Antibacterial activities of OPC-17116, ofloxacin, and ciprofloxacin against 200 isolates of Neisseria gonorrhoeae

OPC-17116 is a new fluoroquinolone with potent activity against aerobic and anaerobic organisms. We evaluated the susceptibilities of 200 clinical gonococcal isolates including organisms with plasmid and chromosomally mediated resistance to beta-lactams and tetracycline. The antibiotics studied included OPC-17116, ofloxacin, ciprofloxacin, penicillin, tetracycline, erythromycin, azithromycin, and ceftriaxone. All isolates tested were susceptible to the quinolone class of antibiotics. The MICs of ciprofloxacin, ofloxacin, and OPC-17116 for 90% of isolates tested were 0.004, 0.03, and 0.004 micrograms/ml, respectively. For organisms with chromosomally mediated resistance to penicillin and tetracycline, geometric mean MICs of all antibiotics including the quinolones were increased.     

Comparative activities of clinafloxacin, grepafloxacin, levofloxacin, moxifloxacin, ofloxacin, sparfloxacin, and trovafloxacin and nonquinolones linozelid, quinupristin-dalfopristin, gentamicin, and vancomycin against clinical isolates of ciprofloxacin-resistant and -susceptible Staphylococcus aureus strains

The activities of eight fluoroquinolones and linezolid, quinupristin-dalfopristin (Synercid), gentamicin, and vancomycin were tested against 96 ciprofloxacin-susceptible and 205 ciprofloxacin-resistant Staphylococcus aureus strains. Overall, clinafloxacin, followed by moxifloxacin and trovafloxacin, was the most active quinolone tested. For all isolates, linezolid and quinupristin-dalfopristin showed activities that were at least comparable to vancomycin, with no cross-resistance to any other test compound.     

Comparative antimycobacterial activities of the newly synthesized quinolone AM-1155, sparfloxacin, and ofloxacin

AM-1155 is a newly synthesized 6-fluoro-8-methoxy quinolone. We assessed its in vitro antimycobacterial activity using sparfloxacin (SPFX) and ofloxacin (OFLX) as comparison drugs. The MICs of these agents for various mycobacterial strains were determined by the agar dilution method with 7H11 medium. AM-1155 had lower MICs for 50 and 90% of tested strains of Mycobacterium kansasii, M. marinum, and M. fortuitum-M. chelonae complex than SPFX and OFLX, and the values for M. tuberculosis, M. scrofulaceum, and the M. avium-M. intracellulare complex were similar to those of SPFX and considerably lower than those of OFLX. In addition, the antimicrobial activity of AM-1155 against M. tuberculosis and M. intracellulare phagocytosed into murine peritoneal macrophages was compared with that of OFLX. AM-1155 (1 microgram/ml) inhibited the intracellular growth of both M. tuberculosis and M. intracellulare, whereas OFLX at the same concentration failed to show any such effect. Moreover, AM-1155 (10 micrograms/ml) exhibited a steady bactericidal action against M. tuberculosis, whereas OFLX at the same concentration had only a weak effect. AM-1155 (10 micrograms/ml) also inhibited the growth of M. intracellulare more effectively than OFLX.     

Antistaphylococcal and antistreptococcal killing kinetics of ciprofloxacin, ofloxacin, sparfloxacin, and trovafloxacin

BACKGROUND: Use of blood culture studies for early diagnosis of Mycobacterium avium complex (MAC) infection has become important due to the recent development of effective antibiotic therapy for this condition. This study assessed the abdominal computed tomography (CT) findings in patients with AIDS who presented with bacteraemic MAC infection. METHODS: A retrospective analysis of abdominal CT scans was performed in 24 patients who presented with MAC-positive blood culture. CT images were reviewed specifically to evaluate for lymph node enlargement and attenuation, hepatomegaly, splenomegaly, bowel wall abnormality and for any other pathological changes. Comparison was made to prior reports of the CT findings in this disease process. RESULT: Enlarged intra-abdominal mesenteric and/or retroperitoneal lymph nodes were found in 10 patients (42%). These nodes were characterized by homogeneous, soft-tissue attenuation in eight of the 10 patients. Hepatomegaly, splenomegaly and small bowel wall thickening were noted in 12 (50%), 11 (46%) and four (14%) patients, respectively. CT findings were evaluated as normal in six (25%) patients. CONCLUSIONS: Enlarged mesenteric and/or retroperitoneal lymph nodes in AIDS patients with bacteraemic MAC were observed much less frequently on CT than previously reported in AIDS patient populations. Normal abdominal CT findings do not exclude this diagnosis and may reflect a trend towards earlier detection of MAC disease.     

