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PubMed1984

In vivo protection of penicillin-susceptible Bacteroides melaninogenicus from penicillin by facultative bacteria which produce beta-lactamase.

We investigated the possibility that beta-lactamase producing strains of Klebsiella pneumoniae and Staphylococcus aureus can protect organisms of the Bacteroides melaninogenicus group from penicillin. A mixed infection was induced in mice in the form of a subcutaneous abscess involving a penicillin-susceptible encapsulated B. melaninogenicus, and a beta-lactamase producing strain of either K. pneumoniae or S. aureus. The infected animals were treated for 7 days with single or combined antimicrobial therapy. The single agents used were penicillin, clavulanic acid, metronidazole, and gentamicin. The antimicrobial combinations were penicillin and clavulanic acid, penicillin and gentamicin, and metronidazole and gentamicin. Administration of a single agent was effective in treating abscesses caused by susceptible organisms. The only effective therapy for mixed infections was by combination therapy of penicillin and clavulanic acid or metronidazole and gentamicin. This study supports the hypothesis that beta-lactamase producing facultative bacteria may shield their anaerobic counterparts from penicillin therapy, thereby contributing to the persistence of the infection.

Abscess↗
PubMed1989

Comparative effects of three beta-lactam antibiotics on anti-PC direct plaque-forming cells.

Penicillin G, cefotaxime and clavulanic acid administered intravenously were studied for their immunomodulating properties. BALBC/c mice were immunized using PC-KLH as thymus-dependent antigen at the same time as the antibiotic was injected. The effect on antibody response was evaluated 5 days after immunization. Critical immunological parameters such as direct antibody-producing cells, Ab-secretion median rate, secretion rate heterogeneity and cellular viability, were studied. The most stimulatory effects were with penicillin G at the 4 x 10(6) IU/kg dose (+73%), cefotaxime at the 366 mg/kg dose (+80%) and clavulanic acid at 1 mg/kg (+218%). The experiments using inhibition of plaque formation with free hapten demonstrate that all the drugs studied decreased the antibody secretion rate and this parameter appeared more heterogeneous when cefotaxime and clavulanic acid were given; however, with penicillin this parameter was more heterogeneous at 2 x 10(5) mg/kg and 1 x 10(3) IU/kg respectively. When clavulanic acid was injected, the number of lymphocytes per spleen, size and friability of the spleen were increased versus the control mice. The present data show that all of the drugs studied present immunostimulating effects on humoral response, against thymus-dependent antigen, but have differently pronounced enhancements.

Animals↗
PubMed1989

In vitro effects of beta-lactams combined with beta-lactamase inhibitors against methicillin-resistant Staphylococcus aureus.

The effects of combinations of beta-lactams with two beta-lactamase inhibitors, sulbactam and clavulanic acid, were determined in vitro against 22 clinical isolates of methicillin-resistant Staphylococcus aureus. Combinations of cefpirome, cefotaxime, and cefazolin with sulbactam (10 micrograms/ml) showed synergistic effects against more than 70% of the strains. Combinations of methicillin and penicillin G with sulbactam also showed synergistic effects against 50 and 68% of the strains, respectively, while cefotiam, moxalactam, flomoxef, and cefmetazole in combination with sulbactam showed such effects against only 40% or fewer. Clavulanic acid was synergistic only when combined with penicillin G, the effect probably being due to the beta-lactamase inhibition by the inhibitor. Sulbactam did not improve the antimicrobial activities of the beta-lactams against methicillin-susceptible S. aureus strains. At 42 degrees C the MICs of cefotaxime, methicillin, and flomoxef alone were markedly decreased from the values at 35 degrees C, and no synergy between these beta-lactams and sulbactam appeared. The resistance to penicillin G was not inhibited by incubation at 42 degrees C, and combinations of penicillin G with sulbactam and clavulanic acid showed synergy. The amounts of beta-lactamase produced were not related to the decreases in the MICs of the beta-lactams, except for penicillin G combined with sulbactam. Clavulanic acid showed slightly stronger beta-lactamase-inhibiting activity than sulbactam did. These results suggest that the synergy between sulbactam and the beta-lactams, except for penicillin G, may not be due to beta-lactamase inhibition but to suppression of the methicillin-resistant S. aureus-specific resistance based on other factors.

Anti-Bacterial Agents↗
PubMed1986

Detection, distribution and inhibition of Branhamella catarrhalis beta-lactamases.

