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The aim of the study was to comparatively assess delafloxacin and levofloxacin activities against 96 anaerobic and some microaerophilic isolates. Delafloxacin minimal inhibitory concentrations (MICs) were strikingly lower than those of levofloxacin. Delafloxacin MIC 90 against clostridia, other Gram-positive rods, anaerobic/microaerophilic cocci and Gram-negative rods were 0.75, 0.032, 0.38 and 0.5 μg/mL, respectively. The highest (≥4 μg/mL) MICs of the newer fluoroquinolone were found in only 4.2% of isolates versus 46.9% by levofloxacin. The present results and the potency in acidic conditions showed delafloxacin advantages over levofloxacin in terms of usefulness for treatment of mixed anaerobic-aerobic infections and activity against Clostridioides (Clostridium) difficile., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The in vitro activities of lascufloxacin were evaluated by comparison with seven reference compounds using 412 clinical isolates of anaerobes and Streptococcus anginosus group. Lascufloxacin showed potent and broad antibacterial activities greater than those of existing quinolones against the clinical isolates used in this study., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

DS-8587 is a novel parenteral fluoroquinolone, which has an activity equivalent to sitafloxacin against various pathogens including anaerobes. We examined the in vivo anti-anaerobic activity of DS-8587, and compared it with that of levofloxacin (LVFX), using a murine model of Fusobacterium necrophorum-induced liver abscess developed via blood borne infection. Mice with liver abscess infection caused by F. necrophorum were treated with saline (control), DS-8587 (0.8, 4, and 20 mg/kg twice daily), or LVFX (20 and 100 mg/kg) for a day. After treatment, the number of viable bacteria in liver was analyzed. We also analyzed the pharmacokinetics of these agents in plasma and the liver after initial treatment. The MICs of DS-8587 and LVFX were 0.015 and 1 mg/mL, respectively. DS-8587 eradicated the viable bacteria in the liver even at doses as low as 4 mg/kg. In contrast, the liver bacteria were not eradicated in any of the LVFX-treated mice even at a dose of 100 mg/kg (P < 0.05 compared with DS-8587, 4 or 20 mg/kg). The pharmacokinetic parameter AUC/MIC ratios for DS-8587 (4 mg/kg) and LVFX (100 mg/kg) were 96.7 and 60.8 in plasma and 600 and 145.6 in the liver, respectively. The AUC/MIC ratio showed the best correlation with efficacy of DS-8587. DS-8587 significantly reduced the number of viable bacteria in a murine model of F. necrophorum-induced liver abscess compared to LVFX. Our study demonstrated that the anti-anaerobic activity of quinolones in vivo was different from the MICs in vitro., (Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Introduction: There has been a striking increase in the emergence of multidrug-resistant pathogens in recent times. Delafloxacin is a novel, broad-spectrum fluoroquinolone with antimicrobial activity against resistant Gram-positive, Gram-negative and anaerobic organisms. It has the potential to treat a variety of infections including complicated skin and skin structure infections and respiratory tract infections., Areas Covered: In this review, the authors report the microbiological spectrum of activity of delafloxacin as well as its pharmacokinetic characteristics. They also report the results of recent studies investigating its safety and efficacy., Expert Opinion: The profile of delafloxacin offers several advantages. Delafloxacin presents a broad spectrum of activity against pathogens involved in respiratory infections and complicated skin and skin structure infections (SSSIs), including methicillin-resistant Staphylococcus aureus. It has also shown activity against Gram-negative pathogens, such as quinolone-susceptible and -resistant strains of Escherichia coli and Klebsiella pneumoniae and quinolone-susceptible Pseudomonas aeruginosa. The availability of an oral formulation supports its use in sequential therapy. The efficacy and tolerability of delafloxacin have been demonstrated in Phase II clinical trials in comparison with moxifloxacin for respiratory infections and linezolid and vancomycin in SSSIs. Compared with other quinolones such as moxifloxacin, delafloxacin showed comparable efficacy and a lower rate of adverse effects. The results of new Phase III studies are awaited to confirm delafloxacin's future applications in the treatment of SSSIs.

Delafloxacin is a fluoroquinolone lacking a basic substituent in position 7. It shows MICs remarkably low against Gram-positive organisms and anaerobes and similar to those of ciprofloxacin against Gram-negative bacteria. It remains active against most fluoroquinolone-resistant strains, except enterococci. Its potency is further increased in acidic environments (found in many infection sites). Delafloxacin is active on staphylococci growing intracellularly or in biofilms. It is currently evaluated as an intravenous and intravenous/oral stepdown therapy in Phase III trials for the treatment of complicated skin/skin structure infections. It was also granted as Qualified Infectious Disease Product for the treatment of acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia, due to its high activity on pneumococci and atypical pathogens.

The activity of finafloxacin against 73 strains of the Bacteroides fragilis group, 10 other Gram-negative anaerobic rods and 31 Clostridium difficile strains was determined by the broth microdilution technique. The activity was compared with that of moxifloxacin, levofloxacin, ciprofloxacin, clindamycin, imipenem, piperacillin/tazobactam and metronidazole. MIC(50/90) values (minimum inhibitory concentration, in μg/mL, at which 50% and 90% of the isolates tested are inhibited, respectively) for finafloxacin for the different species were determined: B. fragilis group, 0.5/2; other Gram-negative rods, 0.06/0.25; and C. difficile, 4/16. Furthermore, the MICs against 11 selected B. fragilis strains were determined under acidic conditions and resulted in MIC(50/90) values for finafloxacin of 0.25/4 μg/mL. Thus, finafloxacin shows promising activity against several pathogenic species of anaerobes. Furthermore, finafloxacin has increased activity against selected B. fragilis strains under acidic conditions compared with activity at neutral pH., (Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

