Susceptibility to cephalosporins of penicillin-susceptible and penicillin-resistant strains of Neisseria gonorrhoeae from Philadelphia.

Using agar dilution, we determined MICs of penicillin, cefoxitin, ceftriaxone, cefmetazole, tetracycline, and spectinomycin for 129 strains of Neisseria gonorrhoeae. All strains were susceptible to ceftriaxone (MIC range, less than or equal to 0.008 to 0.06 micrograms/ml) and spectinomycin (16 to 32 micrograms/ml). The MICs for 50, 90, and 100% of strains tested were 1.0, 2.0, and greater than 8.0 micrograms/ml; 0.12, 1.0, and greater than 8.0 micrograms/ml; 0.5, 1.0, and 2.0 micrograms/ml; and 1.0, 2.0, and greater than 8.0 micrograms/ml for cefmetazole, penicillin, cefoxitin, and tetracycline, respectively. Seven strains were beta-lactamase producers; eight were chromosomally resistant to penicillin. There was a log-linear relation for non-beta-lactamase-producing strains between the MICs of cefmetazole, cefoxitin, and tetracycline and the MIC of penicillin (Pearson r = 0.787, 0.544, and 0.358, respectively).     

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.     

Role of beta-lactamase and different testing conditions in oxacillin-borderline-susceptible staphylococci.

A group of staphylococcal isolates for which oxacillin MICs were intermediate (1 to 4 micrograms/ml) were studied to establish the role of beta-lactamase in this phenomenon. MICs and MBCs of oxacillin and penicillin with and without clavulanic acid or sulbactam (4 or 16 micrograms/ml, respectively) were determined for 11 Staphylococcus aureus and 2 coagulase-negative Staphylococcus isolates for which oxacillin MICs were 1 to 4 micrograms/ml. The susceptibility studies were done with incubation at 35 and 30 degrees C, and the MICs were read at 24 and 48 h. Of the 13 isolates, 4 became resistant when longer incubation or 30 degrees C incubation was used, and the MICs for 9 remained in the intermediate range. Only three of these strains were susceptible to penicillin, and beta-lactamase was not detected. For 6 of 10 beta-lactamase-positive strains, there was a greater-than-twofold-dilution reduction in oxacillin MICs with the addition of clavulanic acid or sulbactam. Of the four strains that became resistant with incubation at the lower temperature, a clavulanic acid effect was observed in three but only at 35 degrees C. The oxacillin MIC for one of the beta-lactamase-negative strains was also reduced with clavulanic acid; however, this strain was inhibited by 1 microgram of clavulanic acid per ml alone. Bactericidal activity was observed with two or four times the oxacillin MIC in eight strains tested at both temperatures, and the combination with clavulanic acid was bactericidal at higher than four times the MIC in five of the strains at 30 degrees C. Our results suggest that oxacillin intermediate MICs for staphylococcal isolates are due not only to beta-lactamase hyperproduction but also some other unidentified factor. The reduction in oxacillin MIC observed when clavulanic acid was added to one strain was probably due to the intrinsic inhibitory activity of clavulanic acid.     

Antimicrobial susceptibilities of Neisseria gonorrhoeae strains representing five distinct resistance phenotypes.

The susceptibilities of 109 strains of Neisseria gonorrhoeae to penicillin G, tetracycline, amoxicillin-clavulanic acid, cefotetan, cefoxitin, ceftriaxone, ciprofloxacin, and fleroxacin were determined. The activities of cefmetazole, cefuroxime, cefixime, and ofloxacin were also determined against 62 of these strains. Strains represented penicillin-susceptible (Pen(s)) N. gonorrhoeae; penicillinase-producing N. gonorrhoeae (PPNG) possessing 2.9-, 3.05-, 3.2-, or 4.4-MDa beta-lactamase plasmids; strains with high-level, plasmid-mediated tetracycline resistance (TRNG); strains with plasmid-mediated resistance to penicillin and tetracycline; and strains with chromosomally mediated resistance to penicillin and tetracycline (CMRNG). Ceftriaxone, cefixime, and ciprofloxacin were the most active agents tested against all strains. Pen(s), TRNG, and PPNG strains possessing a 3.2-MDa beta-lactamase plasmid were more susceptible to amoxicillin-clavulanic acid, extended- and broad-spectrum cephalosporins, and quinolones than were either PPNG strains possessing a 2.9-, a 3.05-, or a 4.4-MDa beta-lactamase plasmid or CMRNG strains.     

