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Roxithromycin versus amoxicillin-clavulanic acid in the treatment of respiratory tract infections.

A multicenter, double-blind, double-dummy trial was conducted in 96 general practice patients with upper and lower respiratory tract infection to compare the efficacy and tolerance of roxithromycin (150 mg b.i.d.) and amoxicillin-clavulanic acid (500 mg/125 mg t.i.d.). Good clinical response was obtained in 96% and 95% of cases, respectively, but only 4% of patients receiving roxithromycin volunteered adverse events possibly or probably related to their test treatment, as opposed to 17% of those receiving amoxicillin-clavulanic acid. The results indicate that both drugs are equally effective in the treatment of respiratory tract infection, but that roxithromycin is better tolerated.

Adult↗

Beta-lactam resistance in Nocardia brasiliensis is mediated by beta-lactamase and reversed in the presence of clavulanic acid.

Forty clinical isolates and the type strain of Nocardia brasiliensis were screened for susceptibility to 20 beta-lactams. Isolates exhibited a single pattern of resistance, with large zones of inhibition by disk diffusion and low MICs by broth and agar dilutions only to cefotaxime, ceftriaxone, ceftizoxime, Augmentin, and Timentin. All strains produced beta-lactamase, with five different enzyme patterns by isoelectric focusing. Despite the differences in their isoelectric points, the enzymes had the same substrate profiles, with equivalent activity against penicillin, ampicillin, cefamandole, cephalothin, and cephalordine. In an in vitro assay, the enzymes were highly susceptible to clavulanic acid. The MIC50 and MIC90 for the combination of amoxicillin and clavulanic acid (Augmentin) was 2 and 4 micrograms/ml, respectively, compared with 16 micrograms/ml for both values for amoxicillin alone. These studies suggest that beta-lactamase is the major mechanism of beta-lactam resistance in this species and that Augmentin is the first oral beta-lactam with good potential for treating infections due to N. brasiliensis.

Amoxicillin↗

[Activity of the amoxicillin-clavulanic acid (augmentin) combination on strains of hospital isolates].

All strains of Staphylococcus aureus and Gram negative bacilli (Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter) isolated from 01.01 to 03.31.83 were studied using agar diffusion with augmentin-impregnated discs (amoxicillin 20 micrograms + clavulanic acid 10 micrograms). Augmentin is active against penicillinase-producing Staphylococci susceptible to methicillin, whereas methicillin-resistant strains are also resistant to augmentin. According to the susceptibility of strains to amoxicillin, carbenicillin and cefalotin, Enterobacteriaceae can be divided into five main phenotypes, of which four are resistant. "RSR" and "RRR" phenotypes, which are cephalosporinase producers, are chiefly found among Enterobacter, Serratia, Citrobacter and indole + Proteus; in these groups a change in inhibition diameters indicating activity of augmentin is observed only in a significant number of Proteus vulgaris strains. "RRS" and "RRI" strains are penicillinase producers found mainly among E. coli, Klebsiella pneumoniae and oxytoca, and Proteus mirabilis; they emerge as very susceptible to augmentin. Pseudomonas aeruginosa is never susceptible to augmentin. Augmentin is slightly more active than amoxicillin on some Acinetobacter strains but the difference is too inconsiderable to be of clinical significance.

Acinetobacter↗

[The effectiveness of preventive use of antibiotics in Cesarean section with a single dose: comparison of cefotaxime with amoxicillin plus clavulanic acid].

The effectiveness of a single prophylactic dose of two broad spectrum antibiotics, during Caesarean section, was compared and evaluated. In 119 consecutive cases at the Cantonal Hospital in Winterthur, Switzerland, either 1 g i.v. cefotaxime or 1,2 g amoxicillin plus clavulanic acid were administered after clamping the umbilical cord during Caesarean section. The study shows that single dose prophylaxis of either regimen provides adequate cover in preventing morbidity in Caesarean section, in both high-risk and low-risk groups.

Adult↗

Amoxicillin and clavulanic acid in the treatment of actinomycetoma.