In vitro activity of sitafloxacin (STFX) and various oral antimicrobial agents against bacterial isolates recovered from clinical specimens between January and December 2012, at different healthcare facilities in Japan was evaluated. A total of 1,620 isolates including aerobic and anaerobic organisms were available for the susceptibility testing using the microbroth dilution methods recommended by Clinical and Laboratory Standards Institute. The minimum inhibitory concentration of STFX at which 90% of isolates (MIC90) was 0.5 microg/mL for methicillin-susceptible Staphylococcus aureus and was 2 times lower than that of garenoxacin (GRNX), 4 times lower than that of moxifloxacin (MFLX), and 16 times lower than that of levofloxacin (LVFX). STFX inhibited the growth of all the isolates of Streptococcus pneumoniae at 0.06 microg/mL or less. The MIC90 of STFX was 0.03 microg/mL and was 2 times lower than that of GRNX, 4 times lower than that of MFLX, and 32 times lower than that of LVFX. Against Streptococcus pyogenes, the MIC90 of STFX was 0.06 microg/mL and was 2 times lower than that of GRNX, 8 times lower than that of MFLX, and 32 times lower than that of LVFX. The MIC90 of STFX was 2 microg/mL for Enterococcus faecalis, and was 4 times lower than that of GRNX, 8 times lower than that of MFLX, and 32 times lower than that of LVFX. The MIC90 of STFX for Escherichia coli was 2 microg/mL, and the MIC90(s) of other 10 species of Enterobacteriaceae which were the lowest values of the quinolones tested ranged from 0.03 to 1 microg/mL. The MIC90 of STFX for Pseudomonas aeruginosa isolates recovered from urinary infections was 4 microg/mL and was 32 times lower than those of GRNX, MFLX and LVFX. The MIC90 of STFX for P. aeruginosa isolates recovered from respiratory infections was 4 microg/mL and was 8 to 16 times lower than those of GRNX, MFLX, and LVFX. STFX inhibited the growth of all the isolates of Haemophilus influenzae at 0.004 microg/mL or less, and was 4 times lower than that of GRNX, 16 times lower than that of MFLX, and 8 times lower than that of LVFX. The MIC90 of STFX was 0.015 microg/mL for Moraxella catarrhalis, and was equal to that of GRNX, 4 times lower than those of MFLX and LVFX. The MIC90(s) of STFX ranged from 0.03 to 0.25 microg/mL for all the species of anaerobic bacteria and were the lowest values of all the antimicrobial agents tested. In conclusion, the activity of STFX against Gram-positive cocci was comparable or superior to those of GRNX, MFLX and LVFX. STFX showed the most potent activity against Gram-negative bacteria and anaerobic bacteria of all the antimicrobial agents tested in this study.

Pradofloxacin is a new veterinary 8-cyano-fluoroquinolone developed for use against bacterial infections in dogs and cats involving both aerobic and anaerobic bacteria. The minimal bactericidal concentrations have been determined against clinical isolates of Staphylococcus pseudintermedius, Staphylococcus aureus, Escherichia coli, Pasteurella multocida, Streptococcus canis, Proteus spp., Fusobacterium spp., Porphyromonas gingivalis and Prevotella species. A subset of these species was selected, and the in vitro rate of kill by pradofloxacin was determined. For 27 of the 30 tested aerobic strains the pradofloxacin MBC was within two doubling dilutions of the MIC. For the remaining strains, the MIC and MBC were within three to four doubling dilutions. Pradofloxacin also demonstrated bactericidal activity against all anaerobic strains, and the MBC was equal to the MIC for four of the strains, within 1 doubling dilution for three strains, within 2 dilutions for a further 3 strains and within 3 dilutions for the remaining five strains. As pradofloxacin concentration was increased, a faster rate of killing was observed; bactericidal effects were seen in all cases at concentrations ≤ 0.25 μg/mL. The bactericidal activity against the anaerobic strains was marked, of particular relevance was the complete absence of regrowth even at 48 h at concentrations as low as 0.125 μg/mL. In conclusion, pradofloxacin exhibits clear bactericidal activity in terms of MBC and kill kinetics against aerobic and anaerobic clinical isolates from dogs and cats at concentrations that are greatly exceeded within the systemic circulation after administration of the recommended therapeutic doses to the target animals. It is expected that such a rapid rate of kill will play a significant role in clinical efficacy. These data demonstrate the complete and rapid killing of anaerobic bacteria by a veterinary 8-cyano-fluoroquinolone., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Introduction: During the past 20 years, several studies at a national level in different countries followed resistance trends for Bacteroides sp. and Clostridium difficile. This study analysed antimicrobial susceptibility 73 anaerobic bacteria strains of Bacteroides fragilis group (BFG) and C. difficile to fluoroquinolones and other antimicrobial drugs., Methods: The strictly anaerobes strains isolated in different hospitals were sent to the Department of Medical Microbiology, Medical Uniwersity of Warsaw, where species determination was carried out with the API20 ANA (bioMerieux SA, Marcy-l'Etoile, France) system. Susceptibility to antimicrobials was determined using E-test., Results: The rates of high resistance to ciprofloxacin and moxifloxacin of BFG was respectively 84% and 31% and among of C. difficile strains respectively 92% and 36%). The percentage of BFG strains resistant to erythromycin and clindamycin were respectively 84% and 46%. The percentage of C. difficile strains resistant to erythromycin and clindamycin was 52%. Reduced level of susceptibility of BFG strains to amoxicillin/clavulanic acid (8%) was confirmed. Resistance to cefoxitin was 16% of BFG strains. All tested strains as well as BFG and C. difficile were susceptible to metronidazole. Was observed reduced leve (EUCAST) of susceptibility of C. difficile strains to vancomycin (13%). CONCLUSIONS. Increasing resistance to various antimicrobial agents is a significant problem in Poland. This demonstrate the need to continue with antibiotic resistance testing and surveys in anaerobic bacteria.

Garenoxacin, a des-(F)6-quinolone, was tested using the agar dilution method against 536 anaerobic bacteria, composed of 408 unusual strains from various sources and 128 pelvic isolates. Only 33/408 (8%) unusual isolates and 6/128 (4.7%) pelvic isolates had garenoxacin MICs ≥ 4 μg/mL, and 18 and 3 (4.4% and 2.3% of the respective totals) had MICs ≥ 8 μg/mL. Less susceptible unusual isolates included 7/15 Veillonella sp. from various clinical sources, 6/14 Fusobacterium varium from predominantly abdominal infections, 5/5 F. russii (cat bites), and 6/9 Actinomyces israelii. Overall, garenoxacin showed good activity against the isolates studied and has potential utility in mixed aerobic/anaerobic infections., (Copyright © 2011 Elsevier Inc. All rights reserved.)

