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At least 19 recordsLinked to original sources

PubMed1987

In vitro activity of ampicillin alone and in combination with different concentrations of 6 beta-bromopenicillanic acid, clavulanic acid and mecillinam.

The antibacterial activity of ampicillin against Enterobacteriaceae strongly increased when combined with 6 beta-bromopenicillanic acid (BPA) or clavulanic acid (CA). In vitro, the combination ampicillin: BPA in the ratio 1:1 proved to be the most effective one. The antibacterial activity of mecillinam against Enterobacteriaceae was strongly potentiated by the addition of ampicillin. The combination mecillinam:ampicillin in the ratio 4:5 showed an antibacterial activity comparable to that of new beta-lactam compounds such as cefotaxime and ceftazidime.

Amdinocillin↗

PubMed1979

The inhibition of staphylococcal beta-lactamase by clavulanic acid.

Clavulanic acid inhibited both the extracellular and cell-extract beta-lactamases of the four Staphylococcus aureus strains tested. The inhibition of S. aureus Russell cell-extract enzyme appeared to be active-site-directed and proceeded in a first-order fashion consistent with the formation of a covalent intermediate. Inhibited enzyme free of excess clavulanic acid was shown to regenerate enzyme activity slowly at pH 7.0, but the rate of reactivation increased at acid pH. When the enzyme was incubated with excess clavulanic acid complete inhibition was rapidly obtained, during further incubation clavulanic acid was shown to disappear slowly and complete loss of clavulanic acid from the reaction mixture coincided with the onset of the return of enzyme activity. A reactive enamine resulting from enzymic hydrolysis of the beta-lactam ring of clavulanic acid has been proposed as a possible intermediate in the inhibitory mechanism.

Anti-Bacterial Agents↗

PubMed1985

Positive direct antiglobulin tests due to clavulanic acid.

Clavulanic acid, a beta-lactamase inhibitor, was found to be associated with the development of a positive direct antiglobulin test. Of 23 antibiotic courses in patients treated with ticarcillin, clavulanic acid, and tobramycin, 10 (43.5%) developed positive direct antiglobulin tests versus 2 of 26 (7.7%) patients treated with piperacillin and tobramycin (P = 0.0044). In vitro immunohematological studies showed that clavulanic acid caused a nonimmunologic adsorption of plasma proteins onto the erythrocyte surface. Hemolysis was not associated with such nonimmunologic adsorption. However, the resulting positive antiglobulin test might delay cross matching of blood products for transfusions or interfere with the evaluation of true immune-mediated hemolytic anemia.

Clavulanic Acid↗

PubMed1987

[Measure by turbidimetry and bactericidal effect of the speed of action of clavulanic acid, amoxicillin and their combinations on a Haemophilus influenzae producer of beta-lactamase].

The amoxicillin-acid clavulanic acid combination is known to be active on H. influenzae beta-lactamase producer. Clavulanic acid possesses its own antibacterial activity at high concentrations. As the combination of two beta-lactams is sometimes antagonist, we studied the action of amoxicillin, clavulanic acid alone and in combination on H. influenzae beta-lactamase producer by kinetic turbidimetry and time-kill curve. Clavulanic acid alone has slowed down the growth at 8 micrograms/ml, has inhibited at 32 micrograms/ml and was bactericidal at 128 micrograms/ml. The amoxicillin-clavulanic acid combination (proportion 4/1) was bactericidal at 2-0.5 micrograms/ml. The speed of bactericidal activity was only slightly dependent on concentrations. The increase in biomass measured by turbidimetry has been important. As for all beta-lactams it was due to the formation of spheroplasts, non viable after 24 h.

Amoxicillin↗

PubMed1989

In vitro activity of amoxycillin plus clavulanic acid and ticarcillin plus clavulanic acid compared with that of other antibiotics against anaerobic bacteria.