Increased activity of a new chlorofluoroquinolone, BAY y 3118, compared with activities of ciprofloxacin, sparfloxacin, and other antimicrobial agents against anaerobic bacteria

A total of 435 clinical isolates of anaerobes were tested with a broth microdilution method to determine the activity of BAY y 3118 compared with those of other agents against anaerobic bacteria. All strains of Bacteroides capillosus, Prevotella spp., Porphyromonas spp., Fusobacterium spp., Clostridium spp., Eubacterium spp., Peptostreptococcus spp., and Veillonella parvula were susceptible (MICs of < or = 2 micrograms/ml) to BAY y 3118. Against the 315 strains of the Bacteroides fragilis group, five strains required elevated MICs (> or = 4 micrograms/ml) of BAY y 3118. Only imipenem and metronidazole were active against all anaerobes. Overall, BAY y 3118 was more active than ciprofloxacin, sparfloxacin, piperacillin, cefotaxime, and clindamycin against the test isolates.     

Antibacterial activities and inhibitory effects of sitafloxacin (DU-6859a) and its optical isomers against type II topoisomerases

The in vitro inhibitory effects of sitafloxacin (DU-6859a) and its three stereoisomers on bacterial DNA gyrase from Escherichia coli, topoisomerase IV from Staphylococcus aureus, and topoisomerase II from human placenta were compared. No correlation was observed between the inhibitory activities of quinolones against bacterial type II topoisomerases and those against human topoisomerase II. Sitafloxacin showed the most potent inhibitory activities against bacterial type II topoisomerases and the lowest activity against human type II topoisomerase.     

Susceptibilities of non-Pseudomonas aeruginosa gram-negative nonfermentative rods to ciprofloxacin, ofloxacin, levofloxacin, D-ofloxacin, sparfloxacin, ceftazidime, piperacillin, piperacillin-tazobactam, trimethoprim-sulfamethoxazole, and imipenem

Agar dilution MICs of 10 agents against 410 non-Pseudomonas aeruginosa gram-negative nonfermentative rods were determined. MICs at which 50 and 90% of the isolates were inhibited, respectively, were as follows (in micrograms per milliliter): sparfloxacin, 0.5 and 8.0; levofloxacin, 1.0 and 8.0; ciprofloxacin, 2.0 and 32.0; ofloxacin, 2.0 and 32.0; D-ofloxacin, 32.0 and > 64.0; ceftazidime, 8.0 and 64.0; piperacillin with or without tazobactam, 16.0 and > 64.0; trimethoprim-sulfamethoxazole, 0.5 and > 64.0; imipenem, 2.0 and > 64.0. With the exception of those for Stenotrophomonas maltophilia, Burkholderia cepacia, and Alcaligenes faecalis-A. odorans, agar dilution MICs for all strains tested were within 1 dilution of inhibitory (bacteriostatic) levels as determined by time-kill methodology.     