In vitro activity of sitafloxacin (STFX) and various oral antimicrobial agents against bacterial isolates recovered from clinical specimens between January and December 2009, at different healthcare facilities in Japan was evaluated. A total of 1,620 isolates including aerobic and anaerobic organisms was available for the susceptibility testing using the microbroth dilution methods recommended by Clinical Laboratory Standard Institute. The minimum inhibitory concentration of STFX at which 90% of isolates (MIC90) was 0.06 microg/mL for methicillin-susceptible Staphylococcus aureus and was equal to that of garenoxacin (GRNX), 2 times lower than that of moxifloxacin (MFLX), and 8 times lower than that of levofloxacin (LVFX). STFX inhibited the growth of all the isolates of Streptococcus pneumoniae at 0.06 microg/mL or less. The MIC90s of STFX ranged from 0.03 to 0.06 microg/mL and were 1 to 2 times lower than those of GRNX, 2 to 4 times lower than those of MFLX, and 16 to 32 times lower than those of LVFX. Against Streptococcus pyogenes, the MIC90 of STFX was 0.06 microg/mL and was 2 times lower than that of GRNX, 4 times lower than that of MFLX, and 32 times lower than that of LVFX. The MIC90 of STFX was 0.25 microg/mL for Enterococcus faecalis, and was 2 times lower than those of GRNX and MFLX, and 8 times lower than that of LVFX. The MIC90 of STFX for E. coli was 2 microg/mL, and the MIC90s of other 10 species of Enterobacteriaceae which were the lowest values of the quinolones tested ranged from 0.03 to 1 microg/mL. The MIC90 of STFX for Pseudomonas aeruginosa isolates recovered from urinary infections was 8 microg/mL and was 16 times lower than those of GRNX, MFLX and LVFX. The MIC90 of STFX for P aeruginosa isolates recovered from respiratory infections was 2 microg/mL and was 32 times lower than those of GRNX and MFLX, and 16 times lower than that of LVFX. STFX inhibited the growth of all the isolates of Haemophilus influenzae at 0.004 microg/mL or less, and was 2 to 4 times lower than those of GRNX, 8 times lower than those of MFLX, and 4 times lower than those of LVFX. The MIC90 of STFX was 0.008 microg/mL for Moraxella catarrhalis, and was 2 times lower than that of GRNX, 8 times lower than those of MFLX and LVFX. The MIC90s of STFX ranged from 0.015 to 0.12 microg/mL for all the species of anaerobic bacteria and were the lowest values of all the antimicrobial agents tested. In conclusion, the activity of STFX against Gram-positive cocci was comparable or superior to those of GRNX, MFLX and LVFX. STFX showed the most potent activity against Gram-negative bacteria and anaerobic bacteria of all the antimicrobial agents tested in this study.

The antibacterial spectrum of besifloxacin, a novel fluoroquinolone recently approved for treatment of ocular infections, was studied using 2,690 clinical isolates representing 40 species. Overall, besifloxacin was the most potent agent tested against gram-positive pathogens and anaerobes and was generally equivalent to comparator fluoroquinolones in activity against most gram-negative pathogens. Besifloxacin demonstrated potent, broad-spectrum activity, which was particularly notable against gram-positive and gram-negative isolates that were resistant to other fluoroquinolones and classes of antibacterial agents.

Various analysis based on PK-PD (pharmacokinetics-pharmacodynamics) theory were performed for prediction on the efficacy of antimicrobial agents for infectious diseases. However, there have been few reports when causative organisms would be anaerobic bacteria. Although the antimicrobial activity of fluoroquinolones against anaerobes has been weak, gatifloxacin (GFLX), moxifloxacin (MFLX), and garenoxacin (GRNX) are considered as anti-anaerobic quinolones in recent days. Therefore, we investigated prediction on the efficacy of fluoroquinolones for anaerobic infections using Monte Carlo Simulation. Although the target attainment of fluoroquinolones (levofloxacin, GFLX, and MFLX) on AUC/MIC value has not established yet, we have assumed 40 and 125 as the target attainment of AUC/MIC value. GFLX and MFLX would be effective against anaerobic infections caused by Prevotella intermedia, Fusobacterium nucleatum, Micromonas micros, which are the causative organisms for respiratory tract infections. From these results, GFLX and MFLX would be effective against anaerobic infections in respiratory tract as anti-anaerobic fluoroquinolones.

Objectives: To compare the intrinsic activity of pradofloxacin, a new fluoroquinolone developed for use in veterinary medicine, with other fluoroquinolones, against anaerobic bacteria isolated from dogs and cats., Methods: One hundred and forty-one anaerobes were isolated from dogs and cats and comparative MICs of pradofloxacin, marbofloxacin, enrofloxacin, difloxacin and ibafloxacin were determined according to standardized agar dilution methodology., Results: Pradofloxacin exerted the greatest antibacterial activity followed by marbofloxacin, enrofloxacin, difloxacin and ibafloxacin. Based on the distinctly lower MIC(50), MIC(90) and mode MIC values, pradofloxacin exhibited a higher in vitro activity than any of the comparator fluoroquinolones., Conclusions: Pradofloxacin, a novel third-generation fluoroquinolone, has broad-spectrum anti-anaerobe activity and offers utility as single-drug therapy for mixed aerobic/anaerobic infections.

The usefulness of fluoroquinolones for the treatment of mixed aerobic and anaerobic infections has been investigated since these agents started being used in clinical practice. Newer compounds have increased in vitro activity against anaerobes, but clinically relevant susceptibility breakpoints for these bacteria have not been established. Pharmacodynamic analyses and corroboration by new data from clinical trials have enhanced our knowledge concerning the use of fluoroquinolones to treat selective anaerobic pathogens. These studies suggest that newer agents could be useful in the treatment of several types of mixed aerobic and anaerobic infections, including skin and soft-tissue, intra-abdominal, and respiratory infections. The major concerns with expanding the use of fluoroquinolones to treat anaerobic infections have been reports of increasing resistance in Bacteroides group isolates and the impact of these antibiotics on the incidence of Clostridium difficile-associated disease.

Objectives: The aim of the study was to analyse the susceptibility of unique and non-duplicate aerobic and anaerobic isolates from surgical patients to a novel des-F(6)-quinolone (garenoxacin) and other selected antimicrobial agents., Methods: Eleven hundred and eighty-five aerobic and anaerobic isolates from general, vascular, cardiothoracic and otolaryngologic surgical patients were tested for susceptibility to garenoxacin and seven other antibiotics (ciprofloxacin, moxifloxacin, levofloxacin, piperacillin/tazobactam, imipenem, clindamycin and metronidazole) using the referenced microbroth and agar-dilution method., Results: Garenoxacin exhibited greater antimicrobial activity than comparator quinolones such as ciprofloxacin, levofloxacin and other antimicrobials when tested against selected gram-positive organisms. The in vitro aerobic and anaerobic activity of garenoxacin was similar to that of moxifloxacin. All fluoroquinolones tested were effective against most gram-negative facultative anaerobes including Escherichia coli. Garenoxacin and moxifloxacin demonstrated similar in vitro antimicrobial activity against selected anaerobic gram-positive and gram-negative anaerobic bacteria such as members of the Bacteroides fragilis group. Overall, the in vitro activity of the advanced spectrum quinolones against anaerobic surgical isolates compared favourably with selected comparator agents, metronidazole, imipenem and piperacillin/tazobactam., Conclusions: These findings suggest that 82.4% of aerobic surgical isolates were susceptible to a concentration of garenoxacin < or = 1.0 mg/L, whereas 84.5% of the anaerobic isolates were susceptible to a garenoxacin concentration < or = 1.0 mg/L. Garenoxacin may be a valuable surgical anti-infective for treatment of serious head and neck, soft tissue, intra-abdominal and diabetic foot infections.

