Effect of clavulanic acid on the activities of ten beta-lactam agents against members of the Bacteroides fragilis group.

Clavulanic acid reduced the MICs of amoxicillin, carbencillin , cefamandole, cefotaxime, ceftazidime, ceftizoxime, cephalothin, and penicillin G, but not of cefoxitin or moxalactam, against 77 isolates of the Bacteroides fragilis group, all rapidly beta-lactamase positive by the nitrocefin slide test. It had no effect on the susceptibilities of eight Bacteroides distasonis strains that were slowly beta-lactamase positive (18 h of incubation).     

Role of the beta-lactamase of Campylobacter jejuni in resistance to beta-lactam agents.

We studied the role of the beta-lactamase of Campylobacter jejuni in resistance to beta-lactam agents. beta-Lactamase-positive strains were more resistant than beta-lactamase-negative strains to amoxicillin, ampicillin, and ticarcillin (P less than 0.05). With penicillin G, piperacillin, imipenem, and six cephalosporins, the susceptibility levels were similar for both beta-lactamase-positive and -negative strains. By using spectrophotometric and microbiological assays, the beta-lactamase from three strains hydrolyzed ampicillin, amoxicillin, penicillin G, cloxacillin, and, partially, cephalothin. Ticarcillin and piperacillin were partially hydrolyzed in the microbiological assay. There was no activity against five other cephalosporins or imipenem. Isoelectric focusing of the enzyme showed a pI of 8.8. Tazobactam was the best inhibitor of the enzyme, followed by clavulanic acid, sulbactam, and cefoxitin, while EDTA and p-chloromercuribenzoate had no activity. All beta-lactamase-positive strains became susceptible to amoxicillin and ampicillin with 1 micrograms of clavulanic acid per ml. With the same inhibitor, there was a reduced but significant effect for ticarcillin but no effect for penicillin G or piperacillin. Sulbactam had no effect and tazobactam was effective only at 2 micrograms/ml on amoxicillin and ampicillin. The beta-lactamase of C. jejuni seems to be a penicillinase with a role in resistance for only amoxicillin, ampicillin, and ticarcillin.     

Susceptibilities of beta-lactamase-positive and -negative strains of Campylobacter coli to beta-lactam agents.

The percentages of susceptibility of 28 strains of Campylobacter coli to beta-lactam agents were 96% for amoxicillin and ampicillin, 57% for ticarcillin, 4% for cefoxitin and cefuroxime, 61% for cefotaxime, and 11% for ceftazidime. None of the strains were susceptible to penicillin G, piperacillin, cefazolin, cephalothin, cefamandole, and cefoperazone. All strains were susceptible to imipenem and ciprofloxacin, and 21% were susceptible to erythromycin. A beta-lactamase was detected in 68% of the strains by cefinase disks and by the nitrocefin method. The beta-lactamase-positive strains were significantly less susceptible to amoxicillin, ampicillin, and ticarcillin than the beta-lactamase-negative strains (P < or = 0.003). Clavulanic acid (0.25 microgram/ml) but not sulbactam and tazobactam (2 micrograms/ml) lowered to susceptible levels the amoxicillin and ampicillin MICs of the only strain of C. coli resistant to amoxicillin, ampicillin, and ticarcillin.     

Inactivation of cefoxitin and moxalactam by Bacteroides bivius beta-lactamase.

Moxalactam and cefoxitin are known for their high stability against Bacteroides beta-lactamases. We investigated the beta-lactamase activity of crude extracts obtained from three strains of Bacteroides bivius and two strains of Bacteroides fragilis against cefoxitin and moxalactam. In a spectrophotometric antibiotic assay with a 24-h incubation period, B. bivius extracts decreased the initial concentration (10 micrograms/ml) of moxalactam and cefoxitin by 60%, whereas B. fragilis extracts had no effect. In a microbiological assay, when B. bivius or B. fragilis extracts were added to cephalothin (10 micrograms/ml) or cefamandole (4 micrograms/ml), we observed complete disappearance of the inhibitory zones against the indicator strain (Clostridium perfringens ATCC 13124). Only the B. bivius extracts were able to decrease the inhibitory activity (from 10 to 100%) of cefoxitin and moxalactam (each at 10 micrograms/ml). Prior addition of clavulanic acid to crude extracts prevented the losses of antibacterial activity. Furthermore, the inhibition of the beta-lactamase hydrolysis of nitrocefin by cefoxitin or moxalactam was prevented by a 12-h preincubation of the beta-lactam with the B. bivius extracts but not with the B. fragilis extracts. Finally, with the B. bivius strain producing the most beta-lactamase, we showed an effect of inoculum size on the MICs of cefoperazone, cefoxitin, and moxalactam with a broth dilution technique. Increasing the inoculum size with the B. fragilis strains had no effect on the MISs of cefoxitin and moxalactam. These results indicate a slow and clavulanate-sensitive beta-lactamase activity of B. bivius extracts against cefoxitin and moxalactam.     