Effects of DU-6859a, a new quinolone antimicrobial, on theophylline metabolism in in vitro and in vivo studies

In vitro and in vivo studies were conducted to investigate the drug interaction between a new quinolone antimicrobial, DU-6859a, and theophylline (TP). The effect of DU-6859a on TP metabolism was evaluated in vitro by measuring the rate of TP metabolite formation by using human liver microsomes. DU-6859a inhibited the metabolism of TP, especially the formation of 1-methylxanthine, in vitro, but to a lesser extent than other drugs that are known to interact with TP. TP was administered alone (200 mg twice a day [b.i.d.] for 9 days) or in combination with DU-6859a (50 or 100 mg b.i.d. for 5 days) to six healthy subjects. DU-6859a administered at a dose of 50 mg resulted in no changes in serum TP concentrations, and slight increases in serum TP concentrations were observed at a dose of 100 mg. Moreover, the administration of 100 mg of DU-6859a resulted in decreases in all urinary TP metabolites, with significant differences. It appears that although DU-6859a has a weak inhibitory effect on TP metabolism in vitro, its concomitant use with TP at clinical dosage levels does not cause any adverse effects, showing only a slight increase in blood TP concentrations and a decrease in urinary metabolites.     

Comparative in vitro activities of trovafloxacin (CP-99,219) against 221 aerobic and 217 anaerobic bacteria isolated from patients with intra-abdominal infections

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.     

Postantibiotic effect and postantibiotic sub-MIC effect of levofloxacin compared to those of ofloxacin, ciprofloxacin, erythromycin, azithromycin, and clarithromycin against 20 pneumococci

The postantibiotic effect (PAE) (10 times the MIC of quinolones, 5 times the MIC of macrolides) and postantibiotic sub-MIC effect (PAE-SME) at 0.125, 0.25, and 0.5 times the MIC were determined for levofloxacin, ciprofloxacin, ofloxacin, erythromycin, azithromycin, and clarithromycin against 20 pneumococci. Quinolone PAEs ranged between 0.5 and 6.5 h, and macrolide PAEs ranged between 1 and 6 h. Measurable PAE-SMEs (in hours) at the three concentrations were 1 to 5, 1 to 8, and 1 to 8, respectively, for quinolones and 1 to 8, 1 to 8, and 1 to 6, respectively, for macrolides.     

In vitro activity of Bay 12-8039, a new 8-methoxyquinolone, compared to the activities of 11 other oral antimicrobial agents against 390 aerobic and anaerobic bacteria isolated from human and animal bite wound skin and soft tissue infections in humans

The in vitro activity of Bay 12-8039, a new oral 8-methoxyquinolone, was compared to the activities of 11 other oral antimicrobial agents (ciprofloxacin, levofloxacin, ofloxacin, sparfloxacin, azithromycin, clarithromycin, amoxicillin clavulanate, penicillin, cefuroxime, cefpodoxime, and doxycycline) against 250 aerobic and 140 anaerobic bacteria recently isolated from animal and human bite wound infections. Bay 12-8039 was active against all aerobic isolates, both gram-positive and gram-negative isolates, at < or = 1.0 microg/ml (MICs at which 90% of isolates are inhibited [MIC90s < or = 0.25 microg/ml) and was active against most anaerobes at < or = 0.5 microg/ml; the exceptions were Fusobacterium nucleatum and other Fusobacterium species (MIC90s, > or = 4.0 microg/ml) and one strain of Prevotella loeschii (MICs, 2.0 microg/ml). In comparison, the other quinolones tested had similar in vitro activities against the aerobic strains but were less active against the anaerobes, including peptostreptococci, Porphyromonas species, and Prevotella species. The fusobacteria were relatively resistant to all the antimicrobial agents tested except penicillin G (one penicillinase-producing strain of F. nucleatum was found) and amoxicillin clavulanate.     

Comparative tear concentrations of topically applied ciprofloxacin, ofloxacin, and norfloxacin in human eyes

