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.     

In vitro comparative activity (E test) of sparfloxacin and other 8 antimicrobial agents against bacteria isolated from patients with respiratory infections acquired in the community

Sparfloxacin is a new antimicrobial that, while maintaining a good activity against gram negative bacilli, has a better in vitro activity against gram positive bacteria such as S pneumoniae, intracellular pathogens and anaerobic bacteria. The aim of this work was to study the in vitro activity of sparfloxacin against bacteria isolated from patients with community acquired respiratory infections between October 1994 and January 1995. Using the E-test technique, we studied the susceptibility to sparfloxacin, ciprofloxacin, ampicillin, amoxicillin/clavulanic acid, cefuroxime, cefotaxime, erythromycin, methicillin and nalidixic acid of 50 strains of S pneumoniae, 50 strains of H. influenzae, 50 strains of S aureus and 50 strains of S pyogenes. Sparfloxacin was active against 100% of S pneumoniae, H influenzae and S pyogenes strains. Twenty two percent of S aureus strains were resistant and the MIC 90 was 12 micrograms/ml. Sparfloxacin showed the best in vitro activity against H influenzae and S aureus, a similar activity with ampicillin and cefotaxime against S pneumoniae and a similar activity with ampicillin but superior to all other studied antimicrobial against S pyogenes. It is concluded that sparfloxacin is a good antimicrobial for bacteria isolated from patients with respiratory infections.     

Comparative in vitro activities of DU-6859a, levofloxacin, ofloxacin, sparfloxacin, and ciprofloxacin against 387 aerobic and anaerobic bite wound isolates

The activities of DU-6859a, levofloxacin, ofloxacin, sparfloxacin, and ciprofloxacin against bite wound isolates were determined by the agar dilution method. DU-6859a was the most active compound (MICs, < or = 0.125 microg/ml) against all Pasteurella species, Staphylococcus aureus, and streptococci; anaerobes were susceptible to < or = 0.5 microg/ml, except fusobacteria, which were susceptible to < or = 2 microg/ml. Against aerobes, levofloxacin was more active than ofloxacin (MIC at which 90% of isolates are inhibited [MIC90], < or = 1.0 microg/ml for both) and sparfloxacin and ciprofloxacin were also active (MIC90s, < or = 0.25 and < 1 microg/ml, respectively).     

Activity of cefamandole and other cephalosporins against aerobic and anaerobic bacteria

The activity of cefamandole was comparable to that of cephalothin, cefazolin, and cephaloridine against Staphylococcus aureus, Streptococcus pyogenes, and Diplococcus pneumoniae. In contrast, cefamandole was considerably more active than cephalothin, cefazolin, or cephaloridine against gram-negative facultative bacilli, including Haemophilus influenzae, the most striking disparities being noted with indole-positive Proteus and Enterobacter. Bacteroides fragilis was more susceptible to cefoxitin than to cefamandole or cefazolin (median minimal inhibitory concentration, approximately 8, 32, and 32 mug/ml, respectively); cephalothin exhibited still less activity against this species. The majority of other anaerobes were inhibited by relatively low concentrations of all four cephalosporins. The results indicate a potentially valuable role for cefamandole against facultative gram-negative bacilli, including H. influenzae, but no exceptional activity against anaerobes.     

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

The in vitro activity of the fluoroquinolone BAY 12-8039 against 66 strains of different mycoplasma species and 30 strains of Ureaplasma urealyticum was compared with those of three other antimicrobial agents. BAY 12-8039 at 0.5 microg/ml inhibited 100% of all the mycoplasmal and ureaplasmal strains tested. The minimal bactericidal concentrations of BAY 12-8039 increased only two- to eightfold compared to the MICs. Furthermore, they were comparable to those of sparfloxacin and lower than those of doxycycline and clarithromycin.     

