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PubMed1986

A comparison of agar dilution, identification of beta-lactamases and disc diffusion methods for assessing the sensitivity to ticarcillin-clavulanic acid.

The in-vitro antibacterial activity of Timentin has been evaluated with a view to proposing valid criteria for sensitivity and resistance. Minimal inhibitory concentrations (MIC) were determined for 284 strains including Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter spp., staphylococci and enterococci. The same strains were also used for the determination of inhibition zones around discs containing 75 micrograms ticarcillin and 10 micrograms clavulanic acid, and a straight regression line was drawn correlating MIC with inhibition zones. The bacterial population was subsequently grouped according to the diameters of inhibition zones of the antibiogram for 2427 strains of Enterobacteriaceae classified by phenotypes. The comparison of MICs of Timentin and ticarcillin for these strains shows that for penicillinase-producing strains, the Timentin MIC is lower than for ticarcillin whereas cephalosporinase-producing strains have equal MICs for the two. Finally strains that produce many different beta-lactamases are not affected by the presence of clavulanic acid. These results should make it possible to propose provisional zone diameters for determining sensitivity and resistance to Timentin.

Agar↗
PubMed1995

Comparative study of marbofloxacin and amoxicillin-clavulanic acid in the treatment of urinary tract infections in dogs.

One hundred and four dogs with clinical signs of urinary tract infection were selected by 15 practitioners in a multicentric, controlled and randomised study. The clinical diagnosis was confirmed by urinalysis and imaging. Each dog received either marbofloxacin (2 mg/kg orally once daily or 4 mg/kg by subcutaneous injection every four days) or amoxicillin-clavulanic acid tablets (12.5 mg/kg twice daily) for 10 or 28 days, depending on the clinical diagnosis. Rectal temperature, general condition, appetite, urinary signs, defecation disorders and pain on abdominal palpation were monitored at each visit, the timetable depending on diagnosis: three urinalyses and at least three examinations per case were performed. Side effects were also thoroughly sought at each examination. Marbofloxacin and amoxicillin-clavulanic acid both yielded good bacteriological cure rates (96.2 per cent versus 85.0 per cent, respectively) and clinical cure rates (83.3 per cent versus 69.7 per cent). Fewer relapses were observed in those dogs that received marbofloxacin. Few mild side effects were recorded with both products.

Administration, Oral↗
PubMed1990

Comparative in vitro activities of amoxicillin-clavulanic acid, cefuroxime, cephalexin, and cephalothin against trimethoprim-resistant Escherichia coli isolated from stools of children attending day-care centers.

A high prevalence of fecal colonization with trimethoprim-resistant Escherichia coli was found in diapered children attending day-care centers in Houston, Tex. In the present study, 100 isolates of E. coli resistant to multiple antibiotics, including trimethoprim (100%), sulfisoxazole (100%), streptomycin (94%), and ampicillin (87%), were obtained over a 5-month period from stool samples of diapered children attending four day-care centers and tested for their susceptibilities to amoxicillin-clavulanic acid, cefuroxime, cephalexin, and cephalothin. The MICs for 50 and 90% of strains tested were 16 and 32 micrograms/ml, respectively, for amoxicillin-clavulanic acid, 4 and 16 micrograms/ml, respectively, for cefuroxime, 4 and 64 micrograms/ml, respectively, for cephalexin, and 32 and greater than 64 micrograms/ml, respectively, for cephalothin. Although all three oral beta-lactams tested were generally active at concentrations likely to be achieved in urine, cefuroxime and cephalexin were more potent and are thus more likely to be inhibitory at the concentrations needed for systemic infections.

Amoxicillin↗
PubMed2002

CcaR is an autoregulatory protein that binds to the ccaR and cefD-cmcI promoters of the cephamycin C-clavulanic acid cluster in Streptomyces clavuligerus.

