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PubMed1985

Relevance of urinary bladder models to clinical problems and to antibiotic evaluation.

Applications and shortcomings of models of the bladder which employ urine as a medium have been described. A 'continuous culture' model was no better than conventional susceptibility tests in predicting response of patients with acute uncomplicated urinary infections to amoxicillin, but gave a good correlation with a mouse infection protection test for synergy studies with mecillinam and ampicillin. Some Enterobacteriaceae destroyed high concentrations of amoxicillin in urine under conditions resembling the milieu of the infected human bladder. Destruction was enhanced at increased residual urinary volumes and did not occur in the presence of clavulanic acid. The beneficial effects of clavulanic acid at urinary, as opposed to tissue, concentrations may be due to its antibacterial, as well as its antienzymic, activity.

Animals↗
PubMed1987

In-vitro bacterial killing kinetics of ticarcillin/clavulanic acid.

An in-vitro model was developed to study the rates of killing by ticarcillin/clavulanic acid combinations of various beta-lactamase producing, ticarcillin resistant, logarithmic phase clinical isolates. Killing, defined as a 3 log reduction, was dependent on the organism, the concentration of clavulanic acid and the duration of exposure. For most isolates studied an optimum period of exposure to and concentration of clavulanic acid could be defined. Certain test strains showed optimum response to readily attainable in-vivo concentrations of clavulanic acid while other strains, although sensitive by MIC data showed a poor response. The clinical implications of this are discussed.

Bacteria↗
PubMed1994

[Susceptibility of strict anaerobic bacteria to antibiotics in France: a multicenter study].

During 1992, the in vitro antibiotic susceptibility of 462 anaerobic bacteria was performed in 7 hospitals, by the reference agar dilution method. Among the 222 Bacteroides fragilis group strains, only one Bacteroides fragilis strain was resistant to imipenem and all bêtalactams, even combined with bêtalactamase-inhibitors while metronidazole resistance could not be detected. One major outer membrane protein (probably a porin) was lacking in some of the six amoxicillin-clavulanic acid resistant Bacteroides fragilis group strains. Evolution in antibiotic resistance rates could be assessed only for clindamycin and piperacillin whose resistance rates increased to 14 and 15.8 p. cent, respectively. On the whole anaerobic strains resistance rates were: imipenem 0.2, ticarcillin-clavulanic acid 0.5, amoxicillin-clavulanic acid or metronidazole 1.5, piperacillin 9.1, cefotaxime-sulbactam 9.7, cefoxitin 12.8, clindamycin 13.7, cefotaxime 27.2, amoxicillin 45 and ciprofloxacin 70, respectively.

Anti-Bacterial Agents↗
PubMed2003

[Meta-analysis of clarithromycin compared with other antimicrobial drugs in the treatment of upper respiratory tract infections].

The goal of this meta-analysis was to evaluate the effectiveness of clarithromycin versus most commonly used treatments for upper respiratory infections. We performed a systematic review of comparative clinical trials found in the literature. Regarding effectiveness, no significant differences were found in comparisons between clarithromycin and amoxicillin-clavulanic acid for upper respiratory infections, nor for cephalosporins, amoxicillin or amoxicillin-clavulanic acid for otitis media, nor oral penicillin for classic streptococcal tonsillitis. Clarithromycin was more effective than betalactam antibiotics for sinusitis (OR: 1.27, 95% CI: 1.01-1.61 in intent-to-treat analysis). The effectiveness of clarithromycin was better than that for azithromycin, but only reached statistical significance in the per-protocol analysis. The global analysis including all 33 clinical trials showed a small benefit for clarithromycin reaching statistical significance in the fixed-effects model (OR: 1.12, 95% CI: 1.01-1.25). Regarding safety, the incidence of adverse events was significantly lower for clarithromycin compared to amoxicillin and amoxicillin-clavulanic acid. No differences were found when comparing adverse events due to cephalosporins, azithromycin and betalactam antibiotics, but the incidence of adverse events for clarithromycin was higher compared to that of oral penicillin for streptococcal tonsillitis treatment. Overall, all the compared drugs were well tolerated; discontinuations due to adverse events were very low: 2.2% for clarithromycin treatment and 2.5% for the other antibiotics. It was concluded that clarithromycin is an effective and safe treatment for upper respiratory infection, and its new formulation in a single daily dose may improve therapeutic compliance.