Beta-lactamase-producing isolates of Branhamella catarrhalis were first detected in France in 1977. The frequency of beta-lactamase producers has increased, especially since 1980. An agar iodometric test, a fast chromogenic test and an acidimetric test were used to assess the beta-lactamase-producing capabilities of 188 isolates of B. catarrhalis obtained mainly from sputum and the pharynx. Data from the first 2 procedures indicated positive beta-lactamase activity for all 49 strains of B. catarrhalis identified, but there were some discrepancies in the acidimetric test results. Evidence from a diffusion technique showed significant increases in the inhibition diameters surrounding filter discs impregnated with amoxycillin in the presence of clavulanic acid, or with ampicillin in the presence of sulbactam, compared with discs of the penicillins used alone. Two types of enzyme activity emerged from examination of isoelectric focusing patterns. Type I, having pI values of 5.35, 5.55 and 5.85, accounted for 87.2% of the enzyme-producing isolates. Type II, with pIs of 5.5, 5.9 and 6.25, occurred in 12.8% of isolates and appeared to be less widely distributed. The beta-lactamase inhibitors clavulanic acid and sulbactam in combination with benzylpenicillin produced potentiated effects, as demonstrated by significant reductions in MIC (33- and 44-fold decreases, respectively). Higher concentrations of each inhibitor similarly affected the MICs of amoxycillin. A weak synergy occurred with cefoxitin, a beta-lactamase-resistant beta-lactam antibiotic, and the 2 beta-lactamase inhibitors. Because B. catarrhalis has been shown to be a beta-lactamase-producing pathogenic organism, the addition of enzyme inhibitors, such as clavulanic acid and sulbactam, to standard therapy may be beneficial.

Anti-Bacterial Agents↗
PubMed1988

Antimicrobial prophylaxis for major head and neck surgery in cancer patients.

A total of 113 patients were randomly allocated to receive either ticarcillin plus clavulanic acid (total dose, 20.8 g) or clindamycin (total dose, 2.4 g) plus amikacin (total dose, 1 g) as perioperative antimicrobial prophylaxis for major head and neck surgery. The two groups were similar in age, prior antineoplastic treatment (surgery, chemotherapy, and radiotherapy) or tracheostomy, and the various types of surgery including radical neck dissection. The wound infection rate was 10% in the group of patients receiving clindamycin plus amikacin and 36% in the group receiving ticarcillin plus clavulanic acid (P less than 0.05). Initiation of systemic antibiotic therapy within 15 days of surgery was necessary for 20 and 45% of these patients, respectively (P less than 0.05). The distribution of microorganisms causing wound infections was comparable in both groups, except for anaerobes, which were isolated predominantly from patients who had received ticarcillin plus clavulanic acid.

Adult↗
PubMed1999

Pharmacokinetic properties of beta-lactamase inhibitors.

OBJECTIVES: In recent years, the use of combinations of beta-lactam-antibiotics with beta-lactamase inhibitors has been proven to be a useful and effective strategy to improve upon the therapeutic value of beta-lactam antibiotics. The objective of this article is to evaluate the pharmacokinetic properties of three commercially available beta-lactamase inhibitors. MATERIALS AND METHODS: Based on published articles in the literature, the pharmacokinetic properties of the beta-lactamase inhibitors clavulanic acid, sulbactam and tazobactam are reviewed and compared. RESULTS: There are some considerable differences between these three compounds: Only clavulanic acid is orally bioavailable. Tazobactam and sulbactam are eliminated renally to a larger extent than clavulanic acid. Tazobactam's total body clearance is almost twice that of sulbactam, and the two drugs differ significantly in their degree of protein-binding. Furthermore, sulbactam has a larger volume of distribution than tazobactam. CONCLUSIONS: When choosing combinations of a beta-lactam antibiotic with a beta-lactamase inhibitor, it is important to make sure that the pharmacokinetic properties of drug and inhibitor are similar and remain similar under changing pathophysiological conditions. Hence, beta-lactam inhibitors should not be freely interchanged, but for each beta-lactam antibiotic the best partner needs to be identified. If this is done properly, fixed combinations of beta-lactam-antibiotic and beta-lactamase inhibitor are appropriate and convenient. This situation may represent one of the few cases in pharmacotherapy, where fixed combinations of two drugs are beneficial.

