of Bacteroides spp. and some clostridia, all anaerobes had tosufloxacin MICs less than 1 mg/L.     

In vitro activity of dirithromycin against Chlamydia trachomatis.

Dirithromycin is a new macrolide antibiotic with an active metabolite, erythromycylamine. We evaluated the in vitro activities of both drugs against 16 isolates of Chlamydia trachomatis and compared them with that of doxycycline. In vitro susceptibility testing was performed with McCoy cell monolayers. The MIC was defined as the lowest concentration of antibiotic without inclusions. The MBC was defined as the lowest concentration of antibiotic yielding no inclusions after passage onto 24-h-old antibiotic-free McCoy cell monolayers. Dirithromycin and erythromycylamine appeared to be equally effective against these 16 strains of C. trachomatis (MIC for 90% of strains tested, 1 mg/ml; MBC for 90% of strains tested, 2 micrograms/ml). Both were less active than doxycycline (MIC for 90% of strains tested, 0.06 micrograms/ml; MBC for 90% of strains tested, 0.12 micrograms/ml). The combination of dirithromycin and erythromycylamine appeared to be additive.     

Susceptibilities of penicillin-susceptible and -resistant strains of Streptococcus pneumoniae to RP 59500, vancomycin, erythromycin, PD 131628, sparfloxacin, temafloxacin, win 57273, ofloxacin, and ciprofloxacin.

The MICs of four new quinolones, sparfloxacin (AT-4140, CI-978), PD 131628 (the active form of the prodrug CI-990), temafloxacin, and Win 57273, compared with those of ciprofloxacin and ofloxacin were tested against 53 penicillin-susceptible, 35 penicillin intermediate-resistant, and 51 penicillin-resistant pneumococci. Susceptibility to RP 59500, a new streptogramin, was also tested and compared with those to the quinolones, erythromycin, and vancomycin. All MICs were determined by a standardized agar dilution method by using Mueller-Hinton agar supplemented with sheep blood. Quinolone, vancomycin, and RP 59500 susceptibilities were not affected by susceptibility or resistance to penicillin. For Win 57273, the MICs for 50% (MIC50) and 90% (MIC90) of strains tested were 0.015 and 0.03 micrograms/ml, respectively. MIC50S of both sparfloxacin and PD 131628 were 0.25 micrograms/ml, and MIC90S were 0.5 micrograms/ml. The MIC50 of temafloxacin was 0.5 micrograms/ml, and the MIC90 was 1.0 micrograms/ml. By comparison, ofloxacin and ciprofloxacin both yielded MIC50S of 1.0 micrograms/ml and MIC90s of 2.0 micrograms/ml. RP 59500 yielded an MIC50 of 0.5 microgram/ml and an MIC90 of 1.0 microgram/ml and was only 1 doubling dilution less active against 17 erythromycin-resistant strains. Vancomycin was active against all strains (MIC50, 0.25 microgram/ml; MIC90, 0.5 microgram/ml). All four experimental quinolones as well as RP 59500 show promise for therapy of infections with penicillin-resistant and -susceptible pneumococci.     

In-vitro activities of temafloxacin, tosufloxacin (A-61827) and five other fluoroquinolone agents

Tosufloxacin (A-61827) is the tosylate salt of A-60969 (T-3262). Temafloxacin (A-62254) is the hydrochloride salt of A-63004. Both compounds were tested against 945 aerobic bacterial isolates and their in-vitro activities were compared to those of five other fluoroquinolones. Ciprofloxacin and tosufloxacin were similar in their activity against the Enterobacteriaceae and Pseudomonas species. Temafloxacin and ofloxacin were similar in their activity against the Gram-negative bacilli. Strains that were susceptible to ciprofloxacin were also susceptible to ofloxacin, temafloxacin and tosufloxacin. Against nalidixic acid-resistant enteric bacilli, the potency of all seven fluoroquinolones was compromised. Enoxacin and fleroxacin were the least active drugs against Gram-positive species. Tosufloxacin was particularly active against the Gram-positive species; ciprofloxacin, difloxacin and temafloxacin were less active.     

Antimicrobial activities of two investigational fluoroquinolones (CI-960 and E4695) against over 100 Legionella sp. isolates.