In vitro antimicrobial activity of DR-3355, a new quinolone antibacterial agent, against clinical isolates of enteritis-causing bacteria]

We determined the minimum inhibitory concentration (MIC) of DR-3355, a newly developed quinolone-derivative antibacterial agent, against clinical isolates of various bacterial species from enteritis patients, and compared them with those of ofloxacin (OFLX), ciprofloxacin (CPFX), nalidixic acid (NA), ampicillin (ABPC), kanamycin (KM). MIC90 of DR-3355 against 94 strains of Shigella spp. and 5 strains of Escherichia coli, 36 strains of Salmonella spp., 22 strains of Vibrio cholerae, 5 strains of Vibrio parahaemolyticus, and 19 strains of Campylobacter jejuni were 0.05, 0.10, 0.0025, 0.39, and 0.78 micrograms/ml, respectively. These values were 1/2 of that of OFLX, and two times of that of CPFX. MIC90 of DR-3355, OFLX and CPFX against C. jejuni were 0.78 micrograms/ml. MIC90 of DR-3355 against isolates from enteritis patients except for Vibrio spp., were 1/30 to 1/60 of those of NA, ABPC, and KM.     

Comparative in-vitro and in-vivo activity of AM-1155 against anaerobic bacteria

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.     

E-4695, a new C-7 azetidinyl fluoronaphthyridine with enhanced activity against gram-positive and anaerobic pathogens

E-4695, (-)-7-[3-(R)-amino-2-(S)-methyl-1-azetidinyl]-1-cyclopropyl-1,4- dihydro-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid, is a new fluorinated naphthyridine with an azetidine moiety. The MICs of E-4695 at which 90% of the isolates were inhibited (MIC90s) were 0.06 to 0.5 microgram/ml for gram-positive cocci, including species of the genera Staphylococcus, Streptococcus, and Enterococcus, and the MIC90s against gram-negative pathogens such as members of the family Enterobacteriaceae (with the exception of Providencia spp. [MIC90, 8 micrograms/ml]) and Pseudomonas aeruginosa were 0.015 to 0.5 microgram/ml. E-4695 inhibited 90% of the Clostridium perfringens and Bacteroides fragilis isolates at 0.25 and 4 micrograms/ml, respectively. Against gram-positive cocci the potency of E-4695 was 2- to 8-fold higher than that of ciprofloxacin, 4- to 8-fold higher than that of ofloxacin, and 8- to 16-fold higher than that of fleroxacin. Against enteric bacteria and P. aeruginosa the potency of E-4695 was, in general, similar to that of ciprofloxacin and eightfold higher than those of ofloxacin and fleroxacin. E-4695 was four- and eightfold more potent than ciprofloxacin against C. perfringens and B. fragilis isolates, respectively. E-4695 and ciprofloxacin showed similar properties when the effects of pH or magnesium concentration were tested on them. E-4695 and ciprofloxacin had substantial reductions of activity only when pH decreased below 4.8. E-4695 and ciprofloxacin activities were not markedly affected by the presence of 5 or 10 mM Mg2+. The presence of serum and human urine at pH 7.2 decreased the activity of E-4695 between two- and fourfold. After an oral dose of 50 mg/kg of body weight, the maximum level in serum, the biological half-life, and the area under the concentration-time curve from 0 to 10 h for E-4695 were 13.2 microgram/ml, 3.3 h, and 45.6 microgram . h/ml, respectively. The area under the concentration-time curve from 0 to 4 h for ciprofloxacin was 2.3 microgram . h/ml at the same dose. Fifty-percent effective doses (ED50S) against Staphylococcus aureus HS-93 infections in mice were 4.5 mg/kg with E-4695 and 37.6 mg/kg with ciprofloxacin. Infection with Streptococcus pneumoniae 29206 was more effectively treated with E-4695 (ED50, 41,2 mg/kg) than with ciprofloxacin (ED50, 200 mg/kg). The ED50 of E-4695 for infections with Streptococcus pneumoniae 1625 was 132.2 mg/kg; ciprofloxacin was ineffective at 400 mg/kg against this strain. E-4695 was also more potent than ciprofloxacin in treatment of infections caused by gram-negative organisms such as Escherichia coli HM-42 (ED50S, 1.0 and 3.9 mg/kg, respectively). The ED50S of E-4695 and ciprofloxacin were 33.0 and 145.5 mg/kg against P. aeruginosa HS-116 and 9.6 and 18.9 mg/kg against P. aeruginosa B-120, respectively. The therapeutic efficacy of E-4695 may depend not only on its in vitro activity but also on its improved pharmacokinetic properties.     