Absorption↗
PubMed1996

A cost-effectiveness evaluation of 3 antimicrobial regimens for the prevention of infective complications after abdominal surgery.

OBJECTIVE: To measure the cost and effectiveness of 3 established antimicrobial regimens for the prevention of infective complications after abdominal surgery. DESIGN: A prospective randomized trial was performed involving a total of 1070 patients undergoing abdominal surgery. SETTING AND PATIENTS: All patients having upper gastrointestinal tract, colorectal, appendiceal, or biliary surgery at a major teaching hospital in Melbourne, Australia, were considered for entry into the study. INTERVENTIONS: Patients were randomized prior to surgery to receive a single dose of cefotaxime sodium (1 g), ticarcillin plus clavulanic acid (3.1 g), or ceftriaxone sodium, (1 g). All drugs were given intravenously at the start of anesthesia. MAIN OUTCOME MEASURES: Rates of major wound infections, minor wound infections, other wound problems, and other infective complications. The acquisition and administrative costs of the drugs used and the costs of the infective complications were measured. RESULTS: A Total of 1070 patients were entered into the study. Major wound infections occurred in 21 patients (2.0%). Twenty-five patients (2.3%) developed a minor wound infection. Other infective complications developed in 107 patients. There were significantly fewer minor wound infections in the ceftriaxone-treated group as compared with the other 2 groups. There was no differences in the frequency of major wound infections, other wound problems, or other infective complications. The acquisition costs of cefotaxime and ticarcillin plus clavulanic acid were less than those of ceftriaxone. The estimated cost of treating the infective complications in the group of patients who received ticarcillin plus clavulanic acid ($128,039) was greater than the cost associated with the groups being treated with cefotaxime ($91,243) or ceftriaxone ($96,095). CONCLUSIONS: The study indicates that each of the 3 regimens was associated with highly satisfactory control of postoperative infective complications after abdominal surgery. On the basis of the estimated costs of infective complications, cefotaxime and ceftriaxone appear equally effective for the prevention of infective complications after abdominal surgery. Acquisition costs for cefotaxime were lower and it is recommended as the preferred agent on this basis.

Anti-Bacterial Agents↗
PubMed1987

The role of beta-lactamase and the permeability barrier on the activity of cephalosporins against members of the Bacteroides fragilis group.

The role of beta-lactamase and the permeability barrier on the activity of some beta-lactams against 53 strains of the Bacteroides fragilis group was investigated. Minimal inhibitory concentrations of cefamandole, cefoxitin, and cephalothin were determined with or without the addition of clavulanic acid and (or) ethylenediaminetetraacetate using an agar dilution technique. A significant increase of susceptibility with clavulanic acid indicated a role for beta-lactamase, and with ethylenediaminetetraacetate, a role for a permeability barrier. We found that both beta-lactamase and low permeability decreased the activity of the beta-lactams to some extent depending on the bacterial species and the antibiotic. The species-specific exception was B. distasonis which showed only a permeability barrier to all antibiotics tested.

Bacteroides↗
PubMed1991

Intrahepatic cholestasis induced by amoxicillin/clavulanic acid (Augmentin): a report on two cases.

Two patients who developed a severe but reversible cholestatic jaundice during and after treatment with an amoxicillin/clavulanic acid preparation (Augmentin) are described. The diagnosis of drug-induced intrahepatic cholestasis was based on the clinical course, biochemical pattern and on histological findings. Since amoxicillin alone does not induce liver injury, the combination of amoxicillin and clavulanic acid or clavulanic acid alone could be responsible for this adverse reaction, probably through a metabolic idiosyncrasy or a hypersensitivity mechanism. Although more than 100 cases of hepatotoxic reactions have been reported to the pharmaceutical company (Beecham Laboratories) and several reports have been published, the incidence of hepatotoxicity of this antibiotic is relatively rare, since this antibiotic has been widely used. However, recognition of this benign and reversible cholestatic syndrome is important to avoid unnecessary, expensive and invasive diagnostic procedures.

Aged↗
PubMed1999

In vitro bactericidal activity of peak serum concentrations of co-amoxiclav, amoxicillin and vancomycin against methicillin-resistant Staphylococcus aureus.