Anti-Bacterial Agents↗
PubMed2005

Monitoring complex media fermentations with near-infrared spectroscopy: comparison of different variable selection methods.

Near-infrared spectroscopy (NIRS) is known to be a suitable technique for rapid fermentation monitoring. Industrial fermentation media are complex, both chemically (ill-defined composition) and physically (multiphase sample matrix), which poses an additional challenge to the development of robust NIRS calibration models. We investigated the use of NIRS for at-line monitoring of the concentration of clavulanic acid during an industrial fermentation. An industrial strain of Streptomyces clavuligerus was cultivated at 200-L scale for the production of clavulanic acid. Partial least squares (PLS) regression was used to develop calibration models between spectral and analytical data. In this work, two different variable selection methods, genetic algorithms (GA) and PLS-bootstrap, were studied and compared with models built using all the spectral variables. Calibration models for clavulanic acid concentration performed well both on internal and external validation. The two variable selection methods improved the predictive ability of the models up to 20%, relative to the calibration model built using the whole spectra.

Algorithms↗
PubMed1996

Antibiotic susceptibilities of Haemophilus influenzae in central Scotland.

OBJECTIVE: To ascertain the incidence of antibiotic resistance in Haemophilus influenzae in central Scotland and the beta-lactamases produced by these isolates. METHODS: A total of 213 H. influenzae isolates from four medical centers in Scotland [Aberdeen (n=58), Edinburgh (n=55), Glasgow (n=64) and Dundee (n=36)] were tested for susceptibility to a range of antimicrobials including beta-lactams, beta-lactam/beta-lactamase-inhibitor combinations, and a representative 4-quinolone, antifolate and macrolide. Susceptibility testing of the beta-lactam/beta-lactamase-inhibitor combination amoxicillin plus clavulanic acid was conducted at both 2:1 and 4:1 ratios and with clavulanic acid fixed at a concentration of 2 mg/L. Each strain was further investigated for the presence of beta-lactamase activity. RESULTS: Although the incidence of resistance to amoxicillin was 15%, in the presence of clavulanic acid, this resistance was reduced to 4.2%, 5.6% and 4.2% with the 2:1 ratio, 4:1 ratio and 2 mg/L fixed concentration, respectively. Sixteen percent of the isolates demonstrated immediate beta-lactamase production. Isoelectric focusing showed that 77.4%, 16.1% and 6.5% of the beta-lactamase-positive strains were found to contain TEM-1, VAT-1 and both TEM-1 and VAT-1 beta-lactamases, respectively. A further 29% of the strains were recognized as being beta-lactamase-positive after prolonged incubation with nitrocephin. CONCLUSIONS: This study suggests that current testing for beta-lactamases may underestimate the prevalence of beta-lactamase production in H. influenzae.

Journal Article↗
PubMed1988

[Comparative characteristics of penicillin-binding proteins of representatives of the genus Streptomyces].

Penicillin-binding proteins (PBPs) in Strepomyces strains producing clavulanic acid and beta-lactamase and in Streptomyces strains not producing these compounds were studied comparatively. In S. clavuligerus, the organism producing clavulanic acid, there were detected 3 PBPs in the membrane fraction. S. griseus, the organism producing beta-lactamase, contained 6 PBP. In S. cacaoi and S. olivaceus, organisms producing neither beta-lactams nor beta-lactamase, there were detected 5 and 4 PBP, respectively. The set of the PBP in the organism producing clavulanic acid varied during fermentation. In a variant of S. clavuligerus isolated after protoplasting of the mycelial cells and their regeneration the content of the electrophoretically most mobile PBP lowered. The PBP of S. clavuligerus did no show any high affinity to other beta-lactams such as methicillin and ampicillin tested as competing agents of 14C-benzylpenicillin.