Background and Methods: The in vitro activity of nadifloxacin (OPC-7251), a novel topical fluoroquinolone, was assessed and compared with those of ofloxacin, oxacillin, flucloxacillin, cefotiam, erythromycin, clindamycin, and gentamicin against 144 Gram-positive bacteria: 28 Staphylococcus aureus, 10 Streptococcus spp., 68 coagulase-negative staphylococci (CNS), 36 Propionibacterium acnes, and 2 Propionibacterium granulosum strains. All strains originated from bacterial-infected skin disease and were isolated from patients with impetigo, secondary infected wounds, folliculitis and sycosis vulgaris, and impetiginized dermatitis. In vitro susceptibility of all clinical isolates was tested by agar dilution procedure and minimum inhibitory concentrations (MICs) were determined., Results: Nadifloxacin was active against all aerobic and anaerobic isolates. MIC(90) (MIC at which 90% of the isolates are inhibited) was 0.1 microg/ml for S. aureus, 0.78 microg/ml for both Streptococcus spp. and CNS, and 0.39 microg/ml for Propionibacterium spp. On the other hand, resistant strains with MICs exceeding 12.5 mug/ml were found in tests with the other antibiotics. For both CNS and Propionibacterium acnes, MIC(90) values > or =100 microg/ml were demonstrated for erythromycin. Ofloxacin, cefotiam, erythromycin, clindamycin and gentamicin exhibited MIC(90) values < or =1 microg/ml for some bacterial species tested. Both oxacillin and flucloxacillin were active against all investigated bacterial species with MIC(90) values < or =1 microg/ml., Conclusion: In summary, nadifloxacin, a topical fluoroquinolone, was found to be highly active against aerobic and anaerobic bacteria isolated from patients with infected skin disease, and seems to be a new alternative for topical antibiotic treatment in bacterial skin infections.

Agar dilution MIC methodology was used to compare the activity of WCK 771 with those of ciprofloxacin, levofloxacin, moxifloxacin, gatifloxacin, piperacillin, piperacillin-tazobactam, imipenem, clindamycin, and metronidazole against 350 anaerobes. Overall, the MICs (in micrograms per milliliter) at which 50 and 90%, respectively, of the isolates tested were inhibited were as follows: WCK 771, 0.5 and 2.0; ciprofloxacin, 2.0 and 32.0; levofloxacin, 1.0 and 8.0; gatifloxacin, 0.5 and 4.0; moxifloxacin, 0.5 and 4.0; piperacillin, 2.0 and 64.0; piperacillin-tazobactam, < or =0.125 and 8.0; imipenem, 0.125 and 1.0; clindamycin, 0.125 and 16.0; and metronidazole, 1.0 and >16.0.

The purpose of the study was to determine the in vitro activity of ABT-492 compared with that of other antimicrobial agents against anaerobic bacteria. The activity of ABT-492 was investigated against 369 clinical isolates of anaerobic bacteria by the agar dilution method and was compared with that of moxifloxacin, piperacillin, cefoxitin, imipenem, clindamycin and metronidazole. ABT-492 and imipenem were the most active antimicrobial agents tested.

The antimicrobial activities of garenoxacin and eight other antibiotics against 641 anaerobic isolates were evaluated with the NCCLS agar dilution method. Overall, the MICs of garenoxacin for 50 and 90% of the strains tested (in micrograms per milliliter) were as follows: Bacteroides fragilis group, 0.5 and 2; Prevotella spp., 0.25 and 2; Fusobacterium spp., 0.25 and 0.5; Porphyromonas spp., 0.125 and 0.25; Bilophila wadsworthia, 0.5 and 1; Veillonella spp., 0.25 and 0.5; Clostridium spp., 0.25 and 1; Clostridium difficile, 2 and >64; Bifidobacterium spp., 1 and 2; Eggerthella lenta, 0.25 and 1; Propionibacterium spp., 0.5 and 0.5; gram-positive cocci, 0.125 and 0.25.

The activity of gatifloxacin, a new fluoroquinolone derivative, was compared with the activities of ciprofloxacin, levofloxacin, amoxicillin, amoxicillin-clavulanate, imipenem, clindamycin and metronidazole against 204 anaerobes isolated from clinical specimens, by MIC determination, using the reference agar dilution method. When determining the overall activity against anaerobes, the MIC50/90 (mg/L) values were amoxicillin 16/>64, amoxicillin-clavulanate 0.125/1, imipenem 0.25/0.5, clindamycin 0.5/>256, metronidazole 1/8, ciprofloxacin 2/32, levofloxacin 1/8 and gatifloxacin 0.5/4. The broad in vitro spectrum of gatifloxacin is promising for the treatment of mixed anaerobic infections, especially those of the respiratory tract, ear, sinus, skin and soft tissues, and bite wounds. These data suggest that gatifloxacin may have a clinical role in the treatment of infections in which anaerobic pathogens are involved.

The activities of garenoxacin, ciprofloxacin, levofloxacin, moxifloxacin, trovafloxacin, amoxicillin-clavulanate, piperacillin-tazobactam, imipenem, clindamycin, and metronidazole against 20 anaerobes were tested. At two times the MIC, garenoxacin was bactericidal against 19 of 20 strains after 48 h and against 17 of 20 after 24 h. Other drugs, except clindamycin (which gave lower killing rates), gave killing rates similar to those for garenoxacin.

