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PubMed2003

Emergence of resistance in normal human aerobic commensal flora during telithromycin and amoxicillin-clavulanic acid treatments.

Mean fecal global yeast counts increased similarly during 7 days of treatment with telithromycin (800 mg once daily) or amoxicillin-clavulanic acid (amoxiclav) (1 g of amoxicillin and 125 mg of clavulanic acid 3 times daily) in human volunteers and decreased slowly thereafter. On skin, coagulase-negative staphylococci of decreased susceptibility (DS) to telithromycin increased in the telithromycin group, whereas those with DS to methicillin increased in the amoxiclav group. A similar antibiotic-related shift towards homologous DS was observed for oral nongroupable streptococci (NGS), but in addition, the prevalence of NGS resistant to both classes of antibiotics was significantly greater in the amoxiclav group at days 8 (P < 0.01) and 45 (P < 0.015).

Adult↗
PubMed1986

Comparison of oral treatment of uncomplicated urogenital and rectal gonorrhoea with cefuroxime axetil ester or clavulanic acid potentiated amoxycillin (Augmentin).

In a randomised study of two drugs for the oral treatment of uncomplicated urogenital and rectal gonorrhoea the therapeutic effect of cefuroxime axetil ester (CAE) and amoxycillin plus clavulanic acid (A + C) was compared. Cefuroxime axetil ester 1.5 g was given to 129 men and 118 women. Amoxycillin 3.0 g and clavulanic acid 0.25 g was given to 131 men and 122 women. Both treatments were combined with probenecid 1.0 g and administered in a single oral dose. Of the 500 patients thus treated, 376 were assessable. In the group taking CAE, failure rates were 0.9% for the men and 0% for the women; and the overall failure rate was 0.5%. In the group taking A + C the equivalent failure rates were 4.6%, 1.2%, and 3.1%. The differences were not significant. Penicillinase producing Neisseria gonorrhoeae (PPNG) was isolated from 5.6% of the assessable patients. All 10 PPNG infections in the group taking CAE and four of 11 PPNG infections in the group taking A + C were cured. These numbers were too small to draw a definite conclusion about the efficacy of both drugs in this type of infection. Postgonococcal urethritis was observed in 35% of the men in the group taking CAE and in 32% of those in the group taking A + C. Side effects were noted in 38% of the group taking CAE and 28% of the group taking A + C. Nausea and vomiting were more commonly observed in the group taking CAE; and diarrhoea was more commonly observed in the group taking A + C.

Administration, Oral↗
PubMed2004

False-positive Aspergillus galactomannan enzyme-linked immunosorbent assay results in vivo during amoxicillin-clavulanic acid treatment.

Positive Platelia Aspergillus test results were observed in consecutive serum samples from an immunocompromised host during amoxicillin-clavulanic acid treatment, and a correlation between plasmatic amoxicillin concentration and galactomannan optical density index was observed. Amoxicillin-clavulanic acid vials tested positive for galactomannan but were negative for Aspergillus DNA.

Amoxicillin-Potassium Clavulanate Combination↗
PubMed1995

Incidence and mechanisms of resistance to the combination of amoxicillin and clavulanic acid in Escherichia coli.