In order to explore the bactericidal activity of concentrations similar to the peak serum concentrations obtained after a single i.v. dose of 2,000/200 mg co-amoxiclav and 500 mg vancomycin, killing curves with co-amoxiclav (69/10 microg/ml), amoxicillin (69 microg/ml), clavulanic acid (10 microg/ml), and vancomycin (15 microg/ml) were performed against two isogenic (ss-lactamase positive and negative) methicillin-resistant Staphylococcus aureus strains in cation-supplemented Mueller-Hinton broth with 2% NaCl incubated at 35 degrees C. Colony counts were performed at 0, 1, 2, 3 and 4 hours in Mueller- Hinton plates supplemented with 4% NaCl and 25 microg/ml oxacillin to measure the resistant population. Similar initial inocula reductions were obtained for amoxicillin-clavulanic acid and vancomycin for both strains, and significant differences were found in comparison to the control. Clavulanic acid decreased the growth rate of the ss-lactamase negative strain when compared to control curves. The penicillin-binding protein 2a affinity of old ss-lactams in conjunction with clavulanic acid overcoming ss-lactamase resistance may explain these results.

Amoxicillin↗
PubMed1998

Molecular characterization of OXA-20, a novel class D beta-lactamase, and its integron from Pseudomonas aeruginosa.

The Pseudomonas aeruginosa Mus clinical isolate produces OXA-18, a pI 5.5 class D extended-spectrum beta-lactamase totally inhibited by clavulanic acid (L. N. Philippon, T. Naas, A.-T. Bouthors, V. Barakett, and P. Nordmann, Antimicrob. Agents Chemother. 41:2188-2195, 1997). A second beta-lactamase was cloned, and the recombinant Escherichia coli clone pPL10 expressed a pI 7.4 beta-lactamase which conferred high levels of amoxicillin and ticarcillin resistance and which was partially inhibited by clavulanic acid. The 2.5-kb insert from pPL10 was sequenced, and a 266-amino-acid protein (OXA-20) was deduced; this protein has low amino acid identity with most of the class D beta-lactamases except OXA-2, OXA-15, and OXA-3 (75% amino acid identity with each). OXA-20 is a restricted-spectrum oxacillinase and is unusually inhibited by clavulanic acid. OXA-20 is a peculiar beta-lactamase because its translation initiates with a TTG (leucine) codon, which is rarely used as a translational origin in bacteria. Exploration of the genetic environment of oxa20 revealed the presence of the following integron features: (i) a second antibiotic resistance gene, aacA4; (ii) an intI1 gene; and (iii) two 59-base elements, each associated with either oxa20 or aacA4. This integron is peculiar because it lacks the 3' conserved region, and therefore is not a sul1-associated integron like most of them, and because its 3' end is located within tnpR, a gene involved in the transposition of Tn5393, a gram-negative transposon. P. aeruginosa Mus produces two novel and unrelated oxacillinases, OXA-18 and OXA-20, both of which are inhibited by clavulanic acid.

Amino Acid Sequence↗
PubMed1990

[Acute otitis media in children: a randomized and open clinical trial of the efficacy of 2 major antibiotics (erythromycin ethylsuccinate/acetyl sulfafurazole vs amoxicillin/clavulanic acid)].

In a prospective randomized open study, 111 young children with otitis media were orally treated during 10 days with Pediazole (50 mg/kg/day in 3 divided doses) or amoxicillin + clavulanic acid (40 mg/kg/day in 3 or 4 divided doses) for efficacy and safety evaluation. 51 children wer assigned to amoxicillin + clavulanic acid (group I) and 60 to erythromycin-sulfisoxazole (group II). Mean age was respectively 24.7 months in group I and 23.4 months in group II. Results of efficacy evaluation were as follows: (table; see text) there was no statistically significant difference between the two treatment groups for efficacy. Overall safety was good. The treatment was discontinued only in four cases (3 in the amoxicillin + clavulanic acid group and 1 in the EES-sulfisoxazole group). In conclusion, Erythromycin sulfisoxazole combination (Pediazole) fits in with current epidemiological profile of Acute Otitis Media and represents a therapy of choice in this indication.

Acute Disease↗
PubMed1998

In vitro activities of co-amoxiclav at concentrations achieved in human serum against the resistant subpopulation of heteroresistant Staphylococcus aureus: a controlled study with vancomycin.

