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

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

In vitro activity of ciprofloxacin, a new carboxyquinoline antimicrobial agent.

The in vitro activity of ciprofloxacin (Bay o 9867), a new carboxyquinoline antimicrobial agent, was compared with those of norfloxacin, nalidixic acid, and several other oral and parenteral antimicrobial agents. Ciprofloxacin was substantially more active than nalidixic acid or cinoxacin against all gram-negative bacteria tested. Virtually all strains of Enterobacteriaceae were inhibited by the new drug at concentrations of less than or equal to 0.125 micrograms/ml. Ciprofloxacin was more active than norfloxacin against Klebsiella sp., Enterobacter sp., and Serratia marcescens, and it was the most active agent against Pseudomonas aeruginosa (MIC90, 0.5 micrograms/ml). The new drug also demonstrated significant activity against gram-positive cocci, inhibiting all strains of staphylococci at concentrations of less than or equal to 1.0 microgram/ml. Ciprofloxacin was bactericidal at concentrations near the MIC against most isolates tested. Although stepwise increases in resistance were seen with Escherichia coli and P. aeruginosa during serial passage on plates containing incremental concentrations of the drug, significant resistance did not emerge during incubation of strains in broth containing concentrations of ciprofloxacin above the MBC.     

In vitro susceptibility of Capnocytophaga species to 29 antimicrobial agents.

A hemoglobin-supplemented medium composed of Columbia agar base supplemented with 1% hemoglobin and 1% Polyvitex was used to investigate the in vitro activity of 29 antimicrobial agents against Capnocytophaga species. Clindamycin was the most active agent, with all strains being inhibited by 0.06 microgram/ml or less. Amoxicillin-clavulanic acid and imipenem were the most active among the beta-lactam antibiotics (MIC for 90% of strains tested [MIC90], 0.50 microgram/ml); other very active drugs were BMY 28142, cefpirome, cefotaxime, ceftazidime, and ceftriaxone (MIC90, 0.06 to 0.50 micrograms/ml), although at least one strain showed resistance to each of these antibiotics (MIC, greater than or equal to 16 micrograms/ml). Ciprofloxacin was the most active among the quinolones, with all strains being inhibited by 0.50 microgram/ml. The MICs of the other four drugs ranged from 0.12 to 4 micrograms/ml. Ampicillin, penicillin G, ticarcillin, aztreonam, and temocillin were moderately active (MIC90, 1 to 8 micrograms/ml; MIC range, less than or equal to 0.03 to greater than 128 micrograms/ml). All strains were uniformly resistant to the aminoglycosides, polymyxin B, vancomycin, trimethoprim, and amphotericin B. Three strains produced beta-lactamase. No significant difference was found between the susceptibility of strains isolated from various sources or patients.     

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

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

Antimicrobial activity, spectrum, and recommendations for disk diffusion susceptibility testing of ceftibuten (7432-S; SCH 39720), a new orally administered cephalosporin.

The antimicrobial activity and spectrum of ceftibuten (7432-S; SCH 39720) was determined on a wide variety of bacterial species selected for resistance to oral and parenteral beta-lactam antimicrobial agents. Ceftibuten was found to be the most active beta-lactam tested against members of the family Enterobacteriaceae, inhibiting 81.6% of strains at less than or equal to 8.0 micrograms/ml compared with 75.0 and 54.8% of strains inhibited by cefixime and cefuroxime, respectively. All strains of Haemophilus influenzae (MIC for 90% of strains [MIC90], less than or equal to 0.06 microgram/ml), Branhamella catarrhalis (MIC90, 3.0 micrograms/ml), and pathogenic Neisseria spp. (MIC90, less than or equal to 0.06 and 0.019 microgram/ml) were susceptible to ceftibuten. Beta-hemolytic Streptococcus spp. (serogroups A, B, C, and G) were also inhibited by ceftibuten, but penicillin-resistant pneumococci were generally resistant to cefixime and ceftibuten. The activity and spectrum of ceftibuten seem most applicable to infections of the respiratory and urinary tract plus those infections caused by pathogenic Neisseria spp. Ceftibuten disks (30 micrograms) were evaluated and found to have an acceptable correlation (r = 0.88) with ceftibuten MICs. Preliminary zone size interpretive criteria for MIC breakpoints of less than or equal to 4.0 and less than or equal to 8.0 micrograms/ml were calculated.     