The tear pharmacokinetic profiles of 0.3% ciprofloxacin, 0.3% ofloxacin, and 0.3% norfloxacin ophthalmic solutions after a single drop topically administrations in the eyes of 30 healthy volunteers were evaluated. Tear samples collected at 30, 120, 180, and 240 minutes, were analyzed for drug concentrations by high performance liquid chromatography (HPLC) with fluorometric detection. Topically applied ciprofloxacin, ofloxacin, and norfloxacin achieved the mean tear concentrations (mean +/- SD) of 11.28 +/- 6.98, 6.52 +/- 4.06, and 13.28 +/- 8.78 micrograms/g at 30 min, and then fell to 3.52 +/- 1.30, 4.82 +/- 1.80, and 5.79 +/- 4.80 micrograms/g at 240 min, respectively. Topical norfloxacin achieved mean tear level significantly higher than ofloxacin at 30 min (p = 0.031). There were no statistically significant differences in the mean tear levels of ciprofloxacin versus ofloxacin (at 30, 120, 180, and 240 min), ciprofloxacin versus norfloxacin (at 30, 120, 180, and 240 min) and ofloxacin versus norfloxacin (at 120, 180, and 240 min). However, the mean tear levels, 240 min after dosing ciprofloxacin and norfloxacin, fell to the statistically significant concentrations (p = 0.02 and p = 0.01, respectively). But, it is concluded that concentrations of ciprofloxacin, ofloxacin, and norfloxacin in tears were still significantly greater than the minimum inhibitory concentrations for the most sensitive organisms, 240 min after a single drop application.     

Pharmacokinetics and tolerance of DU-6859a, a new fluoroquinolone, after single and multiple oral doses in healthy volunteers

The pharmacokinetics and tolerance of DU-6859a, 7-[(7S)-7-amino-5-azaspiro[2,4]heptan-5-yl]-8-chloro-6-fluor o-1-[(1R, 2S)-2-fluoro-1-cyclopropyl]-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid sesquihydrate, were investigated in healthy male Japanese volunteers after single (25, 50, 100, and 200 mg) and multiple (100 mg three times a day for 6 days plus once a day on the 7th day and 50 mg every 12 h for 13 doses) oral doses. DU-6859a was well tolerated at all doses, and all 36 subjects completed the study; mild transient soft stool in five volunteers and mild transient diarrhea in one volunteer on the multiple-dose (100 mg three times a day) study were the only side effects reported. No drug crystals were observed in the urine after the single 200-mg dose and the 100-mg three times a day regimen. DU-6859a was rapidly absorbed in the fasted state. The mean maximum concentration in serum (Cmax) ranged from 0.29 to 1.86 micrograms/ml for the 25- to 200-mg dose, and the mean time to reach Cmax ranged from 1.0 to 1.3 h. The terminal half-life ranged from 4.4 to 5.0 h. The area under the curve increased dose dependently. The serum protein binding of the drug was approximately 50%. The apparent volume of distribution clearly exceeded 1 liter/kg, suggesting good tissue penetration. Within 48 h, the cumulative urinary recovery of unchanged drug amounted to 69 to 74% of the dose administered, while fecal excretion up to 48 h after the 200-mg dose accounted for ca. 3% of the dose. Food intake did not affect the rate and extend of absorption of DU-6859a to a clinically significant extent. During multiple oral dosing, the accumulation of the drug in serum was close to the theoretically predicted values, which indicated that there was virtually no drug accumulation.     

In vitro activity of levofloxacin against a selected group of anaerobic bacteria isolated from skin and soft tissue infections

The in vitro activity of levofloxacin was compared to the activities of ofloxacin, ciprofloxacin, ampicillin-sulbactam (2:1), cefoxitin, and metronidazole for a selected group of anaerobes (n = 175) isolated from skin and soft tissue infections by using the National Committee for Clinical Laboratory Standards-approved Wadsworth method. Ampicillin-sulbactam and cefoxitin inhibited 99% of the strains of this select group, levofloxacin and ofloxacin inhibited 73 and 50%, respectively, at 2 microg/ml, and ciprofloxacin inhibited 51% at 1 microg/ml. The geometric mean MIC of levofloxacin was lower than those of ofloxacin and ciprofloxacin for every group except Veillonella.     

