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PubMedDate not supplied

Comparative in vitro susceptibilities of 504 bacteremic isolates to ticarcillin plus clavulanic acid and other antimicrobial agents.

A total of 504 clinical bacteremic isolates were tested for susceptibility to ticarcillin-clavulanic acid and 12 other antibiotics. Ticarcillin-clavulanic acid showed superior antibacterial activity compared to penicillin, mezlocillin, piperacillin, ticarcillin, gentamicin, and amikacin against bacteremic isolates of methicillin-susceptible Staphylococcus aureus and Staphylococcus epidermidis. However, ticarcillin-clavulanic acid's activity was inferior to that of vancomycin against methicillin-resistant isolates of S. aureus and S. epidermidis. For Escherichia coli, Klebsiella oxytoca, Proteus mirabilis, Providencia stuartii, and lactose nonfermenting aerobic gram-negative bacilli, the activity of ticarcillin-clavulanic acid surpassed that of mezlocillin, piperacillin, and ticarcillin. Of the antimicrobial agents tested, ticarcillin, piperacillin, ceftazidime, and amikacin were the most active antibiotics against Pseudomonas aeruginosa.

Anti-Bacterial Agents↗
PubMed1988

In-vitro susceptibility of Mycobacterium tuberculosis, Mycobacterium bovis and Mycobacterium kansasii to amoxycillin and ticarcillin in combination with clavulanic acid.

The in-vitro susceptibility of Mycobacterium tuberculosis, M. bovis, and M. kansasii to amoxycillin alone and in combination with 2 mg/l of clavulanic acid was evaluated by broth dilution. The MIC90 of amoxycillin plus clavulanic acid was 4 mg/l compared with greater than 32 mg/l for amoxycillin alone when tested against M. tuberculosis (n = 27). M. bovis (n = 8) was the most susceptible species with an MIC90 of amoxycillin 8 mg/l, compared with 0.5 mg/l for the combination. M. kansasii (n = 6), with an MIC90 of 16 mg/l for amoxycillin plus clavulanic acid was more resistant than either M. tuberculosis or M. bovis. Ticarcillin plus clavulanic acid with an MIC90 of 32 mg/l was less active against M. tuberculosis (n = 28) than amoxycillin plus clavulanic acid. The addition of clavulanic acid to amoxycillin greatly improves its in-vitro activity against M. tuberculosis and M. bovis.

Amoxicillin↗
PubMed1992

Efficacy of ticarcillin-clavulanic acid for treatment of experimental Staphylococcus aureus endocarditis in rats.

The efficacy of ticarcillin-clavulanic acid was compared with the efficacies of standard antistaphylococcal agents (flucloxacillin, oxacillin, nafcillin, and vancomycin) and ticarcillin in an experimental model of Staphylococcus aureus endocarditis. Therapy was either initiated soon (8 h) after infection, when numbers of bacteria in aortic valve vegetations were relatively low (approximately 6 to 8 log10 CFU/g), or delayed until 24 h after infection, when the vegetations usually contained greater than 9 log10 CFU/g. Doses of the antibiotic were selected to produce peak concentrations in rat serum similar to those achievable in humans after administration of parenteral therapeutic doses. Ticarcillin-clavulanic acid was more effective overall than ticarcillin alone against endocarditis caused by beta-lactamase-producing strains of S. aureus, illustrating the beta-lactamase-inhibitory activity of clavulanic acid in vivo. Ticarcillin-clavulanic acid was as effective as the standard antistaphylococcal beta-lactam agents flucloxacillin, oxacillin, and nafcillin in these infections, whereas vancomycin was generally less active. These results illustrate the clinical potential of ticarcillin-clavulanic acid in the prophylaxis or therapy of severe staphylococcal infections.

Animals↗
PubMed1981

The inhibition of beta-lactamases from gram-negative bacteria by clavulanic acid.