National collaborative study of the prevalence of antimicrobial resistance among clinical isolates of Haemophilus influenzae.

A total of 2,811 clinical isolates of Haemophilus influenzae were obtained during 1986 from 30 medical centers and one nationwide private independent laboratory in the United States. Among these, 757 (26.9%) were type b strains. The overall rate of beta-lactamase-mediated ampicillin resistance was 20.0%. Type b strains were approximately twice as likely as non-type b strains to produce beta-lactamase (31.7 versus 15.6%). The MICs of 12 antimicrobial agents were determined for all isolates. Ampicillin resistance among strains that lacked beta-lactamase activity was extremely uncommon (0.1%). Percentages of study isolates susceptible to cefamandole, cefaclor, cephalothin, and cephalexin were 98.7, 94.5, 87.3, and 43.3%, respectively. For 14 strains (0.5% of the total), chloramphenicol MICs were greater than or equal to 8.0 micrograms, and thus the strains were considered resistant. All of these resistant strains produced chloramphenicol acetyltransferase. In addition, all 14 strains were resistant to tetracycline; 11 produced beta-lactamase. The percentage of isolates susceptible to tetracycline was 97.7%. In contrast, erythromycin and sulfisoxazole were relatively inactive. The combination of erythromycin-sulfisoxazole (1/64) was more active than erythromycin alone but essentially equivalent in activity to sulfisoxazole alone. Finally, small numbers of clinical isolates of H. influenzae were resistant to trimethoprim-sulfamethoxazole and rifampin.     

influence of TEM-1 beta-lactamase on the pharmacodynamic activity of simulated total versus free-drug serum concentrations of cefditoren (400 milligrams) versus amoxicillin-clavulanic acid (2,000/125 milligrams) against Haemophilus influenzae strains exhibiting an N526K mutation in the ftsI gene

The aim of this study was to explore bactericidal activity of total and free serum simulated concentrations after the oral administration of cefditoren (400 mg, twice daily [bid]) versus the oral administration of amoxicillin-clavulanic acid extended release formulation (2,000/125 mg bid) against Haemophilus influenzae. A computerized pharmacodynamic simulation was performed, and colony counts and beta-lactamase activity were determined over 48 h. Three strains were used: ampicillin-susceptible, beta-lactamase-negative ampicillin-resistant (BLNAR) (also resistant to amoxicillin-clavulanic acid) and beta-lactamase-positive amoxicillin-clavulanic acid-resistant (BLPACR) strains, with cefditoren MICs of < or =0.12 microg/ml and amoxicillin-clavulanic acid MICs of 2, 8, and 8 microg/ml, respectively. Against the ampicillin-susceptible and BLNAR strains, bactericidal activity (> or =3 log(10) reduction) was obtained from 6 h on with either total and free cefditoren or amoxicillin-clavulanic acid. Against the BLPACR strain, free cefditoren showed bactericidal activity from 8 h on. In amoxicillin-clavulanic acid simulations the increase in colony counts from 4 h on occurred in parallel with the increase in beta-lactamase activity for the BLPACR strain. Since both BLNAR and BLPACR strains exhibited the same MIC, this was due to the significantly lower (P < or = 0.012) amoxicillin concentrations from 4 h on in simulations with beta-lactamase positive versus negative strains, thus decreasing the time above MIC (T>MIC). From a pharmacodynamic point of view, the theoretical amoxicillin T>MIC against strains with elevated ampicillin/amoxicillin-clavulanic acid MICs should be considered with caution since the presence of beta-lactamase inactivates the antibiotic, thus rendering inaccurate theoretical calculations. The experimental bactericidal activity of cefditoren is maintained over the dosing interval regardless of the presence of a mutation in the ftsI gene or beta-lactamase production.     