The antimicrobial activities of two investigational fluoroquinolones (CI-960 and E4695) were compared with those of five similar compounds and four comparison drugs against 103 strains of Legionella pneumophila and five other Legionella species type strains. When concentrations inhibiting 90% of strains tested (MIC90s) for L. pneumophila were determined, CI-960 and temafloxacin emerged as the most active (0.015 microgram/ml) and were followed in potency by E4695 (0.03 microgram/ml). This activity was two- to fourfold greater than that of the reference drug, ciprofloxacin, and approached that of rifampin (MIC90, 0.008 microgram/ml). All fluoroquinolones studied were more active than erythromycin (MIC90, 0.5 microgram/ml). These two investigational fluoroquinolones appear well suited for further in vivo study of legionellosis therapy.     

In vitro activity of the new fluoroquinolone CP-99,219.

The in vitro activity of the new fluoroquinolone CP-99,219 [7-(3-azabicyclo[3.1.0]hexyl)naphthyridone] was compared with those of four other quinolones against 541 gram-negative, 283 gram-positive, and 70 anaerobic bacterial isolates. CP-99,219 inhibited 90% of many isolates in the family Enterobacteriaceae at a concentration of < or = 0.25 micrograms/ml (range, < 0.008 to 1 microgram/ml), an activity comparable to those of tosufloxacin and sparfloxacin and two times greater than that of temafloxacin. Ninety percent of the Proteus vulgaris, Providencia rettgeri, Providencia stuartii, and Serratia marcescens isolates were inhibited by 0.5 to 2 micrograms of CP-99,219 per ml. CP-99,219 inhibited 90% of the Pseudomonas aeruginosa and Haemophilus influenzae isolates at 1 and 0.015 micrograms/ml, respectively. The compound inhibited methicillin-susceptible Staphylococcus aureus at 0.06 micrograms/ml, whereas a ciprofloxacin concentration of 1 microgram/ml was required to inhibit these organisms. CP-99,219 inhibited 90% of methicillin-resistant S. aureus isolates at a concentration of < or = 4 micrograms/ml, while ciprofloxacin and temafloxacin had MICs against these isolates of > 16 micrograms/ml. Streptococci were inhibited by < or = 0.25 micrograms/ml, an activity comparable to that of tosufloxacin. CP-99,219 was eight times more active than ciprofloxacin against Streptococcus pneumoniae. Bacteroides species were inhibited by CP-99,219 at a concentration of 2 micrograms/ml, whereas inhibition of these species required 4- and 16-microgram/ml concentrations of tosufloxacin and ciprofloxacin, respectively. The MBCs of CP-99,219 ranged from two to four times the MICs, and inoculum size had a minimal effect on MIC. CP-99,219 was active against P. aeruginosa at pH 5.5, with only a fourfold increase in MIC compared with values obtained at pH 7.5. The addition of up to 9 mM Mg(2+) increased the MIC range from 0.03 to 0.06 microgram/ml to 0.12 to 0.5 microgram/ml. In view of its excellent in vitro activity against both gram-positive and gram-negative bacteria, CP-99,219 merits further study to determine it's clinical pharmacologic properties and potential for therapeutic use.     

Antimicrobial activity of gemifloxacin (SB-265805), a newer fluoroquinolone, against clinical isolates of Neisseria gonorrhoeae, including fluoroquinolone-resistant isolates

Antimicrobial activity of gemifloxacin (SB-265805), a newly developed fluoroquinolone, to Japanese isolates of Neisseria gonorrhoeae was compared with those of various fluoroquinolones, including norfloxacin, ciprofloxacin, tosufloxacin, levofloxacin, sparfloxacin, and trovafloxacin. Among the fluoroquinolones tested, gemifloxacin was most active against N. gonorrhoeae isolates. The MIC90 values of gemifloxacin for 94 N. gonorrhoeae isolated from 1992 through 1993 and 100 isolated from 1996 through 1997 were 0.03 and 0.125 microg/ml, respectively. On the other hand, MIC90 values of the other fluoroquinolone for the 1992-1993 isolates and the 1996-1997 isolates ranged from 0.125 to 2 microg/ml and from 0.5 to 8 microg/ml, respectively. Gemifloxacin was also the most potent fluoroquinolone against 31 ciprofloxacin-resistant isolates with the ciprofloxacin MIC of 1 to 16 microg/ml, for which the gemifloxacin MIC50 and MIC90 values were 0.25 and 2 microg/ml, respectively. Moreover, the activity of gemifloxacin against fluoroquinolone-resistant gonococcal isolates containing multiple amino acid substitutions in both GyrA and ParC proteins was superior to those of the other compounds.     