The putative regulatory CcaR protein, which is encoded in the beta-lactam supercluster of Streptomyces clavuligerus, has been partially purified by ammonium sulfate precipitation and heparin affinity chromatography. In addition, it was expressed in Escherichia coli, purified as a His-tagged recombinant protein (rCcaR), and used to raise anti-rCcaR antibodies. The partially purified CcaR protein from S. clavuligerus was able to bind DNA fragments containing the promoter regions of the ccaR gene itself and the bidirectional cefD-cmcI promoter region. In contrast, CcaR did not bind to DNA fragments with the promoter regions of other genes of the cephamycin-clavulanic acid supercluster including lat, blp, claR, car-cyp, and the unlinked argR gene. The DNA shifts obtained with CcaR were prevented by anti-rCcaR immunoglobulin G (IgG) antibodies but not by anti-rabbit IgG antibodies. ccaR and the bidirectional cefD-cmcI promoter region were fused to the xylE reporter gene and expressed in Streptomyces lividans and S. clavuligerus. These constructs produced low catechol dioxygenase activity in the absence of CcaR; activity was increased 1.7- to 4.6-fold in cultures expressing CcaR. Amplification of the ccaR promoter region lacking its coding sequence in a high-copy-number plasmid in S. clavuligerus ATCC 27064 resulted in a reduced production of cephamycin C and clavulanic acid, by 12 to 20% and 40 to 60%, respectively, due to titration of the CcaR regulator. These findings confirm that CcaR is a positively acting autoregulatory protein able to bind to its own promoter as well as to the cefD-cmcI bidirectional promoter region.

Amino Acid Isomerases↗
PubMed1989

Influence of ranitidine, pirenzepine, and aluminum magnesium hydroxide on the bioavailability of various antibiotics, including amoxicillin, cephalexin, doxycycline, and amoxicillin-clavulanic acid.

Two randomized double-blind crossover studies and one randomized crossover study were performed to document possible drug-drug interactions between antacids (aluminum magnesium hydroxide, 10 ml per dose for 10 doses), antimuscarinic drugs (pirenzepine, 50 mg per dose for 4 doses), and H2-blockers (ranitidine, 150 mg per dose for 3 doses) and amoxicillin (1,000 mg), cephalexin (1,000 mg), doxycycline (200 mg), and amoxicillin-clavulanic acid (625 mg). Ten healthy volunteers participated in each study. Concentrations in serum and urine were measured by bioassay, and pharmacokinetic parameters were calculated by the usual open one- or two-compartment models (statistics were determined by the Wilcoxon test). The antacid, pirenzepine, and ranitidine had no influence on the bioavailability of amoxicillin, cephalexin, and amoxicillin-clavulanic acid. Only small differences could be observed in the pharmacokinetic parameters, but they are not of therapeutic importance. However, the antacid caused a significant (P less than 0.01) reduction in the gastrointestinal absorption of doxycycline (area under the concentration-time curve, 38.6 +/- 22.7 mg.h/liter, fasting; 6.0 +/- 3.2 mg.h/liter, with antacid), resulting in subtherapeutic levels of doxycycline.

Adult↗
PubMed1989

[Pediatric suspensions of amoxicillin and clavulanic acid in the treatment of bacterial infections of otorhinolaryngologic importance and the upper respiratory tract].

Thirty children, 20 males and 10 females, aged 6.57 +/- 0.78 on the average (range: from 13 to 6 months), weighing 21.60 +/- 2.25 kg with bacterial infections of the upper respiratory tract and ear were admitted to the present trial. A chemotherapeutic agent based on amoxycillin and clavulanic acid in the suspension for children of 312.5 mg/5 ml (4:1 ratio) at the dosage of about 17 mg/kg in two daily administrations according to the weight of the patients was used. The therapy was prolonged for 8.87 +/- 0.30 days on the average, from a minimum of 3 to a maximum of 11 days. In the course of the treatment the symptom parameters and the objective signs progressively reduced until disappearance; the body temperature came promptly back to normal values, confirming the definite improvement and the regression of the infectious pictures. The microbiological data also fully confirmed the successful activity of the chemoantibiotic drug used. No side effects were found and, as regards local and general tolerance, no signs of an even slight impairment related to the administration of the drug were found. The final judgement expressed on the efficacy, on the basis of the more or less quick and complete symptom regression, evolution of the infectious picture and good tolerance were the following: excellent in 22 cases, good in 6, fair in 1 and not able to be evaluated in 1 case (a female patient who left off the trial).