Neisseria gonorrhoeae strains isolated in Hong Kong: in vitro susceptibility to 13 antibiotics.

Fifty-five Neisseria gonorrhoeae strains isolated in Hong Kong over a period of 6 months were tested for their in vitro susceptibility to 13 antimicrobial agents by the agar dilution method. Six strains were beta-lactamase producing. In addition, five beta-lactamase strains from Singapore were tested. Among the non-beta-lactamase-producing strains, 34 (62%) had intermediate resistance to penicillin, with minimal inhibitory concentrations (MICs) ranging from 0.125 to 0.5 microgram/ml, and 15 strains were fully susceptible to penicillin (MICs, 0.015 to 0.06 microgram/ml). The MICs of penicillin for all beta-lactamase-producing strains were 2 microgram/ml, and the strains were resistant to ampicillin. Although a direct correlation between the MICs for resistance to penicillin and the other antibiotics tested was not observed, the gonococci isolated in Hong Kong were notably more resistant to tetracycline and streptomycin than has been reported elsewhere, with 78% of strains requiring for inhibition an MIC of tetracycline of greater than 2 microgram/ml and 51% of the isolates requiring an MIC of streptomycin of greater than 128 microgram/ml. All strains were susceptible to spectinomycin and kanamycin as well as to sulfamethoxazole-trimethoprim (ratio, 19:1). Among the cephalosporins, the order of effectiveness was cefuroxime, cefamandole, and cefoxitin. The older generation of cephalosporins, cephradine and cephalexin, was the least effective: 45 and 37% of the strains, respectively, required for inhibition MICs of greater than or equal to 8 microgram/ml. Cefotaxime, a new parenteral cephalosporin, was the most active; the median MIC was at least 10-fold lower than that of cefuroxime.     

Long-term trends in susceptibility of Moraxella catarrhalis: a population analysis

A retrospective, population analysis of antimicrobial susceptibility patterns was performed on Moraxella catarrhalis isolates recovered from a single medical centre to detect temporal trends and infer potential mechanisms of reduced susceptibility. The duration of this study, June 1984 to July 1994, encompassed the period during which the frequency of beta-lactamase production expanded from 30 to 96% in the population. MICs of penicillin G, cefamandole, ceftriaxone, amoxycillin/clavulanate, imipenem, clarithromycin, tetracycline, ciprofloxacin and trimethoprim/sulphamethoxazole for a representative sample of 375 isolates were determined. Analyses were conducted to test for variation in susceptibility among isolates, correlations of susceptibility levels among different antimicrobial agents, and temporal patterns in susceptibility. All antimicrobials except clarithromycin displayed significant differences among isolates within years, and mean MICs of all antimicrobial agents except tetracycline and clarithromycin varied significantly between years. Temporal trends to a reduction in susceptibility were detected to four of five beta-lactam antimicrobials (all except cefamandole). Significant correlations in MICs were uncovered among all pairs of four beta-lactam antimicrobials in both producers and non-producers of beta-lactamase. In contrast, cefamandole MICs were correlated only with ceftriaxone and penicillin, and these were limited to beta-lactam producing isolates; cefamandole and amoxycillin/clavulanate showed a correlation limited to non-producing isolates. For some antimicrobials, trends toward decreasing susceptibility may have been caused by an increased proportion of beta-lactamase producing isolates in the population, but the observation of significant decreases in susceptibility limited to beta-lactamase-producing isolates suggests that the underlying factors were different forms of beta-lactamase, beta-lactamase-dependent modifiers and/or additional factors.     