Effect of clavulanic acid on susceptibility of Campylobacter jejuni and Campylobacter coli to eight beta-lactam antibiotics.

The effect of clavulanic acid on the susceptibility of 32 strains of Campylobacter jejuni and Campylobacter coli to eight beta-lactam agents was studied. Almost all strains tested became susceptible to amoxicillin and ticarcillin with 1 microgram of clavulanic acid per ml. This compound had little or no effect on susceptibility to penicillin G, cephalothin, cefamandole, and cefoxitin. Clavulanic acid had a marginal effect on cefotaxime and moxalactam susceptibility.     

In-vitro activity of amoxycillin and ticarcillin in combination with clavulanic acid compared with that of new beta-lactam agents against species of the Bacteroides fragilis group

One hundred and one isolates representing five species of the Bacteroides fragilis group were examined for their susceptibility to amoxycillin and ticarcillin alone or in combination with clavulanic acid, as well as to cefoxitin, latamoxef (moxalactam), ceftizoxime, imipenem, chloramphenicol, clindamycin and metronidazole by the proposed NCCLS agar dilution method. Bactericidal activity of amoxycillin, ticarcillin, combinations of amoxycillin-clavulanic acid and ticarcillin-clavulanic acid, cefoxitin and latamoxef against 54 strains was further assessed by a dilution test in broth. The most active agents were imipenem and the combinations of amoxycillin-clavulanic acid and ticarcillin-clavulanic acid. MIC results indicated that Bacteroides fragilis and B. vulgatus were more susceptible to beta-lactams than were B. distasonis, B. ovatus and B. thetaiotaomicron. Clavulanic acid greatly potentiated the activity of amoxycillin and ticarcillin against the 94 beta-lactamase positive strains but had no effect on the seven B. distasonis isolates that were beta-lactamase negative. Synergistic bactericidal activities could be observed by the amoxycillin-clavulanic and ticarcillin-clavulanic combinations.     

Cephalosporin-resistance in the Bacteroides fragilis group and the effect of clavulanic acid

Thirty-five beta-lactam-resistant isolates of the Bacteroides fragilis group were examined for the susceptibility to eight cephalosporins, alone, and in combination with a subinhibitory concentration of the beta-lactamase inhibitor, clavulanic acid. The majority of strains tested became fully susceptible to cephaloridine, cefotaxime and ceftriaxone in the presence of clavulinic acid whereas the effect of the inhibitor on the susceptibility to compounds such as cefsulodin and ceftazidime and to a lesser extent cefoperazone varied according to species. Bact. fragilis strains almost invariably showed substantial reductions in MICs whereas those of other species, especially Bact. thetaiotaomicron, were influenced to a lesser extent. Susceptibility to cefoxitin was unaffected by the inhibitor but a few strains with high level resistance to latamoxef (moxalactam) became susceptible in the presence of clavulanic acid. All strains were found to produce beta-lactamase as determined by the nitrocefin test and these were characterized by isoelectric focusing.     

Beta-lactamase production and susceptibilities to amoxicillin, amoxicillin-clavulanate, ticarcillin, ticarcillin-clavulanate, cefoxitin, imipenem, and metronidazole of 320 non-Bacteroides fragilis Bacteroides isolates and 129 fusobacteria from 28 U.S. centers.

