Postantibiotic effects of grepafloxacin compared to those of five other agents against 12 gram-positive and -negative bacteria.

The postantibiotic effect (PAE) (10x the MIC) and the postantibiotic sub-MIC effects (0.125, 0.25, and 0.5x the MIC) were determined for six compounds against 12 strains. Measurable PAEs ranged between 0 and 1.8 h for grepafloxacin, 0 and 2.2 h for ciprofloxacin, 0 and 3. 1 h for levofloxacin, 0 and 2.2 h for sparfloxacin, 0 and 2.4 h for amoxicillin-clavulanate and 0 and 4.8 h for clarithromycin. Reexposure to subinhibitory concentrations increased the PAEs against some strains.

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 activities of cefminox against anaerobic bacteria compared with those of nine other compounds.

The agar dilution MIC method was used to test the activity of cefminox, a beta-lactamase-stable cephamycin, compared with those of cefoxitin, cefotetan, moxalactam, ceftizoxime, cefotiam, cefamandole, cefoperazone, clindamycin, and metronidazole against 357 anaerobes. Overall, cefminox was the most active beta-lactam, with an MIC at which 50% of isolates are inhibited (MIC50) of 1.0 microg/ml and an MIC90 of 16.0 microg/ml. Other beta-lactams were less active, with respective MIC50s and MIC90s of 2.0 and 64.0 microg/ml for cefoxitin, 2.0 and 128.0 microg/ml for cefotetan, 2.0 and 64.0 microg/ml for moxalactam, 4.0 and > 128.0 microg/ml for ceftizoxime, 16.0 and > 128.0 microg/ml for cefotiam, 8.0 and >128.0 microg/ml for cefamandole, and 4.0 and 128.0 microg/ml for cefoperazone. The clindamycin MIC50 and MIC90 were 0.5 and 8.0 microg/ml, respectively, and the metronidazole MIC50 and MIC90 were 1.0 and 4.0 microg/ml, respectively. Cefminox was especially active against Bacteroides fragilis (MIC90, 2.0 microg/ml), Bacteroides thetaiotaomicron (MIC90, 4.0 microg/ml), fusobacteria (MIC90, 1.0 microg/ml), peptostreptococci (MIC90, 2.0 microg/ml), and clostridia, including Clostridium difficile (MIC90, 2.0 microg/ml). Time-kill studies performed with six representative anaerobic species revealed that at the MIC all compounds except ceftizoxime were bactericidal (99.9% killing) against all strains after 48 h. At 24 h, only cefminox and cefoxitin at 4x the MIC and cefoperazone at 8x the MIC were bactericidal against all strains. After 12 h, at the MIC all compounds except moxalactam, ceftizoxime, cefotiam, cefamandole, clindamycin, and metronidazole gave 90% killing of all strains. After 3 h, cefminox at 2 x the MIC produced the most rapid effect, with 90% killing of all strains.

Postantibiotic effect of sanfetrinem compared with those of six other agents against 12 penicillin-susceptible and -resistant pneumococci.

The postantibiotic effect (PAE) and postantibiotic sub-MIC effect (PAE-SME) of sanfetrinem were compared to those of penicillin G, amoxicillin, cefpodoxime, ceftriaxone, imipenem, and clarithromycin against four penicillin-susceptible, four intermediately susceptible, and four resistant pneumococci. The MICs of imipenem were the lowest against all of the strains (0.03 to 0.5 microg/ml), followed by those of sanfetrinem (0.016 to 1.0 microg/ml), amoxicillin and ceftriaxone (0.016 to 2.0 microg/ml), and cefpodoxime (0.03 to 8.0 microg/ml). High-level resistance to clarithromycin (MIC, >64.0 microg/ml) was seen in three selected strains. The PAEs of all of the oral beta-lactams tested were similar for all of the strains, ranging from 1 to 6.5 h. The PAEs of ceftriaxone and imipenem ranged from 1 to 8 h, and those of clarithromycin ranged from 1 to 7 h. The mean PAEs of all of the beta-lactams and clarithromycin were 2.8 to 4.3 and 2.5 h, respectively. PAE-SMEs could not be determined for all of the strains due to complete killing, especially at high subinhibitory concentrations. However, the overall pattern with all of the compounds tested was that PAE-SMEs were longer than PAEs. Measurable PAE-SMEs of sanfetrinem at the three subinhibitory concentrations (0.125, 0.25, and 0.5 times the MIC) were 2 to 7, 2 to 7, and 3 to 6 h, while those of amoxicillin and cefpodoxime were 1 to 7.5, 2 to 4, and 4 to 9 and 2 to 7, 4 to 7, and 4 to 6 h, respectively. Measurable PAE-SMEs of ceftriaxone and imipenem were 1 to 6.5, 2 to 9, and 2 to 9 and 1.5 to 6, 2 to 5.8, and 4 to 7.7 h, respectively. Measurable clarithromycin PAE-SMEs were 1 to 5, 1 to 5, and 1 to 6 h at the three concentrations.