BACKGROUND: Mycetoma is a relatively frequent disease in tropical countries. Drugs commonly used need a long period of treatment, and some cases are resistant to these drugs, especially those with bone or visceral involvement. The combination of amoxicillin-clavulanic acid has shown effectiveness against strains of Nocardia brasiliensis in vitro. METHODS: We have used this combination in two cases of mycetoma caused by N. brasiliensis, both with bone involvement and resistance to the drugs usually used. A dose of three tablets a day for 5 to 6 months was given (each tablet contains 500 mg of amoxicillin and 125 mg of clavulanic acid). RESULTS: Clinical and mycologic amelioration was observed in the two cases after completing the treatment. There were no side effects or relapses after 3 to 6 months of follow-up after treatment. CONCLUSIONS: We propose this antibiotic as a new option for the treatment of some special cases of actinomycetoma with bone or visceral involvement or resistance to the drugs commonly used in this disease.

Amoxicillin↗

[Prophylactic antibiotic therapy with amoxicillin-clavulanic acid in oropharyngeal surgery].

The present paper shows the results of a randomized, prospective trial carried out on 170 patients undergoing elective surgery for oropharyngeal cancer. These patients were distributed in two groups that received a prophylactic therapy with amoxicillin and clavulanic acid, for 24 hours and 5 days, respectively. Comparing results of short-term and long-term prophylaxis. Among patients undergoing only total or partial laryngectomies, no differences between both groups were found. Among patients who already had a tracheostomy, the rate of local infection was higher in the short-time group. Duration of prophylaxis in high-risk surgery, such as that requiring flap reconstruction, needs further investigation.

Amoxicillin↗

Serum digoxin levels after concomitant ticarcillin and clavulanic acid administration.

Recently it has been recognized that steady-state serum digoxin concentrations may increase or fall to ineffective levels when the glycoside is administered together with several antibiotics. Our study was designed to assess if serum digoxin levels may be modified by the concomitant use of a ticarcillin and clavulanic acid. The study was carried out in 15 hospitalized patients suffering from exacerbation of their chronic bronchitis without liver disease and renal failure. Serum digoxin levels were not significantly modified by the concomitant use of a ticarcillin and clavulanic acid, although peak digoxin serum concentrations were slightly lower. However, the average time to achieve the maximum concentration and area under the curve over 24 h did not change.

Aged↗

Prophylactic administration of amoxicillin and clavulanic acid in pregnant women with premature rupture of the membranes.

Seventy-five pregnant women (mean gestational age 32.26 weeks, range 20-36 weeks) with premature rupture of the membranes (PROM) were admitted in our department during 1989 and the first 6 months of 1990. Amoxicillin and clavulanic acid was initially administered at a dose of 1.2 g i.v. every 8 hours for 3-4 days and was followed by oral administration of 625 mg every 8 hours until labor. Sixty-one patients (mean gestational age 32.6 +/- 2.3 weeks, range 26-36 weeks) achieved an uncomplicated course of their pregnancies with a mean time of 11.4 +/- 5.7 days (range 3-27 days), from rupture to delivery. Fourteen women (mean gestational age 30.8 +/- 5 weeks, range 20-36 weeks) developed chorioamnionitis 3.5 +/- 0.9 days (range 1.4-5.6 days) after the rupture with several degrees of leukocyte infiltration of the membranes, placenta and the umbilical cord. Five women (mean gestational age 23.8 +/- 2.3 weeks, range 20-26 weeks) had complications resulting in fetal/infant death, three of them because of fetal sepsis (Escherichia coli, Pseudomonas aeroginosa, Staphylococcus aureus). The newborns were followed up 6 months from delivery and had no signs of drug influence. Few side effects were observed with the chief complaints involving the gastrointestinal tract (4%). No one discontinued the drug. It seems therefore, that the prophylactic administration of amoxicillin and cluvalanic acid in women with PROM is associated with a significant prolongation of pregnancy and with a reduction in the incidence of fetal/maternal infections.

Amoxicillin↗

Amoxycillin-clavulanic acid combination in bronchopulmonary infection due to beta-lactamase-producing Branhamella catarrhalis. Preliminary report.

