In vitro study of clavulanic acid in combination with penicillin, amoxycillin, and carbenicillin

Abstract

showed considerably increased susceptibility to amoxycillin in combination with clavulanic acid. Two beta-lactamase-producing strains of Pseudomonas aeruginosa remained resistant to carbenicillin in the presence of clavulanic acid.Clavulanic acid was isolated from Streptomyces clavuligerus, and the structure, which resembles the penicillin nucleus, has the formula pug/ml was incorporated into the agar both alone and in combination with clavulanic acid at concentrations of 10, 5, and 1.0 (or 0.5) ,ug/ml. Penicillin-free clavulanic acid control plates were included throughout.After inoculation, the plates were incubated at 370C for 24 h. Ten percent C02 was added to the environment for cultivation of H. influenzae and N. gonorrhoeae, and a GasPak system (BBL) was used for the anaerobes. The minimum inhibitory concentration (MIC) of penicillin alone and in combination with clavulanic acid was defined as the lowest amount of antibiotic giving a decrease in colony count of 99.9% compared with the initial inoculum. Any inhibitory effect of the clavulanic acid when acting alone was also noted.Beta-lactamase production by bacterial isolates was detected by the chromogenic cephalosporin method as described by O'Callaghan et al. (2). RESULTSAgainst the majority of organisms tested, clavulanic acid alone had no antibacterial activity at a concentration of 10, 5, 1.0, or 0.5 ,ug/ml. The exceptions were five strains of B. fragilis; two were inhibited by 10 ,ug of clavulanic acid per ml and three were inhibited by 5 ,ug/ml, both with an inoculum of 103 CFU/pl. These were not included in Fig. 2. Most strains of N. gonorrhoeae were inhibited by 1 ,ug or more of clavulanic acid per ml (Table 1).

Clavulanic Acid, a Novel Inhibitor of β-Lactamases

“…2 /B-Lactamase-resistant competitive inhibitors of the common ,B-lactamases are present in the form of antistaphylococcal penicillins of the isoxazoyl class, but these agents, probably by virtue of their bulky side chains, have not proved to be useful with intact bacteria and are even less useful clinically. Clavulanic acid has, as earlier studies (12,18) and this one illustrate, excellent inhibitory activity against selected /3-lactamases. This inhibitory activity covers /3-lactamases of the Richmond classes II, III, IV, and V. The inhibition of 8-lactamase hydrolytic activity is a time-dependent reaction and is irreversible.…”

β-Lactams and β-Lactamase Inhibitors: An Overview

“…In general, none of the inhibitors has useful antibacterial activity as monotherapy, although there are several notable exceptions. Clavulanic acid alone has been reported to have an MIC as low as 1 mg/mL against N. gonorrhoeae (Wise et al 1978); sulbactam has modest activity against wild-type Acinetobacter spp. 8 and 10 mg/mL, respectively (Jacoby and Sutton 1989;Fass et al 1990), but does not retain activity against isolates with multiple resistance mechanisms (Dong et al 2014).…”

Drug repurposing screens and synergistic drug‐combinations for infectious diseases

“…New drugs have been developed to overcome some specific drug‐resistant mechanisms. For example, clavulanic acid (Wise et al , 1978), sulbactam (Retsema et al , 1980), tazobactam (Jacobs et al , 1986) and avibactam (Stachyra et al , 2009) are the β‐lactamase inhibitors that are used in combinations with β‐lactam antibiotics to overcome the resistance of β‐lactamase‐producing bacteria.…”