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Omeprazole, azithromycin and amoxicillin or amoxicillin plus clavulanic acid in eradication of Helicobacter pylori in duodenal ulcer disease.

Treatment with omeprazole (OME), azithromycin (AZI) and amoxicillin (AMO) resulted in encouraging Helicobacter pylori cure rates in pilot and control studies. The aim of this study was to establish whether OME + AZI in combination with either AMO or ACA (amoxicillin plus clavulanic acid) are effective in curing H. pylori infection. A hundred patients with active duodenal ulcer and H. pylori infection were treated with OME (day 1-10: 2 x 40 mg/day, day 11-24: 40 mg/day, day 25-42: 20 mg/day) plus AZI 500 mg/day for the first 6 days. Patients were randomly assigned to either AMO 2 x 1000 mg/day (group A, n = 50) or ACA 2 x 1250 mg/day (group B, n = 50) during the first 10 days of treatment. H. pylori status was determined by urease test and histology before and 6 weeks after completion of therapy. Ninety-five patients completed the study. H. pylori infection was eradicated in 85.4% (41/48) patients from group A (intention-to-treat (ITT) analysis: 82%) versus 91.5% (43/47) patients from group B (ITT) analysis: 86%) (NS). All ulcer had healed after 42 days of omeprazole treatment. Side effects, usually minor, were recorded in 12.5% (group A) and 14.9% (group B) of patients (NS). Therapy had to be discontinued in two patients (one in group A and one group B) only. Ten-days treatment with OME and AZI (for the first 6 days) with AMO or ACA are simple and highly effective regimens to cure H. pylori infection in patients with duodenal ulcer disease.

Adult↗

Amoxicillin-clavulanic acid in the treatment of lower respiratory tract infections caused by beta-lactamase-positive Haemophilus influenzae and Branhamella catarrhalis.

Twenty-one adult patients hospitalized with lower respiratory tract infections due to Branhamella catarrhalis or Haemophilus influenzae or both were treated with the combination of oral amoxicillin and potassium clavulanate (Augmentin) in an open, noncomparative clinical trial. Diseases included pneumonia, empyema, and exacerbations of bronchiectasis and chronic lung disease. Thirteen of 16 B. catarrhalis and six of nine H. influenzae isolates were beta-lactamase positive. The patients with B. catarrhalis were treated for a mean of 5.3 days, and those with H. influenzae were treated for a mean of 7.0 days. The overall response to therapy was excellent, with 18 of 19 beta-lactamase-producing strains eradicated on therapy. One patient secondarily infected with Pseudomonas aeruginosa was a clinical failure, and two patients with H. influenzae who became culture positive again after therapy were considered microbiologic failures. Gastrointestinal side effects (especially nausea) were common, although all patients completed a course of therapy. Sputum levels of amoxicillin were surprisingly low (less than 0.05 to 0.54 micrograms/ml), a finding which may explain the high relapse rate (22%) seen with H. influenzae, as these are below the usual MICs of amoxicillin for this organism. The combination of amoxicillin plus potassium clavulanate appears to be an excellent drug for treatment of beta-lactamase-producing strains of these two species, although mild gastrointestinal side effects are common.

Aged↗

Substitution of Met-69 by Ala or Gly in TEM-1 beta-lactamase confer an increased susceptibility to clavulanic acid and other inhibitors.

