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PubMed2002

[Amoxicillin-clavulanic acid induced hepatotoxicity with progression to cirrhosis].

Amoxicillin-clavulanic acid is a commonly used antibiotic in clinical practice. It is usually prescribed on an empirical basis and several cases of hepatotoxicity with cholestasis have been described. We report the case of a 42-year-old man who developed an acute hepatocellular lesion with progression to cirrhosis. The patient received amoxicillin-clavulanic acid twice with an interval of four months. Other causes of hepatic failure were excluded. Although amoxicillin-clavulanic acid-induced hepatotoxicity has been widely documented, there are no other reports describing its progression to cirrhosis in an adult.

Adult↗
PubMedDate not supplied

The influence of flucloxacillin and amoxicillin with clavulanic acid on the aerobic flora of the alimentary tract.

In a randomized study, 42 patients undergoing extensive maxillo-facial surgery (correction of the position of the mandible or maxilla by using autologous bone transplants) received prophylactically ten-day courses of either flucloxacillin or amoxicillin with clavulanic acid. Patients were comparable with regard to age and type of surgery. During the prophylactic treatment the effect of antibiotics used on the microbial flora of the alimentary tract was studied. Patients receiving flucloxacillin showed increased numbers of Klebsiella spp. isolated from the faeces (59% of the patients versus 19% of the patients receiving amoxicillin with clavulanic acid). Patients receiving amoxicillin with clavulanic acid showed higher colonization rates of oropharynx with Enterobacteriaceae than patients receiving flucloxacillin (ten patients versus five patients). 60% of those strains isolated from patients receiving amoxicillin with clavulanic acid were resistant to this combination, as compared to 20% of gram-negative bacilli isolated from patients receiving flucloxacillin. In 50% of patients receiving amoxicillin with clavulanic acid, colonization of the gut with yeast occurred, as compared to 18% of patients receiving flucloxacillin. Only one infection leading to a partial loss of the graft was seen in the group of patients receiving flucloxacillin.

Adolescent↗
PubMed2002

Antimicrobial prophylaxis in laparotomic gynecologic surgery: a prospective randomized study comparing amoxicillin-clavulanic acid with cefazolin.

A prospective randomized study was conducted at the Department of Obstetrics and Gynecology, University of Bari to compare two antimicrobial regimens, amoxicillin-clavulanic acid with cefazolin as ultra-short term prophylaxis in laparotomic gynecologic surgery. Patients were randomly allocated to receive a single dose of amoxicillin-clavulanic acid (2.2 g) [Group A] or cefazolin (2 g) [Group B] 30 minutes before surgery. Each patient was assessed daily until discharge for fever and the presence of infection of the surgical wound, urinary tract and respiratory tract. In the amoxicillin-clavulanic acid (Group A) and cefazolin (Group B) groups, overall 258 and 253 patients, respectively were evaluable for prophylactic efficacy at hospital discharge. Infectious complications were infrequent in both arms. Febrile morbidity occurred in 16 (6.3%) and 21 (8.1%) patients respectively in the amoxicillin-clavulanic acid and cefazolin groups. Wound infection and urinary tract infection were also higher but not significantly in the cefazolin group (0.8% versus 0% and 2.7% versus 2.0% respectively). There was no respiratory tract infection or septic death in either group. It is concluded that ultra-short term prophylaxis with both amoxicillin-clavulanic acid and cefazolin is safe and effective in elective laparotomic gynecologic surgery.

Adult↗
PubMed1988

Comparison of ticarcillin plus clavulanic acid with clindamycin and gentamicin in the treatment of postcesarean endomyometritis.

The efficacy of a single antibiotic--Timentin (ticarcillin with clavulanic acid)--was compared with a standard two antibiotic regimen (clindamycin and gentamicin) for the treatment of endomyometritis after cesarean delivery. The regimens were 3 grams of ticarcillin plus 100 milligrams of clavulanic acid given intravenously every four hours, or 600 milligrams of clindamycin given intravenously every six hours plus 3 to 5 milligrams per kilogram per day of gentamicin given intramuscularly. The diagnosis of endomyometritis was based upon an oral temperature of 100.4 degrees F. or higher on any two occasions, excluding the first 24 hours post partum, uterine tenderness and the absence of another focus of infection. Ninety-one patients were treated. Treatment failure rates were three of 49 in the clindamycin and gentamicin group and four of 42 of the ticarcillin plus clavulanic acid group. Treatment failures did not appear to be different from successes demographically or in risk factors for endomyometritis. The results of this study suggest that ticarcillin with clavulanic acid is as effective in the treatment of postcesarean endomyometritis as the standard regimen of clindamycin and gentamicin.