In vitro activity of Ro 23-6240, a new difluoroquinolone derivative, compared with that of other antimicrobial agents.

Ro 23-6240 is a new difluorinated quinolone antimicrobial agent. Its in vitro activity against a wide range of bacteria was compared with those of other quinolones and beta-lactams. Generally, members of the family Enterobacteriaceae were inhibited by low concentrations of Ro 23-6240 (MIC90 [MIC for 90% of isolates tested], less than or equal to 1 microgram/ml). Ninety percent of Staphylococcus aureus (including methicillin-resistant strains) and Neisseria gonorrhoeae isolates were inhibited by 0.5 microgram/ml. Pseudomonas aeruginosa (MIC90, 2 micrograms/ml) and Bacteroides fragilis (MIC90, 4 micrograms/ml) showed intermediate susceptibility, and Streptococcus pneumoniae (MIC90, 8 micrograms/ml) was less susceptible. Strains resistant to nalidixic acid were less susceptible to all the quinolones tested. The protein binding of Ro 23-6240 (5 micrograms/ml) was 27%.     

Antimicrobial activity of coumermycin and recommendations for disk diffusion tests with 5- and 15-micrograms disks

Coumermycin was found to be extremely active against methicillin-susceptible and -resistant Staphylococcus spp. (MIC 90, less than or equal to 0.002 microgram/ml). Vancomycin and coumermycin were equally active against Streptococcus spp. (MIC 90s, 0.5 microgram/ml) and both were superior to fusidic acid (MIC 90, 8.0 micrograms/ml). The enterococci had the highest MICs for all three drugs. Disk diffusion susceptibility tests using either 5 or 15 micrograms coumermycin disks seem reliable. The tentative interpretive breakpoints for testing the Staphylococcus spp. only are: 5 micrograms disk-susceptible greater than or equal to 17 and resistant less than or equal to 13 mm; 15 micrograms disk-susceptible greater than or equal to 20 mm and resistant less than or equal to 16 mm. These zone criteria have approximate coumermycin MIC correlates of less than or equal to 0.12 microgram/ml for susceptible and greater than or equal to 0.5 microgram/ml for resistant.     

Comparative in vitro activities of sparfloxacin (CI-978; AT-4140) and other antimicrobial agents against staphylococci, enterococci, and respiratory tract pathogens.

The in vitro activity of sparfloxacin (CI-978; AT-4140) was compared with those of other antimicrobial agents against isolates of staphylococci, enterococci, and various respiratory tract pathogens. Sparfloxacin was the most active drug tested against staphylococci (MIC for 90% of the strains tested [MIC90], 0.125 micrograms/ml) and enterococci (MIC90, 1.0 microgram/ml). It was also active against Haemophilus influenzae (MIC90, less than or equal to 0.06 microgram/ml), Moraxella (Branhamella) catarrhalis (MIC90, 0.125 microgram/ml), Streptococcus pneumoniae (MIC90, 0.5 microgram/ml), and Streptococcus pyogenes (MIC90, 1.0 microgram/ml).     

Susceptibility of clinical isolates of Campylobacter pyloridis to 11 antimicrobial agents.

The activities of 11 antimicrobial agents, including two bismuth salts, against 70 strains of Campylobacter pyloridis isolated from gastric biopsy specimens were tested. The isolates were very susceptible to penicillin (the MIC for 90% of the strains tested [MIC90] was 0.03 microgram/ml), erythromycin, cefoxitin (MIC90, 0.12 microgram/ml), gentamicin, and ciprofloxacin (MIC90, 0.25 microgram/ml). The bismuth salts and nalidixic acid had moderate activity (MIC90, 16 to 64 micrograms/ml). Twenty percent of the isolates were resistant to metronidazole (MIC, greater than 1 micrograms/ml), and all were resistant to sulfamethoxazole and trimethoprim (MIC90, greater than 256 micrograms/ml).     