Among Escherichia coli organisms isolated at St. Thomas's Hospital during the years 1990 to 1994, the frequency of resistance to amoxicillin-clavulanic acid (tested by disk diffusion in a ratio of 2:1) remained constant at about 5% of patient isolates (10 to 15% of the 41 to 45% that were amoxicillin resistant). Mechanisms of increased resistance were determined for 72 consecutively collected such amoxicillin-clavulanic acid-resistant isolates. MICs of the combination were 16-8 micrograms/ml for 51 (71%) of these and > or = 32-16 micrograms/ml for the remainder. The predominant mechanism was hyperproduction of enzymes isoelectrically cofocusing with TEM-1 (beta-lactamase activities, > 200 nmol of nitrocefin hydrolyzed per min per mg of protein) which was found in 44 isolates (61%); two isolates produced smaller amounts (approximately 150 nmol/min/mg) of such enzymes, and two isolates hyperproduced enzymes cofocusing with TEM-2. Eleven isolates produced enzymes cofocusing with OXA-1 beta-lactamase, which has previously been associated with resistance to amoxicillin-clavulanic acid. Ten isolates produced increased amounts of chromosomal beta-lactamase, and four of these additionally produced TEM-1 or TEM-2. Three isolates produced inhibitor-resistant TEM-group enzymes. In one of the enzymes (pI, 5.4), the amino acid sequence change was Met-67-->Val, and thus the enzyme is identical to TEM-34. Another (pI, 5.4) had the substitution Met-67-->Ile and is identical to IRT-I67, which we propose now be given the designation TEM-40. The third (pI, 5.2) had the substitution Arg-241-->Thr; this enzyme has not been reported previously and should be called TEM-41. The rarity and diversity of inhibitor-resistant TEM-group enzymes suggest that they are the result of spontaneous mutations that have not yet spread.

Amoxicillin↗
PubMed2000

[Pharmacodynamic basis for the use of amoxicillin-clavulanic acid in respiratory infections due to Streptococcus pneumoniae: In vitro studies in an experimental model].

Amoxicillin-clavulanic acid is a first choice treatment for respiratory tract infections caused by Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. In a previous study we observed its high efficacy against penicillin-susceptible and intermediate-resistant strains of S. pneumoniae. We aimed to study the efficacy of this antibiotic against three strains of S. pneumoniae (susceptible, intermediate and resistant to penicillin) in a mouse model of pneumonia, and to determine the influence of the time of starting treatment and the in vitro postantibiotic effect. We also determined the serum levels of the antimicrobial agent in the mice, and correlated the pharmacodynamic parameters (Cmax/MIC, AUC/MIC and T>MIC) with the survival rate to establish the best predictor of efficacy. MICs with amoxicillin-clavulanic acid were 0. 03 mg/l, 0.25 mg/l and 2 mg/l for the penicillin-susceptible, -intermediate and -resistant strains, respectively. The ED90 were approximately 5 mg/kg for susceptible strains, 25 mg/kg for the intermediate and 50 mg/kg for the resistant strains. We observed a lower survival rate (approximately 55%) when the treatment began 31 h after infection than when it began 5 h (100%) and 19 h (approximately 90-100%) afterwards. Serum levels were dose dependent and the correlation with the pharmacodynamic parameters showed a significant association between survival and the T>MIC (r = 0.946). In vitro postantibiotic effects with 1, 4 and 10 times the MIC were 0.96 to 1.69 h for susceptible strains, 0.38 to 1.23 h for intermediate, and 1.52 to 2. 20 h for resistant strains. These results show the high efficacy of this antibiotic combination against strains with variable susceptibility to penicillin, with this activity being related mainly to the T>MIC of the microorganism. The postantibiotic effect would prolong the effect of the antibiotic in the dosing interval. These parameters and antimicrobial effects are important in terms of the clinical application of this antimicrobial agent.

Amoxicillin-Potassium Clavulanate Combination↗
PubMed2006

Characterization of pbpA and pbp2 encoding penicillin-binding proteins located on the downstream of clavulanic acid gene cluster in Streptomyces clavuligerus.

Two genes, pbpA (orf18) and pbp2 (orf19) located on the downstream of clavulanic acid (CA) gene cluster of Streptomyces clavuligerus were cloned into pET-28a(+), and confirmed to encode a family of high molecular-weight penicillin-binding proteins (PBPs). Both genes were amplified from genomic DNA by PCR and expressed in E. coli BL21 (DE3). Hydropathy plots of the proteins revealed a single stretch of hydrophobic amino acids indicating them to be transmembrane proteins. Pbp2 had lower affinity to penicillin G compared to PbpA, and was essential to the cell growth in contrast to PbpA.

Amino Acid Sequence↗
PubMed1995

[False sensitivity of Enterococcus faecium to amoxicillin-clavulanic acid with the MicroScan system].