Adult↗
PubMed2000

Administration of ticarcillin in combination with clavulanic acid intravenously and intrauterinely to clinically normal oestrous mares.

Ticarcillin and clavulanic acid (potassium clavulanate) were administered to normal oestrous mares intravenously (i.v.) at a dose of 50 and 1.67 mg/kg for ticarcillin and clavulanate, respectively. In a crossover design, the same drugs were administered intrauterine (i.u.) at a dose of 12.4 and 0.4 mg/kg for ticarcillin and clavulanate, respectively. The i.u. dose was administered in 100 mL of saline solution. Endometrial tissue biopsies and plasma samples were collected after drug administration for the determination of ticarcillin and clavulanate concentrations by high-pressure liquid chromatography and pharmacokinetic calculations. After i.u. administration both drugs were poorly absorbed into the plasma. The ticarcillin half-life from tissue and plasma was short after i.v. administration. Although concentrations in tissue were higher after i.u. administration than i.v., concentrations of ticarcillin declined rapidly, which would necessitate frequent treatment in order to maintain drug concentrations above the minimum inhibitory concentrations (MIC) throughout the treatment period. Clavulanate concentrations in tissue were either low or persisted for only a short time after administration via either route. It appears that addition of clavulanate to the formulation for treatment of i.u. infections in mares is of questionable value based on these concentrations.

Animals↗
PubMed1985

Comparison of ticarcillin plus clavulanic acid with cefoxitin in the treatment of female pelvic infection.

Ninety-three female patients with post-cesarean endometritis, post-hysterectomy pelvic cellulitis, and other miscellaneous moderately severe pelvic soft-tissue infections were treated in a randomized fashion with either ticarcillin plus clavulanic acid or cefoxitin. Of the 47 patients treated with ticarcillin plus clavulanic acid, 38 had clinical cures, four showed improvement, therapy failed in three, and two were nonevaluable, for a failure rate of 6.7 percent. Of the 46 patients treated with cefoxitin, 33 had clinical cures, five showed improvement, therapy failed in seven, and one was nonevaluable, for a failure rate of 15.6 percent. Bacteriologically, the addition of clavulanic acid to ticarcillin was found to broaden the antibacterial spectrum to include some Escherichia coli, most Klebsiella, many coagulase-negative staphylococci, and all isolates of Staphylococcus aureus. Adverse reactions were few, with only one patient having therapy with cefoxitin discontinued because of side effects. It is concluded that ticarcillin plus clavulanic acid is quite suitable for antibiotic therapy of female pelvic soft-tissue infection, based on the (expanded) coverage of both aerobic and anaerobic bacterial species.

Adolescent↗
PubMed1995

[Bactericidal activity of combinations of ticarcillin-clavulanic acid or other beta-lactams (amoxicillin, piperacillin-tazobactam, ticarcillin) with gentamicin against Enterococcus faecalis and E. faecium].