Time-kill study of the activity of trovafloxacin compared with ciprofloxacin, sparfloxacin, metronidazole, cefoxitin, piperacillin and piperacillin/tazobactam against six anaerobes.

A time-kill method was developed to examine the killing kinetics of trovafloxacin, ciprofloxacin, sparfloxacin, metronidazole, cefoxitin, piperacillin and piperacillin/tazobactam against one strain each of Bacteroides fragilis, Bacteroides thetaiotaomicron, Prevotella melaninogenica, Fusobacterium mortiferum, Peptostreptococcus magnus and Clostridium perfringens. Solutions and suspensions were prepared inside an anaerobic glove box, using syringes and prereduced broth. Bottles were then incubated outside the chamber and viability counts determined after incubation for 0, 6, 24 and 48 h in a shaking water bath, avoiding introduction of air. Bacteriostatic/bactericidal concentrations (mg/L) after 48 h for the six strains were: trovafloxacin, 0.03-1/0.03-1; ciprofloxacin, 0.25-16/0.25-32; sparfloxacin, 0.06-2/0.06-8; metronidazole 1-64/1-64; cefoxitin, 0.125-16/0.125-32; piperacillin, 0.125-64/0.125-64; piperacillin/tazobactam, 0.06-2/0.125-8. Bacteriostatic levels were within two dilutions of broth MICs. By this time-kill method, trovafloxacin had the lowest bacteriostatic concentrations of all compounds tested.

Susceptibilities of 228 penicillin- and erythromycin-susceptible and -resistant pneumococci to RU 64004, a new ketolide, compared with susceptibilities to 16 other agents.

The susceptibilities of 228 penicillin- and erythromycin-susceptible and -resistant pneumococci to RU 64004, a new ketolide, were tested by agar dilution, and the results were compared with those for penicillin G, erythromycin, azithromycin, clarithromycin, rokitamycin, clindamycin, pristinamycin, ciprofloxacin, sparfloxacin, trimethoprim-sulfamethoxazole, doxycycline, chloramphenicol, cefuroxime, ceftriaxone, imipenem, and vancomycin. RU 64004 was very active against all strains tested, with MICs at which 90% of the isolates are inhibited (MIC90s) of 0.016 microg/ml for erythromycin-susceptible strains (MIC, < or = 0.25 microg/ml) and 0.25 microg/ml for erythromycin-resistant strains (MIC, > or = 0.5 microg/ml). All other macrolides had MIC90s of 0.03 to 0.25 and > or = 128 microg/ml for erythromycin-susceptible and -resistant strains, respectively. Among erythromycin-resistant strains, clindamycin MICs for 28 of 91 (30.7%) were < or = 0.125 microg/ml. Pristinamycin MICs for all strains were < or = 1.0 microg/ml. MIC90s of ciprofloxacin and sparfloxacin were 4.0 and 0.25 microg/ml, respectively, and were unaffected by susceptibility to penicillin or erythromycin. Vancomycin and imipenem inhibited all strains at < or = 0.5 and < or = 0.25 microg/ml, respectively. MICs of cefuroxime and cefotaxime rose with those of penicillin G. MICs of trimethoprim-sulfamethoxazole, doxycycline, and chloramphenicol were variable but were generally higher for penicillin- and erythromycin-resistant strains. RU 64004 is the first member of the macrolide group which has low MICs for erythromycin-resistant pneumococci.

Antianaerobic activity of the ketolide RU 64004 compared to activities of four macrolides, five beta-lactams, clindamycin, and metronidazole.