Bacterial Proteins↗
PubMed1987

Clavulanate-potentiated amoxycillin: in vitro antibacterial activity and oral bioavailability in calves.

The minimal inhibitory concentrations (MIC) of amoxycillin and clavulanate-potentiated amoxycillin (amoxycillin:clavulanic acid, 4:1 by weight) were compared for 171 Salmonella, 170 Escherichia coli, and 32 Pasteurella isolates recovered from infected neonatal calves. In the presence of clavulanic acid, the MIC of amoxycillin was reduced to levels less than or equal to 12.5 micrograms/ml for all the Salmonella group B, all the Pasteurella, and for 12 out of the 44 E. coli isolates which were resistant to amoxycillin (MIC greater than or equal to 100.0 micrograms/ml). For isolates sensitive to amoxycillin (MIC less than or equal to 1.56 microgram/ml) there was no change in MIC values in the presence of clavulanic acid. A small proportion of Salmonella and E. coli isolates were resistant to clavulanate-potentiated amoxycillin. In a cross-over trial involving 10 preruminant (2 weeks old) calves, amoxycillin trihydrate and clavulanate-potentiated amoxycillin were administered orally at 10 mg/kg. An analysis of serum amoxycillin level data showed that the pharmacokinetic parameters t1/2ab, Cmax, t1/2 beta, AUC, Cp degree, and f' (estimated drug absorption ratio) were the same after treatment with amoxydrate and clavulanate-potentiated amoxycillin. Administration of clavulanate-potentiated amoxycillin and probenecid resulted in elevation and prolongation of serum amoxycillin levels. Computations showed that in preruminant calves serum amoxycillin concentrations sufficient to inhibit sensitive pathogens can be maintained by oral clavulanate-potentiated amoxycillin treatment at 10 mg/kg TID. At two times that dose rate serum drug concentrations capable of inhibiting 50% of all types of pathogens examined can be maintained.(ABSTRACT TRUNCATED AT 250 WORDS)

Amoxicillin↗
PubMed2001

Interventions for treating melioidosis.

BACKGROUND: Melioidosis is an infectious disease caused by a bacterium (Burkholderia pseudomallei) found particularly in some areas in the tropics. It is a serious condition which can be fatal. Beta lactam antibiotics have dramatically reduced the risk of death, but mortality still remains high. OBJECTIVES: To summarise evidence from randomised trials on the effects of treatment regimens on death and relapse. SEARCH STRATEGY: Cochrane Controlled Trials Register, MEDLINE, EMBASE, BIOSIS from 1966 to September 2000 using MeSH terms "pseudomallei", "melioidosis" together with the terms "randomized-controlled-trial", "random allocation"; reference lists in articles on melioidosis; contact with trialists. SELECTION CRITERIA: Randomised and quasi-randomised trials assessing treatments in patients with melioidosis. DATA COLLECTION AND ANALYSIS: Eligibility and trial quality was assessed by two reviewers independently. MAIN RESULTS: For intravenous therapy in the acute phase, we identified five trials with a total of 519 patients. Chloramphenicol, doxycycline, and co-trimoxazole (trimethoprim-sulphamethoxazole) combination regimens were associated with a mortality of 50% or more (two studies). Patients randomised to regimens that included ceftazidime were more likely to survive (relative risk [RR] 0.46, 95% confidence interval [CI] 0.30 to 0.71). When ceftazidime-containing regimens were compared with beta lactam or alternative beta lactamase inhibitor regimens such as co-amoxiclav (amoxycillin-clavulanic acid) and cefoperazone-sulbactam, mortality rates were similar (RR 1.10, 95% CI 0.83 to 1.46), as was the case in one trial of imipenem. For oral therapy in the maintenance phase, we found two trials of 188 participants. Results showed that treatment with the conventional regimen (chloramphenicol, doxycycline, and trimethoprim-sulphamethoxazole) resulted in fewer fatalities in patients compared to a regimen of amoxycillin-clavulanic acid and doxycycline alone. REVIEWER'S CONCLUSIONS: Regimens for the acute phase of illness should contain ceftazidime or imipenem. It is not yet clear if combinations of treatments in the early phase reduce relapse. For oral therapy after the acute phase of treatment, trials suggest that conventional four drug regimens can be used for treatment.