In vitro activity of temafloxacin compared with those of other agents against 100 clinical isolates of Neisseria gonorrhoeae.

The activity of temafloxacin hydrochloride was evaluated by agar dilution against 100 clinical isolates of Neisseria gonorrhoeae and compared with the activities of penicillin, tetracycline, ceftriaxone, ciprofloxacin, and ofloxacin. Temafloxacin inhibited 100% of study isolates at a concentration of 0.015 microgram/ml or less and was highly active against penicillin- and tetracycline-resistant strains. The in vitro activity of temafloxacin was nearly identical to that of ceftriaxone and was slightly less than that observed with ciprofloxacin and ofloxacin. Temafloxacin represents a promising alternative agent for investigation in the treatment of infection due to N. gonorrhoeae.     

In vitro activities of PD 117,596 and reference antibiotics against 448 clinical bacterial strains.

The in vitro activity of PD 117,596, a new fluoroquinolone antibiotic, was tested against 448 bacterial isolates (15 genera) by agar dilution (inoculum, 10(4) CFU per spot). The activity of PD 117,596 was compared with that of 15 antibiotics against 327 gram-negative strains and with that of 8 other antibiotics against 121 gram-positive strains. PD 117,596 demonstrated the best activity against Klebsiella spp., Enterobacter spp., Acinetobacter spp., Serratia marcescens, and Branhamella catarrhalis (MICs for 90% of the isolates [MIC90S], 0.008 to 0.25 microgram/ml). PD 117,596 (MIC90, 0.25 microgram/ml) was at least twofold more active than ciprofloxacin against Pseudomonas aeruginosa and Pseudomonas spp. PD 117,596 and ciprofloxacin were similar in activity against Escherichia coli, Proteus mirabilis, Haemophilus influenzae, H. parainfluenzae, Neisseria gonorrhoeae, Legionella pneumophila, and Campylobacter jejuni (MIC90, 0.002 to 0.125 microgram/ml). PD 117,596 was more active than ciprofloxacin against streptococcal groups A, B, C, and G, S. pneumoniae, and enterococci (MIC90S, 0.06 to 0.125 microgram/ml). Against Staphylococcus aureus, including methicillin-resistant isolates, PD 117,596 (MIC90S, 0.03 to 0.06 microgram/ml) was 4- to 16-fold more active than ciprofloxacin and was most active against Corynebacterium spp. PD 117,596 appears to be the most active fluoroquinolone to date, with excellent activity against gram-positive bacteria and enhanced activity against gram-negative aerobic-facultative bacteria.     

In vitro activity of CP-74,667. A new fluoroquinolone compared with other quinolones.

CP-74,667, a 6-fluoro-7-bridged piperazinyl-1-cyclopropyl-4 quinolone, inhibited 90% of staphylococci, beta-hemolytic streptococci, enterococci, Enterobacteriaceae, and Pseudomonas aeruginosa at less than or equal to 2 micrograms/ml. Ciprofloxacin-resistant, methicillin-resistant Staphylococcus aureus had minimum inhibitory concentration (MIC50) of 4 micrograms/ml and an MIC90 of 8 micrograms/ml. CP-74,667 was fourfold more active than ciprofloxacin against Streptococcus pneumoniae and St. pyogenes, but equal or less active than tosufloxacin against Gram-positive species. The MIC90 for P. aeruginosa was 5 micrograms/ml similar to temafloxacin. The CP-74,667 MIC90 for Bacteroides fragilis was 2 micrograms/ml, equal to tosufloxacin and temafloxacin. Activity was eight- to 16-fold less at pH 5.5 compared with pH 7.4 and also eight- to 16-fold less in urine. Magnesium ions markedly increased the CP-74,667 minimum bactericidal concentrations (MBCs). The development of resistance to CP-74,667 was similar to that found for other fluoroquinolones.     

Antimicrobial activity of DU-6859, a new potent fluoroquinolone, against clinical isolates.