Adolescent↗
PubMed1988

[Activity of 9 beta-lactam antibiotics combined with clavulanic acid or sulbactam against the strains of broad-spectrum beta-lactamase (CTX-1) producing Enterobacteriaceae isolated at the Henri Mondor Hospital].

Minimal inhibitory concentrations (MICs) of seven cephalosporins: cefotaxime (CTX), ceftriaxone (CRO), ceftazidime (CAZ), latamoxef (MOX), cefoxitin (FOX), cefotetan (CTT) and CM 40876 (CM), of aztreonam (ATM) and imipenem (IPM) were evaluated by agar dilution with and without 5 mg/l of clavulanic acid (AC) or sulbactam (SB) for 28 strains isolated in 1986 (15 K. pneumoniae, 3. K. oxytoca, 4 E. coli, 4 E. cloacae, 1 E. aerogenes and 1 C. freundii). Comparatively to MICs of sensitive strains and to those of cured variants, MICs of these strains were very increased for CTX, CRO, ATM (mode MIC: 1 mg/l), and CAZ (2); weakly increased for MOX and CTT (0.25), and identical for IMP (0.12-0.25), CM (0.06) and FOX (2-4), except for Enterobacter and Citrobacter (64). Association with AC or SB did not modify MICs of FOX, CM and IMP. For the other antibiotics, MICs were reduced by addition of AC: Klebsiella: 5 log2 for CTX and CRO, 4 for CAZ and ATM, 2 for MOX and CTT; E. coli: 4 log2 for CTX and ATM, 3 for CRO and CAZ, 1 for MOX and CTT; Enterobacter and Citrobacter 2 log2 for CTX, CRO, CAZ and ATM, 1 for MOX and CTT. With SB, decrease of MICs was two to for fold lesser than with AC. AC, and less efficiently SB, restored activity of CTX, CRO, CAZ and ATM on CTX-1 producing Enterobacteriaceae, particularly Klebsiella and E. coli. It was the same for MOX and CTT, weakly affected by this resistance. AC and SB had not effect on FOX, CM and IPM which remained active on these strains.

Anti-Bacterial Agents↗
PubMed1992

Characterization of the Streptomyces clavuligerus argC gene encoding N-acetylglutamyl-phosphate reductase: expression in Streptomyces lividans and effect on clavulanic acid production.

The argC gene of Streptomyces clavuligerus encoding N-acetylglutamyl-phosphate reductase (AGPR) has been cloned by complementation of argC mutants Streptomyces lividans 1674 and Escherichia coli XC33. The gene is contained in an open reading frame of 1,023 nucleotides which encodes a protein of 340 amino acids with a deduced molecular mass of 35,224 Da. The argC gene is linked to argE, as shown by complementation of argE mutants of E. coli. Expression of argC from cloned DNA fragments carrying the gene leads to high levels of AGPR in wild-type S. lividans and in the argC mutant S. lividans 1674. Formation of AGPR is repressed by addition of arginine to the culture medium. The protein encoded by the argC gene is very similar to the AGPRs of Streptomyces coelicolor, Bacillus subtilis, and E. coli and, to a lesser degree, to the homologous enzymes of Saccharomyces cerevisiae and Anabaena spp. A conserved PGCYPT domain present in all the AGPR sequences suggests that this may be the active center of the protein. Transformation of S. clavuligerus 328, an argC auxotroph deficient in clavulanic acid biosynthesis, with plasmid pULML30, carrying the cloned argC gene, restored both prototrophy and antibiotic production.