Administration, Oral↗
PubMed1987

The prophylactic use of ticarcillin/clavulanate in the neonate.

A combination of ticarcillin and clavulanic acid (ratio 15:1) was given prophylactically to 24 newborn infants at risk of infection. Serum and urine concentrations of ticarcillin and clavulanic acid were measured after the first parenteral dose. Fifteen of 22 organisms isolated from the infants were sensitive to the drug. The pharmacokinetic profile was satisfactory and the combination was well tolerated.

Bacterial Infections↗
PubMed1986

Timentin in the treatment of nosocomial bronchopulmonary infections in intensive care units.

A clinical trial with Timentin (ticarcillin plus clavulanic acid) was undertaken in patients with hospital-acquired lower respiratory tract infections. Two formulations, 3.2 and 5.2 g consisting of 200 mg clavulanic acid and 3 or 5 g ticarcillin, respectively were usually given three times daily. Eighty-one patients were evaluable for clinical efficacy and 89 for tolerance. The clinical cure rate was 96% of the assessable cases even though all patients had severe concurrent or underlying diseases. The pronounced synergism between ticarcillin and clavulanic acid resulted in a bacteriological elimination rate of 94%. Adverse effects were very rare and of a mild nature, and restricted to those usually seen with the well-tolerated penicillins. No toxicological abnormalities could be detected in extensive laboratory screening. Timentin is a highly effective broad-spectrum antibiotic with good tolerance. Its potentiated action in comparison to other penicillins against beta-lactamase-producing strains, could reduce the usage of aminoglycosides in the future.

Adult↗
PubMed1986

Three day oral course of Augmentin to treat chancroid.

Amoxycillin and clavulanic acid (Augmentin; Beecham Research Laboratories) was used to treat patients with bacteriologically proved chancroid in three different dose regimens. A single dose of Augmentin (amoxycillin 3 g, clavulanic acid 350 mg) was found to be ineffective. A similar dose repeated after 24 hours was equally ineffective, but a dose (amoxycillin 500 mg, clavulanic acid 250 mg) given every 8 hours for three days was found to be effective. The drug was well tolerated and no side effects were noted in any of the patients treated.

Administration, Oral↗
PubMed1984

Treating gonococcal urethritis in men: oral amoxycillin potentiated by clavulanate compared with intramuscular procaine penicillin.

In a study of 121 men with uncomplicated gonococcal urethritis, 64 were treated orally with a single dose of 3 g amoxycillin and 250 mg of the specific beta-lactamase inhibitor, clavulanic acid, and 57 with a single intramuscular injection of 2.4 MU procaine penicillin. After seven days, six (9.4%) patients treated with amoxycillin and clavulanic acid were still culture positive for Neisseria gonorrhoeae, compared with 26.3% of those treated with procaine penicillin.

Administration, Oral↗
PubMedDate not supplied

Surveillance of antibiotic resistance in non invasive clinical isolates of Streptococcus pneumoniae collected in Belgium during winters 2003 and 2004.

