Combined antibacterial activity of amoxicillin with clavulanic acid against ampicillin-resistant strains

Abstract

Strains of bacteria resistant to beta-lactam antibiotics have been increasing in number and are becoming troublesome in clinical medicine. The in vitro antibacterial activity of amoxicillin combined with clavulanic acid was determined on selected ampicillin-resistant clinical isolates. Synergistic effects were produced by amoxicillin with clavulanic acid against ampicillin-resistant strains of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, and Bacteroides fragilis. Inhibition of the beta-lactamases produced by the ampicillin-resistant strains was confirmed, especially against the penicillinases mediated by the R factor and the cephalosporinases produced by P. vulgaris and B. fragilis. The inhibitory effect of clavulanic acid against betalactamases was irreversible because of the high affinity of clavulanic acid to the enzymes.Bacterial strains resistant to beta-lactam antibiotics have been increasing in number. The resistance of these bacteria is due mainly to the production of beta-lactamase (1), and newer semisynthetic beta-lactam antibiotics, i.e., cefuroxime (8) and cefoxitin (12), resistant to betalactamase have been developed. Clavulanic acid (CVA) (2, 10) and CP-45899 (4) were found to be beta-lactamase inhibitors, although they have poor antibacterial activity. Combination of these products with other beta-lactam antibiotics possessing high antibacterial activity but less stability to beta-lactamase will be a new approach to chemotherapy against resistant strains capable of producing beta-lactamase. This paper deals with the combined antibacterial activity of amoxicillin (AMC) with CVA against ampicillin (APC)-resistant strains ofbacteria. MATERIALS AND METHODSTest strains. Stock strains of clinical isolated, maintained in the Reference Laboratory of Bacterial Resistance, Gunma University, were used in this study.Conjugation methods. R factors were conjugally transfered to Escherichia coli strains by a method previously described (5). E. coli ML1410 Nalr (resistant to nalidixic acid) and E. coli x1037 Rifr (resistant to rifampin) were used as the recipients for the conjugal transfer of R plasmid.Antibiotics. CVA, APC, AMC, and cloxacillin were provided by Beecham Yakuhin Co. Ltd., Tokyo, Japan. Cefoxitin was provided by Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan. Other antibiotics, penicillin G and cephalothin, were commercially available.was used for the determination of antibacterial activity. Peptone water was used for liquid culture and consisted of 1% peptone and 0.5% NaCl. GAM (Nissui, Tokyo, Japan) broth and agar were used for the anaerobic bacteria. Antibiotic medium 3 (Difco) was used for the study of bactericidal activity.

Treatment of urinary tract infections with a combination of amoxicillin and clavulanic acid

“…Clavulanic acid, a naturally occurring 3-lactamase inhibitor, may prevent the inactivation of these P-lactams (8,21). Combinations of clavulanic acid and amoxicillin are significantly more active both in vitro and in vivo against certain ,B-lactamase-producing bacteria than is amoxicillin alone (11,18).…”

“…Clavulanic acid, a naturally occurring 3-lactamase inhibitor, may prevent the inactivation of these P-lactams (8,21). Combinations of clavulanic acid and amoxicillin are significantly more active both in vitro and in vivo against certain ,B-lactamase-producing bacteria than is amoxicillin alone (11,18).The purposes of this study were: (i) to determine the efficacy and safety of the combination of amoxicillin and potassium clavulanate in the treatment of urinary tract infections; (ii) to attempt to relate therapeutic responses to the results of antibody-coated bacteria tests (25) …”

Pharmacokinetics of amoxicillin and clavulanic acid administered alone and in combination

“…A very potent 3-lactamase inhibitor is clavulanic acid, a fermentation product of Streptomyces clavuligerus (14,15). Although its intrinsic antibacterial activity is comparatively weak, it irreversibly inhibits a wide range of ,B-lactamases of Richmond types II through V (12), protecting the P-lactam antibiotics administered simultaneously (e.g., amoxicillin from inactivation) and rendering the lactamase-producing organisms susceptible to the action of the antibiotic (8,18). A new formulation of amoxicillin plus clavulanic acid (4:1 by weight) exploits this strongly synergistic effect by combining the two components for oral application (see [1,7,13]).…”

Susceptibility of Pathogenic Bacteria to Amoxicillin/Clavulanic Acid (Augmentin) at a Referral Hospital

“…Previous studies have shown that clavulanic acid not only irreversibly inactivates beta-lac-tamase but also exhibits synergism with amoxicillin against amoxicillin-resistant bacteria. 7,8,18,19 The rate of amoxicillin resistance in Saudi Arabia is markedly higher than those reported in the United States and Europe. 20,21 In this study we found that these same clinical strains of E. coli, Klebsiella pneumoniae, Proteus organisms, and staphylococci showed increased susceptibility to Augmentin as compared to ampicillin.…”