MICs of amoxicillin, piperacillin-tazobactam, ticarcillin and ticarcillin-clavulanic acid were determined against 52 clinical strains of E. faecalis and E. faecium. Modal MICs (mg/l) of these antibiotics were 1, 4, 64 and 64, respectively. Bactericidal activity of the beta-lactams was tested at two concentrations (1/2 MIC and 100 mg/l) alone or combined with gentamicin (4 mg/l) against 10 clinical strains of Enterococcus spp. Activity of ticarcillin was not modified by the addition of clavulanic acid (4 mg/l). Time-kill curves showed that all beta-lactams at 100 mg/l were bactericidal after 18 h of incubation (decrease in bacterial counts > or = 3 log10 CFU/ml) against 6 strains of E. faecalis, with MICs of amoxicillin at 1 mg/l and 2 strains of E. faecium with MICs of amoxicillin at 1 and 2 mg/l. Addition of gentamicin resulted in a bactericidal effect at 3 or 6 hours for the great majority of the combinations studied, except against the two strains highly resistant to gentamicin. Combination of every beta-lactam at 1/2 MIC with gentamicin was synergistic (except in case of high level resistance to gentamicin) and prevented bacterial growth but was not bactericidal. Against two strains of E. faecium with high MICs of amoxicillin (8 mg/l), piperacillin-tazobactam (64 mg/l) and ticarcillin-clavulanic acid (512 mg/l), only combinations of amoxicillin 100 mg/l and gentamicin were always bactericidal. In conclusion, against E. faecalis strains, ticarcillin-clavulanic acid tested at 100 micrograms/ml had a bactericidal activity similar to that of the other beta-lactams tested, alone or combined with gentamicin.(ABSTRACT TRUNCATED AT 250 WORDS)

Amoxicillin↗
PubMed1986

Susceptibility of ticarcillin-resistant gram-negative bacilli to different combinations of ticarcillin and clavulanic acid.

The susceptibility of ticarcillin-resistant and of ticarcillin-susceptible Gram-negative bacilli to different combinations of ticarcillin and clavulanic acid has been investigated. Susceptibility to ticarcillin has been restored in ticarcillin-resistant isolates in proportion to the amount of clavulanic acid in the combination and depending upon the species. The decrease in the MICs of ticarcillin was excellent to good in Proteus, Morganella, Providencia, Escherichia coli and Klebsiella, moderate in Enterobacter, Citrobacter and Serratia, but poor in Pseudomonas aeruginosa. An unfavourable effect of clavulanic acid on the MICs of ticarcillin was observed in some isolates belonging to species with inducible beta-lactamases.

Clavulanic Acid↗
PubMed1985

Comparative in-vitro activities of azlocillin, ticarcillin and ticarcillin plus clavulanic acid against Staphylococcus aureus, Klebsiella pneumoniae and Pseudomonas aeruginosa.

Azlocillin (5 g), ticarcillin (5 g) and ticarcillin (5 g) plus clavulanic acid (200 mg) were administered intravenously on separate days to human volunteers. Serum levels 1 h after the infusion were (mean +/- S.E.): 263 +/- 40 mg/1 for azlocillin, 238 +/- 56 mg/l for ticarcillin and 5.5 +/- 1.9 mg/l for clavulanic acid. Serum withdrawn at 0.5 h was titrated against ten strains of Staphylococcus aureus, ten Klebsiella pneumoniae and nine Pseudomonas aeruginosa of which four were resistant to ticarcillin. Against Staph. aureus and K. pneumoniae, median serum bactericidal activity (SBA) and percentage of sera with SBA greater than or equal to 1:8 were greater with ticarcillin plus clavulanic acid (median SBA 1:32 and 85% of sera with SBA greater than or equal to 1:8) than with the other two regimens. There were no differences in activity against Ps. aeruginosa.

Azlocillin↗
PubMed1984

[Influence of amoxicillin combined with clavulanic acid on the fecal flora in children].

The effect of an amoxycillin-clavulanic acid combination on the intestinal bacterial ecosystem was studied by differential quantitative analysis of the fecal flora in 11 hospitalized pediatric patients aged 8 months to 4 years. The antibiotic combination was given orally to 7 patients and intravenously to 4. The modifications in the intestinal flora are more important with oral route than intravenous route. After treatment, an increase in ampicillin-resistant E. coli with overgrowth of Klebsiella were found. Our previous studies have shown that this microbial overgrowth carries a risk of secondary septicemia. A strain of amoxycillin-resistant Serratia marcescens emerged but did not pullulate . The other aerobic or anaerobic bacteria were not significantly modified. Most strains which emerged after therapy remained susceptible to the combination. Yeasts emerged in two patients. Thus, the amoxycillin-clavulanic acid combination results in intestinal Klebsiella overgrowth, requiring monitoring of the intestinal bacterial ecosystem.

Amoxicillin↗
PubMed1985

Pharmacokinetics of clavulanic acid, given in combination with amoxycillin, in volunteers.