Aldehyde Oxidoreductases↗
PubMed1986

Comparative in vitro activities of amoxicillin-clavulanic acid and imipenem against anaerobic bacteria isolated from community hospitals.

The susceptibilities of recent clinical isolates of anaerobic bacteria from two community hospitals were determined. Thirty percent of pigmented Bacteroides species and bile-sensitive, nonpigmented Bacteroides species produced penicillinase and were resistant to amoxicillin. Cefoxitin and clindamycin showed good activity against most strains, with the exception of rare isolates of the Bacteroides fragilis group and some strains of Clostridium species. While amoxicillin was not active against B. fragilis and other members of the B. fragilis group, amoxicillin-clavulanic acid was very active against almost all of these organisms. Imipenem was the most potent agent against all strains tested.

Amoxicillin↗
PubMed1995

Back mutations to the TEM-1 beta-lactamase from TRC-1 lead to restored sensitivity to clavulanic acid.

Back mutations from the TRC-1 beta-lactamase to the TEM-1 enzyme were selected in vitro. The revertant beta-lactamase was obtained from Escherichia coli strain J62.2 carrying plasmid pUK901 which encodes the TRC-1 beta-lactamase. The revertant was obtained after repeated subculture of E. coli J62.2 (pUK901) in amoxycillin 512 mg/L for 5 days. The revertant beta-lactamase had the same pI as TEM-1 (5.4) and had restored inhibition by clavulanic acid (ID50 reduced from 4.2 microM to 0.15 microM). The prevalence of these beta-lactamases in the clinical population may be the result of a two-way flux, with mutations in both forward and backward directions.

Amoxicillin↗
PubMed1986

In vitro activity of piperacillin, ticarcillin, mezlocillin, ticarcillin-clavulanic acid, aztreonam, ceftazidime, azlocillin, cefoperazone, and thienamycin against Pseudomonas aeruginosa.

The in vitro susceptibility of 103 well-characterized strains of Pseudomonas aeruginosa to nine antimicrobial agents was assessed by means of the Kirby-Bauer disk diffusion assay and the microtiter minimal inhibitory concentration assay. The antimicrobials, from the most to the least active against P aeruginosa, were thienamycin greater than ceftazidime greater than piperacillin greater than azlocillin greater than cefoperazone greater than aztreonam greater than ticarcillin greater than ticarcillin-clavulanic acid greater than mezlocillin. The resistance patterns of the antimicrobial agents suggest that P aeruginosa resistant to a penicillin, cephalosporin, or aztreonam may be susceptible to thienamycin.

Anti-Bacterial Agents↗
PubMed1990

Influence of clavulanic acid on the activity of amoxicillin against an experimental Streptococcus pneumoniae-Staphylococcus aureus mixed respiratory infection.

An experimental respiratory infection caused by Streptococcus pneumoniae was established in weanling rats by intrabronchial instillation. Treatment of this infection with amoxicillin rapidly eliminated the pneumococci from the lung tissue. A beta-lactamase-producing strain of Staphylococcus aureus, when inoculated in a similar manner, did not persist adequately in the lungs long enough to permit a reasonable assessment of the therapy, but staphylococcal survival was extended in the lungs of rats infected 24 h previously with S. pneumoniae. Amoxicillin therapy was relatively ineffective against the pneumococci in this polymicrobial infection and had no effect on the growth of S. aureus. In contrast, amoxicillin-clavulanic acid eliminated the pneumococci from the lung tissue and brought about a reduction in the numbers of staphylococci. The data illustrate the utility of this model for the study of polymicrobial lung infections and demonstrate the role of amoxicillin-clavulanic acid in the treatment of polymicrobial infections involving beta-lactamase-producing bacteria.