The beta-lactamase from Klebsiella pneumoniae E70 behaved in a similar fashion to the TEM-2 plasmid mediated enzyme on reaction with clavulanic acid. Both enzymes produced two types of enzyme-clavulanate complex, a transiently stable species (t((1/2))=4min at pH7.3 and 37 degrees C) and irreversibly inhibited enzyme. In the initial rapid reaction (2.5min) the enzymes partitioned between the transient and irreversible complexes in the ratios 3:1 for TEM-2 beta-lactamase and 1:1 for Klebsiella beta-lactamase. Biphasic inactivation was observed for both enzymes and the slower second phase was rate limited by the decay of the transiently stable complex. This decay released free enzyme for further reaction with fresh clavulanic acid, the products again partitioning between transiently stable and irreversibly inhibited enzyme. This cycle continued until all the enzyme had been irreversibly inhibited. A 115 molar excess of inhibitor was required to achieve complete inactivation of TEM-2 beta-lactamase. Hydrolysis of clavulanic acid with product release appeared to occur with the inhibition reaction, which explained this degree of clavulanic acid turnover. The stoichiometry of the interaction with Klebsiella beta-lactamase was not examined. The penicillinase from Proteus mirabilis C889 was rapidly inhibited by low concentrations of clavulanic acid. The major product was a moderately stable complex (t((1/2))=40min at pH7.3 and 37 degrees C); the proportion of the enzyme that was irreversibly inactivated was small. The cephalosporinase from Enterobacter cloacae P99 had low affinity for the inhibitor and only reacted with high concentrations of clavulanic acid (k=4.0m(-1).s(-1)) to produce a relatively stable complex (t((1/2))=180min at pH7.3 and 37 degrees C). No irreversible inactivation of this enzyme was detected. The rates of decay of the clavulanate-enzyme complexes produced in reactions with Proteus and Enterobacter enzymes were markedly increased at acid pH.

Clavulanic Acid↗
PubMed1985

Antibiotics in penetrating abdominal trauma. Comparison of ticarcillin plus clavulanic acid with gentamicin plus clindamycin.

A comparative trial of ticarcillin plus clavulanic acid with gentamicin plus clindamycin was conducted in 85 patients who sustained penetrating abdominal wounds. The antibiotic regimens were given for 24 hours. The overall wound and/or intra-abdominal infection rate was 5.9 percent. Patients who sustained gunshot wounds to hollow viscera were at highest risk. Infection developed in one of 53 (1.9 percent) patients who received ticarcillin plus clavulanic acid and in four of 32 (12 percent) patients who received gentamicin plus clindamycin. These differences were not statistically significant. These data support the use of short-course (24-hour) antibiotic therapy in this clinical setting and demonstrate that ticarcillin plus clavulanic acid is efficacious as a preventive antibiotic combination.

Abdominal Injuries↗
PubMed1982

The in vitro activity of amoxycillin with clavulanic acid against clinically significant bacteria. A multicentre study.

A multicentre study to evaluate the activity of amoxycillin when combined with clavulanic acid against clinical bacterial isolates was performed in South Africa. Minimum inhibitory concentrations for amoxycillin alone and in combination with clavulanic acid were determined by agar dilution. The majority of amoxycillin-resistant Klebsiella and Escherichia coli strains became sensitive to amoxycillin in the presence of low concentrations of clavulanic acid. Beta-lactamase-producing strains of Staphylococcus aureus showed increased susceptibility to amoxycillin in the presence of clavulanic acid. Minimum bactericidal concentrations indicated that amoxycillin retains bactericidal activity in the presence of clavulanic acid. Enterobacter and Serratia species and Pseudomonas aeruginosa remained amoxycillin-resistant in the presence of clavulanic acid.

Amoxicillin↗
PubMed1984

Disk diffusion susceptibility testing of ticarcillin plus clavulanic acid.

Disk diffusion susceptibility testing of ticarcillin plus the beta-lactamase inhibitor clavulanic acid was performed on 489 clinical isolates, and the results were compared with reference broth microdilution susceptibilities. Four different disks containing 75 micrograms of ticarcillin plus 2.5, 5, 10, and 15 micrograms of clavulanic acid were evaluated. Based on test performance and clavulanic acid stability, the 75-10-micrograms disk is recommended. Interpretive criteria for ticarcillin as published by the National Committee for Clinical Laboratory Standards appear to be satisfactory for the combination drug, but because the number of ticarcillin-clavulanic acid-resistant isolates was small, this proposal must be considered only tentative.

Bacteria↗
PubMed1989

Effect of amoxycillin and clavulanic acid, alone and in combination, on human polymorphonuclear leukocyte function against Staphylococcus aureus.