A total of 391 and 424 non-invasive isolates of Streptococcus pneumoniae collected by 15 laboratories during the 2003 and 2004 survey were tested for their susceptibility by a microdilution technique following NCCLS recommendations. Insusceptibility rates (IR) in the two surveys (2003/2004) were as follows: penicillin 15.0/14.7% [8.4/6.4% Resistance (R)], ampicillin 17.4/14.6% (R 9.0/7.1%), amoxicillin +/- clavulanic acid 2.6/1.2 % (R 0/0%), cefaclor 14.3/14.1% (R 11.5/13.4%), cefuroxime 13.6/12.7% (R 10.5/11.8%), cefuroxime-axetil 10.5/11.8% (R 10.0/9.2%) (breakpoints based on 250 mg), cefotaxime 4.9/6.2% (R 1.3/2.4%), ceftazidime NotTested (NT)/6.4 (R NT/2.6%), cefepime NT/6.4 (R NT/2.6%), imipenem 7.7/8.9 % (R 1.8/1.4%), ertapenem 0.8/NT% (R O/NT%), ciprofloxacin 13.8/9.0% (R 4.3/2.4%), levofloxacin 3.3/2.8% (R 1.5/0.2%), moxifloxacin 0.6/0.2% (R 0.3/0%), ofloxacin 13.5/9.0% (R 4.3/2.4%), erythromycin 26.1/24.7% (R 25.3/24.5%), azithromycin 25.4/24.7% (R 24.6/24.5%), telithromycin 0.8/0.2% (R 0.5/0%), clindamycin 21.2/18.4% (R 19.2/17.7%) and tetracycline 32.3/22.1% (R 29.2/19.3%). There were only minor differences in resistance rates according to age, sample site, admission type (i.e. ambulatory, hospitalized or long-term care facility patients), gender and geographic origin. Overall, telithromycin (MIC50, MIC90 in 2003/2004: 0.015 microg/ml, 0.12 microg/ml/ 0.008,0.06 respectively), ertapenem (0.03; 0.25/NT), moxifloxacin (0.06; 0.25/0.06, 0.12), and amoxicillin +/- clavulanic acid (0.03; 0.25/0.015, 0.5) were the most active compounds in both surveys. In 2003, the most common resistance phenotype was isolated insusceptibility to tetracycline (10.5%) followed by combined insusceptibility to erythromycin and tetracycline (9.3%). Erythromycin-tetracycline resistance (10.4%) was the most common in 2004. Isolates showing resistance to an antibiotic were significantly more present in 2003 than in 2004 (50.4% versus 40.8%). In penicillin-insusceptible isolates, MICs of all beta-lactams were increased but cross-resistance between penicillin and other beta-lactams in the penicillin-insusceptible isolates was not complete. In the 2003 survey, most of these isolates remained fully susceptible to ertapenem (94.9%) and amoxicillin +/- clavulanic acid (83.1%). In the 2004 survey, 91.9% of the penicillin insusceptible isolates remained susceptible to amoxicillin +/- clavulanic acid. In both surveys, the most common serotypes in penicillin insusceptible isolates were 14, 23,19 and 9 (20.0%, 20.0%, 16.4% and 10.9% respectively in 2003; 41.6%, 11.7%, 15.0% and 18.3% respectively in 2004).

Anti-Bacterial Agents↗
PubMed2000

Beta-lactamase patterns and betalactam/clavulanic acid resistance in Escherichia coli isolated from fecal samples from healthy volunteers.