To study the absorption and disposition of clavulanic acid, ten healthy men received one intravenous and one oral dose of 125 mg clavulanic acid in combination with amoxycillin. Serum and urine concentrations were measured with high-performance liquid chromatography. The mean terminal half-lives in serum were 0.97 and 0.94 h, respectively. Total serum clearance was 248 +/- 55 ml/min X 1.73 m2. Renal clearance was 108 +/- 20 and 115 +/- 18 ml/min X 1.73 m2 after intravenous and peroral administration. Urinary recovery over 12 h was 49.4 +/- 8.7% of the intravenous and 35.7 +/- 13.0% of the oral dose. The bioavailability of the oral dose averaged 60.0 +/- 23.1% but varied considerably (range 31.4-98.8%), indicating very variable absorption from the gastrointestinal tract.

Administration, Oral↗
PubMed1986

In vitro activity of clavulanic acid, amoxicillin, and ticarcillin against Chlamydia trachomatis.

In vitro, growth of Chlamydia trachomatis was not entirely eliminated by 960 micrograms of ticarcillin per ml, 64 micrograms of amoxicillin per ml, 32 micrograms of clavulanic acid per ml, a combination of ticarcillin (480 micrograms/ml) and clavulanic acid (32 micrograms/ml), and a combination of amoxicillin (32 micrograms/ml) and clavulanic acid (8 micrograms/ml). However, a greater than or equal to 99% decrease in the number of inclusions was obtained at concentrations readily attainable in serum.

Amoxicillin↗
PubMed1988

In vitro susceptibility of bacteria to a ticarcillin-clavulanic acid combination.

In vitro testing of bacterial susceptibility to a combination of ticarcillin and clavulanic acid was done, using 406 aerobic gram-positive and gram-negative isolates (considered to be pathogens) cultured from equine and small animal specimens. A microdilution broth technique of susceptibility testing was performed, using trays with wells containing a range of doubling concentrations of dehydrated ticarcillin (range, 0.50 to 128 micrograms/ml) with fixed concentration of clavulanic acid (4 micrograms/ml). The following isolates of equine origin were (90%) susceptible to concentrations of ticarcillin and clavulanic acid combinations of less than or equal to 16 and 4 micrograms/ml, respectively: Staphylococcus aureus, S intermedius, Klebsiella pneumoniae, Enterobacter aerogenes, Ent agglomerans, Ent cloacae, Escherichia coli, Actinobacillus sp, Corynebacterium pseudotuberculosis, Rhodococcus equi, Proteus vulgaris, and Bordetella bronchiseptica. Isolates of small animal origin (90%) susceptible to less than or equal to 16 and 4 micrograms of ticarcillinclavulanic/ml included S aureus, S intermedius, Ent aerogenes, Ent agglomerans, Pasteurella multocida, B bronchiseptica, Pr mirabilis, and Serratia sp.

Animal Population Groups↗
PubMed1997

Amoxicillin and clavulanic acid concentrations in gingival crevicular fluid.

The beta-lactams are bactericidal antibiotics, but some of them may be inactivated by bacterial beta-lactamases which destroy the beta-lactam ring. The inactivation of amoxicillin by beta-lactamases of gram negative anaerobic bacteria can be circumvented by the addition of clavulanic acid, a beta-lactamases inhibitor. Thus, most of these bacteria are susceptible to this combination. The aim of this study was to investigate the concentrations of amoxicillin and clavulanic acid in gingival crevicular fluid (GCF). These concentrations were measured in 20 patients with rapidly progressive periodontitis 1 h after a dose of 500 mg (1 tablet Augmentin) on day 0 and 1 h after the 10th intake on day 3. For the sampling of GCF, Periopapers were introduced in 16 gingival sites per subject and time. The GCF volumes collected were estimated using the Periotron 6000. A high performance liquid chromatography method has been developed for the determination of amoxicillin and clavulanic acid in microsamples (1 to 10 microliters) of GCF. The concentrations of amoxicillin and clavulanic acid were respectively, 14.05 micrograms ml-1 and 0.40 microgram ml-1 at day 0, 13.93 micrograms ml-1 and 0.37 microgram ml-1 at day 3. Effective levels of amoxicillin and clavulanic acid, well above the minimal inhibitory concentrations of some susceptible periodontal anaerobes (P. intermedia) involved in destructive periodontal diseases, are achieved following the multiple administration of amoxicillin combined with clavulanic acid.