Amoxicillin↗
PubMed2002

Effects of 0.2% chlorhexidine gluconate and amoxicillin plus clavulanic acid on the prevention of alveolar osteitis following mandibular third molar extractions.

OBJECTIVE: The purpose of this study was to evaluate the use of a 0.2% chlorhexidine gluconate and amoxicillin plus clavulanic acid combination as a prophylactic therapy for the prevention of alveolar osteitis after mandibular third molar extractions and to investigate adverse reactions to chlorhexidine. STUDY DESIGN: This randomized, placebo-controlled, parallel group study was conducted in a group of 177 subjects, from which 3 groups were formed. The first group (n = 62) received 0.2% chlorhexidine gluconate, the second group (n = 56) received a 0.2% chlorhexidine gluconate and amoxicillin plus clavulanic acid combination, and the third group (n = 59) received 0.09% sterile saline solution. All patients were recalled for the diagnosis of alveolar osteitis on the third and seventh postoperative days. RESULTS: When patients in the antibiotic group were compared with those in the other 2 groups, a significant reduction in alveolar osteitis was noted (P <.05). An alteration in taste, the bad taste of the solution, and staining of dentures and oral tissues were the major complaints about chlorhexidine. CONCLUSION: It would be more beneficial to use chlorhexidine solution with a beta-lactamase inhibitor-containing antibiotic to enhance its effectiveness for the prevention of alveolar osteitis.

Adult↗
PubMed1990

In vitro activities of fleroxacin, cefetamet, ciprofloxacin, ceftriaxone, trimethoprim-sulfamethoxazole, and amoxicillin-clavulanic acid against rare members of the family Enterobacteriaceae primarily of human (clinical) origin.

Fleroxacin and cefetamet were evaluated in vitro against 38 infrequently encountered species (250 strains) of the family Enterobacteriaceae and compared with four established compounds. For all the strains tested, the fleroxacin MIC was less than or equal to 0.5 mg/liter, and for 98% of strains the cefetamet MIC was less than or equal to 8 mg/liter; even though the two new compounds did not quite reach the activities (on a weight-by-weight basis) of ciprofloxacin and ceftriaxone, respectively, they nonetheless clearly surpassed trimethoprim-sulfamethaxazole and amoxicillin-clavulanic acid. The very potent new oral compounds tested in this study appear to be promising for the treatment of clinically relevant infections due to uncommon species of Enterobacteriaceae.

Amoxicillin↗
PubMed1995

[Cholestatic jaundice after ingestion of amoxicillin and clavulanic acid].

HISTORY AND FINDINGS: A 61-year-old woman fell ill with recurrent nausea, loss of appetite and tiredness. Five days later she noted increasing jaundice of skin and sclerae, pale stools and dark urine, and she developed itching over the whole body. Among biochemical tests alkaline phosphatase (537 U/l) and bilirubin (32.0 mg/dl) were markedly increased, while both GOT (102 U/l) and GPT (39 U/l) were only slightly elevated. Ultrasonography was normal and extrahepatic cholestasis appeared unlikely on endoscopic retrograde cholangiopancreatography. Cholestasis due to virus hepatitis was also excluded. It was only on repeated and direct questioning that the patient reported having taken three tablets daily of Augmentin (amoxicillin and clavulanic acid) for 12 days 5 weeks before the onset of symptoms. TREATMENT AND COURSE: After symptomatic treatment with Colestyramine (4 g three times daily), ursodeoxycholic acid (250 mg twice daily) and the antihistaminic Clemastine (1 g two times daily) the severe pruritus decreased quickly and alkaline phosphatase concentration became normal. At follow-up examination 4 and 8 weeks later the laboratory tests were normal. CONCLUSIONS: This report of Augmentin-induced cholestasis is not unique. It shows that previous drug intake must be carefully investigated in any case of cholestasis of unknown cause.

Amoxicillin↗