Gatifloxacin (Bristol-Myers Squibb) and moxifloxacin (Bayer) are new methoxyfluoroquinolones with broad-spectrum activity against aerobic and anaerobic pathogens of the respiratory tract. In this investigation, we analyzed the bactericidal activity in serum over time of these antimicrobials against three aerobic (Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus) and four anaerobic (Peptostreptococcus micros, Peptostreptococcus magnus, Fusobacterium nucleatum, and Prevotella melaninogenica) bacteria associated with respiratory tract infections. Serum samples were obtained from 11 healthy male subjects following a single 400-mg oral dose of gatifloxacin and moxifloxacin. These samples were collected prior to and at 2, 6, 12, and 24 h after the dose of each drug. Gatifloxacin exhibited bactericidal activity for a median of 12 h against Streptococcus pneumoniae (MIC = 0.5 micro g/ml), Peptostreptococcus micros (MIC = 0.25 micro g/ml), and F. nucleatum (MIC = 0.5 micro g/ml) and 24 h against H. influenzae (MIC = 0.03 micro g/ml), Staphylococcus aureus (MIC = 0.125 micro g/ml), Peptostreptococcus magnus (MIC = 0.125 micro g/ml), and Prevotella melaninogenica (MIC = 0.5 micro g/ml). Moxifloxacin exhibited bactericidal activity for a median of 24 h against Streptococcus pneumoniae (MIC = 0.125 micro g/ml), H. influenzae (MIC = 0.015 micro g/ml), Staphylococcus aureus (MIC = 0.06 micro g/ml), F. nucleatum (MIC = 0.5 micro g/ml), Prevotella melaninogenica (MIC =0.5 micro g/ml), Peptostreptococcus magnus (MIC = 0.125 micro g/ml), and Peptostreptococcus micros (MIC = 0.25 micro g/ml). The results from this pharmacodynamic study suggest that these fluoroquinolones would have prolonged killing activity against these organisms in vivo and may have clinical utility in the treatment of mixed aerobic-anaerobic respiratory tract infections.

A total of 590 clinical isolates consisting of 33 species of both gram-positive and gram-negative anaerobes were collected from nine centers in the Chicago area in 1998-1999. The largest number of isolates (330 isolates, 56%) belonged to the Bacteroides group. Isolates were tested by agar dilution against garenoxacin (BMS-284756, T-3811 ME), trovafloxacin, moxifloxacin, clindamycin, imipenem, piperacillin-tazobactam, and cefoxitin. All but one species (2% of Bacteroides vulgatus isolates) were fully susceptible to piperacillin-tazobactam and imipenem. A number of species were resistant to clindamycin. Among the fluoroquinolones, garenoxacin and trovafloxacin had an MIC at which 90% of the isolates tested were inhibited of <4 micro g/ml for all but two species (Fusobacterium mortiferum/varium and Peptostreptococcus anaerobius).

The precarious stability of the normal indigenous flora of the human gastrointestinal tract may be disturbed by a number of factors, but frequently and crucially by antibiotic therapy. This article explores recent insights on the collateral and ecologic effects of antibiotics on the microbiologic flora of the human body and the possible consequences of those effects, which are just beginning to be better understood. New data on this subject will not only help in designing better clinical trials but also begin to answer key questions about collateral damage.

BMS-284756, a new des-fluoro(6) quinolone, was very active against 240 aerobic and 180 anaerobic isolates from bite victims. It inhibited 403 of 420 (96%) isolates, including those of Moraxella spp., CDC group EF-4, and Eikenella corrodens at < or = 2 microg/ml and those of all Pasteurella spp. and Bergeyella zoohelcum at < or = 0.015 microg/ml. Fusobacterium russii and 6 of 11 Fusobacterium nucleatum isolates of animal bite origin were resistant, but isolates of human bite origin were susceptible, which suggests that they were of a different subspecies.

Using a microbroth method for aerobes and agar dilution for anaerobes, we studied the comparative in vitro activity of gemifloxacin, three fluoroquinolones, two macrolides and two beta-lactams, against 207 aerobic and 162 anaerobic antral sinus puncture isolates. Gemifloxacin was active at < or = 0.25 ug/mL against 198/207 [96%] aerobes and 127/162 [78%] anaerobes or 325/369 [88%] of all isolates and was the most active quinolone on a weight basis against Gram-positive organisms. All Haemophilus and Moraxella species were susceptible to < or =0.06 ug/mL of gemifloxacin. Thirty-five anaerobic isolates [35/162, 22%] required > or =0.5 ug/mL of gemifloxacin for inhibition, including all Prevotella species [all except one strain of P. bivia were susceptible to < or = 2 ug/mL] and occasional strains of Bacteroides uniformis, Bacteroides fragilis, Bilophila wadsworthia, Peptostreptococcus magnus, Peptostreptococcus micros, Propionibacterium acnes, and Veillonella species. All fusobacteria were susceptible to < or =0.25 ug/mL of gemifloxacin. Based on our in vitro study results, we conclude that gemifloxacin may offer a therapeutic alternative for sinus infections.

The in vitro activity of gemifloxacin was compared to that of other quinolone and nonquinolone antimicrobials against 204 anaerobes by the agar dilution technique. The data indicate that gemifloxacin has a rather selective anaerobic activity. Most Peptostreptococcus, Porphyromonas, and Fusobacterium species are susceptible, while gemifloxacin's activity against other gram-negative anaerobes appears to be variable.

BMS284756, a novel des-fluoro (6) quinolone (formerly T-3811), was tested for activity and spectrum using reference agar dilution (AD) and Etest (AB BIODISK, Solna, Sweden) methods. The antimicrobial activities of BMS284756, ciprofloxacin, gatifloxacin, levofloxacin, and trovafloxacin were evaluated against Campylobacter jejuni (38 strains), Helicobacter pylori (21 strains), Legionella spp. (66 strains), and 197 anaerobic isolates. BMS284756 (MIC(90), 0.008 microg/mL) was four-fold more active than gatifloxacin and trovafloxacin against H. pylori strains. Gatifloxacin and BMS284756 (MIC(50), 0.03 microg/mL) were > or = two-fold more active than levofloxacin against C. jejuni, but their spectrums were judged equivalent overall (89.4% susceptible). Against the Legionella spp., ciprofloxacin and levofloxacin (MIC(90), 0.25 microg/mL) had two-fold greater activity compared to gatifloxacin or BMS284756, but all strains were considered inhibited at clinically achievable levels. BMS284756 and trovafloxacin (MIC(90), 2 and 4 microg/mL, respectively) were four-to-eight-fold more potent than other comparators against the Gram-negative anaerobic species. Against the Gram-positive anaerobes (dominated by Clostridium difficile; 61 strains), BMS284756 activity was generally reduced, but equivalent or superior to trovafloxacin (68% inhibited at < or = 4 microg/mL). Inter-method comparisons (Etest versus AD) of BMS284756 MIC values showed a high correlation for C. jejuni and anaerobes (93.3 to 97.6% +/- two log (2) dilution steps). In conclusion, BMS284756 was very active against C. jejuni, H. pylori, Legionella spp. and most anaerobes, thus the potential role of this des-fluoro compound for treatment of infections caused by these fastidious species warrants further investigation.