The effects of concentrations that simulated those in human serum after a single intravenous dose of amoxicillin (2 g), amoxicillin-clavulanic acid (2,000 and 200 mg, respectively), or vancomycin (500 mg), on the viability and beta-lactamase activity of two isogenic (beta-lactamase and non-beta-lactamase producer) heteroresistant Staphylococcus aureus strains were studied in an in vitro pharmacodynamic model. A reduction of > or = 97% of the initial inoculum was obtained with vancomycin and amoxicillin-clavulanic acid against both strains, with respect to the total bacterial population and the oxacillin-resistant subpopulation. The same pattern was observed with amoxicillin and the beta-lactamase-negative strain. beta-Lactamase activity in the beta-lactamase-positive strain changed over time parallel to viability, decreasing with amoxicillin-clavulanic acid or vancomycin and increasing in the amoxicillin and control groups. Clavulanic acid concentrations achievable in serum that changed over time allowed amoxicillin to act against the beta-lactamase-producing methicillin-resistant S. aureus to a similar extent as vancomycin.

Amoxicillin↗
PubMed2001

Controlled study of the efficacy of clavulanic acid-potentiated amoxycillin in the treatment of Chlamydia psittaci in cats.

Twenty-four specific pathogen-free cats were inoculated with 3 x 10(3) infectious units of a field isolate of Chlamydia psittaci on to the corneal surface. Seven days later they were assigned randomly to three groups of eight and treated orally for 19 days with either clavulanic acid-potentiated amoxycillin, doxycycline or a placebo. Both treated groups responded rapidly, with a marked reduction in isolation rates and clinical scores which were significantly lower than in the placebo group within two and four days, respectively. After two days the group treated with potentiated amoxycillin had a significantly lower isolation score than the group treated with doxycycline. Forty days after they were infected the clinical signs recurred in five of the eight cats treated with potentiated amoxycillin, but a four-week course of potentiated amoxycillin resulted in a complete clinical recovery with no evidence of a recurrence for six months.

Amoxicillin↗
PubMed1985

[Experimental and clinical evaluation of the BRL 25000 (clavulanic acid-amoxicillin) granules in the pediatric field].

BRL 25000 granules containing 2 parts amoxicillin and 1 part potassium clavulanate were administered to children suffering from acute infections at a daily dose of 50 mg/kg in 3 or 4 divided doses for at least 3 days. Infections included acute airway infections (81), scarlet fever and suspected scarlet fever (4), urinary tract infections (4), impetigo contagiosa (1) and acute colitis (1). Bacteria were eradicated in 91.3% (63/69) of cases treated with the BRL 25000 granules, with only 2 strains of Staphylococcus aureus, 2 of Escherichia coli, 1 of Haemophilus influenzae and 1 of Streptococcus pneumoniae remaining. Eight beta-lactamase producing strains were detected amongst the 49 clinical isolates studied and of these, 6 were eradicated after administration of the BRL 25000 granules. Good clinical efficacy was obtained in 97.8% of cases (89/91), with 1 case of acute tonsillitis and 1 of acute colitis showing no improvement. Adverse reactions were limited to 1 case of vomiting and 3 of diarrhea, and no abnormal laboratory findings were detected.

Administration, Oral↗
PubMed1998

Phenotypic study of resistance of beta-lactamase-inhibitor-resistant TEM enzymes which differ by naturally occurring variations and by site-directed substitution at Asp276.

At this time an amino acid substitution at position 276 in the TEM-1 enzyme is associated with an additional substitution at position 69 in natural beta-lactamase-inhibitor-resistant (IRT) beta-lactamases. The effect of the Asn276-->Asp substitution on resistance was assessed with the Asn276Asp variant, generated by site-directed mutagenesis. The mutant was resistant to beta-lactamase inhibitors, but the MICs of amoxicillin combined with clavulanic acid or tazobactam were strikingly different for E. coli strains producing the Asn276Asp variant and those producing naturally occurring IRTs with single or double substitutions. The inhibitory effects of clavulanic acid and tazobactam were the same in IRTs with substitutions at position 69 (IRT-5 and IRT-6). The effect of clavulanic acid on the MICs of amoxicillin for the Asn276Asp variant was greater than that of tazobactam. In IRTs with double substitutions, at positions 69 plus 276 (IRT-4, IRT-7, and IRT-8) or 69 plus 275 (IRT-14), tazobactam was a more potent inhibitor than clavulanic acid. The effect of the Asn276-->Asp substitution on the values of the kinetic constants and the concentration required to inhibit by 50% the hydrolysis of benzylpenicillin confirms that this single mutation is responsible for resistance to beta-lactamase inhibitors. Molecular modeling of the Asn276Asp mutant shows that Asp276 can form two salt bonds with Arg244 close to the penicillin-binding cavity. The addition of the Asp276 mutation to that preexisting at position 69 confers a higher selective advantage to bacteria, as shown by the reduction in beta-lactamase inhibitor efficiencies of the double variants. Therefore, the emergence of multiple mutations in TEM beta-lactamases by virtue of the use of beta-lactamase inhibitors increases selection pressure resulting in the convergent evolution of resistant strains.