In vitro antimicrobial activity of cefoperazone-sulbactam combinations against 554 clinical isolates including a review and beta-lactamase studies

Cefoperazone was tested against 554 clinical isolates alone and with sulbactam in three combinations. The addition of sulbactam in low concentrations (less than or equal to 4 micrograms/ml) improved the spectrum of cefoperazone principally against gram-negative bacilli such as Acinetobacter species, some Pseudomonas species, and beta-lactamase-positive Enterobacteriaceae. Nearly all of the spectrum increase was achieved at a sulbactam level of less than or equal to 2 micrograms/ml. Sulbactam was found to be an effective antimicrobial agent against Acinetobacter species (MIC50, 1.0 microgram/ml), Pseudomonas acidovorans (MIC50, 2.0 micrograms/ml), Neisseria gonorrhoeae (MIC50, less than or equal to 0.5 microgram/ml), and N. meningitidis (MIC50, less than or equal to 0.5 microgram/ml). Sulbactam had a higher affinity and binding constant for the plasmid-mediated beta-lactamases such as TEM-1 and TEM-2 compared to cefoperazone (greater than or equal to 10-fold difference). This finding was important as cefoperazone can be hydrolyzed at a moderate rate by the highly efficient TEM enzymes (less than 2% of clinical Escherichia coli isolates). Sulbactam increased the susceptibility (less than or equal to 16 micrograms/ml) of 220 isolates of Enterobacteriaceae to cefoperazone from 88.6 to 96.3% when 4.0 micrograms/ml of sulbactam was added. The cefoperazone antimicrobial activity was also increased against the nonenteric bacilli from a 69.5 to a 87.4% total inhibition. MICs among cefoperazone-susceptible gram-negative and gram-positive strains were routinely decreased 2- to 32-fold, as calculated from MIC90 results. Therefore, sulbactam should predictably increase the antimicrobial spectrum and clinical effectiveness of cefoperazone against nosocomial and other pathogens such as the plasmid-containing enteric bacilli, Bacteroides species and Acinetobacter species, and possibly provide the opportunity to reduce dosage schedules for infecting species already susceptible to cefoperazone alone.     

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

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

In vitro activities of 12 orally administered antimicrobial agents against four species of bacterial respiratory pathogens from U.S. Medical Centers in 1992 and 1993.

Clinical isolates of Haemophilus influenzae, Streptococcus pneumoniae, Streptococcus pyogenes, and Moraxella catarrhalis were gathered from 19 different clinical laboratories throughout the continental United States. The in vitro activities of 12 orally administered antimicrobial agents were compared by broth microdilution tests with 3,151 bacterial isolates. Among 890 H. influenzae isolates, 30% were capable of producing beta-lactamase enzymes (12 to 41% in different medical centers). Most of the 619 beta-lactamase-negative H. influenzae strains were susceptible to ampicillicin (MIC, < or = 1.0 micrograms/ml): 5 strains were intermediate in susceptibility (MIC, 2.0 micrograms/ml) and 1 strain was ampilicillin resistant (MIC, 4.0 micrograms/ml). Ninety-two percent of 698 M. catarrhalis strains were beta-lactamase positive. Of 799 S. pneumoniae isolates, 15% were intermediate in susceptibility to penicillin and 7% were resistant to penicillin. The prevalence of penicillin-susceptible pneumococci in different institutions ranged from 63 to 95%. Only 1% of 764 S. pyogenes isolates were resistant to the macrolides, but 5% of S. pneumoniae isolates were macrolide resistant. Only 71% of 58 penicillin-resistant S. pneumoniae isolates were erythromycin susceptible, whereas 97% of the 622 penicillin-susceptible strains were erythromycin susceptible. Penicillin-resistant pneumococci were also relatively resistant to the cephalosporins and amoxicillin. Penicillin-susceptible pneumococci were susceptible to amoxicillin-clavulanic acid (MIC for 90% of isolates tested [MIC90], < or = 0.12/0.06 microgram/ml), cefixime (MIC90, 0.25 microgram/ml), cefuroxime axetil (MIC90, < or = 0.5 microgram/ml), cefprozil (MIC90, < or = 0.5 micrograms/ml), cefaclor (MIC90, 0.5 microgram/ml), and loracarbef (MIC90, 1.0 microgram/ml). Most strains of the other species remained susceptible to the study drugs other than amoxicillin.     