The activity of amoxycillin/clavulanic acid (Augmentin) and ticarcillin/clavulanic acid (Timentin) was tested against 303 unselected clinical anaerobic isolates recently collected in seven Belgian university hospitals and compared with that of 11 other antimicrobial agents. Bacteroides spp. accounted for 52.1% of the isolates, Clostridium spp. for 23.4%, anaerobic cocci for 15.5%, nonsporeforming gram-positive bacilli for 4.6% and Fusobacterium spp. for 3.3%. Ticarcillin/clavulanic acid (fixed clavulanic acid concentration of 2 mg/l) was the most active drug with an overall susceptibility rate of 99.7%. Amoxycillin/clavulanic acid (fixed ratio of 2:1) and chloramphenicol inhibited 97.4% of the isolates, metronidazole 95.4%, piperacillin 92.4%, ticarcillin 91.4%, clindamycin 87.8%, cefotetan 81.2%, cefazolin 63.0%, cefuroxime 60.4%, erythromycin 57.8%, penicillin 57.1% and doxycycline 52.1%. beta-lactamases were detected exclusively in Bacteroides spp. isolates (79.1% positive).

Amoxicillin↗

PubMed1979

Studies on the biosynthesis of clavulanic acid. II. Chemical degradations of 14C-labelled clavulanic acid.

Two chemical degradations of clavulanic acid are described which are useful for locating label in 14C-clavulanate. In the first, the beta-hydroxyethylidene side chain of p-bromobenzyl clavulanate is removed by ozonolysis to give p-bromobenzyl (2R, 5R)-3,7-dioxo-4-oxa-1-azabicyclo [3.2.0] heptane-2-carboxylate. The second involves the reaction of p-bromobenzyl clavulanate with dibenzylamine in methanol, to isolate the three beta-lactam carbons as methyl trans-3-(N-N-dibenzyl)amino acrylate. These techniques were used to degrade clavulanic acid derived from fermentations fed with 2-14C-acetate or universally 14C-labelled glycerol. The amount of label retained in the degradation products was in agreement with the distribution of 13C in clavulanic acid derived from 2-13C-acetate, or 1,3-13C2-glycerol, as observed by 13C-NMR.

Anti-Bacterial Agents↗

PubMed1988

[Comparative study of a combination of amoxicillin and clavulanic acid and a combination of ticarcillin and clavulanic acid on 249 enterobacteria].

A comparison between the MIC of amoxicillin (AMX) and ticarcillin (TIC) in the presence of clavulanic acid (Augmentin: AUG and Claventin: CLV) was made on 168 strains of Escherichia coli resistant to amoxicillin (MIC greater than 16 mg/l) and yet sensitive to ceftriaxone (MIC less than or equal to 4 mg/l) and 81 strains of Klebsiella pneumoniae sensitive to Ceftriaxone. All those strains have been isolated between 1986-87 in Bellevue Hospital in Saint-Etienne. On 168 Escherichia coli, 142 have a MIC greater than 128 mg/l of TIC. Those 142 Escherichia coli are sensitive or of an intermediary sensitivity to Cephalothin (MIC less than or equal to 32 mg/l) in 57% cases. Those 142 strains are sensitive to AUG (MIC less than or equal to 4 mg/l) in 13.4% cases, intermediary sensitive to AUG (4 less than MIC less than or equal to 16) in 30.3% cases, sensitive to CLV (CMI less than or equal to 16 mg/l) in 23.3% cases and intermediary sensitive to Claventin (16 less than MIC less than or equal to 64) in 47.2% cases. The 26 Escherichia coli of MIC less than or equal to 64 mg/l of TIC and resistant to Cephalothin (MIC greater than 32 mg/l) have MIC less than or equal to 4 mg/l of AUG In 3.8% cases and MIC less than or equal to 16 mg/l of Claventin in 79.6% cases. The 81 Klebsiella pneumoniae

Amoxicillin↗

PubMed1995

[Comparative study of ofloxacin+amoxicillin-clavulanic acid versus doxycycline+amoxicillin-clavulanic acid combination in the treatment of pelvic Chlamydia trachomatis infections].

OBJECTIVE: To evaluate the efficacy and safety of ofloxacin+coamoxiclav versus doxycycline-coamoxiclav in the treatment of chlamydial pelvic infections. DESIGN: An open, comparative, randomised, monocentric study. SUBJECTS: A hundred and eighteen patients (85 endometritis and 33 salpingitis) were included. Clinical, laparoscopic and bacteriological assessments were performed before treatment. 30.4% of salpingitis were considered as severe (COGIT score > 6). 25.4% of acute pelvic infections were only caused by Chlamydia trachomatis. TREATMENT: A hundred and eighteen patients were treated orally with 3 week combination ofloxacin (200 mg b.i.d.) + coamoxiclav (1 g b.i.d.) (n = 60) or with a 6 week coamoxiclav (1 g b.i.d.) + doxycycline (100 mg b.i.d.) (n = 58). RESULTS: Oral combination ofloxacin-coamoxiclav is as effective as oral combination doxycycline+coamoxyclav with respectively 96.7% versus 96.6% and 100% versus 98.4% satisfactory clinical et bacteriological results.