beta-Lactamase production (nitrocefin disk method) and agar dilution susceptibility of amoxicillin, amoxicillin-clavulanate, ticarcillin, ticarcillin-clavulanate, cefoxitin, imipenem, and metronidazole were determined for 320 Bacteroides species (not Bacteroides fragilis group) and 129 fusobacteria from 28 U.S. centers. Overall, 64.7% of Bacteroides species and 41.1% of fusobacteria were beta-lactamase positive. Among the Bacteroides species, positivity rates were highest for B. bivius (85.0%), followed by B. splanchnicus (83.3%), B. eggerthii (77.8%), and B. oralis (77.1%); 54.5% of black-pigmented Bacteroides species were beta-lactamase positive. Among the fusobacteria, Fusobacterium mortiferum showed the highest rate of beta-lactamase positivity (76.9%). MICs of amoxicillin (128 micrograms/ml) and ticarcillin (64 micrograms/ml) for 90% of all beta-lactamase-positive strains were reduced to 4 and 2 micrograms/ml, respectively, with the addition of clavulanate. MICs of amoxicillin and ticarcillin for 90% of all beta-lactamase-negative strains were 1 and 4 micrograms/ml, respectively, and greater than or equal to 98.4% of the strains were susceptible to the beta-lactams tested. Of the beta-lactamase-producing strains, 45.9% were susceptible to amoxicillin at less than or equal to 4 micrograms/ml and 93.4% were susceptible to ticarcillin at less than or equal to 64 micrograms/ml; the addition of clavulanate raised the rates to 90.4 and 100%, respectively. All strains were susceptible to cefoxitin, imipenem, and metronidazole. The activity of amoxicillin against 29 beta-lactamase-producing strains (10 Bacteroides species and 19 fusobacteria) was not enhanced by the addition of clavulanate; however, 82.7% of these strains were susceptible to amoxicillin, and all were susceptible to ticarcillin. Although beta-lactamase positivity is on the increase in non-B. fragilis group Bacteroides species and fusobacteria, amoxicillin-clavulanate, ticarcillin, cefoxitin, imipenem, and metronidazole should be suitable for the treatment of infections with these strains. The addition of clavulanate does not appreciably improve the efficacy of ticarcillin against these organisms.     

Increase in the activity of third-generation cephalosporins in combination with clavulanic acid and Sulbactam against Bacteroides fragilis

We studied the sensitivity of 160 strains of Bacteroides fragilis (74 beta-lactamase-positive and 86 beta-lactamase-negative) to four third-generation cephalosporins, alone as well as in combination with clavulanic acid and Sulbactam. For susceptibility testing we used a dilution method in agar. Detection of beta-lactamase production by this micro-organism was performed using chromogenic cephalosporin (Nitrocefin). There was a substantial improvement in cephalosporin activity with both positive and negative strains when they were combined with the inhibitors, although this was more significant in beta-lactamase-producing organisms. Generally, the results achieved in combination with clavulanic acid were better than those with Sulbactam, the highest increase in activity being obtained with Ceftizoxime in combination with any one of the inhibitors.     

National Committee for Clinical Laboratory Standards agar dilution susceptibility testing of anaerobic gram-negative bacteria.

One hundred nine recent clinical isolates of anaerobic gram-negative bacteria were tested in triplicate by the National Committee for Clinical Laboratory Standards agar dilution procedure for their susceptibility to 32 antimicrobial agents. All isolates were inhibited by imipenem, but there were significant numbers of strains resistant to other beta-lactam drugs, and therefore the in vitro response to these antimicrobial agents cannot be predicted. This was particularly true for the bile-resistant or Bacteroides fragilis group. beta-Lactamase production was detected in 82% of the bacteroides with the nitrocefin test. Clavulanic acid combined with amoxicillin and ticarcillin and sulbactam combined with ampicillin resulted in synergistic activity against all beta-lactamase-positive organisms. Ceftizoxime was the most active of the cephalosporins. Two percent of the isolates were resistant to chloramphenicol and metronidazole. Clindamycin resistance was detected in 38% of the B. fragilis group, which is a marked increase from the 4% detected 10 years ago at this institution.     

Susceptibility of Haemophilus influenzae to amoxicillin/clavulanic acid, erythromycin, cefaclor, and trimethoprim/sulfamethoxazole