In some inhibitor-resistant TEM-derived beta-lactamases, Met-69 is substituted by Leu, Ile or Val. Residue 69 is located in a region of strong structural constraints, at the beginning of H2 alpha-helix, and in the vicinity of B3 and B4 beta-strands. Analysis of the three-dimensional structure of TEM-1 beta-lactamase suggests that alteration of the substrate-binding site can be produced by changes of the size of residue 69 side chain. Met-69 was substituted by alanine or glycine in TEM-Bs beta-lactamase (a TEM-1-related enzyme) using site-directed mutagenesis. The minimum inhibitory concentrations of the mutants compared with the wild-type revealed an increased susceptibility to beta-lactamase inhibitor-beta-lactam combinations and to first-generation cephalosporins. Comparing the Met69Ala and Met69Gly beta-lactamases with TEM-Bs, K(m) constants of the mutants showed an increased affinity for most beta-lactams but the kcat for most substrates did not change substantially. Mutants also demonstrated lower IC50 for the three inhibitors (clavulanic acid, tazobactam and sulbactam). The two substitutions of the residue 69 by alanine and glycine had a noticeable effect on K(m) values of TEM-Bs beta-lactamase, and on affinity for beta-lactamase inhibitors.

Alanine↗

Ototoxicity of topical ticarcillin and clavulanic acid in the chinchilla.

BACKGROUND: Currently available topical otic preparations contain a variety of antibiotics and other ingredients that are potentially damaging to the middle and inner ear. There is therefore a need to identify agents that are safe as well as effective for topical otologic use. In pursuit of that goal, we used an animal model to evaluate the ototoxic potential of the broad-spectrum, penicillin derivative ticarcillin--both alone and combined with clavulanic acid (a beta-lactamase inhibitor). METHODS: Twenty chinchillas served as subjects. Ten of the animals were given a single middle ear application of ticarcillin; the remaining 10 animals received ticarcillin disodium plus clavulanate potassium (Timentin). Five animals from each of the two groups were killed after 1 week to assess short-term effects and the other five animals in each group were kept for 4 weeks before their temporal bones were removed for histologic study. RESULTS: Significant toxic effects, involving both the middle and inner ear, were observed in all experimental groups. Alterations of the middle ear at 1 week included inflammation, hemorrhage, and effusions. Middle ear cholesteatomas were observed at 4 weeks. Inner ear changes seen at 1 and 4 weeks included hair cell loss, supporting cell degeneration, and strial damage. CONCLUSION: The study results indicate that ticarcillin should not be considered for further evaluation as a possible antibiotic for use in ototopical preparations.

Administration, Topical↗

[Appearance of Escherichia coli strain with high production of cephalosporinase during treatment with an amoxicillin and clavulanic acid combination].

In the course of an Escherichia coli cholecystitis, demonstrated by positive blood cultures, the authors observed a therapeutic failure with amoxicillin/clavulanate, probably related to the isolation in blood cultures, nine days after the beginning of the treatment, of a beta-lactam resistant E. coli strain (MICs of the amoxicillin combined with clavulanate was 64 mg/l and ceftazidim 16 mg/l). The strains which were recovered before and after treatment were shown to have the same biotype and the same electrophoretic profile for bacterial esterases. The second strain exhibited a high level production of the mediated chromosomal cephalosporinase. In the agar diffusion test, this mutant was more easily detected by ceftazidim than by other third generation cephalosporins. In the middle-stay unit where the patient was cured, cephalosporinase high producing mutants of E. coli were recovered in 0.6 p. cent of the strains versus 5, 1 p. cent for strains with cephalosporinase phenotype and 46.6 p. cent for strains with penicillinase phenotype. This report illustrates the importance of associating two synergistic antibiotics to prevent the emergence of beta-lactam resistant mutants in the course of severe E. coli infections.

Acute Disease↗

[Prophylactic antibiotic therapy (amoxicillin + clavulanic acid) before embryo transfer for IVF is useless. Results of a randomized study].