Adolescent↗

PubMed1991

Acquired resistance of Nocardia brasiliensis to clavulanic acid related to a change in beta-lactamase following therapy with amoxicillin-clavulanic acid.

Previous studies have demonstrated that Nocardia brasiliensis is susceptible to amoxicillin-clavulanic acid and that its beta-lactamases are inhibited in vitro by clavulanic acid. A cardiac transplant patient with disseminated infection caused by N. brasiliensis was treated with this drug combination with good response, but relapsed while still on therapy. The relapse isolate was found to be identical to the initial isolate by using genomic DNA restriction fragment patterns obtained by pulsed field gel electrophoresis, but it was resistant to amoxicillin-clavulanic acid. On isoelectric focusing, the beta-lactamase from the relapse isolate exhibited a shift in the isoelectric point (pI) of its major band from 5.10 to 5.04 compared with the enzyme from the pretreatment isolate. As determined by using values of the amount of beta-lactamase inhibitor necessary to give 50 +/- 5% inhibition of beta-lactamase-mediated hydrolysis of 50 microM nitrocefin, the beta-lactamase of the relapse isolate was also 200-fold more resistant than the enzyme from the pretreatment isolate to clavulanic acid and was more resistant to sulbactam, tazobactam, cloxacillin, and imipenem. The beta-lactamase of the relapse isolate exhibited a 10-fold decrease in hydrolytic activity for cephaloridine and other hydrolyzable cephalosporins compared with that for nitrocefin. Acquired resistance to amoxicillin-clavulanic acid in this isolate of N. brasiliensis appears to have resulted from a mutational change affecting the inhibitor and active site(s) in the beta-lactamase.

Amoxicillin↗

PubMed1983

Synthesis and beta-lactamase inhibitory activities of some clavulanic acid analogues.

Clavulanic acid analogs lacking the C-3 carboxyl group are potent inhibitors of both plasmid and chromosomally mediated beta-lactamases. They exhibit only low intrinsic anti-bacterial activity, but potentiate the activity of ampicillin and cephaloridine against beta-lactamase producing Escherichia coli and Enterobacter cloacae in vitro. No synergism was observed in beta-lactamase negative strains. The E. coli TEM 1 and the E. cloacae P99 enzymes are inhibited in a progressive and irreversible manner by these compounds.

Anti-Bacterial Agents↗

PubMed1978

Chemical studies on the inactivation of Escherichia coli RTEM beta-lactamase by clavulanic acid.

Incubation of clavulanic acid with the beta-lactamase from Escherichia coli RTEM leads to enzyme-catalyzed depletion of clavulanic acid, to transient inhibition, and to irreversible inactivation of the enzyme. Both the transiently inhibited and the irreversibly inactivated species show a marked increase in the absorbance at 281 nm that is proportional to the decrease in enzyme activity. Hydroxylamine treatment of irreversibly inactivated enzyme restores about one-third of the catalytic activity, with a concomitant decrease in absorbance at 281 nm. Polyacrylamide isoelectric focusing of the irreversibly inactivated enzyme shows three bands of approximately equal intensity, different from native enzyme. Upon hydroxylamine treatment, one of the three bands disappears and now focuses identically with native enzyme. It is evident that the irreversible inactivation of enzyme by an excess of clavulanic acid generates three products, one of which can be reactivated by hydroxylamine.

Escherichia coli↗

PubMed1986

Differential effect of impaired renal function on the kinetics of clavulanic acid and amoxicillin.