BACKGROUND: We have observed by using MicroScan automatic system discrepancies in susceptibility results of Enterococcus faecium strains to ampicillin and amoxicillin/clavulanic acid. METHODS AND RESULTS: Seventy-six strains of E. faecium were studied with MicroScan; 98.7% of them were inhibited by 16 mg/l of amoxycillin-clavulanic acid versus 60.5% inhibited by the same concentration of ampicillin. We have evaluated the susceptibility to ampicillin, amoxicillin and amoxicillin-clavulanic acid of 7 strains of E. faecium by both MicroScan and standard microdilution assay. MIC values of ampicillin were similar by both methods but MIC values of amoxicillin/clavulanic acid obtained by MicroScan (< or = 4/2 mg/l in 6 strains) were considerably lower than those obtained by standard microdilution (> or = 16/8 in 6 strains). This phenomenon was not dependent of betalactamase production or bacterial inocula. CONCLUSIONS: When using MicroScan, E. faecium strains resistant to ampicillin (betalactamase non producers) must be also considered resistant to amoxicillin/clavulanic acid without considering the values obtained by this system.

Amoxicillin↗
PubMed1992

Transfer of Timentin (ticarcillin and clavulanic acid) across the in vitro perfused human placenta: comparison with other agents.

OBJECTIVES: In vitro perfusion of human placentas was used to quantify the net placental transfer of ticarcillin and clavulanic acid. STUDY DESIGN: Placentas were obtained from uncomplicated pregnancies at term. The maternal and fetal circulations were reestablished at flow rates of 17.5 ml/min and 5 ml/min, respectively. Open circulations were used to evaluate steady-state pharmacodynamics and transplacental gradient formation. Drug levels were measured by high-pressure liquid chromatography. RESULTS: The clearance index of ticarcillin was 0.037 +/- 0.004. The fetal/maternal ratio was 0.91. Therapeutic concentrations of clavulanate (2 to 6 micrograms/ml) in the maternal media resulted in undetectable transfer to the fetal compartment. By using higher levels of clavulanate, a clearance index of 0.061 +/- 0.001 (mean +/- SEM) and 1:1 fetal/maternal gradient was obtained. CONCLUSIONS: These data correspond to relatively low transfer of ticarcillin with a cord/maternal ratio of < 1. Clavulanate transfer is slightly greater. Agents with similar activity and superior transfer would optimize intrauterine treatment.

Clavulanic Acid↗
PubMed1997

Manipulation of the physiology of clavulanic acid production in Streptomyces clavuligerus.

This paper reports a novel use of cluster analysis for the identification of intermediary metabolites that are produced at rates closely correlated with those of antibiotic biosynthesis. This information was used to devise culture feeds resulting in enhanced production of clavulanic acid, an antibiotic of current worldwide commercial interest. The feeding strategies apparently alleviated a rate-limiting supply of the C3 precursor of clavulanic acid. C3 limitation may be a consequence of unusual nitrogen and carbon metabolism in Streptomyces clavuligerus. This approach has potential as a generic method for influencing biosynthetic pathway fluxes using feeds without knowledge of the biosynthetic pathway.

Amino Acids↗
PubMed1986

Variation in the potentiation of beta-lactam antibiotic activity by clavulanic acid and sulbactam against multiply antibiotic-resistant bacteria.

Using a broth microdilution method, we studied 120 strains of beta-lactamase-producing clinical isolates to determine the potentiating effect of clavulanic acid and sulbactam (both beta-lactamase inhibitors) on the antibacterial activity of a variety of beta-lactam antibiotics. All antibiotics were tested alone and in combination with each inhibitor simultaneously using low (10(5) cfu/ml) and high (10(7) cfu/ml) inocula. Against the strains of Escherichia coli and Haemophilus influenzae the addition of both inhibitors significantly potentiated the activity of most antibiotics at the low inoculum. At the high inoculum, however, this effect was abrogated against E. coli and most strains of H. influenzae. Antibiotic activity was significantly enhanced by the inhibitors at both inoculum sizes with Bacteroides fragilis. Antibiotic resistance of Pseudomonas aeruginosa was little affected by the inhibitors. Among methicillin-resistant staphylococci, antibiotic potentiation by the inhibitors was more significant for Staphylococcus aureus than the coagulase-negative staphylococci.