The effect of amoxycillin and clavulanic acid on the interaction in vitro of human polymorphonuclear leukocytes with Staphylococcus aureus was examined. The exposure of a non-penicillinase producing Staphylococcus aureus strain to one-fourth the MIC of amoxycillin or clavulanic acid alone significantly increased the uptake of both unopsonized and opsonized bacteria by human polymorphonuclear leukocytes. This effect was also observed when bacteria were exposed to one-fourth the MIC of different proportions of the combination of amoxycillin and clavulanic acid (4/1, 1/1, 1/8 and 1/32). When a penicillinase-producing Staphylococcus aureus strain was used, only clavulanic acid significantly increased the uptake of unopsonized bacteria. The production of superoxide radicals by human polymorphonuclear leukocytes was impaired only by the presence of high concentrations (100 mg/l) of both clavulanic acid or the combination amoxycillin/clavulanic acid (4/1). At this high concentration, however, amoxycillin/clavulanic acid (4/1) significantly increased the intracellular killing of Staphylococcus aureus.

Amoxicillin↗
PubMed1995

Simultaneous determination of the binary mixtures of cefsulodin and clavulanic acid by using first-derivative spectrophotometry.

Two-component mixtures of cefsulodin and clavulanic acid were analysed by a first-derivative spectrophotometric method using a zero-crossing technique of measurement. The relative ease offered by this derivative technique for the quantification of these drugs, with closely overlapping spectral bands, was clearly demonstrated. As the absorption band of clavulanic acid closely overlaps with that of cefsulodin, both direct and derivative spectrophotometric methods have been investigated and evaluated by an exhaustive statistical analysis of the experimental data. The first-derivative spectrophotometric method was found to be more rapid, accurate and reproducible. The procedure does not require any separation step. The calibration graphs were linear in the range 2.0-56.0 micrograms ml-1 for cefsulodin and 2.0-28.0 micrograms ml-1 for clavulanic acid. The lower detection limits of cefsulodin and clavulinic acid (P 0.05 level) were calculated to be 0.16 and 0.24 microgram ml-1, respectively. Mixtures of cefsulodin and clavulanic acid in ratios of 1:4-7:2 were satisfactorily resolved. Both components were also determined in physiological solutions used to prepare intravenous infusions of these antibiotics.

Anti-Bacterial Agents↗
PubMed1980

Clavulanic acid and amoxycillin: a clinical, bacteriological, and pharmacological study.

Clavulanic acid is an inhibitor of certain beta-lactamases, notably those enzymes which inactivate the penicillins and cause resistance of important bacteria to these antibiotics. Microbiological, pharmacological, and clinical studies show that clavulanic acid in combination with amoxycillin is effective and safe in the treatment of urinary-tract infection caused by amoxycillin-resistant bacteria.

Administration, Oral↗
PubMedDate not supplied

Efficacy of empirically prescribed amoxicillin and amoxicillin + clavulanic acid in children's reactive arthritis: a randomised trial.

OBJECTIVE: To evaluate the efficacy of early empiric prescription of amoxicillin and amoxicillin + clavulanic acid in children with reactive arthritis (ReA) when the arthritis-triggering microorganism is not identified. METHODS: 138 children, ranging in age from 2 to 16 years, with ReA of up to 3 months duration were randomly assigned to 3 groups and either prescribed antibacterial treatment with amoxicillin or amoxicillin + clavulanic acid (amoxicillin-potassium clavulanate combination) or were not given antibiotics (control group). Patients in all 3 groups were prescribed the usual treatment with nonsteroidal antiinflammatory drugs. Both groups of patients under antibacterial treatment were randomised into 2 subgroups: patients given a 10- to 14-day or a 28-day-duration antibacterial course. The results of the study were evaluated after 1 and 3 months of observation by determining the percentage of patients that had no clinical or laboratory signs of disease activity. RESULTS: After 1 month of observation no signs of disease activity were found in 48.0% of patients who were prescribed amoxicillin, in 58.5% of patients treated with amoxicillin + clavulanic acid, and only in 13.0% of patients from the control group (p < 0.001 for either antibacterial treatment in comparison with the control group). After 3 months of observation no disease activity was found in 92.0% of patients who used amoxicillin, in 95.1% of those treated with amoxicillin + clavulanic acid, and in 58.7% of children from the control group (p < 0.001 for either antibacterial treatment in comparison with the control group). There was no significant difference in the efficacy of amoxicillin and amoxicillin + clavulanic acid. The duration of the antibacterial course showed no influence on the results of treatment. CONCLUSION: Amoxicillin or amoxicillin + clavulanic acid in 10- to 14-day courses are advisable, in addition to the antirheumatic treatment, for children in the early stage of ReA when the arthritis-triggering microorganism is not identified.