Agar dilution MIC methodology was used to compare the activity of BMS 284756 with those of ciprofloxacin, levofloxacin, moxifloxacin, trovafloxacin, amoxicillin-clavulanate, piperacillin-tazobactam, imipenem, clindamycin, and metronidazole against 357 anaerobes. Overall, the respective MICs at which 50% of the isolates tested were inhibited (MIC(50)s) and MIC(90)s (in micrograms per milliliter) were as follows: BMS 284756, 0.5 and 2.0; ciprofloxacin, 2.0 and 16.0; levofloxacin, 1.0 and 8.0; moxifloxacin, 0.5 and 4.0; trovafloxacin, 0.5 and 2.0; amoxicillin-clavulanate, 0.5 and 2.0; piperacillin-tazobactam, 0.25 and 8.0; imipenem, 0.06 and 1.0; clindamycin, 0.25 and 8.0; and metronidazole, 1.0 and >16.0. BMS 284756 is a promising new quinolone with excellent antianaerobic activity.

The in vitro spectrum of a novel des-fluoro(6) quinolone, BMS-284756, was compared with those of five fluoroquinolones (trovafloxacin, moxifloxacin, levofloxacin, ofloxacin, and ciprofloxacin). BMS-284756 was among the most active and often was the most active quinolone against staphylococci (including methicillin-resistant strains), streptococci, pneumococci (including ciprofloxacin-nonsusceptible and penicillin-resistant strains), and Enterococcus faecalis. BMS-284756 inhibited approximately 60 to approximately 70% of the Enterococcus faecium (including vancomycin-resistant) strains and 90 to 100% of the Enterobacteriaceae strains and gastroenteric bacillary pathogens at the anticipated MIC susceptible breakpoint (

We determined the influence of a new quinolone, DU-6859a, and two oral carbapenems, CS-834 and L-084, on the rat and mouse caecal microflora. The caecum-skin fistula-implanted rats and conventional mice were given oral antimicrobials at doses of 30 mg/kg bid for 5 days. DU-6859a generated a marked decrease in the numbers of caecal flora except for enterococci. CS-834 and L-084 had little impact on the rat caecal flora. CS-834 caused a great decrease in the numbers of mouse caecal flora but L-084 did not. In vitro studies suggest that the difference is due to the extension of inactivation of antimicrobials by caecum contents.

Chequerboard titrations were used to test the activity of trovafloxacin, alone and in combination with clindamycin or metronidazole, against 156 Gram-positive or Gram-negative anaerobes, including 47 Bacteroides fragilis group, 36 Prevotella spp., 26 fusobacteria, 21 peptostreptococci and 26 clostridia. MIC50/MIC90 values (mg/L) of each drug alone against all 156 strains were: trovafloxacin, 0.5/1; clindamycin, 0.25/2; metronidazole, 1/2. Synergy (FIC indices 0. 5-2.0); no antagonism (FIC indices >4.0) was seen. In addition, synergy was tested by time-kill methodology for each of the above combinations against 12 Gram-positive or Gram-negative strains. Results indicated that synergy (defined as a >/= 2 log(10) decrease in cfu/mL at 48 h compared with the more active drug alone) was found between trovafloxacin at or below the MIC and both clindamycin and metronidazole at or below the MIC in one strain each of Bacteroides fragilis, Bacteroides thetaiotaomicron, Prevotella intermedia, Fusobacterium varium, Peptostreptococcus asaccharolyticus and Clostridium bifermentans. Synergy between trovafloxacin (

The in vitro antibacterial spectrum of gatifloxacin was compared with those of ciprofloxacin and ofloxacin. Gatifloxacin was two- to four-fold more potent than comparator quinolones against staphylococci, streptococci, pneumococci and enterococci (gatifloxacin MIC90s, < or =1 mg/L, except 4 mg/L against methicillin-resistant Staphylococcus aureus and Enterococcus faecium). Gatifloxacin was two-fold less potent than ciprofloxacin, and the same as or two-fold more potent than ofloxacin against Enterobacteriaceae (MIC90s, 0.06-0.5 mg/L against most members of the Enterobacteriaceae and < or =1 mg/L against Proteus/Morganella spp.). Relative to the comparator quinolones, gatifloxacin was two- to four-fold more potent against Providencia spp., and had good potency against Acinetobacter spp. (MIC90s, 0.25-1 mg/L). Gatifloxacin and ofloxacin had similar anti-pseudomonal potency, with corresponding MIC90s of 4, 8 and 0.25 mg/L for Pseudomonas aeruginosa, Pseudomonas fluorescens and Pseudomonas stutzeri, while ciprofloxacin had two- to eight-fold more potency. The three quinolones were equipotent against Burkholderia cepacia (MIC90s, 8 mg/L), but gatifloxacin was two-fold more potent against Stenotrophomonas maltophilia (MIC90, 4 mg/L). Gatifloxacin was highly potent (MIC90s, 0.03-0.06 mg/L) against Haemophilus influenzae, Legionella spp., Helicobacter pylori and had at least eight-fold better anti-chlamydial and anti-mycoplasma potency (gatifloxacin MIC90s, 0.13 mg/L). The higher quinolone MICs for ureaplasma (MIC90s, 4-8 mg/L) may be due to the acidic pH of the ureaplasma test medium, which antagonizes quinolones. Like other quinolones, gatifloxacin had poor potency against Mycobacterium avium-intracellulare, though it was eight- to 16-fold more potent against Mycobacterium tuberculosis (MIC90, 0.25 mg/L). Of the three quinolones, only gatifloxacin had activity against Bacteroides fragilis and Clostridium difficile. In summary, gatifloxacin is a broad-spectrum 8-methoxy fluoroquinolone that is more potent than ciprofloxacin and ofloxacin against Gram-positive bacteria, chlamydia, mycoplasma, mycobacteria and anaerobes.