Since 1978 we have taken an interest in lower respiratory tract infections associated with Branhamella catarrhalis in Christchurch, New Zealand. In a preliminary trial, 20 patients with bronchopulmonary infection caused by beta-lactamase-producing B. catarrhalis were treated with a combination tablet of amoxycillin 500 mg and clavulanic acid 125 mg ('Augmentin') 3 times daily for 5 days. Sputum cultures were negative for B. catarrhalis within 3 days in all patients. Two of 7 patients whose sputum cultures were positive for this organism at a review 2 to 4 weeks later were successfully treated with a further course of amoxycillin/clavulanic acid.

Amoxicillin↗

[Cholestatic hepatitis and amoxicillin-clavulanic acid combination. Personnel case report and literature review].

The association amoxicillin-clavulanic acid is a widely used medication. Only about 15 cases of cholestatic hepatitis were reported in Belgium between 1990 and 1993; about 100 cases have been reported to the pharmaceutical company. This effect is severe but reversible. The injury is probably idiosyncratic or immunologically based. Age, sex and treatment duration are as many agents of risk. The diagnosis is undertaken on basis of clinical examination, chronological study, biological evolution and histology.

Age Factors↗

In vitro activity of ticarcillin plus clavulanic acid (BRL 28500, 'Timentin') against ticarcillin-resistant gram-negative rods.

A study was carried out to investigate the in vitro susceptibility of 211 clinical isolates of ticarcillin resistant (MICs greater than 128 micrograms/ml) Gram-negative rods to a combination of ticarcillin plus clavulanic acid. The combination demonstrated superior activity; 90% of the Proteus spp. and 50% of E. coli and Klebsiella spp. isolates were inhibited at a concentration of 64 micrograms/ml. It was 2 to 8-times more active than ticarcillin alone against E. coli, Proteus and Klebsiella spp. in half to three-quarters of the strains under test. This enhanced activity was only marginal, however, against Enterobacter, Acinetobacter, Citrobacter, Serratia and Pseudomonas spp. Against 161 ticarcillin sensitive strains the combination did not have any potentiation effect.

Clavulanic Acid↗

Plasmid encoded beta-lactamases resistant to inhibition by clavulanic acid produced by calf faecal coliforms.

Two new plasmid encoded beta-lactamase enzymes produced by a strain of Escherichia coli and a strain of Citrobacter freundii isolated from calf faeces have been characterised. Both enzymes were similar to TEM-1 in terms of substrate and inhibition profiles and physical properties but differed from TEM-1 in being far less susceptible to the beta-lactamase inhibitors clavulanic acid or tazobactam. In each case transfer of the plasmid E coli K12 rendered it clinically resistant to the combination of amoxycillin and clavulanic acid. The beta-lactamase from the E coli had an iso-electric point (pI) of 5.4 and was encoded on a plasmid of 95 Kbp which also mediated resistance to tetracycline, sulphonamides, apramycin, streptomycin and gentamicin. The beta-lactamase from the C freundii had a pI of 5.2 and was encoded on a 75 Kbp plasmid which also mediated resistance to trimethoprim, chloramphenicol, apramycin, gentamicin and tobramycin.

Amoxicillin↗

Comparative in vitro surveillance of amoxicillin-clavulanic acid and four oral comparators against 21232 clinical isolates from europe.

The present study was conducted to determine the in vitro activity of amoxicillin-clavulanic acid compared to that of four newer antimicrobial agents (ampicillin, azithromycin, cefuroxime and trimethoprim-sulfamethoxazole). All of the agents were tested against 21232 recent clinical isolates encompassing 37 species submitted from 16 European countries between 1997 and 1999. After 20 years of clinical use, amoxicillin-clavulanic acid continues to retain much of its initial activity against targeted gram-positive organisms, selected gram-negative organisms and major respiratory pathogens.

Administration, Oral↗

Displacement of bilirubin from cord serum by sulphadimethoxine, amoxycillin, clavulanic acid in combination with either amoxycillin or ticarcillin, temocillin and cloxacillin.