Amoxicillin↗
PubMed1999

Molecular typing of multiresistant Klebsiella pneumoniae isolated from children from northern Jordan.

Twenty-nine clinical isolates of community acquired Klebsiella pneumoniae obtained from 17 children with malnutrition were characterized by antibiotic susceptibility, plasmid analysis, and random amplified polymorphic DNA (RAPD) techniques. Disc diffusion methodology was used to test the susceptibility of the isolates to 13 antibiotics: amoxycillin, cephapirin, ceftazidime, cefoxitin, cefotaxime, aztreonam, gentamicin, ciprofloxacin, chloramphenicol, erythromycin, nalidixic acid, trimethoprim and amoxycillin-clavulanic acid. All the isolates showed multiresistance patterns (15 patterns) ranging from resistance to two antibiotics to resistance to 10 antibiotics. All isolates were resistant to amoxycillin and erythromycin. Ten K. pneumoniae isolates producing extended-spectrum beta-lactamases (ESBLs) as evidenced by the double-disc diffusion synergy test were isolated sporadically from six patients. Six of these 10 isolates were hyperproducers of ESBL, which resulted in increased resistance to the beta-lactam-beta-lactamase inhibitor combination amoxycillin-clavulanic acid. Plasmid analysis showed plasmid ranging in size from 48 kilobases (kb) to 1.4 kb. All the 29 isolates shared the same plasmid 26 kb. There was a consistent relationship between antibiotype and plasmid profiles for each pair of isolates obtained from five individual patients. RAPD analysis using a single (10-mer) primer demonstrated that the isolates that have the same antibiotype and the same plasmid profile had different RAPD fingerprint patterns. These results demonstrate that the RAPD technique is better than antibiotype characterization and a plasmid analysis profile for typing K. pneumoniae as well as for revealing strain differences.

Anti-Bacterial Agents↗
PubMed1999

In vitro activity and pharmacodynamics of oral beta-lactam antibiotics against Streptococcus pneumoniae from southeast Missouri.

STUDY OBJECTIVES: To determine the frequency of reduced susceptibility to penicillin, and to compare the in vitro activity and pharmacodynamics of oral beta-lactam antibiotics against clinical isolates of Streptococcus pneumoniae from southeast Missouri. SETTING: Cape Girardeau, Missouri (population 35,500). Interventions. Minimum inhibitory concentrations (MICs) were determined for penicillin, amoxicillin, amoxicillin-clavulanic acid, cefprozil, cefuroxime, cefpodoxime, cefaclor, and loracarbef by E test for 108 isolates of S. pneumoniae. The MIC50, MIC90, and percentage susceptibility were calculated for each agent. Pharmacokinetic variables were obtained from the literature, and serum concentration-time profiles were simulated for a 25-kg child taking pediatric dosages commonly administered to treat otitis media. The average time above MIC (T > MIC) was calculated as percentage of the dosing interval using free concentrations and the MIC for each individual isolate. Analysis of variance (Scheffe post hoc test) was used to determine differences among agents for in vitro activity and T > MIC (level of significance, p<0.05). MEASUREMENTS AND MAIN RESULTS: The frequency of penicillin-nonsusceptible S. pneumoniae was 28.7% (31/108). For 25 penicillin-intermediate isolates, amoxicillin and amoxicillin-clavulanic acid were significantly more active than cefprozil, cefaclor, and loracarbef. The T > MIC for amoxicillin and amoxicillin-clavulanic acid, simulated at 13.3 mg/kg every 8 hours, was significantly longer than that for all other beta-lactams. CONCLUSION: Amoxicillin and amoxicillin-clavulanic acid have superior in vitro activity and longer T > MIC for penicillin-intermediate isolates than the other oral beta-lactams.

Administration, Oral↗