OBJECTIVES: We studied the implantation rate during IVF cycles according to the prescription or not of antibiotics. MATERIALS AND METHODS: During a 5-month period all the patients aged less than 38 years were randomized into two groups according to an independent personal variable. In group 1 amoxicilline + clavulanic acid 1g/125 mg were administrated from the ovum pick-up day for 6 days. In the group 2 no antibiotic treatment was administered. RESULTS: The two groups were identical for all the criteria (type of stimulation, IVF/ICSI report, indications, average age). The average number of collected oocytes, obtained embryos and transferred embryos was similar in the two groups. The implantation rate per transfer was similar in the two groups (36.9% versus 36.5%; p>0.95). The pregnancy loss rate (biological pregnancy, early and late miscarriages or extra uterine pregnancy) was increased in a non significant manner (p=0.15) in the group with antibiotic: 33.3% (16/48) versus 20.8% (11/53) in the group without antibiotic. CONCLUSION: This prospective randomised study leads us not to recommend this antibiotic prescription at the time of the embryo transfer during in vitro fertilisation attempt.

Adult↗

The positive activator of cephamycin C and clavulanic acid production in Streptomyces clavuligerus is mistranslated in a bldA mutant.

In Streptomyces coelicolor bldA encodes the principal leucyl tRNA for translation of UUA codons and controls pigmented antibiotic production by the presence of TTA codons in the genes encoding the pathway-specific activators of actinorhodin and undecylprodigiosin biosynthesis. In Streptomyces clavuligerus the gene encoding the pathway-specific activator of both cephamycin C and clavulanic acid production, ccaR, also contains a TTA codon and was expected to exhibit bldA-dependence. A cloned S. clavuligerus DNA fragment containing a sequence showing 91% identity to the S. coelicolor bldA-encoded tRNA was able to restore antibiotic production and sporulation to bldA mutants of S. coelicolor and the closely related Streptomyces lividans. A null mutation of the bldA gene in S. clavuligerus resulted in the expected sporulation defective phenotype, but unexpectedly had no effect on antibiotic production. Transcript analysis showed no difference in the levels of ccaR transcripts in the wild-type and bldA mutant strains, ruling out any effect of elevated levels of the ccaR mRNA. Furthermore, when compared to the wild-type strain, the bldA mutant showed no differences in the levels of CcaR, suggesting that the single TTA codon in ccaR is mistranslated efficiently. The role of codon context in bldA dependence is discussed.

Bacterial Proteins↗

Comparative effect of thiamphenicol glycinate, thiamphenicol glycinate N-acetylcysteinate, amoxicillin plus clavulanic acid, ceftriaxone and clarithromycin on pulmonary clearance of Haemophilus influenzae in an animal model.

BACKGROUND: Thiamphenicol glycinate (TG) and its derivative thiamphenicol glycinate N-acetylcysteinate (TGA) could be a valid therapeutic option in the treatment of respiratory tract infections. METHODS: Time-kill curves of TG and TGA and pulmonary clearance in Haemophilus influenzae infected guinea pigs were compared with those of clarithromycin, ceftriaxone and amoxicillin plus clavulanic acid. RESULTS: The bacterial activities of the tested antibiotics were comparable. When compared to the control group, lung bacterial counts were significantly lower for the TGA group at 3 h vs. controls, while for the other treatments, significant decreases were recorded after 6 h. All drugs showed a log count of <2.0 at 24 h with respect to the control while at 48 h all groups demonstrated a log count of <2.0. CONCLUSIONS: Although the in vitro activity of the tested drugs evaluated by time-kill curves seemed comparable, some pharmacokinetic and pharmacodynamic characteristics of TGA contribute to improving the resolution of the infective process.

Acetylcysteine↗

Incidence of gonorrhoea due to penicillinase producing Neisseria gonorrhoeae in Japan 1981-3 and treatment using a new antibiotic combination, BRL25000 (amoxycillin and clavulanic acid).