The displacement of bilirubin from its binding sites in cord serum by sulphadimethoxine and various penicillins was studied using Sephadex gel filtration. Sulphadimethoxine displaced bilirubin at concentrations well within the normal therapeutic range of sulphonamide concentrations. Amoxycillin, clavulanic acid in combination with either amoxycillin or ticarcillin, temocillin and cloxacillin displaced bilirubin at concentrations much higher than those found clinically. It was concluded that the primary binding site/s of sulphadimethoxine and the secondary binding site/s of the penicillins were at or near the primary bilirubin binding site.

Amoxicillin↗

Treatment of respiratory tract infections in children: a study of a combination of amoxycillin and clavulanic acid.

In an open study, 70 in-patients and 23 out-patients aged between 1 and 14 years with sinusitis (n = 1), perforated otitis media (n = 4), pharyngotonsillitis (n = 25), tracheobronchitis (n = 30) or broncho-pneumonia (n = 33) were treated daily with a combination of 40 mg/kg amoxycillin and 10 mg/kg clavulanic acid in three equal doses for between 6 and 15 days. Purulent specimens were cultured when obtainable and pathogenic organisms identified were Staphylococcus aureus, beta-haemolytic streptococcal group A, Pseudomonas aeruginosa, Pseudococcus species and Klebsiella pneumoniae infections, of which 45.7% were beta-lactamase-producing and 54.3% were ampicillin-susceptible. After treatment, only one beta-lactamase-producing Streptococcus and one Staphylococcus infection persisted. Side-effects (vomiting, nausea, diarrhoea, maculopapular exanthema, rash) occurred in 16 patients and treatment was withdrawn in eight. It is concluded that the amoxycillin--clavulanic acid combination is a suitable first choice for the treatment of respiratory tract infections in children in whom the pathogenic organism may not have been established.

Adolescent↗

The argG gene of Streptomyces clavuligerus has low homology to unstable argG from other actinomycetes: effect of amplification on clavulanic acid biosynthesis.

The argG gene of Streptomyces clavuligerus (Scl) has been cloned by complementation of argG mutants of Escherichia coli and S. lividans (Sl). The argG nucleotide (nt) sequence showed that it corresponds to a new type of argG different from the corresponding genes of S. coelicolor (Sco) and Sl. It encodes a 43,250-Da protein that showed higher similarity to argininosuccinate synthetases (ASS) from Methanococcus vannielii and Methanosarcina barkeri than to ASS deduced from other Streptomyces argG. No hybridization of the Scl argG was found with the homologous genes of Sl or Sco. The argH gene was located downstream from argG in Scl. The genomic region around argG and argH in Scl was different from the homologous regions in other Streptomyces and is not genetically unstable, unlike in Sco and Sl. Amplification of argG in transformant Scl[pULAR113] results in a 2.3-fold increase in the production of clavulanic acid (CA) in relation to the control strain Scl[pIJ699].

Amino Acid Sequence↗

In vitro activity of cefmetazole, cefotetan, amoxicillin-clavulanic acid, and other antimicrobial agents against anaerobic bacteria from endometrial cultures of women with pelvic infections.

The MICs of the new antimicrobial agents cefmetazole, cefotetan, and amoxicillin-clauvulanic acid were compared with the MICs of other antimicrobial agents against anaerobic bacteria from endometrial cultures from women with pelvic inflammatory disease or endometritis. The activity of cefmetazole was similar to that of cefoxitin and generally greater than that of cefotetan. Amoxicillin-clavulanic acid was generally more active than all cephamycins tested.

Amoxicillin↗

The biosynthetic genes for clavulanic acid and cephamycin production occur as a 'super-cluster' in three Streptomyces.

The cosmid cloning vector pHC79 has been used to clone fragments of chromosomal DNA from the Streptomyces: S. clavuligerus, S. jumonjinensis and S. katsurahamanus. These strains all produce both the beta-lactam antibiotic, cephamycin and the beta-lactamase inhibitor, clavulanic acid. Although structurally related these two beta-lactams are known to be derived from different biosynthetic precursors. Hybridisation studies and restriction mapping have shown that the gene clusters encoding the two biosynthetic pathways are chromosomally adjacent in these strains, thus creating a 'super-cluster' of genes involved in both the production and enhancement of activity of a beta-lactam antibiotic.

Bacterial Proteins↗