Adolescent↗
PubMed1983

The beta-lactamase stability of amoxycillin with the beta-lactamase inhibitor, clavulanic acid.

The stability of low concentrations of amoxycillin in the presence of clavulanic acid (potassium salt) was determined for a wide range of clinically important beta-lactamases including the staphylococcal and TEM plasmid mediated enzymes. Even with enzyme preparations which completely hydrolysed the amoxycillin within a minute, clavulanic acid provided significant protection. The time course of the protection of amoxycillin reflected the time dependent action of clavulanic acid.

Amoxicillin↗
PubMed1996

Are the adverse drug reactions of amoxycillin and amoxycillin-clavulanic acid similar?

UNLABELLED: In an attempt to assess the relative toxicity of amoxycillin and amoxycillin-clavulanic acid, we compared the adverse drug reactions reports collected using the spontaneous reporting system of a Regional Drug Surveillance Centre of Spain for both drugs between November 1986 and December 1992. During the 7-year period 1986-92, the 247 reports of amoxycillin-clavulanic acid represent twice the number of reports of amoxycillin alone, and the number of reports related with sales received concerning the association were higher than those concerning amoxycillin alone. The adverse effects classified as severe were quantitatively and qualitatively similar for both drugs and gastrointestinal and skin are the most common system-organ affected by both drugs. With amoxycillin-clavulanic acid there is a higher proportion of stomatological reactions reported and a later onset of adverse drug reactions related with oropharyngeal lesions, and the reaction of the resistance mechanism when compared with the other organs and systems affected. The duration of the adverse drug reactions to amoxycillin-clavulanic acid is longer than for amoxycillin alone. IN CONCLUSION: (i) the adverse drug reactions profile of both drugs is different; (ii) the higher reporting rate for amoxycillin-clavulanic acid may be due to more recent marketing; and (iii) amoxycillin-clavulanic acid produces proportionately more gastrointestinal and fewer skin adverse reactions than amoxycillin alone.

Journal Article↗
PubMed1985

Amoxycillin and clavulanic acid combination in the treatment of experimentally induced bacterial cystitis in cats.

Clavulanic acid (CA) competitively inhibits beta-lactamase hydrolysis of penicillins in vitro. Treatment with amoxycillin combined with clavulanic acid (A-CA) was compared with placebo in a blind study in cats with experimental cystitis caused by Escherichia coli demonstrating in vitro resistance to amoxycillin. Bacterial cystitis was induced in 20 cats by bladder infusion of 5 ml of 0.05 per cent alcoholic salicylic acid followed after 24 hours by a brain-heart infusion broth of E coli (10(8) colony forming units ml-1) previously found to be resistant to amoxycillin in vitro (minimum inhibitory concentration over 512 micrograms ml-1). Four days after infection, cats were randomly divided into two groups of 10 and treated with amoxycillin combined with clavulanic acid or placebo for 10 days. When compared to the placebo-treated group, the A-CA treated group showed: reduced quantitative bacterial counts in urine on days 7 (P less than 0.001) and 14 (P less than 0.02); reduced culture positive urine on days 7 (P less than 0.001) and 14 (P less than 0.001); and less severe inflammation on histological examination of the bladder and urethra (P less than 0.01). It was concluded that A-CA was effective in reducing the bacterial count and reducing the histopathological changes in the bladder and urethra in an experimental model of acute bacterial cystitis in cats infected with an E coli demonstrating in vitro resistance to amoxycillin.

Amoxicillin↗
PubMed2004

Two proteins with ornithine acetyltransferase activity show different functions in Streptomyces clavuligerus: Oat2 modulates clavulanic acid biosynthesis in response to arginine.