Agar dilution methodology (with added Oxyrase in the case of the macrolide group to allow incubation without added CO2) was used to compare the activity of RU 64004, a new ketolide, with the activities of erythromycin, azithromycin, clarithromycin, roxithromycin, clindamycin, amoxicillin with and without clavulanate, piperacillin with and without tazobactam, metronidazole, and imipenem against 379 anaerobes. Overall, RU 64004 yielded an MIC at which 50% of the isolates are inhibited (MIC50) of 1.0 microg/ml and an MIC90 of 16.0 microg/ml. In comparison, MIC50s and MIC90s of erythromycin, azithromycin, clarithromycin, and roxithromycin were 2.0 to 8.0 and >64.0 microg/ml, respectively. MICs of macrolides, including RU 64004, were higher for Bacteroides ovatus, Fusobacterium varium, Fusobacterium mortiferum, and Clostridium difficile than for the other species. RU 64004 was more active against gram-positive rods and cocci, Prevotella and Porphyromonas spp., and fusobacteria other than F. mortiferum and F. varium than against the Bacteroides fragilis group. Overall MIC50s and MIC90s (in micrograms per milliliter), respectively, of other compounds were as follows: clindamycin, 1.0 and 16.0; amoxicillin, 4.0 and 64.0; amoxicillin-clavulanate, 0.5 and 4.0; piperacillin, 8.0 and >64.0; piperacillin-tazobactam, 1.0 and 16.0; metronidazole, 1.0 and 4.0; and imipenem, 0.25 and 1.0.

Bactericidal activity of DU-6859a compared to activities of three quinolones, three beta-lactams, clindamycin, and metronidazole against anaerobes as determined by time-kill methodology.

The activities of DU-6859a, ciprofloxacin, levofloxacin, sparfloxacin, piperacillin, piperacillin-tazobactam, imipenem, clindamycin, and metronidazole against 11 anaerobes were tested by the broth microdilution and time-kill methods. DU-6859a was the most active drug tested (broth microdilution MICs, 0.06 to 0.5 microg/ml), followed by imipenem (MICs, 0.002 to 4.0 microg/ml). Broth macrodilution MICs were within 3 (but usually 1) dilutions of the broth microdilution MICs. All compounds were bactericidal at the MIC after 48 h; after 24 h, 90% killing was shown for all strains when the compounds were used at four times the MIC. DU-6859a at < or = 0.5 microg/ml was bactericidal after 48 h.

Time-kill studies on susceptibility of nine penicillin-susceptible and -resistant pneumococci to cefditoren compared with nine other beta-lactams.

Broth MIC and time-kill methodology was used to determine the activity of cefditoren relative to those of penicillin G, ampicillin, amoxycillin, WY-49605, cefuroxime, cefpodoxime, cefdinir, cefixime and cefaclor against three penicillin-susceptible, three intermediate and three penicillin-resistant pneumococci. MICs of all agents rose with those of penicillin G. Cefditoren was the most active agent (MICs 0.002-0.5 mg/L), followed by WY-49605 (0.008-1.0 mg/L), amoxycillin (0.015-2.0 mg/L), cefuroxime (0.015-4.0 mg/L), cefpodoxime (0.03-4.0 mg/L), ampicillin (0.015-8.0 mg/L), cefdinir (0.03-16.0 mg/L), cefixime (0.125-64.0 mg/L) and cefaclor (0.5-128.0 mg/L). All beta-lactams were bactericidal at the MIC after 24 h, and produced 90% killing after 12 h at concentrations above the MIC. Bactericidal concentrations of cefditoren, even for penicillin-resistant strains, were < or = 0.5 mg/L at 24 h. Additionally, cefditoren and WY-49605 were the only compounds that killed 99% of all strains after 6 h at > or = 4 x MIC. Cefditoren and amoxycillin killed 90% of all strains at 8 x MIC, and WY-49605 at 4 x MIC, after 4 h. Ampicillin had time-kill kinetics similar to those of amoxycillin, but MICs were 1-2 dilutions higher than the latter drug. Cefuroxime and cefpodoxime were the most active of other oral cephalosporins tested. Cefditoren and WY-49605 had the lowest MICs and most favourable time-kill kinetics of all beta-lactams tested.

MIC and time-kill studies of antipneumococcal activity of GV 118819X (sanfetrinem) compared with those of other agents.