Amoxicillin and clavulanic acid are prescribed as a fixed drug combination. The purpose of the present study was to assess the influence of various degrees of renal insufficiency (glomerular filtration rate [GFR], less than 5 to greater than 75 ml/min per 1.73 m2) on the pharmacokinetics of amoxicillin and clavulanic acid following oral (500 and 125 mg of amoxicillin and clavulanic acid, respectively) and intravenous (1,000 and 200 mg, respectively) dosing. The volume of distribution and the systemic availability were independent of the renal function, while the total body clearance and the renal and the nonrenal clearance of amoxicillin and clavulanic acid decreased with decreasing renal function. The decrease in the total body clearance was more pronounced for amoxicillin than for clavulanic acid. This explains the increase in the ratio of the area under the plasma concentration versus time curve of amoxicillin to that of clavulanic acid with decreasing glomerular filtration rate after oral dosing; for example for a GFR of 75 ml/min, the ratio of amoxicillin to clavulanic acid was 4.9 +/- 1.2; for a GFR of 35 to 75 ml/min, 5.3 +/- 2.4; for a GFR of 10 to 35 ml/min, 11.9 +/- 5.8; for a GFR of 5 to 10 ml/min, 13.4 +/- 9.1; and for patients on hemodialysis, 14.7 +/- 5.3. Dosage recommendations are suggested which prevent undue accumulations of amoxicillin while maintaining adequate concentrations of clavulanic acid.

Amoxicillin↗

PubMed1984

Pharmacokinetics and urinary excretion of clavulanic acid after oral administration of amoxicillin and potassium clavulanate.

Clavulanic acid is a beta-lactamase inhibitor which prevents microbial lactamase inactivation of beta-lactam antibiotics. The pharmacokinetics and urinary excretion of clavulanic acid were studied in eight healthy adult volunteers after oral administration of 500 mg amoxicillin and 125 mg potassium clavulanate. Serum and urine clavulanic acid concentrations were assayed using high-performance liquid chromatography. Pharmacokinetic parameters were: t 1/2 beta = 1.019 +/- 0.090 hour, t 1/2 alpha = 0.276 +/- 0.031 hour, lag time = 0.321 +/- 0.018 hour, tmax = 1.042 +/- 0.80 hour, Cmax = 2.098 +/- 0.441 micrograms/ml, and AUC = 4.897 +/- 0.979 micrograms X hr/ml. Cumulative urinary excretion of clavulanic acid (as percentage of dose administered) was: 14.05 +/- 2.87 within 2 hours, 25.77 +/- 3.98 within 4 hours, and 27.85 +/- 4.27 within 6 hours after administration.

Administration, Oral↗

PubMed1985

Pharmacokinetic study of a paediatric formulation of amoxycillin and clavulanic acid in children.

A combination of amoxycillin and clavulanic acid 4:1 was administered to 35 children (aged 2 to 10 years) with infections. The combination was administered orally as a suspension, every 8 h for 5 to 7 days. Sixteen children (aged 2 to 5 years), received 125 mg amoxycillin and 31.25 mg clavulanic acid, and 19 (6 to 10 years) received 250 mg amoxycillin and 62.5 mg clavulanic acid per dose. Following the first dose serum concentrations of amoxycillin and clavulanic acid were determined by microbiological assay. In the younger group receiving the lower dosage (mean: amoxycillin 9.11 mg/kg and clavulanic acid 2.34 mg/kg), the mean peak concentration of amoxycillin was 3.5 mg/l and of clavulanic acid 1.2 mg/l, occurring 1.32 h and 1.39 h, respectively, after administration. In the older group receiving the higher dosage (mean: amoxycillin 12.35 mg/kg and clavulanic acid 3.14 mg/kg) the mean peak serum level of amoxycillin was 4.0 mg/l and of clavulanic acid 1.3 mg/l, occurring 1.43 h and 1.23 h, respectively, after administration. The higher dose per kilogram body weight resulted in a higher peak serum concentration both of amoxycillin and clavulanic acid. The formulation was well tolerated by all the children and no serious side-effects were recorded. Treatment was considered clinically effective in all cases.

Amoxicillin↗

PubMed1985

Pharmacokinetics and serum bactericidal activity of ticarcillin and clavulanic acid.

The pharmacokinetics of ticarcillin 5.0 g and clavulanic acid 0.2 g were examined both alone and combined (3.0 or 5.0 g ticarcillin + 0.2 g clavulanic acid as 3.2 or 5.2 g timentin) after a 15 min infusion in ten healthy volunteers. At the same time, the serum bactericidal activity of 5.0 g ticarcillin alone and 5.2 g Timentin was determined against two ticarcillin resistant strains each of Klebsiella oxytoca and Pseudomonas aeruginosa in the first and sixth hour after administration. The serum kinetics of both ticarcillin and clavulanic acid could best be described by an open 2-compartment model. Both substances showed similar kinetic behaviour in serum with a T 1/2 beta of 74.8 +/- 11.5 min for ticarcillin and 76.6 +/- 4.6 min for clavulanic acid. The total clearance of clavulanic acid was 158 +/- 23 ml/min and thus clearly exceeded that of ticarcillin (112 +/- 9 ml/min). The recovery rate in the 24 h urine was 41.3% for clavulanic acid as compared to 79.4% for ticarcillin. Concomitant administration of both substances led to a limited change in the kinetics of both ticarcillin and clavulanic acid. A significant enhancement of the serum bactericidal action of ticarcillin and clavulanic acid was only detected for both Klebsiella species and not for the Ps. aeruginosa species, and only in the first hour.