Fecal specimens from 50 healthy volunteers living in Izmir, Turkey, were examined for the presence of beta-lactamase producing Escherichia coli by selection on agar plates containing ampicillin (10 mg/L). Thirty-nine (78%) of the strains were ampicillin-resistant and ampicillin MIC50 values for these isolates were > or =1024 microg/ml (range 32- > or =1024 microg/ml). Ampicillin MIC values remained above 64 microg/ml in 16 (41%) strains despite addition of clavulanic acid (2 mg/L). Beta-lactamase production of the clavulanate-resistant strains was further investigated by analytical isoelectric focusing (pI). Enzymes with pIs of 5.4, 5.6, 7.4, 7.6 and >8.5 were detected. Sixty-nine percent of the isolates produced a pI 5.4 enzyme that cofocused with TEM-1. Beta-lactamase assays revealed that hyperproduction of these enzymes was the predominant mechanism for clavulanate resistance. Twelve (75%) of the isolates were able to transfer their ampicillin resistance. The ampicillin and ampicillin plus clavulanic acid MIC values of all transconjugants were above 256 microg/ml. Transferable ampicillin resistance was associated with resistance to other antibacterials at the following frequencies: tetracycline 92%, trimethoprim 83%, streptomycin 50%, gentamicin 25%, and chloramphenicol 8%. In conclusion, it has been suggested that commensal bacteria in normal populations make up the largest reservoir of antibiotic-resistant genes. Although the exact molecular mechanisms could not be determined, the current study shows that the incidence of ampicillin and clavulanic acid resistance is also high in commensal fecal flora.

Ampicillin↗
PubMed1996

Potentiation of human polymorphonuclear leukocyte phagocytosis and intracellular bactericidal activity by amoxycillin/clavulanic acid.

The use of broad spectrum beta-lactamase inhibitors in association with beta-lactam agents provides one strategy to overcome the enzymatic resistance. Clavulanic acid is a potent inhibitor of a wide range of bacterial beta-lactamases and its potentiating effect on amoxycillin has been established both in vitro and in clinical trials. Since the efficacy of an antimicrobial agent in the therapy of infections depends on the interaction of bacteria, antibiotic and phagocytes, we investigated the effect of amoxycillin/clavulanic acid on the in vitro interaction between human polymorphonuclear cells (PMNs) and beta-lactamase producing strains of Klebsiella pneumoniae and Staphylococcus aureus. Clavulanic acid did not have any significant influence upon the PMN phagocytosis and killing against intracellular bacteria. Interestingly, the presence of the suicide inhibitor, with its beta-lactamase inhibitory properties, potentiated the activity of amoxycillin against the beta-lactamase producing strains of K. pneumoniae and S. aureus in such a manner that bacteria became significantly more susceptible to either phagocytosis or microbicidal activities of human phagocytes, compared to both the control and amoxycillin systems.

Amoxicillin↗
PubMed1987

Amoxycillin/clavulanate in acute purulent exacerbations of chronic bronchitis.

Twenty patients, all admitted to hospital with acute purulent exacerbations of chronic bronchitis associated with Haemophilus influenzae, Streptococcus pneumoniae or beta-lactamase producing Branhamella catarrhalis were treated twice daily for ten days with amoxycillin/clavulanate. Ten patients were first given 1000 mg amoxycillin with 200 mg potassium clavulanate intravenously bd for three days, before crossing to the standard oral regimen of 1000 mg amoxycillin + 250 mg potassium clavulanate bd. Clinical results on day 10 were excellent in 16/20 patients, but 14 patients developed recurrences or reinfections within a week of the end-of-treatment, five of them with beta-lactamase producing B. catarrhalis. Bacteriological and kinetic studies showed that the branhamella beta-lactamases were inhibited by 0.25 mg/l clavulanic acid and that the mean sputum concentration of clavulanic acid was 0.16 mg/l, that of amoxycillin being 0.92 mg/l. The importance of the follow-up of such infections is stressed.

Aged↗
PubMed1996

Antimicrobial susceptibilities of Campylobacter jejuni and Campylobacter coli to 12 beta-lactam agents and combinations with beta-lactamase inhibitors.

The in vitro activities of 12 beta-lactam agents against 100 thermophilic Campylobacter strains were tested. Beta-Lactamase production was detected in 88% of all strains tested. Clavulanic acid was the best inhibitor by susceptibility testing. The beta-lactams which displayed high levels of in vitro activity against Campylobacter isolates were imipenem, amoxicillin-clavulanic acid, and cefepime and, to a lesser degree, amoxicillin, ampicillin, and cefotaxime.

Anti-Bacterial Agents↗