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 Response to Chloramphenicol, Tetracycline, Ampicillin, Gentamicin, and Beta-Lactamase Production by Halophilic Vibrios from Human and Environmental Sources

Isolates of Vibrio parahaemolyticus and V. alginolyticus from human and environmental sources were examined for antibiotic susceptibility by the methods of minimal inhibitory concentration (MIC) in broth and agar diffusion. These strains were found to be almost uniformly susceptible to chloramphenicol and tetracycline within attainable serum levels. The relationships of zone sizes to MICs for these two antimicrobial agents and ampicillin conformed essentially to those obtained by standard methods with gram-negative rods. Most strains were resistant to ampicillin and exhibited beta-lactamase activity, which accounted for this resistance. Nine of 30 V. alginolyticus strains from environmental sources were ampicillin resistant but did not produce measurable amounts of beta-lactamase. Three strains exhibited multiresistance to high concentrations of chloramphenicol, tetracycline, and ampicillin, which suggests the presence of plasmids. Although the great majority of vibrios appeared to be susceptible to gentamicin by agar diffusion, susceptibility could not be measured by MIC because the added NaCl, required for growth by the halophilic vibrios, diminished gentamicin activity.     

A national collaborative study of resistance to antimicrobial agents in Haemophilus influenzae in Australian hospitals. The Australian Group for Antimicrobial Resistance (AGAR).

An Australia-wide survey of the prevalence of resistance to antimicrobial agents among Haemophilus influenzae was conducted on clinically significant isolates collected between July 1988 and September 1990. Laboratories from the capital cities of each Australian state and territory participated. Nine hundred and seventy clinical isolates were examined for beta-lactamase production and the MICs of ampicillin, coamoxiclav, chloramphenicol, cefaclor, ceftriaxone, cefotaxime, tetracycline, rifampicin, trimethoprim, sulphamethoxazole and co-trimoxazole were determined using the NCCLS agar dilution method with Haemophilus Test Medium. A smaller number of isolates were tested against penicillin V, penicillin G, ciprofloxacin, piperacillin and erythromycin in addition. The proportion of beta-lactamase producing strains was higher among invasive strains (21.6%) than non-invasive strains (14.2%) and varies considerably between states. The highest prevalence of ampicillin resistance was found in invasive strains from Canberra (40.8%), the lowest in non-invasive strains from Adelaide (5.1%). Paradoxically, in non-invasive strains, although beta-lactamase production was less common, resistance to other antimicrobials was commoner than in invasive strains and also varied between states.     

Effect of clavulanic acid on activity of beta-lactam antibiotics in Serratia marcescens isolates producing both a TEM beta-lactamase and a chromosomal cephalosporinase.

An isolate of Serratia marcescens that produced both an inducible chromosomal and a plasmid-mediated TEM-1 beta-lactamase was resistant to ampicillin and amoxicillin and also demonstrated decreased susceptibility to extended-spectrum beta-lactam antibiotics (ESBAs). Clavulanic acid did not lower the MICs of the ESBAs, but it decreased the MICs of the penicillins. The TEM-1-producing plasmid was transferred to a more susceptible S. marcescens strain that produced a well-characterized inducible chromosomal beta-lactamase. The MICs of the ESBAs remained at a low level for the transconjugant. Ampicillin and amoxicillin which were good substrates for the plasmid-mediated enzyme, were not well hydrolyzed by the chromosomal enzymes; the ESBAs were hydrolyzed slowly by all the enzymes. When each of the S. marcescens strains was grown with these beta-lactam antibiotics, at least modest increases in chromosomal beta-lactamase activity were observed. When organisms were grown in the presence of clavulanic acid and an ESBA, no enhanced induction was observed. The increases in the MICs of the ESBAs observed for the initial clinical isolate may have been due to a combination of low inducibility, slow hydrolysis, and differences in permeability between the S. marcescens isolates. When clavulanic acid and a penicillin were added to strains that produced both a plasmid-mediated TEM and a chromosomal beta-lactamase, much higher levels of chromosomal beta-lactamase activity were present than were observed in cultures induced by the penicillin alone. This was due to the higher levels of penicillin that were available for induction as a result of inhibition of the TEM enzyme by clavulanate.     