A total of 126 strains of Haemophilus influenzae were examined for susceptibility to amoxicillin/clavulanic acid, trimethoprim/sulfamethoxazole, cefaclor, and erythromycin by an agar dilution procedure. Fifty strains (eight type B, 42 non-type B), all with ampicillin minimal inhibitory concentrations (MIC) of greater than or equal to 6.2 micrograms/ml, produced beta-lactamase. The remaining 76 strains (18 type B, 59 non-type B) were beta-lactamase-negative. All of these strains had ampicillin MICs of less than or equal to 0.8 micrograms/ml. The combination of amoxicillin and clavulanic acid (2:1) was highly active against all strains tested. With the exception of two strains with amoxicillin/clavulanic acid MICs of 1.6/0.8 ug/ml, all strains were inhibited by concentrations of less than or equal to 0.8/0.4 ug/ml. Trimethoprim/sulfamethoxazole was also found to be highly active (MICs uniformly less than or equal to 0.1/1.9 ug/ml). Cefaclor and erythromycin were the least active of the agents tested. Fourteen strains (10.6%) had cefaclor MICs of greater than 32 ug/ml. Forty-seven strains (35.6%) had erythromycin MICs of greater than 8 micrograms/ml. With the exception of amoxicillin/clavulanic acid beta-lactamase production did not seem to influence the activity of any of the antimicrobials tested. Minimum inhibitory concentrations of amoxicillin/clavulanic acid, although still well within achievable serum levels, were approximately one twofold dilution higher with beta-lactamase-producing H. influenzae type B strains than with beta-lactamase-negative strains.     

In vitro susceptibility of Mycobacterium fortuitum to amoxicillin or cephalothin in combination with clavulanic acid

The comparative in vitro activity of cefoxitin, cephalothin, amoxicillin, and clavulanic acid in combination with the latter two agents against 13 isolates of Mycobacterium fortuitum was evaluated by agar dilution susceptibility testing. Amoxicillin was more active than cephalothin but less active than cefoxitin against the strains tested. Clavulanic acid in combination with these beta-lactams usually improved the activity by one or two dilutions compared with the beta-lactams alone.     

Susceptibility of multiply resistant Haemophilus influenzae to newer antimicrobial agents

One hundred and six isolates of Haemophilus influenzae from a national antimicrobial surveillance study demonstrated resistance to two or more of 10 primary antimicrobial agents by mechanisms other than or in addition to beta-lactamase. Of particular note were strains multiply resistant to ampicillin (by beta-lactamase production), chloramphenicol, trimethoprim/sulfamethoxazole, and tetracycline in various combinations. All of the aforementioned strains were shown to be highly susceptible to amoxicillin/clavulanate, the second generation cephalosporins cefuroxime and cefonicid, and the third generation cephalosporins cefotaxime, ceftizoxime, ceftriaxone, ceftazidime, moxalactam, and cefixime. However, 68 strains that demonstrated resistance or marginal susceptibility (MIC greater than or equal to 2 micrograms/ml) to ampicillin by mechanisms other than beta-lactamase, also demonstrated reduced susceptibility to amoxicillin/clavulanate (MICs up to 8 micrograms/ml) and the second generation cephalosporins (MICs up to 32 micrograms/ml). While the latter strains were susceptible to the third generation cephalosporins, MICs were often 10-fold higher than MICs of ampicillin susceptible isolates or of beta-lactamase producing isolates. All of the multiply antimicrobial-resistant strains were highly susceptible (MIC less than or equal to 0.25 micrograms/ml) to the two quinolones ciprofloxacin and pefloxacin.     

Activity of cefoperazone and two beta-lactamase inhibitors, sulbactam and clavulanic acid, against Bacteroides spp. correlated with beta-lactamase production.

A total of 102 isolates of Bacteroides spp. were studied for beta-lactamase production and susceptibility to cefoperazone alone or in combination with either of the beta-lactamase inhibitors sulbactam and clavulanic acid. The geometric mean minimal inhibitory concentration of cefoperazone alone was 31.5 micrograms/ml and when combined with 10 micrograms of sulbactam per ml or 2 micrograms of clavulanic acid per ml was reduced to 5.4 and 9.2 micrograms/ml, respectively. When bacterial suspensions were tested for beta-lactamase production with nitrocefin, 91 (89.2%) of these isolates produced the enzyme. The geometric mean minimal inhibitory concentrations of cefoperazone rose only slightly for isolates with low or intermediate enzyme activity but rose significantly for those with high activity. The addition of EDTA to cefoperazone significantly more frequently enhanced the activity of cefoperazone against beta-lactamase-negative as opposed to beta-lactamase-positive isolates. Furthermore, EDTA resulted in synergistic activity of the cefoperazone-sulbactam combination on beta-lactamase-positive isolates for which the combination had previously not shown a synergistic effect. This study demonstrates the relationship between beta-lactamase production and the resistance of Bacteroides spp. to cefoperazone and shows that inhibition of these enzymes can reverse this resistance.     