The oat2 gene, located in the clavulanic acid gene cluster in Streptomyces clavuligerus, is similar to argJ, which encodes N-acetylornithine:glutamic acid acetyltransferase activity. Purified proteins obtained by expression in Escherichia coli of the argJ and oat2 genes of S. clavuligerus posses N-acetyltransferase activity. The kinetics and substrate specificities of both proteins are very similar. Deletion of the oat2 gene did not affect the total N-acetylornithine transferase activity and slightly reduced the formation of clavulanic acid under standard culture conditions. However, the oat2 mutant produced more clavulanic acid than the parental strain in cultures supplemented with high levels (above 1 mM) of arginine. The purified S. clavuligerus ArgR protein bound the arginine box in the oat2 promoter, and the expression of oat2 was higher in mutants with a disruption in argR (arginine-deregulated), confirming that the Arg boxes of oat2 are functional in vivo. Our results suggest that the Oat2 protein or one of its reaction products has a regulatory role that modulates clavulanic acid biosynthesis in response to high arginine concentrations.

Acetyltransferases↗
PubMed1987

[In vitro comparison of the beta lactamase-inhibitory action of clavulanic acid and sulbactam in ampicillin-resistant enterobacteria].

Comparative in vitro Studies of the beta-Lactamase Inhibitory Effects of Clavulanic Acid and Sulbactam on Ampicillin-resistant Enterobacteria. Clavulanic acid and sulbactam alone are infective against Pseudomonas and enterococci. Staphylococci and enterobacteriaceae are inhibited by high concentrations not attainable under clinical conditions. Strains of Acinetobacter, especially A. lwoffii are susceptible to clavulanic acid and highly susceptible to sulbactam. The sulbactam-ampicillin combination is superior to clavulanic acid-ampicillin against C. freundii, Enterobacter spp. and M. morganii. The latter combination is superior against Klebsiella spp. and E. coli. Antagonistic effects are more frequent with the clavulanic acid combination (Enterobacter spp. and C. freundii) but are rarely observed with the sulbactam combination (Providencia spp. and P. rettgeri).

Ampicillin↗
PubMedDate not supplied

[Activity of sulbactam and clavulanic acid, alone and combined, on Acinetobacter calcoaceticus].

Sulbactam and clavulanic acid, both beta-lactamase inhibitors, were studied alone or associated on 85 isolates of Acinetobacter calcoaceticus. When sulbactam was tested alone the minimal inhibitory concentration (MIC) was less than 2 micrograms/ml with the carbenicillin-sensitive strains of A. Calcoaceticus and between 8 to 16 micrograms/ml with the carbenicillin-resistant strains. In the presence of clavulanic acid (5 or 10 micrograms/ml) the MIC of sulbactam on all the carbenicillin-resistant strains decreased to less than 4 micrograms/ml.

Acinetobacter↗
PubMed1983

Susceptibility of gram-negative bacteria and Staphylococcus aureus to combinations of ticarcillin and clavulanic acid.

Four hundred and fifty-nine blood culture isolates were tested for susceptibility to ticarcillin alone and ticarcillin plus clavulanic acid, a potent beta-lactamase inhibitor. The susceptibilities of the Staphylococcus aureus strains to cloxacillin, methicillin, vancomycin, rifampicin, cefoperazone, ceftriaxone and moxalactam and of the gram-negative strains to Augmentin, azlocillin, mezlocillin, piperacillin, cefoperazone, ceftriaxone, cefotaxime, cefsulodin and tobramycin were also measured. Seventy-one percent of staphylococcal strains were beta-lactamase positive. In the presence of clavulanic acid the ticarcillin spectrum was extended to include beta-lactamase producing Staphylococcus aureus, Serratia marcescens and Klebsiella. All the ticarcillin-resistant Enterobacteriaceae were rendered ticarcillin-sensitive by clavulanic acid. The anti-Pseudomonas activity of ticarcillin plus clavulanic acid differed little from that of azlocillin and piperacillin and was comparable to that of the third generation cephalosporins. The combination of ticarcillin with clavulanic acid should be tested in the treatment of patients with infections caused by ticarcillin-sensitive and ticarcillin-resistant bacteria.

Clavulanic Acid↗