In vitro activity and beta-lactamase stability of FK-037, a parenteral cephalosporin.

The in vitro activity of FK-037, 5-amino-2-[[(6R, 7R)-7-[[(Z)-2-(2-amino-4-thiazolyl)-2- methoxyimino) acetyl] amino]-2-carboxy-8-oxo-5-thia-1- azabicyclo[4.2.0]oct-2-en-3-yl]methyl]-1-(2-hydroxyethyl)-1H-pyrazoli um hydroxide, inner salt, sulfate (1:1), a new parenteral cephem, was compared with those of cefepime, ceftazidime, imipenem, and ciprofloxacin. FK-037 inhibited methicillin-susceptible staphylocci at < or = 4 micrograms/ml. Of 98 isolates of homogenous methicillin-resistant Staphylococcus aureus, 55 (56.1%) were inhibited by 8 micrograms of FK-037 per ml, compared to 3.1% for cefepime. Imipenem was the most active beta-lactam tested against staphylococci. The MIC of FK-037 for 90% of the strains tested (MIC90) was 0.06 micrograms/ml for hemolytic streptococci, Streptococcus pneumoniae, viridans group streptococci, and Streptococcus bovis. The MIC90 for many of the members of the family Enterobacteriaceae was 1 microgram/ml, similar to that of cefepime and lower than those of ceftazidime and imipenem. The MIC90 for Klebsiella pneumoniae and Enterobacter cloacae was 8 micrograms/ml, similar to that for cefepime, but all isolates were inhibited by 2 micrograms of imipenem per ml. K. pneumoniae isolates with cefotaxime and ceftazidime MICs of > 32 micrograms/ml with Bush type 2b' beta-lactamases were inhibited by 4 micrograms of FK-037 per ml. E. cloacae, Citrobacter freundii, and S. aureus stably resistant to FK-037 could be selected by repeated transfer in the presence of FK-037. The FK-037 MIC90 for Pseudomonas aeruginosa was 4 microgram/ml, compared to 32 microgram/ml for cefepime and ceftazidime and 8 microgram/ml for imipenem. Xanthomonas maltophilia, Pseudomonas cepacia, Acinetobacter anitratus, and Bacteroides species were resistant to FK-037 (MIC, more than or equal 32 microgram/ml). MBCs were identical to or within twofold of the MICs except for a 32-fold greater MBC for P. aeruginosa. Inoculum size and acid environment did not lower the activity of FK-037. FK-037 was not appreciably hydrolyzed by Bush group 1, 2a, 2b, and 2e beta-lactamases but was hydrolyzed by 2b' and 2d enzymes at rates comparable to that of ceftazidime. Nonetheless, FK-037 inhibited bacteria possessing TEM-3, -5, and -7 and SHV -5 at less than or equal 8 microgram/ml. Overall, FK-037 has lower MICs against staphylococci and P. aeruginosa than the currently available iminomethoxy aminothiazolyl cephalosporins and has activity against members of the family Enterobacteriaceae comparable to that of cefepime.     

In vitro activity of BMY-28100, a new oral cephalosporin.

The activity of BMY-28100, a new orally administered cephalosporin, was compared with those of cephalexin and cefaclor. BMY-28100 was the most active drug against Staphylococcus aureus (MIC for 90% of strains tested [MIC90], 1.0 microgram/ml), streptococci (MIC90S, less than or equal to 0.125 microgram/ml), and Klebsiella pneumoniae (MIC90, 2 micrograms/ml). The drug was active against Haemophilus influenzae and gonococci but not against other organisms generally resistant to cephem antibiotics.     

Differing activities of quinolones against ciprofloxacin-susceptible and ciprofloxacin-resistant, methicillin-resistant Staphylococcus aureus.