During the three years 1981-3, 134 (9.1%) of 1473 patients presenting at our clinics were found to be infected with penicillinase producing strains of Neisseria gonorrhoeae (PPNG). Minimum inhibitory concentrations (MICs) of benzylpenicillin and ampicillin against these PPNG strains were 8 mg/l or more, whereas against non-PPNG strains they were consistently 4 mg/l or less. In contrast, the MIC of BRL25000 (two parts amoxycillin and one part clavulanic acid, the beta lactamase inhibitor) was 4 mg/l or less even against PPNG strains. MICs of a number of other drugs commonly used to treat gonorrhoea, such as cephaloridine, cefoxitin, tetracycline, doxycycline, minocycline, kanamycin, and spectinomycin, showed no appreciable differences between non-PPNG and PPNG strains and the MIC of cephaloridine in particular was relatively high. BRL25000 proved to be very effective in the treatment of PPNG infection and cured all of 121 patients treated. A daily dose of 2.25g, cured 105 patients in two days, 11 patients in three days, four patients in four days, and one patient in five days. A new rapid diagnostic method for detecting PPNG strains, capable of application at an outpatient clinic and providing a result on the following day, is described.

Amoxicillin↗

[Amoxicillin and clavulanic acid suspension for children in the treatment of bronchopulmonary infections].

The present study has been tested on 30 children, 14 males and 16 females, average age 4.11 +/- 0.44 (range 9 months to 10 years), weight of 17.08 +/- 1.25 Kg, with infections concerning low respiratory tract (8 cases of broncho-pneumonia, 9 cases of acute bronchitis and 13 cases of lobar pneumonia). It has been used a chemotherapy composed of amoxycillin and clavulanic acid in pediatric suspension of 312.5 mg/5 ml (in the ratio of 4 to 1); the daily dosage, related to the children's weight has been of 43.91 +/- 1.21 mg/Kg in two daily doses. On the average the therapy has lasted for 6.43 +/- 0.19 days from a minimum of 4 to a maximum of 8 days. During the treatment the symptomatologic parameters (dyspnoea, cough), and the objective ones (pathological lung signs, rales, hypophonesis, bronchial breath...) have progressively improved till they have disappeared; morning and evening body temperature has promptly returned to normal. Both the physical and radiological exams of the chest confirm either the improvement or the regression of the infection in most of the cases. Side effects due to the antibiotic have not been registered and local and general tolerability was excellent. Considering the more or less fast and complete symptomatological regression, the evolution of the infective clinical picture and the tolerability, the final evaluations have been: excellent efficacy in 13 cases, good efficacy in 9 cases, fairly good in 5 cases and poor in 3 cases.

Amoxicillin↗

Measurement of cefaclor and amoxicillin-clavulanic acid levels in middle-ear fluid in patients with acute otitis media.

Concentrations of cefaclor (CFC) or amoxicillin-clavulanic acid (AMX/CA) in middle-ear fluid collected preserving the stability and clearing the cell contents has been compared to those obtained using the traditional method. Sixty-seven children with effusive otitis media were treated orally with CFC (20 mg/kg of body weight) or AMX/CA (20 mg/kg) (4:1 ratio). The concentrations in cell-free fluid (C-) appear higher than those in the total fluid (C+) (as assayed traditionally).

Acute Disease↗

[The combination of amoxicillin-clavulanic acid and ofloxacin in the treatment of multidrug-resistant Mycobacterium tuberculosis].

A 67-year-old [correction of 53] man with multidrug resistant tuberculosis (MDR-TB) had been persistently positive for acid-fast bacilli (AFB) both on sputum smear and also on culture with the Ogawa egg medium for 30 years since 1951. The case had been treated previously with isoniazid, rifampin, streptomycin, ethambutol, kanamycin, ethionamide, paraaminosalicylate and cycloserine; however, M. tuberculosis strains isolated from this patient acquired a high resistance to all of these agents. Then, a new regimen of chemotherapy, INH combined with ofloxacin (OFLX) and amoxicillin-clavulanic acid (AMPC/ CVA), was applied to the case. He was successfully treated with this regimen, and a marked decrease in the amount of AFB on smear as well as on culture was observed during the course of chemotherapy. No adverse effects were seen meanwhile. These data suggest that it is worth while to try a regimen containing AMPC/CVA and OFLX in the treatment of MDR-TB.

Aged↗