Anti-Bacterial Agents↗
PubMed1991

[Evaluation of ciprofloxacin versus amoxicillin + clavulanic acid or erythromycin for the empiric treatment of community-acquired pneumonia].

For the empiric management of community-acquired pneumonia, ciprofloxacin (750 mg b.i.d.) was compared with two antibiotics frequently used in this indication, i.e., amoxicillin + clavulanic acid and erythromycin. One hundred and forty-two patients were randomized in this prospective study. Among them, the 63 patients with bacteriologically documented disease were evaluated. Clinical recovery was achieved in 73.3% of patients in the ciprofloxacin group (22/30) versus 81.8% of patients in the amoxicillin + clavulanic acid or erythromycin group (27/33) (non-significant difference). Clinical failures seen with ciprofloxacin were found to be correlated with recovery of Streptococcus pneumoniae. Ciprofloxacin is effective in pneumonia but should be used only in cases where Streptococcus pneumoniae can be excluded as the causative agent.

Adult↗
PubMed1989

[Treatment of upper genital infections in women. Multicenter study of the comparative efficacy and tolerance of an amoxicillin-clavulanic acid combination and of a triple antibiotic combination].

Eighty-two patients with laparoscopically confirmed salpingitis were randomly divided into two groups in a multicentre and prospective trial. Single drug therapy with the amoxicillin-clavulanic acid combination was used in 42 patients (group A). The other 40 patients were given a combination of penicillin, aminoside and metronidazole (group B). For each case a secondary prescription for a tetracycline was discussed. Clinical results were comparable in both groups: sooner (at the end of the hospitalization period) in group A: 10 cured, 30 improved and 2 failures against 9 cured, 30 improved in group B. Later (evaluation after 5 to 8 weeks) a relapse was noted in five patients in group A and included one case of angioedema in group B. It is concluded that amoxicillin-clavulanic acid combination is a satisfactory alternative to the penicillin-aminoside-metronidazole combination, especially as it is simpler to use.

Adolescent↗
PubMed1984

Amoxicillin plus clavulanic acid in the treatment of recurrent urinary tract infections.

Forty-four patients (43 female, 1 male), all with a history of recurrent urinary tract infections, were treated with 250 mg of amoxicillin plus 125 mg of clavulanic acid (one tablet of Augmentin) every 8 h for 7 days. The microbiological cure rates were 84% 1 week after the end of treatment and 67% 1 month later. Side effects, which were reported by 20% of the patients, were mild and in no case caused interruption of treatment. In view of the increasing trend in resistance to agents commonly used for the treatment of urinary tract infections in outpatients, the combination of amoxicillin and clavulanic acid may now be considered a first-line drug in patients with recurrent urinary tract infections.

Adult↗
PubMed1988

Induction of chromosomal beta-lactamases by different concentrations of clavulanic acid in combination with ticarcillin.

The effect of different concentrations of clavulanic acid (CA) in combination with ticarcillin on beta-lactamase production and ticarcillin MIC was studied in four clinical isolates of Pseudomonas aeruginosa, Enterobacter cloacae, Serratia marcescens, Citrobacter freundii and indole positive Proteus strains. Ticarcillin alone showed a low inducing effect for all species tested, Ser. marcescens excepted. The increase in beta-lactamase activity after addition of CA (2-10 mg/l) was strain and species dependent. No synergy or antagonism was observed on the ticarcillin MIC for the micro-organisms producing only a chromosomally mediated beta-lactamase, though the susceptibility to ticarcillin strongly increased if the strains also produced a plasmid-mediated beta-lactamase. Addition of 50 or 100 mg/l CA resulted in all strains. C. freundii excepted, in a strong increase in beta-lactamase activity and in a strong synergistic effect on the ticarcillin MIC. However, these concentrations are unlikely to be achieved at clinical doses. Thus, irrespective of the inducing effect of ticarcillin and CA (2-10 mg/l) combinations, induction of the chromosomal beta-lactamase did not result in a decrease in ticarcillin susceptibility.