Comparative in vitro activities of new quinolones against coryneform bacteria

The in vitro activities of eight quinolones against 115 coryneform bacteria (20 Corynebacterium jeikeium, 15 Corynebacterium minutissimum, 15 Corynebacterium striatum, 25 Corynebacterium urealyticum, 10 Corynebacterium xerosis, 10 Corynebacterium group ANF-1, 10 Corynebacterium group 12, and 10 Listeria monocytogenes) were determined. The MICs of ciprofloxacin, ofloxacin, and sparfloxacin for 90% of C. jeikeium, C. urealyticum, and C. xerosis isolates tested were > 16 micrograms/ml. Those of BAY Y 3118 and clinafloxacin against these species were 0.5 and 1 to 2 micrograms/ml, respectively. The MICs for 90% of all 115 strains tested were 0.5 microgram/ml for BAY Y 3118, 1 microgram/ml for clinafloxacin, 2 micrograms/ml for E-5068, 4 micrograms/ml for E-5065, and > 16 micrograms/ml for ciprofloxacin, ofloxacin, sparfloxacin, and E-4868.     

In vitro evaluation of activities of nitazoxanide and tizoxanide against anaerobes and aerobic organisms

The antibacterial activities of nitazoxanide and its main metabolite, tizoxanide, were tested against a broad range of bacteria, including anaerobes. Metronidazole, amoxicillin, amoxicillin-clavulanic acid, piperacillin, cefoxitin, imipenem, and clindamycin were used as positive controls. MICs were determined by reference agar dilution methods. The 241 anaerobes were all inhibited by nitazoxanide, with the MICs at which 90% of isolates are inhibited (MIC90S) being between 0.06 and 4 mg/liter with the exception of those for Propionibacterium species, for which the MIC90 was 16 mg/liter. The MIC90s of nitazoxanide were 0.5 mg/liter for the Bacteroides fragilis group (80 strains), 0.06 mg/liter for Clostridium difficile (21 strains), and 0.5 mg/liter for Clostridium perfringens (16 strains). Metronidazole showed a level of activity comparable to that of nitazoxanide except against Bifidobacterium species, against which it was poorly active, and Propionibacterium species, which were resistant to metronidazole. The other antibiotics showed various levels of activity against anaerobes, with imipenem along with nitazoxanide being the most active agents tested. Tizoxanide was less effective than nitazoxanide except against the B. fragilis group, against which its activity was similar to that of nitazoxanide. Under aerobic conditions, nitazoxanide demonstrated poor activity against members of the family Enterobacteriacae and Pseudomonas, Staphylococcus, and Enterococcus species. The same results were obtained when culture was performed under anaerobic conditions with the notable exception of the results against Staphylococcus aureus. The MICs of nitazoxanide were in the range of 2 to 4 mg/liter for 34 clinical isolates of S. aureus, 12 of which were methicillin resistant, while tizoxanide was not effective.     

In vitro activities of meropenem, PD 127391, PD 131628, ceftazidime, chloramphenicol, co-trimoxazole, and ciprofloxacin against Pseudomonas cepacia

In a study of 110 Pseudomonas cepacia isolates from patients without cystic fibrosis, the in vitro potencies of three new compounds, meropenem, PD 127391, and PD 131628, were comparable to those of ceftazidime and ciprofloxacin and exceeded those of chloramphenicol and co-trimoxazole. The MICs of ceftazidime, ciprofloxacin, meropenem, and the PD compounds for 90% of strains tested were < or = 4 micrograms/ml, whereas they were 32 micrograms/ml for chloramphenicol and co-trimoxazole. Data for 20 isolates from patients with cystic fibrosis indicated that the isolates were less susceptible to all seven antibiotics tested, with the most active compounds being meropenem and PD 127391.     

In vitro susceptibility of Coxiella burnetii to trovafloxacin in comparison with susceptibilities to pefloxacin, ciprofloxacin, ofloxacin, doxycycline, and clarithromycin

The antibiotic susceptibilities of eight Greek isolates of Coxiella burnetii to trovafloxacin were determined by the shell vial assay. MICs of trovafloxacin and ofloxacin ranged from 1 to 2 microg/ml, those of pefloxacin ranged from 1 to 4 microg/ml, those of ciprofloxacin ranged from 4 to 8 microg/ml, those of doxycycline ranged from 1 to 2 microg/ml, and those of clarithromycin ranged from 2 to 4 microg/ml. Trovafloxacin exhibited no activity against C. burnetii at 4 microg/ml.