In vitro activities of antimicrobial agents, alone and in combination, against Acinetobacter baumannii isolated from blood

In vitro activities of 15 antimicrobial agents against 90 strains of Acinetobacter baumannii isolated from blood cultures from hospitalized patients were determined using the agar dilution method. Imipenem, ofloxacin, and ciprofloxacin had the best antimicrobial activity with minimum inhibitory concentrations (MIC50s) of 0.25 mu g/ml and MIC90s of 0.5-1 mu g/ml. beta-lactam antibiotics other than imipenem had poor activity, with MIC50s ranging from 8 to 64 mu g/ml and MIC90s from 32 to > or = 256 mu g/ml. The checkerboard titration method was used to study the effects of combination of two antimicrobial agents. Combinations of ceftazidime, aztreonam, imipenem, or ciprofloxacin with amikacin showed either synergistic effects or partial synergistic effects for 40.9%-86.4% of 22 tested strains. The best in vitro activity was observed with the combination of imipenem and amikacin. No antagonistic effects were observed with the combination of imipenem and amikacin. Synergistic effects were confirmed by time-kill curve studies. In conclusion, imipenem, ofloxacin, and ciprofloxacin were the three most active agents against human blood isolates of A. baumannii. The combination of a beta-lactam or ciprofloxacin with amikacin was synergistic for some of the isolates.     

In vitro activities of two new glycylcyclines, N,N-dimethylglycylamido derivatives of minocycline and 6-demethyl-6-deoxytetracycline, against 339 strains of anaerobic bacteria

The in vitro activities of the N,N-dimethylglycylamido derivatives of minocycline (DMG-MINO) and 6-demethyl-6-deoxytetracycline (DMG-DMDOT) were compared with those of minocycline, tetracycline, clindamycin, and metronidazole by using the National Committee for Clinical Laboratory Standards-approved Wadsworth agar dilution method. The MICs of DMG-MINO, DMG-DMDOT, and metronidazole at which 90% of the strains were susceptible (0.5, 1, and 1 micrograms/ml, respectively) were lower than those for clindamycin, minocycline, and tetracycline (4, 8, and 32 micrograms/ml, respectively). All of the strains of anaerobes tested, except one strain of Bacteroides ovatus (MIC, 16 micrograms/ml), were susceptible to DMG-MINO and DMG-DMDOT at 8 micrograms/ml.     

Efficacy of carbamazepine compared with other agents: a clinical practice survey

BACKGROUND: To gain an impression of the experience with and efficacy of carbamazepine relative to other agents and relative to its use in treating psychiatric and neurologic disorders in general clinical practice, a survey was distributed in 1988 to psychiatrists practicing in the United States. METHOD: The survey was mailed to 9030 members of the American Psychiatric Association (APA) who had expressed an interest in the study and treatment of affective disorders in a 1982 APA survey. The survey sampled clinicians' experience of the efficacy and side effects of carbamazepine in a number of psychiatric and neurologic conditions. Each clinician also provided global impression ratings of the efficacy of a variety of traditional and novel treatments. RESULTS: Completed surveys were returned by 2543 (28%) physicians. Carbamazepine was reported to be moderately to markedly effective in the following percentage of patients: partial complex seizures, 85.2%; generalized seizures, 82.9%; trigeminal neuralgia, 81.5%; mania prophylaxis, 72.9%; acute bipolar depression, 67.5%; intermittent explosive disorder, 65.2%; acute mania, 62.2%; schizoaffective disorder, 58.8%; other pain syndromes, 51.2%; posttraumatic stress disorder, 48.1%; borderline personality disorder, 43.0%; unipolar depression, 32.2%; schizophrenia, 25.7%; and alcohol withdrawal, 15.9%. About 4.4% of the patients reported were withdrawn from carbamazepine because of side effects. CONCLUSION: Carbamazepine was widely used to treat a variety of psychiatric conditions in 1988 and found to be of use in the acute and long-term treatment of bipolar illness. It was rated slightly less effective than lithium, electroconvulsive therapy, or neuroleptics, but more effective than several other agents. The results of the survey highlight many areas in need of further systematic investigation.     