The in vitro activities of nine quinolones (seven fluoroquinolones, nalidixic acid, and acrosoxacin) against methicillin-resistant Staphylococcus aureus (MRSA) were compared with those of the glycopeptides teicoplanin and vancomycin. MICs against 160 strains of ciprofloxacin-susceptible (MIC, less than 2.0 micrograms/ml) MRSA and 40 strains of ciprofloxacin-resistant (MIC, greater than or equal to 2.0 micrograms/ml) MRSA were determined. The following MICs for 50% of the strains tested (in micrograms per milliliter) were obtained for ciprofloxacin-susceptible and -resistant strains, respectively: tosufloxacin, 0.06 and 2.0; ofloxacin, 0.25 and 16; ciprofloxacin, 0.5 and 16; pefloxacin, 0.5 and 32; acrosoxacin, 1.0 and greater than 256; enoxacin, 1.0 and 64; fleroxacin, 1.0 and 32; norfloxacin, 2.0 and 64; nalidixic acid, 64 and 512; teicoplanin, 1.0 and 1.0; vancomycin, 2.0 and 2.0. In mutation rate studies using a range of antibiotic concentrations to reflect those achievable in vivo, resistant mutants grew only on plates containing nalidixic acid (rate of mutation to resistance, 10(-7) to 10(-8) and on plates containing low concentrations of ciprofloxacin, enoxacin, and norfloxacin (rate of mutation to resistance, 10(-8) to 10(-9). In time-kill studies, 99.9% killing was found within 8 h for all of the quinolones tested (norfloxacin and nalidixic acid were not tested). Teicoplanin and vancomycin were less rapidly bactericidal. For the clinical isolates of ciprofloxacin-resistant MRSA, different levels and patterns of quinolone resistance were found. Generally, cross-resistance among the fluoroquinolones was complete; however, incomplete cross-resistance did occur with the nonfluorinated quinolone acrosoxacin.     

In vitro activity of Ro 23-6240, a new fluorinated 4-quinolone.

The in vitro activity of Ro 23-6240 (AM833), 6,8-difluoro-1-(2-fluoroethyl)-1,4-dihydro-4-oxo-7(4-methyl-1-piper azinyl) quinolone-3-carboxylic acid, was compared with those of norfloxacin, enoxacin, ofloxacin, and ciprofloxacin. Ro 23-6240 inhibited the majority of Enterobacteriaceae isolates at a concentration of less than or equal to 0.5 microgram/ml. It was especially active against Shigella sp., Salmonella sp., Escherichia coli, and Yersinia enterocolitica, with an MIC for 90% of the strains of less than or equal to 0.12 microgram/ml. The MIC for 90% of the strains was 1 microgram/ml for Serratia marcescens and 8 micrograms/ml for Pseudomonas aeruginosa. Staphylococcus aureus isolates, including methicillin-resistant strains, were inhibited by less than or equal to 1 microgram/ml. Streptococcal and anaerobic species were inhibited by 8 to 16 micrograms/ml. Ro 23-6240 inhibited beta-lactamase-producing bacteria resistant to broad-spectrum cephalosporins. The overall activity of Ro 23-6240 was similar to those of enoxacin, norfloxacin, and ofloxacin, but less than that of ciprofloxacin. The frequency of spontaneous resistance was low, although resistant bacteria could be isolated by repeated subculture. The activity of Ro 23-6240 was decreased in the presence of magnesium at concentrations similar to those present in urine.     