Inhibition of β-Lactamase in Neisseria gonorrhoeae by Sodium Clavulanate

Sodium clavulanate at subinhibitory concentrations affected the activity of penicillin G, ampicillin, or amoxicillin on beta-lactamase-positive strains of Neisseria gonorrhoeae as demonstrated by marked reduction in the minimal inhibitory concentrations of the drugs for the organisms. The compound did not affect the activity of these penicillins on beta-lactamase-negative strains of N. gonorrhoeae. It also had no effect on the activity of cefoxitin against either beta-lactamase-negative or -positive strains. The reduction in minimal inhibitory concentrations of the penicillins for the beta-lactamase-positive organisms brought about by sodium clavulanate is probably due to inhibition of the beta-lactamase by the compound.     

Comparison of the inoculum effects of members of the family Enterobacteriaceae on cefoxitin and other cephalosporins, beta-lactamase inhibitor combinations, and the penicillin-derived components of these combinations.

We compared the inoculum effects of 105 recent clinical isolates of the family Enterobacteriaceae on cefoxitin, other cephalosporins, aztreonam, and three beta-lactamase inhibitors (clavulanic acid, sulbactam, and tazobactam) and their penicillin-derived components. Piperacillin and aztreonam showed the largest inoculum effect, and cefoxitin showed the smallest. The other cephalosporins tested (cefotetan, ceftizoxime, and ceftriaxone) showed an intermediate inoculum effect. In general, the inoculum effect was of greater magnitude for the penicillin and beta-lactamase inhibitor combinations than for the cephalosporins tested. Bactericidal activity was assayed and morphologic changes were monitored for selected strains exhibiting a large inoculum effect. MICs correlated with bactericidal activity at an inoculum level of 10(5) CFU/ml, while activity at 10(8) CFU/ml was variable. Cefoxitin demonstrated the least filamentous transformation and the most rapid bactericidal activity. Aztreonam showed the most marked filamentous transformation and was no longer bactericidal at 10(8) CFU/ml. The beta-lactamase inhibitor combinations showed variable bactericidal activity, and regrowth occurred with a number of strains with all three agents tested.     

Influence of the beta-lactam resistance phenotype on the cefuroxime versus cefditoren susceptibility of Streptococcus pneumoniae and Haemophilus influenzae recovered from children with acute otitis media

OBJECTIVES: To study the influence of resistance phenotypes (based on sentinel antibiotics: penicillin and amoxicillin with/without clavulanate) on the cefuroxime versus cefditoren susceptibility of Streptococcus pneumoniae and Haemophilus influenzae recovered from children with acute otitis media. METHODS: Middle ear isolates (193 S. pneumoniae and 114 H. influenzae) received in the Spanish Reference Laboratory (Instituto de Salud Carlos III) were tested. Antimicrobial susceptibility to penicillin, amoxicillin with/without clavulanate, cefuroxime and cefditoren was determined by agar dilution using Mueller-Hinton agar supplemented with 5% sheep blood for S. pneumoniae and Haemophilus Test Medium for H. influenzae. Strains were classified according to penicillin susceptibility (S. pneumoniae) or beta-lactamase production (H. influenzae). RESULTS: The decrease in penicillin susceptibility of S. pneumoniae (from the susceptible to the resistant category) decreased amoxicillin and cefuroxime susceptibility rates from 100% to 34% and 0%, respectively. All pneumococcal strains were inhibited by 0.5 mg/L cefditoren, including those from penicillin-resistant serotypes 14, 23F, 6B and 9V with higher amoxicillin versus penicillin MICs. Susceptibility rates of beta-lactamase-positive H. influenzae strains were 93.8% and 85.4% to amoxicillin/clavulanate and cefuroxime, respectively. Resistance to amoxicillin/clavulanate (MIC>or=8/4 mg/L) was 12.1% (8 out of 66) and 6.3% (3 out of 48) in beta-lactamase-negative and -positive strains, respectively. All H. influenzae strains were inhibited by 相似文献   

Susceptibilities of 394 Bacteroides fragilis, non-B. fragilis group Bacteroides species, and Fusobacterium species to newer antimicrobial agents.