In vitro activity of RU 64004, a new ketolide antibiotic, against gram-positive bacteria

The comparative in vitro activity of RU 64004 (also known as HMR 3004), a new ketolide antibiotic, was tested by agar dilution against approximately 500 gram-positive organisms, including multiply resistant enterococci, streptococci, and staphylococci. All streptococci were inhibited by < or = 1 microg of RU 64004 per ml. The ketolide was more potent than other macrolides against erythromycin A-susceptible staphylococci and was generally more potent than clindamycin against erythromycin A-resistant strains susceptible to this agent. Clindamycin-resistant staphylococci (MIC, > 128 microg/ml) proved resistant to the ketolide, but some erythromycin A- and clindamycin-resistant enterococci remained susceptible to RU 64004.     

In vitro antibacterial activity of a new fluoroquinolone, fleroxacin, against hospital bacteria and regression curve

Minimal inhibitory concentrations (MICs) of fleroxacin (FLE) were determined by agar dilution for 1261 bacterial strains isolated in 1992 in 4 university hospitals; in addition, antibiograms by agar diffusion were performed with 5 micrograms disks. Activity of FLE against nalidixic acid (NAL) susceptible (S) Enterobacteriaceae was close to that of other fluoroquinolones (FQ) (MIC 50 and 90: 0.12-0.25 micrograms/ml); like for other FQ, this activity was reduced against NAL intermediate and resistant (R) Enterobacteriaceae (4-32). MICs of FLE against P. aeruginosa were between 1 and 128 (8-128). FLE had also a good activity against NAL-S A. baumannii (0.12-0.5) but this activity is reduced against NAL-R Acinetobacter (64-128). FLE was highly active against Haemophilus (0.06-0.12), Gonococci (0.03-0.25), Meningococci (0.016-0.03) and B. catarrhalis (0.12-0.25). FLE showed activity close to the currently available FQ against methicillin susceptible Staphylococci (0.25-1); the resistant strains (32- > 128) are usually methicillin resistant. FLE is less effective against Enterococci (4-128), Streptococci (8-16) and Pneumococci (4-8). The coefficient correlation of the regression curve is 0.93; for MIC breakpoints of 1 and 4 micrograms/ml, zone diameter breakpoints should be 20 and 15 mm.     

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.     

In vitro activity of omeprazole in combination with several antimicrobial agents against clinical isolates of Helicobacter pylori

An agar dilution checkerboard method was used to evaluate the in vitro activity of omeprazole combined with clarithromycin, amoxicillin, and ceftibuten, respectively, against clinical isolates of Helicobacter pylori. Mueller-Hinton agar plus 5% horse blood, an inoculum of 10(6) cfu/ml, and incubation of 72 h in a CO2 atmosphere were used. With the omeprazole and clarithromycin combination, synergism was observed in 51.5% and partial synergism in 39.3% of 33 strains; with omeprazole and amoxicillin, synergism was observed in 3% and partial synergism in 60.6% of 33 strains; and with omeprazole and ceftibuten, synergism was observed in 33.3% and partial synergism in 50% of 24 strains. Antagonism between omeprazole and each antibiotic was exhibited in 0%, 6.1%, and 4.1% of these groups of strains, respectively. Of the antibiotic combinations tested, omeprazole plus clarithromycin exhibited synergism (partial or total) in the highest percentage of strains.     