Relationship between outer membrane alterations and susceptibility to antimicrobial agents in isogenic strains of Klebsiella pneumoniae

The activities of beta-lactams, chloramphenicol, tetracycline, fluoroquinolones and aminoglycosides against Klebsiella pneumoniae C3 (O1:K66, producing porins OmpK35 and OmpK36) and a set of isogenic mutants derived from it lacking the O antigen of lipopolysaccharide (LPS), capsular K antigen, or one or both porins were determined. MICs remained within one dilution step in mutants deficient in antigen O, in capsule or in one of the two porins. No increases in the MICs of aminoglycosides, fluoroquinolones, tetracycline and chloramphenicol were observed for strains deficient in the two porins, but the MICs of ampicillin, cephalothin, cefoxitin, cefotaxime and ceftazidime for this type of mutant increased four- to >256-fold. The highest MICs of beta-lactams were obtained in a porin-deficient mutant expressing increased beta-lactamase activity. It is concluded that isolated outer membrane alterations in K. pneumoniae are not decisive factors in increasing resistance to antimicrobial agents, but porin loss co-operates with beta-actamase production to increase resistance to beta-lactams.     

Disk diffusion susceptibility of Branhamella catarrhalis and relationship of beta-lactam zone size to beta-lactamase production.

We tested 231 isolates of Branhamella catarrhalis for beta-lactamase production and drug susceptibility by the National Committee for Clinical Laboratory Standards disk diffusion method. The nitrocephin disk (Cefinase) identified beta-lactamase in 98% of the enzyme-producing strains, and a zone diameter of inhibition of less than or equal to 29 mm for penicillin correctly predicted the presence of beta-lactamase in 99% of the isolates. No resistance to erythromycin, tetracycline, trimethoprim-sulfamethoxazole, or amoxicillin-clavulanic acid was observed.     

Sensitivity of gonococci to rosoxacin compared with that of penicillin, cefuroxime and tetracycline

The in vitro activity of rosoxacin, a pyridyl quinolone derivative against Neisseria gonorrhoeae is compared with that of penicillin, cefuroxime and tetracycline. Three groups of gonococci comprising of beta-lactamase-positive and negative strains and gonococci with high penicillin MICs are studied. Rosoxacin was the most active against the entire spectrum of gonococci tested in vitro and its activity is not affected by the production of beta-lactamase by some gonococci.     

Rapidly increasing prevalence of beta-lactamase-nonproducing, ampicillin-resistant Haemophilus influenzae type b in patients with meningitis

A total of 395 Haemophilus influenzae strains from 226 Japanese institutions participating in the Nationwide Surveillance Study Group for Bacterial Meningitis were received from 1999 to 2002. All strains were analyzed by PCR to identify the resistance genes, and their susceptibilities to beta-lactam agents were determined. Of these strains, 29.1% were beta-lactamase nonproducing and ampicillin (AMP) susceptible (BLNAS) and lacked all resistance genes; 15.4% were beta-lactamase producing and AMP resistant and had the bla(TEM-1) gene; 30.6% were beta-lactamase nonproducing and AMP resistant (low-BLNAR) and had a Lys-526 or His-517 amino acid substitution in ftsI encoding PBP 3; 13.9% were beta-lactamase nonproducing and AMP resistant (BLNAR) and had an additional substitution of Thr-385 in ftsI; 9.1% were amoxicillin-clavulanic acid resistant (BLPACR I) and had the bla(TEM-1) gene and a Lys-526 or His-517 amino acid substitution in ftsI; and 1.8% showed resistance similar to that of the BLPACR I group (BLPACR II) but had bla(TEM-1) gene and ftsI substitutions, as was the case for the BLNAR strains. All but three strains were serotype b. The prevalence of BLNAR strains has increased rapidly: 0% in 1999, 5.8% in 2000, 14.1% in 2001, and 21.3% in 2002. The MICs at which 90% of BLNAR isolates were inhibited were as follows: AMP, 16 micro g/ml; cefotaxime, 1 micro g/ml; ceftriaxone, 0.25 micro g/ml; and meropenem, 0.5 micro g/ml. All of these values were higher than those for the BLNAS counterpart strains. The relatively wide distributions of the beta-lactam MICs for BLNAR strains presumably reflect variations in ftsI gene mutations. Pulsed-field gel electrophoresis suggested the rapid spread of specific H. influenzae type b strains throughout Japan. Expedited vaccination, rapid identification, and judicious antibiotic use could slow their spread.     