Agar dilution MIC methodology was used to test the activities of GV 118819X (sanfetrinem), ampicillin, amoxicillin, amoxicillin-clavulanate, cefpodoxime, loracarbef, levofloxacin, clarithromycin, ceftriaxone, imipenem, and vancomycin against 53 penicillin-susceptible, 84 penicillin-intermediate and 74 penicillin-resistant pneumococci isolated in the United States. GV 118819X was the most active oral beta-lactam, with MIC at which 50% of the isolates were inhibited (MIC50)/MIC90 values of 0.008/0.03, 0.06/0.5, and 0.5/1.0 micrograms/ml against penicillin-susceptible, -intermediate, and -resistant stains, respectively. Amoxicillin and amoxicillin in the presence of clavulanate (2:1) were the second most-active oral beta-lactams, followed by ampicillin and cefpodoxime; loracarbef was not active against penicillin-intermediate and -resistant strains. Clarithromycin was most active against penicillin-susceptible strains but was less active against intermediate and resistant stains. All pneumococcal stains were inhibited by ceftriaxone and imipenem at MICs of < or = 4.0 and < or = 1.0 micrograms/ml, respectively. The activities of levofloxacin and vancomycin were unaffected by penicillin susceptibility. Time-kill studies of three penicillin-susceptible, three penicillin-intermediate, and three penicillin-resistant pneumococci showed that all compounds, at the broth microdilution MIC, yielded 99.9% killing of all strains after 24 h. Kinetic patterns of all oral beta-lactams, ceftriaxone, and vancomycin were similar relative to the MIC, with 90% killing of all strains first observed after 12 h. However, killing by amoxicillin-clavulanate, imipenem, and levofloxacin was slightly faster and that by clarithromycin was slower than that by the above-described drugs. At 2 x the MIC, more strains were killed earlier than was the case at the MIC, but the pattern seen at the MIC prevailed. When MICs and kill kinetics were combined, sanfetrinem was the most active oral antipneumococcal agent in this study.

Comparative activities of LY 333328, a new glycopeptide, against penicillin-susceptible and -resistant pneumococci.

Microdilution MIC testing was used to test the susceptibility of 202 pneumococci to LY 333328 and six other agents. LY 333328 was the most active glycopeptide (MIC at which 90% of the pneumococci were inhibited [MIC90], 0.008 microgram/ml), followed by teicoplanin (MIC90, 0.06 microgram/ml) and vancomycin (MIC90, 0.5 microgram/ml). Rifampin resistance was seen in some penicillin-resistant strains. The MICs of imipenem and ceftriaxone rose with those of penicillin. Time-kill testing confirmed the excellent antipneumococcal activity of LY 333328.

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.

Activities of RPR 106972 (a new oral streptogramin), cefditoren (a new oral cephalosporin), two new oxazolidinones (U-100592 and U-100766), and other oral and parenteral agents against 203 penicillin-susceptible and -resistant pneumococci.

Agar dilution was used to determine the MICs of RPR 106972 (a new oral streptogramin), cefditoren (a new oral cephalosporin), two new oxazolidinones (U-100592 and U-100766), and other oral and parenteral agents for 203 penicillin-susceptible and -resistant pneumococci. All pneumococci were inhibited by RPR 106972 at < or = 0.5 microgram/ml. Cefditoren was very active against all pneumococcal groups, with MICs of < or = 2.0 micrograms/ml. Amoxicillin with or without clavulanate was the next most active oral beta-lactam, followed by cefdinir, cefuroxime, cefpodoxime, and cefprozil. U-100592 and U-100766 were very active against all classes of pneumococci, with all MICs < or = 1.0 microgram/ml.

Susceptibilities of 201 anaerobes to erythromycin, azithromycin, clarithromycin, and roxithromycin by oxyrase agar dilution and E test methodologies.

The susceptibility of 201 anaerobes to erythromycin, azithromycin, clarithromycin, and roxithromycin was tested by agar dilution and E test methods by using a commercially available plate and dish system (OxyDish) to provide anaerobic conditions. Plates were incubated for 48 h. MICs for 50% of strains tested and MICs for 90% of strains tested by agar dilution and E test methods corresponded within 1 doubling dilution for all compounds. When all antibiotics were considered together, agar and E test MICs were within 1 and 2 doubling dilutions of each other in 84 to 91% and > 99% of cases, respectively.