Bacteria↗
PubMed1982

Activity of cefoperazone and two beta-lactamase inhibitors, sulbactam and clavulanic acid, against Bacteroides spp. correlated with beta-lactamase production.

A total of 102 isolates of Bacteroides spp. were studied for beta-lactamase production and susceptibility to cefoperazone alone or in combination with either of the beta-lactamase inhibitors sulbactam and clavulanic acid. The geometric mean minimal inhibitory concentration of cefoperazone alone was 31.5 micrograms/ml and when combined with 10 micrograms of sulbactam per ml or 2 micrograms of clavulanic acid per ml was reduced to 5.4 and 9.2 micrograms/ml, respectively. When bacterial suspensions were tested for beta-lactamase production with nitrocefin, 91 (89.2%) of these isolates produced the enzyme. The geometric mean minimal inhibitory concentrations of cefoperazone rose only slightly for isolates with low or intermediate enzyme activity but rose significantly for those with high activity. The addition of EDTA to cefoperazone significantly more frequently enhanced the activity of cefoperazone against beta-lactamase-negative as opposed to beta-lactamase-positive isolates. Furthermore, EDTA resulted in synergistic activity of the cefoperazone-sulbactam combination on beta-lactamase-positive isolates for which the combination had previously not shown a synergistic effect. This study demonstrates the relationship between beta-lactamase production and the resistance of Bacteroides spp. to cefoperazone and shows that inhibition of these enzymes can reverse this resistance.

Anti-Bacterial Agents↗
PubMedDate not supplied

Comparison of two oral antibiotics, roxithromycin and amoxicillin plus clavulanic acid, in lower respiratory tract infections.

In a randomized, multicenter, open-label study, 490 ambulatory adult patients with lower respiratory tract infection (LRTI) were randomized to roxithromycin (ROX) 150 mg b.i.d. orally (n = 244) or amoxicillin plus clavulanic acid (AMX + CA) as 500 mg AMX + 125 mg CA t.i.d orally (n = 24). Clinical results were analyzed in 477 patients with acute bronchitis (79%), chronic bronchitis (CB) (14%), and pneumonia (7%). There were significantly more patients with underlying disease (cardiovascular diseases, p = 0.045; and alcoholism, (p less than 0.001), and more patients over the age of 65 years (p = 0.045) in the ROX group. Overall clinical efficacy was similar in both groups: 88% (206:235) in the ROX group and 85% (205:242) in the AMX + CA group. Side effects were reported in 67 cases (28%) in the AMX + CA group and in 21 cases (9%) in the ROX group (p less than 0.0001), causing withdrawal in 21 and three cases, respectively (p less than 0.001). Thus, despite being administered to a significantly older and more ill group of patients with LRTI, roxithromycin was as effective as amoxicillin plus clavulanic acid and better tolerated.

Acute Disease↗
PubMed1990

Increase in the activity of third-generation cephalosporins in combination with clavulanic acid and Sulbactam against Bacteroides fragilis.

We studied the sensitivity of 160 strains of Bacteroides fragilis (74 beta-lactamase-positive and 86 beta-lactamase-negative) to four third-generation cephalosporins, alone as well as in combination with clavulanic acid and Sulbactam. For susceptibility testing we used a dilution method in agar. Detection of beta-lactamase production by this micro-organism was performed using chromogenic cephalosporin (Nitrocefin). There was a substantial improvement in cephalosporin activity with both positive and negative strains when they were combined with the inhibitors, although this was more significant in beta-lactamase-producing organisms. Generally, the results achieved in combination with clavulanic acid were better than those with Sulbactam, the highest increase in activity being obtained with Ceftizoxime in combination with any one of the inhibitors.

Bacteroides fragilis↗