DU-6859, (-)-7-[(7S)-amino-5-azaspiro(2,4)heptan-5-yl]-8-chloro-6- fluoro-1-[(1R,2R)-cis-2-fluoro-1-cyclopropyl]-1,4-dihydro-4-oxoquinol one-3- carboxylic acid, is a new fluoroquinolone with antibacterial activity which is significantly better than those of currently available quinolones. The MICs for 90% of methicillin-susceptible and -resistant Staphylococcus aureus and Staphylococcus epidermidis clinical isolates (MIC90s) were 0.1, 3.13, 0.1, and 0.39 microgram/ml, respectively. MIC50s of DU-6859 against quinolone-resistant, methicillin-resistant S. aureus were 8-, 32-, 64-, and 128-fold lower than those of tosufloxacin and sparfloxacin, ofloxacin and fleroxacin, ciprofloxacin, and lomefloxacin, respectively. DU-6859 inhibited the growth of all strains of Streptococcus pneumoniae and Streptococcus pyogenes at 0.1 and 0.2 microgram/ml, respectively, and was more active against enterococci than the other quinolones tested. Although the activity of DU-6859 against Pseudomonas aeruginosa was roughly comparable to that of ciprofloxacin at the MIC50 level, it was fourfold more active than ciprofloxacin at the MIC90 level. DU-6859 was also more active against other glucose-nonfermenting bacteria, Haemophilus influenzae, Moraxella catarrhalis, and Neisseria gonorrhoeae, than the other drugs tested. Strains of Bacteroides fragilis and Peptostreptococcus spp. were susceptible to DU-6859; MIC90s were 0.39 and 0.2 microgram/ml, respectively. DU-6859 generally showed activities twofold or greater than those of ciprofloxacin and the other drugs against almost all members of the family Enterobacteriaceae. The action of DU-6859 against the clinical isolates was bactericidal at concentrations near the MICs. DU-6859 activity was not affected by different media, pH, inoculum size, or human serum but was decreased in human urine.     

Susceptibilities of Neisseria gonorrhoeae and Ureaplasma urealyticum isolates from male patients with urethritis to several antibiotics including telithromycin

BACKGROUND: The minimal inhibitory concentrations (MICs) of erythromycin, azithromycin, clarithromycin, telithromycin, tetracycline, doxycycline, ciprofloxacin, ofloxacin, norfloxacin, levofloxacin, gemifloxacin and moxifloxacin against 78 Neisseria gonorrhoeae and 31 Ureaplasma urealyticum strains, which were isolated from patients with urethritis in Istanbul, were determined and compared. Additionally, the activities of penicillin and ceftriaxone against N. gonorrhoeae strains were explored. METHODS: MICs were determined by agar and broth dilution methods for N. gonorrhoeae and U. urealyticum, respectively. RESULTS: The susceptibility rates for penicillin and tetracycline in N. gonorrhoeae strains were 35.9 and 24.3%, respectively. All gonococcal strains were susceptible to ceftriaxone, with very low MICs (MIC90 0.008 microg/ml). Telithromycin was highly active against N. gonorrhoeae and U. urealyticum strains (MIC90 0.25 microg/ml for both). Ciprofloxacin was the most active quinolone against N. gonorrhoeae (MIC90 0.008 microg/ml) while quinolone resistance was detected in a single strain (1.3%). CONCLUSIONS: Tetracycline and penicillin should not be the option in empirical treatment of N. gonorrhoeae infections due to the very low susceptibility rates. Ceftriaxone continues to be the first choice antibiotic in the treatment of gonococcal urethritis.     

In vitro activity of BAY 12-8039, a new fluoroquinolone.