Antimicrobial activity of the new carbapenem biapenem compared to imipenem, meropenem and other broad-spectrum beta-lactam drugs

The in vitro activity of biapenem was compared to that of imipenem, meropenem and other broad-spectrum beta-lactams. A total of 716 isolates from recent cases of clinical septicemia and an additional 137 stock strains possessing known beta-lactamases or other well-characterized resistance mechanisms were tested. The minimal concentrations inhibiting 90% of strains (MIC90) of Enterobacteriaceae species were for biapenem 0.03 to 1 mg/l and for imipenem 0.25 to 2 mg/l. No member of the Enterobacteriaceae was found to be resistant to biapenem. Biapenem and meropenem were the most active drugs against Pseudomonas aeruginosa, with an MIC90 of 1 mg/l. Biapenem was more active than ceftazidime against most gram-negative and gram-positive bacteria tested. Biapenem was as potent as imipenem against anaerobic bacteria (including Bacteroides fragilis), with an MIC90 of 0.25 mg/l. High MICs of biapenem were demonstrated for Xanthomonas maltophilia, oxacillin-resistant Staphylococcus spp. and Enterococcus spp. These species have demonstrated resistance to other carbapenems and to most of the newer cephalosporins. The results of this study, coupled with previously documented favorable qualities of biapenem, endorse further investigation of this broad-spectrum antibacterial agent for clinical use.     

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.     

Susceptibilities of penicillin- and erythromycin-susceptible and -resistant pneumococci to HMR 3647 (RU 66647), a new ketolide, compared with susceptibilities to 17 other agents

Susceptibility of 230 penicillin- and erythromycin-susceptible and -resistant pneumococci to HMR 3647 (RU 66647), a new ketolide, was tested by agar dilution, and results were compared with those of erythromycin, azithromycin, clarithromycin, roxithromycin, rokitamycin, clindamycin, pristinamycin, ciprofloxacin, sparfloxacin, trimethoprim-sulfamethoxazole, doxycycline, chloramphenicol, cefuroxime, ceftriaxone, imipenem, and vancomycin. HMR 3647 was very active against all strains tested, with MICs at which 90% of the strains were inhibited (MIC90s) of 0.03 microg/ml for erythromycin-susceptible strains (MICs, < or =0.25 microg/ml) and 0.25 microg/ml for erythromycin-resistant strains (MICs, > or =1.0 microg/ml). All other macrolides yielded MIC90s of 0.03 to 0.25 and >64.0 microg/ml for erythromycin-susceptible and -resistant strains, respectively. The MICs of clindamycin for 51 of 100 (51%) erythromycin-resistant strains were < or =0.125 microg/ml. The MICs of pristinamycin for all strains were < or =1.0 microg/ml. The MIC90s of ciprofloxacin and sparfloxacin were 4.0 and 0.5 microg/ml, respectively, and were unaffected by penicillin or erythromycin susceptibility. Vancomycin and imipenem inhibited all strains at < or =1.0 microg/ml. The MICs of cefuroxime and cefotaxime rose with those of penicillin G. The MICs of trimethoprim-sulfamethoxazole, doxycycline, and chloramphenicol were variable but were generally higher in penicillin- and erythromycin-resistant strains. HMR 3647 had the best kill kinetics of all macrolides tested against 11 erythromycin-susceptible and -resistant strains, with uniform bactericidal activity (99.9% killing) after 24 h at two times the MIC and 99% killing of all strains at two times the MIC after 12 h for all strains. Pristinamycin showed more rapid killing at 2 to 6 h, with 99.9% killing of 10 of 11 strains after 24 h at two times the MIC. Other macrolides showed significant activity, relative to the MIC, against erythromycin-susceptible strains only.