In vitro susceptibilities of 185 penicillin-susceptible and -resistant pneumococci to WY-49605 (SUN/SY 5555), a new oral penem, compared with those to penicillin G, amoxicillin, amoxicillin-clavulanate, cefixime, cefaclor, cefpodoxime, cefuroxime, and cefdinir.

In vitro susceptibility of 185 penicillin-susceptible and -resistant pneumococci to WY-49605, a new oral penem, was compared with susceptibility to penicillin G, amoxicillin with and without clavulanate, cefixime, cefaclor, cefpodoxime, cefuroxime, and cefdinir. WY-49605 yielded MICs for 50 and 90% of the strains tested (MIC50 and MIC90, respectively) of 0.03 and 0.06, 0.125 and 0.5, and 0.5 and 1.0 micrograms/ml, respectively, against penicillin-susceptible, intermediately resistant, and fully resistant strains, respectively. The MIC50 and MIC90 for both amoxicillin and amoxicillin-clavulanate were identical and approximately 1 doubling dilution higher than those for WY-49605 and were < or = 0.06 and 0.125, 0.25 and 1.0, and 1.0 and 1.0 micrograms/ml, respectively. Cephalosporin MIC90s were all significantly higher than those of the latter three compounds for intermediately resistant and fully resistant strains.

Activity of WY-49605 compared with those of amoxicillin, amoxicillin-clavulanate, imipenem, ciprofloxacin, cefaclor, cefpodoxime, cefuroxime, clindamycin, and metronidazole against 384 anaerobic bacteria.

The National Committee for Clinical Laboratory Standards agar dilution method was used to compare the in vitro activity of WY-49605 (also called SUN/SY 5555 and ALP-201), a new broad-spectrum oral penem, to those of amoxicillin, amoxicillin-clavulanate, imipenem, ciprofloxacin, cefaclor, cefpodoxime, cefuroxime, clindamycin, and metronidazole against 384 clinically isolated anaerobes. These anaerobic organisms included 90 strains from the Bacteroides fragilis group, 87 Prevotella and Porphyromonas strains, non-B. fragilis group Bacteroides strains, 56 fusobacteria, 55 peptostreptococci, 49 gram-positive non-spore-forming rods, and 47 clostridia. Overall, WY-49605 had an MIC range of 0.015 to 8.0 micrograms/ml, an MIC at which 50% of the isolates are inhibited (MIC50) of 0.25 microgram/ml, and an MIC at which 90% of the isolates are inhibited (MIC90) of 2.0 micrograms/ml. Good activity against all anaerobe groups was observed, except for Clostridium difficile and lactobacilli (MIC50s of 4.0 and 2.0 micrograms/ml, respectively, and MIC90s of 8.0 and 2.0 micrograms/ml, respectively). Imipenem had an MIC50 of 0.03 microgram/ml and an MIC90 of 0.25 microgram/ml. Ciprofloxacin was much less active (MIC50 of 2.0 micrograms/ml and MIC90 of 16.0 micrograms/ml). By comparison, all oral beta-lactams were less active than WY-49605, with susceptibilities as follows: amoxicillin MIC50 of 8.0 micrograms/ml and MIC90 of > 256.0 micrograms/ml), amoxicillin-clavulanate MIC50 of 1.0 microgram/ml and MIC90 of 8.0 micrograms/ml, cefaclor MIC50 of 8.0 micrograms/ml and MIC90 of > 32.0 micrograms/ml, cefpodoxime MIC50 of 4.0 micrograms/ml and MIC90 of > 32.0 micrograms/ml, and cefuroxime MIC50 of 4.0 micrograms/ml and MIC90 of > 32.0 micrograms/ml. Clindamycin was active against all groups except some members of the B. fragilis group, Fusobacterium varium, and some clostridia ( overall MIC50 of 0.5 micrograms/ml and overall MIC90 of 8.0 micrograms/ml). Metronidazole was active (MIC of less than or equal to 4.0 micrograms/ml) against all gram-negative anaerobic rods, but most gram-positive non-spore-forming rods, some peptostreptococci, and some clostridia were less susceptible. To date, WY-49605 is the most active oral beta-lactam against anaerobes: these results suggest clinical evaluation for clinical indications suitable for oral therapy.

Activity of CP 99,219 compared with those of ciprofloxacin, grepafloxacin, metronidazole, cefoxitin, piperacillin, and piperacillin-tazobactam against 489 anaerobes.