Objectives: To study trovafloxacin susceptibility among clinical isolates of four anaerobic bacterial species using minimum inhibitory concentrations (MIC) determinations, E test assays and disk diffusion test results and to calibrate the disk diffusion method for these species using single strain regression analysis (SRA)., Methods: One-hundred and eighty-seven clinical isolates of four anaerobic bacterial species were included. Trovafloxacin MIC determinations were performed using the agar dilution technique and MIC estimations using the E test. The disk diffusion test was performed according to Swedish Reference Group for Antibiotics standardization. NCCLS limits for susceptibility categories were applied. SRA was performed using 1, 3, 10, 30, and 100 microg trovafloxacin disk contents and ATCC control strains. The regression lines obtained permitted the calculation of zone equivalents to MIC limits as well as an evaluation of various disk potencies., Results: Trovafloxacin susceptibility (S + I) was noted in 98.9, 100, 100, and 97% of Bacteroides fragilis, Bacteroides thetaiotaomicron, Clostridium perfringens, and Peptostreptococcus magnus strains, respectively, as judged by MIC determinations. Agar dilution and E test estimations gave the same results, but E test values were consistently lower than MIC values by the reference method. Regression lines calculated for the four species using SRA showed different equation constants indicating species-related differences. Interpretive zone diameter breakpoints were calculated for the four species and used for the interpretation of susceptibility., Conclusions: The disk diffusion test was successfully calibrated for trovafloxacin susceptibility testing of four anaerobic species using single strain regression analysis, SRA. There was a good agreement between the results of MIC-tests and disk testing. Interpretive errors of type I are prone to occur among Bacteroides isolates and might require species-related MIC limits. SRA calculations permitted the testing of the effect of different disk potencies on inhibition zones produced at the interpretive MIC limits. Criteria for the selection of a minimal disk content showed that 5 microg trovafloxacin is sufficient, but a 10 microg disk will safeguard against residual laboratory variation without producing too large inhibition zones for very susceptible strains.

The antimicrobial activity of moxifloxacin and seven other antibiotics (four of them quinolones) against 292 strains of obligately anaerobic bacteria was assessed employing a broth microdilution technique performed in Wilkens-Chalgren broth. MIC50/MIC90 values (mg/l) for moxifloxacin were as follows: Bacteroides fragilis (n = 62) 0.25/2, Bacteroides ovatus (n = 70) 1/4, Bacteroides vulgatus (n = 29) 0.25/1, Bacteroides thetaiotaomicron (n = 17) 2/2, Bacteroides caccae (n = 11) 1/2, Prevotella spp. (n = 11) 0.25/2, Fusobacterium spp. (n = 17) 1/4, Bilophila wadsworthia (n = 29) 0.5/1, and Clostridium spp. (n = 29) 0.125/0.5, respectively. MIC50 values (mg/l) for Bacteroides distasonis (n = 8) and Peptostreptococcus spp. (n = 9) were 0.25. The results indicated that moxifloxacin was almost as active as trovafloxacin, as active as gatifloxacin, and more active than levofloxacin and ciprofloxacin against the anaerobes tested.

The activities of gemifloxacin (SB 265805, LB20304) and comparator agents were determined by an agar dilution method against 419 clinical strains of less-commonly identified species of anaerobes. Gemifloxacin was generally more active than trovafloxacin against gram-positive strains by one to two dilutions. Peptostreptococci (Peptostreptococcus asaccharolyticus, Peptostreptococcus magnus, Peptostreptococcus micros, and Peptostreptococcus prevotii) and Porphyromonas spp. (Porphyromonas asaccharolytica, Porphyromonas canoris, Porphyromonas gingivalis, and Porphyromonas macacae) were all susceptible to /=4 microgram/ml).

The activity of the new fluoroquinolone gatifloxacin was compared with those of other quinolones and antimicrobial agents of other classes against 294 anaerobes by the broth microdilution technique. For all strains tested, gatifloxacin MICs at which 50 and 90% of the isolates were inhibited were 0.5 and 2 mg/liter, respectively, and were 3 to 4 dilution steps lower than, e.g., ciprofloxacin.

Gemifloxacin mesylate (SB 265805), a new fluoronaphthyridone, was tested against 359 recent clinical anaerobic isolates by the National Committee for Clinical Laboratory Standards reference agar dilution method with supplemented brucella blood agar and an inoculum of 10(5) CFU/spot. Comparative antimicrobials tested included trovafloxacin, levofloxacin, grepafloxacin, sparfloxacin, sitafloxacin (DU-6859a), penicillin G, amoxicillin clavulanate, imipenem, cefoxitin, clindamycin, and metronidazole. The MIC(50) and MIC(90) (MICs at which 50 and 90% of the isolates were inhibited) of gemifloxacin against various organisms (with the number of strains tested in parentheses) were as follows (in micrograms per milliliter): for Bacteroides fragilis (28), 0.5 and 2; for Bacteroides thetaiotaomicron (24), 1 and 16; for Bacteroides caccae (12), 1 and 16; for Bacteroides distasonis (12), 8 and >16; for Bacteroides ovatus (12), 4 and >16; for Bacteroides stercoris (12), 0.5 and 0.5; for Bacteroides uniformis (12), 1 and 4; for Bacteroides vulgatus (11), 4 and 4; for Clostridium clostridioforme (15), 0.5 and 0.5; for Clostridium difficile (15), 1 and >16; for Clostridium innocuum (13), 0.125 and 2; for Clostridium perfringens (13), 0.06 and 0.06; for Clostridium ramosum (14), 0.25 and 8; for Fusobacterium nucleatum (12), 0.125 and 0.25; for Fusobacterium necrophorum (11), 0.25 and 0.5; for Fusobacterium varium (13), 0.5 and 1; for Fusobacterium spp. (12), 1 and 2; for Peptostreptococcus anaerobius (13), 0.06 and 0.06; for Peptostreptococcus asaccharolyticus (13), 0.125 and 0.125; for Peptostreptococcus magnus (14), 0.03 and 0.03; for Peptostreptococcus micros (12), 0.06 and 0.06; for Peptostreptococcus prevotii (14), 0.06 and 0.25; for Porphyromonas asaccharolytica (11), 0.125 and 0.125; for Prevotella bivia (10), 8 and 16; for Prevotella buccae (10), 2 and 2; for Prevotella intermedia (10), 0.5 and 0.5; and for Prevotella melaninogenica (11), 1 and 1. Gemifloxacin mesylate (SB 265805) was 1 to 4 dilutions more active than trovafloxacin against fusobacteria and peptostreptococci, and the two drugs were equivalent against clostridia and P. asaccharolytica. Gemifloxacin was equivalent to sitafloxacin (DU 6859a) against peptostreptococci, C. perfringens, and C. ramosum, and sitafloxacin was 2 to 3 dilutions more active against fusobacteria. Sparfloxacin, grepafloxacin, and levofloxacin were generally less active than gemifloxacin against all anaerobes.