Inhibition of beta-lactamases by tazobactam and in-vitro antibacterial activity of tazobactam combined with piperacillin

The in-vitro synergistic activity of tazobactam, a new beta-lactamase inhibitor, combined with piperacillin was tested against various beta-lactamase-producing strains. The beta-lactamase inhibitory activity of tazobactam against various known types of beta-lactamase was also tested in comparison with clavulanic acid or sulbactam. Tazobactam caused a remarkable reduction of the piperacillin MICs for penicillinase- and oxyiminocephalosporinase-producing strains and also showed a moderate synergistic effect against cephalosporinase-producing strains. The bactericidal activity of piperacillin was enhanced in combination with tazobactam. Tazobactam inhibited the penicillinases, and the oxyiminocephalosporinase produced by Proteus vulgaris, at low concentration. In these cases its activity was comparable with that of clavulanic acid and stronger than that of sulbactam. Tazobactam demonstrated a better inhibitory capability than sulbactam against the cephalosporinases tested. Tazobactam was able to inactivate intracellular beta-lactamase in Prot. vulgaris and Morganella morganii, confirming its ability to penetrate the cell membrane of these species.     

Antibiotic resistance of degraded strains of Bordetella pertussis.

The susceptibilities to erythromycin, rifampin, polymyxin B, ampicillin, tetracycline, gentamicin, fusidic acid, trimethoprim, and spectinomycin of five virulent phase I strains of Bordetella pertussis and their degraded phase IV descendants were compared. Increases in MICs of 2- to 16-fold were observed for erythromycin, rifampin, tetracycline, fusidic acid, trimethoprim, and spectinomycin for four of the five degraded strains.     

Trends in susceptibility of Neisseria gonorrhoeae to ceftriaxone from 1985 through 1991.

The antimicrobial susceptibilities of 16,441 gonococcal isolates from Seattle-King County were determined for ceftriaxone, cefoxitin, penicillin G, and tetracycline. From 1985 to 1989, ceftriaxone, in combination with doxycycline, was increasingly used for treatment of gonorrhea, and by 1989, it was used as therapy for > 80% of cases in Seattle-King County. MICs of ceftriaxone correlated significantly (P < 0.001) with those of the other beta-lactam antibodies included in this study. Geometric mean MICs of penicillin G for isolates that did not produce beta-lactamase increased from 1985 to 1991. The geometric mean MICs of cefoxitin, ceftriaxone, and tetracycline began to decline in 1987 but increased in 1990 and 1991. The percentage of strains with decreased susceptibility to ceftriaxone (MIC, 0.06 to 0.25 microgram/ml) rose from 0.3% in 1985 to 5.3% in 1987 but subsequently declined steadily to 2.6% in 1991, despite increased use of ceftriaxone as routine therapy for gonorrhea. Changes in patterns of antimicrobial susceptibility may be related not only to antimicrobial selection pressures but also to less well understood population shifts among Neisseria gonorrhoeae strains within a community.     

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).