Agar dilution was used to compare the in vitro activity of CP 99,219 with those of ciprofloxacin, grepafloxacin, metronidazole, cefoxitin, piperacillin, and piperacillin-tazobactam against 489 anaerobes. CP 99,219 yielded a MIC for 50% of the strains tested (MIC50) of 0.25 micrograms/ml and a MIC90 of 1.0 microgram/ml, with 99.6% of the strains susceptible at a breakpoint of 2.0 micrograms/ml. Ciprofloxacin and grepafloxacin were less active (MIC50, 4.0 micrograms/ml; MIC90, 32.0 micrograms/ml and 2.0 and 16.0 micrograms/ml, respectively). Metronidazole was active against all gram-negative rods (MIC90, 4.0 micrograms/ml), but 31% of the gram-positive anaerobes were resistant at > 8.0 micrograms/ml. Cefoxitin was active against 84% of all strains at < or = 16.0 micrograms/ml, with a MIC50 of 4.0 micrograms/ml and a MIC90 of 32.0 micrograms/ml. Tazobactam enhanced the activity of piperacillin against > 95% of the beta-lactamase-producing gram-negative anaerobic rods (MIC90, 16.0 micrograms/ml).

Susceptibilities of 177 penicillin-susceptible and -resistant pneumococci to FK 037, cefpirome, cefepime, ceftriaxone, cefotaxime, ceftazidime, imipenem, biapenem, meropenem, and vancomycin.

MICs of six extended-spectrum cephalosporins (cefotaxime, ceftriaxone, ceftazidime, FK 037, cefpirome, cefepime), three carbapenems (imipenem, meropenem, biapenem), and vancomycin for 49 penicillin-susceptible (S), 77 penicillin intermediate-resistant (I), and 51 penicillin-resistant (R) pneumococci were determined by agar dilution. Compared with ceftazidime (MICs for 90% of strains tested [MIC90s] of 2.0, 16.0, and 16.0 micrograms/ml for S, I, and R strains, respectively), all other cephalosporins yielded lower MICs (MIC90s of 0.06 to 0.125, 0.5 to 1.0, and 1.0 to 2.0 micrograms/ml against S, I, and R strains, respectively). All three carbapenems were very active, with MIC90s, even for R strains, of < or = 1.0 micrograms/ml. All strains were susceptible to vancomycin (MIC90 of 0.5 micrograms/ml).

Effect of CO2 on susceptibilities of anaerobes to erythromycin, azithromycin, clarithromycin, and roxithromycin.

The Oxyrase agar dilution method (Oxyrase, Inc., Mansfield, Ohio), which provides an anaerobic environment without added CO2, was compared with the reference agar dilution method recommended by the National Committee for Clinical Laboratory Standards (anaerobic chamber with 10% CO2) to test the susceptibilities of 302 gram-negative and gram-positive anaerobes to erythromycin, azithromycin, clarithromycin, and roxithromycin. For erythromycin, the overall MIC for 50% of isolates tested (MIC50) was 0.5 micrograms/ml and the MIC90 was 8.0 micrograms/ml by the Oxyrase method, whereas they were 4.0 and 64.0 micrograms/ml, respectively, under standard anaerobic conditions with CO2. At a breakpoint of 4.0 micrograms/ml, 88% of strains were susceptible to erythromycin by the Oxyrase method, whereas 63% were susceptible in the chamber. The corresponding MIC50s and MIC90s of azithromycin, clarithromycin, and roxithromycin by the Oxyrase method were 0.5 and 8.0, 0.25 and 4.0, and 0.5 and 16.0 micrograms/ml, respectively, whereas in the chamber they were 4.0 and > 64.0, 2.0 and 64.0, and 2.0 and 64.0 micrograms/ml, respectively. At a breakpoint of 8.0 micrograms/ml for these three drugs, 89, 92, and 85% of the isolates, respectively, were susceptible by the Oxyrase method, whereas 67%, 72, and 68% of the isolates, respectively, were susceptible in the chamber. Most strains resistant to all four compounds by both methods were Bacteroides distasonis, Fusobacterium mortiferum, Fusobacterium varium and non-Clostridium perfringens Clostridium species. Results of the study may lead to a reappraisal of the role played by macrolides and azalides in the treatment of anaerobic infections.