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, gram-positive, 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 [MIC90S] < or = 1 microgram/ml, except for Serratia spp. MIC90 2 microgram/ml), Neisseria spp. (MIC90S, 0.015 microgram/ml), Haemophilus influenzae (MIC90, 0.03 microgram/ml), and Moraxella catarrhalis (MIC90, 0.12 micrgram/ml), and these results were comparable to those obtained for ciprofloxacin and trovafloxacin. Against Pseudomonas aeruginosa, the quinolones were more active than the beta-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 (MIC90S, 2 micrograms/ml) than to ciprofloxacin. BAY 12-8039 was as active as trovafloxacin but more active than ciprofloxacin against Streptococcus pneumoniae (MIC90, 0.25 microgram/ml) and methicillin-susceptible Staphylococcus auerus (MIC90S, 0.12 micrograms/ml). The activity of BAY 12-8039 against methicillin-resistant S. aureus (MIC90, 2 micrograms/ml) was lower than that against methicillin-susceptible strains. BAY 12-8039 was active against anaerobes (MIC90S < or = 2 micrograms/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 < or = 0.5 micrograms/ml). Against Chlamydia trachomatis and Chlamydia pneumoniae BAY 12-8039 was more active (MICs < or = 0.12 microgram/ml) than either ciprofloxacin or erythromycin and exhibited a greater lethal effect than either to these two agents. The protein binding of BAY 12-8039 was determined at 1 and 5 micrograms/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.     

Comparative in vitro activity of WIN 57273, a new fluoroquinolone antimicrobial agent.

The in vitro activity of WIN 57273, a new fluoroquinolone antimicrobial agent, was evaluated against approximately 600 bacterial isolates. The new drug was 4- to 128-fold more active than ciprofloxacin against a broad range of gram-positive organisms, with the new drug inhibiting 90% of strains of each species except Enterococcus faecium at concentrations of less than or equal to 0.25 microgram/ml. WIN 57273 was four- to eightfold less active than ciprofloxacin against many members of the family Enterobacteriaceae, but the MICs of the new drug for 90% of strains tested (MIC90s) were less than or equal to 8 micrograms/ml (range, 0.25 to 8 micrograms/ml) for all species. Branhamella catarrhalis, Haemophilus influenzae, Neisseria gonorrhoeae, and Legionella spp. were highly susceptible (MIC90s, less than or equal to 0.06 microgram/ml). WIN 57273 demonstrated excellent activity against anaerobes (MIC90s, less than or equal to 0.25 microgram/ml), and the drug was also more active than ciprofloxacin against 30 strains of Mycobacterium avium-M. intracellulare (MIC, 0.1 to 1.0 microgram/ml). The activity of WIN 57273 against gram-positive organisms was minimally affected by pH and increased at low pH (5.4) against gram-negative organisms. The bactericidal activity of WIN 57273 was demonstrated by time-kill techniques against selected organisms. The frequencies of spontaneous resistance to the new agent were low, but resistant colonies could be selected after serial passage of initially susceptible organisms through incremental concentrations of the drug.     

In vitro activity of PD 127,391, an enhanced-spectrum quinolone.

The in vitro activity of PD 127,391, a dihalogenated quinolone, was compared with those of ofloxacin, ciprofloxacin, nalidixic acid, gentamicin, and cefuroxime against 525 recent isolates and well-characterized antimicrobial agent-resistant strains. The MICs of PD 127,391 against 90% of members of the family Enterobacteriaceae, Bacteroides fragilis, Haemophilus influenzae, Neisseria sp., and Streptococcus pneumoniae were less than or equal to 0.12 microgram/ml. Some 90% of Pseudomonas aeruginosa and staphylococci were susceptible to 0.25 micrograms of PD 127,391 per ml. Against most strains, PD 127,391 was 2- to 8-fold more active than ciprofloxacin, but it was 64-fold more active than ciprofloxacin against B. fragilis. Strains of members of the family Enterobacteriaceae which were resistant to nalidixic acid were less susceptible to all of the quinolones tested, including PD 127,391. The MIC and minimum lethal concentration of PD 127,391 against three strains of Chlamydia trachomatis were each 0.06 microgram/ml, and the MIC against 90% of 21 strains of Mycobacterium tuberculosis was 1 microgram/ml. PD 127,391 was less active at pH 5, its maximal activity being at pH 7 to 8. The presence of urine at pH 5.9 decreased the bactericidal activity. The protein binding of PD 127,391 was 2 to 7%, and serum had little effect on activity.     