Adult↗
PubMedDate not supplied

Amoxycillin and clavulanic acid versus cefotaxime and metronidazole as antibiotic prophylaxis in elective colorectal resectional surgery.

In a prospective randomised controlled trial, amoxycillin plus clavulanic acid was compared to a combination of cefotaxime and metronidazole as prophylactic antibiotics in 164 patients who underwent elective colorectal resectional surgery. Wound infection occurred in 15 patients (9.1%) and deep surgical infection in 4 (2.4%). Seven cases of wound infection and 2 cases of deep infection occurred in the amoxycillin plus clavulanic acid arm, while 8 cases of wound infection and 2 cases of deep infection occurred in the cefotaxime plus metronidazole arm. Eighty-eight percent of infections occurred in patients who had low anterior resection or abdominoperineal resection of the rectum. Both the amoxycillin plus clavulanic acid and the combination of cefotaxime and metronidazole offer the same degree of protection against post-operative infection. The use of amoxycillin plus clavulanic acid as antibiotic prophylaxis is recommended because of its easier use and cheaper cost.

Adult↗
PubMed1983

Antibiotic and clavulanic acid treatment of subcutaneous abscesses caused by Bacteroides fragilis alone or in combination with aerobic bacteria.

A subcutaneous abscess model was utilized in investigating the usefulness of various antimicrobial combinations in the treatment of mixed aerobic-anaerobic infections in mice. The infected animals were treated for seven days with single or combined antimicrobial therapy. The single agents used were penicillin, clavulanic acid, oxacillin, metronidazole, and gentamicin. The antimicrobial combinations used were penicillin plus clavulanic acid and metronidazole plus penicillin, oxacillin, or gentamicin. Administration of a single agent was effective in treating abscesses caused by a single susceptible organism. The only effective therapies for mixed infections were the combinations of penicillin plus clavulanic acid or metronidazole plus gentamicin. This study demonstrated the efficacy of penicillin and clavulanic acid in the treatment of infections caused by Bacteroides fragilis alone or in combination with beta-lactamase-producing aerobic bacteria.

Abscess↗
PubMed1981

Inactivation of RTEM beta-lactamase from Escherichia coli by clavulanic acid and 9-deoxyclavulanic acid.

The interaction of the TEM-2 beta-lactamase with 9-deoxyclavulanic acid (3) and with both extensively labeled (2) and specifically labeled (1) clavulanic acid has been studied. The close similarity between 9-doexyclavulanate and clavulanate in kinetics, spectroscopic, and protein chemical terms show that the allyl alcohol group of clavulanate is irrelevant to its action as a beta-lactamase inactivator. Use of the radiolabeled samples of clavulanate shows that, of three irreversibly inactivated forms of the enzymes, two contain the whole clavulanate skeleton and the third only retains the carbon atoms of the original beta-lactam ring. These findings allow the complex interaction between clavulanic acid and the beta-lactamase to be defined more narrowly in chemical terms.

Clavulanic Acid↗
PubMed1986

In-vitro activity of ticarcillin with and without clavulanic acid against clinical isolates of gram-positive and gram-negative bacteria.

The in-vitro activity of ticarcillin with and without clavulanic acid was investigated against 285 freshly isolated clinical strains of Gram-positive and Gram-negative bacteria by the agar-dilution technique on Mueller-Hinton-agar. Clavulanic acid had an excellent or moderate potentiating effect on the in-vitro activity of ticarcillin against staphylococci, Escherichia coli, Klebsiella spp., Enterobacter aerogenes, Proteus mirabilis, Citrobacter spp., Acinetobacter, Haemophilus influenzae and Bacteroides spp. No effect was seen against enterococci, indole-positive Proteus spp., Ent. cloacae, Serratia marcescens and Pseudomonas aeruginosa. The effect of clavulanic acid was dose- and inoculum-dependent.

Bacterial Infections↗