The susceptibilities of 374 selected beta-lactamase-producing gram-negative anaerobes (including 22 cefoxitin-resistant strains and 36 strains refractory to the enhancing effect of beta-lactamase inhibitors) and 20 beta-lactamase-negative strains were tested by agar dilution against selected new agents. The organisms included 217 Bacteroides fragilis group strains, 137 non-B. fragilis group Bacteroides spp., and 40 fusobacteria. All strains were susceptible to piperacillin-tazobactam, imipenem, and meropenem. For the B. fragilis group, 96% were susceptible to ampicillin-sulbactam, 95% were susceptible to amoxicillin-clavulanate and cefoperazone-sulbactam, 94% were susceptible to tosufloxacin, 91% were susceptible to cefoxitin, 88% were susceptible to trospectomycin, and 73% were susceptible to cefotetan. For the beta-lactamase-positive non-B. fragilis group Bacteroides spp., greater than or equal to 94% were susceptible to cefoxitin, amoxicillin-clavulanate, ampicillin-sulbactam, cefoperazone-sulbactam, and trospectomycin, 90% were susceptible to cefotetan, and 85% were susceptible to tosufloxacin (the most resistant strains were B. bivius and B. disiens). For the beta-lactamase-positive fusobacteria, greater than or equal to 97% were susceptible to amoxicillin-clavulanate, ampicillin-sulbactam, cefoperazone-sulbactam, trospectomycin, and cefoxitin, 90% were susceptible to cefotetan, and 89% were susceptible to tosufloxacin. All agents showed excellent activity against beta-lactamase-negative strains (for trospectomycin, 95% were susceptible; for all other drugs, 100% were susceptible). Overall, both carbapenems and piperacillin-tazobactam were most active. Amoxicillin-clavulanate, ampicillin-sulbactam, and cefoperazone-sulbactam lacked activity against some cefoxitin-resistant B. fragilis group strains but had excellent activity against other organisms. Tosufloxacin, a new quinolone, had very good activity against B. fragilis group strains (94% susceptible), good activity against other beta-lactamase-positive strains (less than or equal 85% susceptible), and excellent activity against beta-lactamase-negative strains (100% susceptible; MIC for 90% of strains, 0.5 microgram/ml). Trospectomycin was active against >90% of all strains except for B. fragilis group strains (88% susceptible; MIC for 90% of strains, 32 microgram/ml). Clinical studies are required to delineate the role of newer agents in the therapy of anaerobic infections.     

Antibiotic Susceptibility of Neisseria gonorrhoeae Strains from Europe and Africa

The in vitro activities of 16 antimicrobial agents were tested by a plate dilution method against 268 unselected isolates of Neisseria gonorrhoeae from Belgium, Rwanda, Swaziland, and Zaire. Fifteen beta-lactamase-producing strains isolated in Europe from various origins were also tested. There were significant regional variations in antimicrobial agent susceptibility, even among the African isolates, with the Rwandan and Zairean strains being most resistant. Benzylpenicillin and ampicillin were equally active in all but the beta-lactamase-producing strains. Among the cephalosporins, cefotaxime was by far the most active, followed by cefuroxime, cefamandole, cefoxitin, and cefaclor, in that order. All strains were susceptible to spectinomycin, thiamphenicol, kanamycin, and rifampin, with the exception of one highly rifampin-resistant isolate and a moderately thiamphenicol-resistant strain. Twenty-six percent of the isolates were highly resistant to streptomycin. Six percent of the gonococci had a minimal inhibitory concentration for tetracycline greater than 2 mug/ml. Clavulanic acid inhibited the beta-lactamase activity of the gonococci tested and improved markedly the activities of ampicillin and amoxicillin against beta-lactamase-producing strains.     

Comparative in vitro activity of cefodizime, ceftazidime, aztreonam, and other selected antimicrobial agents against Neisseria gonorrhoeae.

The in vitro activities of three new beta-lactam antimicrobial agents, cefodizime, ceftazidime, and aztreonam (formerly azthreonam), were compared with those of cefotaxime, cefuroxime, cefoxitin, and penicillin against 100 beta-lactamase-negative and 42 beta-lactamase-positive Neisseria gonorrhoeae strains. The three new antimicrobial agents showed excellent activity against N. gonorrhoeae regardless of beta-lactamase production. Cefodizime was as active as cefotaxime and more active than the other test antimicrobial agents. It inhibited all isolates at a concentration of less than or equal to 0.016 micrograms/ml.