Adult↗

PubMed1991

Bactericidal effects of ticarcillin-clavulanic acid against Legionella pneumophila pneumonia in immunocompromised weanling rats.

A model of acute Legionella pneumophila pneumonia in neutropenic weanling rats was developed as a means of assessing the efficacies in vivo of the beta-lactams ticarcillin, ticarcillin-clavulanic acid, and clavulanic acid, agents active against the organism in vitro. Weanling rats were dosed with cyclophosphamide 3 days before and immediately prior to infection by intrabronchial intubation with L. pneumophila. The bacteria persisted in the lungs of untreated animals at high counts (5.0 to 7.0 log10 CFU/g of lung tissue) for up to 168 h after infection, and the histological characteristics of the infection were similar to those of the disease in humans. Transmission electron micrography revealed the presence of L. pneumophila multiplying within alveolar macrophages. Therapy with ticarcillin was ineffective in reducing the bacterial numbers in the lung tissue, whereas ticarcillin-clavulanic acid and clavulanic acid were active, producing bactericidal effects similar to those of erythromycin. The ticarcillin-clavulanic acid combination was significantly more efficacious (P less than 0.01) than corresponding doses of clavulanic acid alone. Synergistic activity between ticarcillin and clavulanic acid against L. pneumophila has been demonstrated in vivo, and the combination showed activity similar to that of erythromycin.

Animals↗

PubMed1984

The pharmacology of clavulanic acid and ticarcillin combined.

The pharmacokinetics of ticarcillin and clavulanic acid were studied in normal volunteers. Ticarcillin at 50 mg/kg was combined with clavulanic acid at 1.7 and 3.4 mg/kg and infused over 30 minutes. Peak serum levels of ticarcillin were 325 micrograms/ml and its pharmacokinetic parameters were similar when combined with either dose of clavulanic acid. Peak serum levels of clavulanic acid were 8 micrograms/ml for 1.7 mg/kg and 15.8 micrograms/ml for 3.4 mg/kg. Serum concentrations of clavulanic acid were greater than or equal to 1 microgram/ml for 2 h with the 1.7 mg/kg dose and for 3 h with the 3.4 mg/kg dose. Serum half-lives of ticarcillin and clavulanic acid were similar, 1.2 hours. Urinary concentrations of ticarcillin exceeded 100 micrograms/ml and clavulanic acid concentrations exceeded 1 microgram/ml for 6 h. The serum and urine levels were such that many beta-lactamase producing organisms would be inhibited by this combination.

Adult↗

PubMed1985

Clinical pharmacology of timentin (ticarcillin and clavulanic acid).

Ticarcillin (4 gm) and clavulanic acid (0.1 gm) were simultaneously administered as timentin to patients with cancer as therapy for infections. The pharmacokinetics of both ticarcillin and clavulanic acid were studied in 15 patients after 30-minute and 2-hour intravenous infusions. The mean (+/- SD) ticarcillin plasma peak concentrations after the two infusions were 341 +/- 76 and 210 +/- 60 micrograms/ml. The plasma terminal t1/2 values of ticarcillin were 80 +/- 32 and 56 +/- 12 minutes. The AUCs were 631 +/- 189 and 601 +/- 230 mg/L X hr. The volumes of distribution of the area were 15 +/- 5 and 21 +/- 7 L and total clearances were 115 +/- 36 and 127 +/- 54 ml/min. The corresponding values for clavulanic acid after the infusions are as follows: mean peak concentrations, 5 +/- 1 and 4 +/- 1 micrograms/ml; plasma terminal t1/2 values, 84 +/- 24 and 74 +/- 36 minutes; AUCs, 11 +/- 3 and 11 +/- 6 mg/L X hr; volumes of distribution of the area, 22 +/- 3 and 32 +/- 6 L; and total clearances, 170 +/- 58 and 175 +/- 68 ml/min.

Adult↗