An in vitro evaluation of HRE 664, a novel penem antibiotic

HRE 664 is a novel parenteral penem with a broad antimicrobial spectrum. In this study, HRE 664 inhibited 90% of Enterobacteriaceae at less than or equal to 2.0 micrograms/ml, Haemophilus influenzae and Neisseria gonorrhoeae at less than or equal to 0.5 microgram/ml, oxacillin-susceptible staphylococci at less than or equal to 0.13 microgram/ml, oxacillin-resistant staphylococci at less than or equal to 8.0 micrograms/ml, enterococci at less than or equal to 8.0 micrograms/ml, and streptococci at less than or equal to 0.13 microgram/ml. All strains of Pseudomonas aeruginosa were resistant (MICs were greater than 32 micrograms/ml). HRE 664 exhibited a minimal inoculum effect and good bactericidal activity with all organisms tested except an oxacillin-resistant Staphylococcus aureus. With the latter, there was a marked inoculum effect and no on-scale bactericidal endpoints. No measurable hydrolysis of HRE 664 occurred with any of the five Gram-negative bacterial beta-lactamases tested. When stored at -20 degrees C, HRE 664 showed no significant loss of activity for up to 6 wk, but detectable deterioration occurred thereafter. At -60 degrees C, no loss in HRE 664 potency was observed for up to 12 wk. Proposed HRE 664 MIC quality control parameters are: 0.03-0.13 microgram/ml for S. aureus ATCC 29213, 0.25-1.0 micrograms/ml for Escherichia coli 25922, and 2.0-8.0 micrograms/ml for Enterococcus faecalis ATCC 29212.     

Emergence of quinolone resistance among clinical isolates of methicillin-resistant Staphylococcus aureus in Ontario, Canada.

One hundred two isolates of methicillin-resistant Staphylococcus aureus (MRSA) randomly selected from across the Canadian province of Ontario were tested for their susceptibility to ciprofloxacin, norfloxacin, and nalidixic acid by the agar dilution method. Forty-nine percent (50 of 102) had high levels of resistance to these quinolone compounds. For the 50 resistant isolates, ciprofloxacin and norfloxacin had high MICs for 90% of isolates (MIC90s) of 128 micrograms/ml and greater than 128 microgram/ml, respectively; for these isolates, the nalidixic acid MIC90 was greater than 640 micrograms/ml. The majority (98%) of the 50 isolates were also resistant to tobramycin (MIC90, greater than 128 micrograms/ml), while 42% of the isolates were resistant to gentamicin (MIC90, 64 micrograms/ml). Quinolone-resistant MRSA isolates were susceptible to bacteriophages from several groups, indicating independent selection of resistant strains. These results suggest that a reappraisal of the use of fluoroquinolones against MRSA in Canada is necessary.     

In vitro antibiotic susceptibilities of Neisseria gonorrhoeae isolates in the Philippines.

Antibiotic susceptibility surveillance testing was performed on clinical isolates of Neisseria gonorrhoeae collected in September 1989 in the Philippines. beta-Lactamase was produced by 77 (55%) of 140 isolates. In vitro MIC testing revealed significant resistance to penicillin (MIC for 90% of isolates [MIC90], greater than 64 micrograms/ml), tetracycline (MIC90, 4 micrograms/ml), and cefmetazole (MIC90, 8 micrograms/ml). Spectinomycin resistance was rare (10 of 117), but the MIC90 was 32 micrograms/ml. Isolates were susceptible to fluoroquinolones and cephalosporins at the time of this survey, as evidenced by the MIC90s of ciprofloxacin (0.25 microgram/ml), norfloxacin (2.0 micrograms/ml), ofloxacin (0.625 microgram/ml), cefpodoxime (2.0 micrograms/ml), cefotaxime (1.0 microgram/ml), ceftazidime (0.25 microgram/ml), ceftizoxime (0.25 microgram/ml), and ceftriaxone (0.06 microgram/ml). To date, ceftriaxone resistance has not emerged, despite the widespread use of this antibiotic in the Philippines.     

BMY28142, cefbuperazone (T-1982), and Sch 34343. Antimicrobial activity against 94 anaerobes compared to seven other antimicrobial agents

Three new beta-lactams were evaluated against 94 anaerobic strains representing 15 species using a Wilkins-Chalgren broth microdilution method. The penems, Sch 29482 and Sch 34343, were most active with all minimum inhibitory concentrations (MICs) at less than or equal to 4.0 micrograms/ml and MIC90s of less than or equal to 0.25 micrograms/ml. BMY 28142 had a more limited antianaerobic activity against Bacteroides fragilis with a MIC50 and MIC90 of 32 and 128 micrograms/ml, respectively. Cefbuperazone (T-1982) had low B. fragilis MICs (MIC90, 8.0 micrograms/ml), but potentially resistant range MIC90 results for the other species in the B. fragilis group and Clostridium species.