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

A-80556 is a novel fluoroquinolone with potent antibacterial activity against gram-positive, gram-negative, and anaerobic organisms. A-80556 was more active than ciprofloxacin, ofloxacin, lomefloxacin, and sparfloxacin against gram-positive bacteria. A-80556 was particularly active against Staphylococcus aureus (MIC for 90% of isolates [MIC90], 0.12 microgram/ml, relative to fluoroquinolone-susceptible strains) and Streptococcus pneumoniae (MIC90, 0.12 microgram/ml). A-80556 was also the most active of the quinolones tested against ciprofloxacin-resistant S. aureus, with an MIC90 of 4.0 micrograms/ml; that of ciprofloxacin was > 128 micrograms/ml. However, the significance of this activity is not known. A-80556 was slightly less active against Escherichia coli (MIC90, 0.06 microgram/ml) and other enteric organisms than ciprofloxacin (MIC90 for E. coli, < or = 0.03 microgram/ml). A-80556 was slightly less active against Pseudomonas aeruginosa (MIC90, 4.0 micrograms/ml) than ciprofloxacin (MIC90, 2.0 micrograms/ml) and more active against Acinetobacter spp. (respective MIC90s, 0.12 and 0.5 microgram/ml). A-80556 was also the most active compound against anaerobes. Against Bacteroides fragilis, the MIC90 of A-80556 was 2.0 micrograms/ml; that of ciprofloxacin was 16 micrograms/ml. The in vivo efficacy of A-80556 in experimental models with both gram-positive and gram-negative infections was consistent with the in vitro activity and pharmacokinetics and oral absorption in mice.     

In vitro activity of difloxacin hydrochloride (A-56619), A-56620, and cefixime (CL 284,635; FK 027) against selected genital pathogens.

Management of sexually transmitted diseases is facilitated by having antimicrobial agents with activity against all of the major genital pathogens. Newer quinolones show promise of being active against Neisseria gonorrhoeae and Chlamydia trachomatis. Two quinolones, difloxacin (A-56619) and A-56620, and an oral cephalosporin, cefixime (CL 284,635; FK 027), were evaluated in vitro. All three were highly active against 400 isolates of N. gonorrhoeae, including penicillinase-producing N. gonorrhoeae, N. gonorrhoeae with chromosomally mediated resistance, and isolates with penicillin MICs of less than 1 microgram/ml. Susceptibilities to one antimicrobial agent were usually strongly correlated with susceptibilities to the other antimicrobial agents evaluated, but isolates with increasing resistance to beta-lactams were least likely to show increasing resistance to quinolones. Difloxacin and, to a lesser extent, A-56620 were active against all 10 strains of C. trachomatis, and both had moderate activity against over 200 strains of Gardnerella vaginalis. Based on in vitro activity, difloxacin and A-56620 merit in vivo assessment for management of both C. trachomatis and N. gonorrhoeae infections, and cefixime shows considerable promise for treatment of N. gonorrhoeae infections.     

In vitro antimicrobial activity of sparfloxacin (AT-4140, CI-978, PD 131501) compared with numerous other quinolone compounds

Sparfloxacin (AT-4140, CI-978, PD 131501) was tested against over 800 recent bacteremic strains and compared with ciprofloxacin and six other fluoroquinolones. The 90% minimum inhibitory concentration (MIC90) ranges for the Enterobacteriaceae species were (a) sparfloxacin, 0.03-1 microgram/ml and (b) ciprofloxacin, 0.015-0.25 microgram/ml. Moraxella catarrhalis, Haemophilus influenzae, and Neisseria gonorrhoeae were very susceptible to sparfloxacin (MIC90s, 0.004- less than or equal to 0.03 microgram/ml) and the other comparison drugs. Staphylococcus aureas and other staphylococci were generally susceptible to the tested fluoroquinolones but very susceptible to sparfloxacin and WIN 57273. All beta-hemolytic streptococci, enterococci, and pneumococci had sparfloxacin MICs of less than or equal to 1 microgram/ml. Sparfloxacin was quite active against anaerobic bacteria including Bacteroides fragilis gr. and Gram-positive strains (MIC90s, less than or equal to 2 micrograms/ml). The most resistant enteric bacilli were among Serratia marcescens and the Proteae, especially the Providencia spp. (two- to eightfold higher MICs). Pseudomonas aeruginosa strains were also susceptible to sparfloxacin (MIC90, 2 micrograms/ml). Magnesium ions, CO2 incubation, and low pH had some adverse effect on sparfloxacin MICs, and resistance development was documented among current clinical isolates of staphylococci, pseudomonas, and some enteric species.