The activity of gatifloxacin against 308 aerobes and 112 anaerobes isolated from bite wound infections was studied. Gatifloxacin was active at

T-3762 is an injectable new quinolone with a broad spectrum of antibacterial activity. Pazufloxacin (T-3761) is an active form of T-3762. The minimal inhibitory concentrations (MICs) of pazufloxacin for 50% of the clinical isolates tested were 3.13 microg/ml for Streptococcus agalactiae, 6.25 microg/ml for Gardnerella vaginalis, 0.025 microg/ml for Escherichia coli, 0.78 microg/ml for Pseudomonas aeruginosa, 6.25 microg/ml for Peptostreptococcus magnus, 6.25 microg/ml for Bacteroides fragilis and 12.5 microg/ml for Prevotella bivia. The MICs of T-3762 for 90% of the clinical isolates tested were 3.13 microg/ml for S. agalactiae, 6.25 microg/ml for G. vaginalis, 0.10 microg/ml for E. coli, 12.5 microg/ml for P. aeruginosa, 25 microg/ml for P. magnus, 12.5 microg/ml for B. fragilis and 25 microg/ml for P. bivia. The results of this study suggest that, subject to confirmation by clinical trials, T-3762, in combination with an agent with reliable activity against anaerobic bacteria, is suitable as an empirical therapy of patients with obstetric and gynecological infections.

Trovafloxacin, once administrated by oral route, is rapidly absorbed and reaches its maximum seric concentration in about one hour. Alatrofloxacin is the prodrug, that is rapidly hydrolyzed to its original state when administered intravenously. Its bioavailability is equivalent when administered either oral or intravenously. It is a fluoroquinolone of extensive in vitro spectrum, with a higher activity for Gram positive coccus, anaerobic and atypical pneumonia-producing bacteria. The average half-life is around eleven hours, with an enhanced protein bound that allows to administrate it only once a day. The renal excretion is under 8%; it doesn't require any doses adjustment in renal insufficiency. Trovafloxacin reaches higher tissue and intracelular concentrations than classic fluoroquinolones. All these pharmacokinetic and pharmacodynamic characteristics allow to consider trovafloxacin as an interesting drug for the treatment of mixed infections or those resistant to the first line drugs.

The agar dilution MIC was used to compare activities of gatifloxacin with those of ciprofloxacin, sparfloxacin, trovafloxacin, ampicillin, ampicillin-sulbactam, clindamycin, and metronidazole against 351 anaerobes. Overall MICs at which 50% of the isolates are inhibited and MICs at which 90% of the isolates are inhibited (in micrograms per milliliter) were as follows: gatifloxacin, 0.5 and 4; ciprofloxacin, 2 and 32; sparfloxacin, 2 and 8; trovafloxacin, 1 and 4; ampicillin, 1 and 64; ampicillin-sulbactam, 0.5 and 4; clindamycin, 0.125 and 8; and metronidazole, 1 and >16, respectively. Gatifloxacin MICs were similar to those of trovafloxacin in all organism groups.

The activity of trovafloxacin and five other oral agents against 250 aerobic and 137 anaerobic strains isolated from human and animal bite wounds was determined by an agar dilution method. Trovafloxacin was active against all aerobic and fastidious facultative isolates at < or = 0.5 mg/L and all anaerobes at < or = 2 mg/L (Bacteroides tectum, Porphyromonas salivosa and Prevotella heparinolytica, < or = 0.25 mg/L; Porphyromonas spp., < or = 0.5 mg/L; Prevotella spp. and peptostreptococci, < or = 2.0 mg/L), except Fusobacterium nucleatum and other fusobacteria (MIC90 < or = 4 mg/L). Levofloxacin was generally one to two dilutions more active than ofloxacin, while ciprofloxacin was active against aerobes (MIC < or = 1 mg/L) but less active against anaerobic strains (MIC90 < or = 16 mg/L).

The in vitro activity of BAY 12-8039 against 360 anaerobic clinical isolates was determined by the agar dilution method and compared to that of five other antimicrobial agents. BAY 12-8039 and imipenem were the most active agents tested. The following MIC90 values were determined for BAY 12-8039: Peptostreptococcus spp. (50 isolates), 1 mg/l; Propionibacterium acnes (30 isolates). 0.25 mg/l; Clostridium perfringens (30 isolates), 0.5 mg/l; Clostridium difficile (50 isolates), 2 mg/l; Bacteroides fragilis (50 isolates), 1 mg/l; non-fragilis Bacteroides, Porphyromonas, and Prevotella spp. (100 isolates), 2 mg/l; and Fusobacterium spp. (50 isolates), 0.25 mg/l. The results of the present study show that BAY 12-8039 may be useful in the treatment and prophylaxis of anaerobic infections.

The in vitro activities of Y-688, a new 7-substituted fluoroquinolone derivative, against 317 nonduplicate anaerobic isolates were determined. Eighty-five percent of the Bacteroides fragilis group (n = 89) were inhibited by < or = 2 mg of Y-688 per liter, while 78, 100, 89, and 98% of gram-negative bacilli (n = 135), gram-positive cocci (n = 59), and non-spore-forming (n = 58) and spore-forming (n = 51) gram-positive bacilli, respectively, were inhibited by < or = 1 mg of Y-688 per liter.

The in-vitro activity of AM-1155, a 6-fluoro-8-methoxy quinolone, was compared with those of temafloxacin, sparfloxacin, tosufloxacin, ciprofloxacin, ofloxacin and cefmetazole, a cephamycin, against a variety of anaerobic bacteria. Although AM-1155 demonstrated only modest activity against the Bacteroides fragilis group and Prevotella bivia (MIC90s > or =3.13 mg/mL), 76% of the B. fragilis strains tested were inhibited at AM-1155 concentrations of 0.78 mg/L. AM-1155 was highly active against Prevotella intermedia, Porphyromonas gingivalis, Fusobacterium spp., Clostridium perfringens and Mobiluncus spp. (MIC90s < or =0.39 mg/L). An in-vivo study using a mixed infection with AM-1155- and tosufloxacin-susceptible B. fragilis and Escherichia coli strains in rat granuloma pouch was performed. AM-1155 was effective against both organisms whereas tosufloxacin was effective only against E. coli. These results correlated well to the higher pouch levels of AM-1155 than those of tosufloxacin. Clostridium difficile overgrowth was found in the caecum of mice treated with ampicillin both 1 and 7 days after 5 days dosing, but not in AM-1155-treated mice. These results suggest that the clinical efficacy of AM-1155 against infections involving most anaerobic bacteria except for the B. fragilis group and P. bivia should be evaluated further.

Four hundred thirty-eight bacteria cultured from specimens of patients with serious intra-abdominal infections were tested by agar dilution against trovafloxacin and other quinolones and antimicrobial agents. Trovafloxacin inhibited 435 strains (99.3%) at < or =2 microg/ml. All the quinolones had similar activities against Enterobacteriaceae and Pseudomonas sp., but trovafloxacin showed superior activities against streptococci, enterococci, and anaerobic organisms. Because of its excellent in vitro activities against diverse bacteria, trovafloxacin has potential use as a single agent for polymicrobial infections.