Synergy of mecillinam and clavulanic acid with other beta-lactam antibiotics

Sjöberg, Berndt; Ekström, Bertil; Forsgren, U; Magni, L.; Pring, Brian G.

doi:10.1007/bf01646058

Cited by 6 publications

(2 citation statements)

References 20 publications

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“…Using a mouse infection with K. pneumoniae, they demonstrated 100% protection by 10 m g/kg amoxycillin plus 10 mg/kg sodium clavulanate, while when each was given alone at these doses the protection was no greater than 10 %. Sjoberg et al (1978), using H. influenzae, have demonstrated a much greater antibacterial potentiating effect between clavulanic acid and ampicillin or carbenicillin than between mecillinam and these penicillins. In a recent report by Wise (1979), clavulanic acid was shown to enhance the activity of the new cephalo sporin H R 756 (cefotaxime) against Bact.…”

Section: -2mentioning

confidence: 99%

‘β-Lactams’ as β-lactamase inhibitors

Cole

1980

Phil. Trans. R. Soc. Lond. B

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The application of inhibitors to block the beta-lactamase destruction of penicillins and cephalosporins by resistant bacteria is a potentially useful way of improving the efficacy of established compounds. Certain semi-synthetic penicillins and cephalosporins have been found to be competitive inhibitors of selected beta-lactamases but an examination of streptomycete culture fluids has revealed two new types of beta-lactam compound: clavulanic acid, which is a progressive inactivator of a wide range of beta-lactamases, and the olivanic acids, which are both broad-spectrum antibiotics and potent beta-lactamase inhibitors. Penicillanic acid sulphone and 6-beta-bromopenicillanic acid have been shown to be significant inhibitors of beta-lactamase. The chemotherapeutic application of these compounds is discussed.

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Section: -2mentioning

confidence: 99%

‘β-Lactams’ as β-lactamase inhibitors

Cole

1980

Phil. Trans. R. Soc. Lond. B

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“…During successive passages in media containing mecillinam, an Aerobacter aerogenes strain developed resistance to mecillinam more rapidly than against ampicillin, cloxacillin, or cephazolin (11). Crossresistance between mecillinam and ampicillin is minimal (1).…”

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confidence: 99%

Effect of beta-lactamase and salt on mecillinam susceptibility of enterobacterial strains

Bongaerts¹,

Bruggeman-Ogle²

1980

Antimicrob Agents Chemother

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Out of 15 selected enterobacterial strains resistant to ampicillin, 12 were able to transfer resistance to mecillinam to Escherichia coli K-12. This resistance to mecillinam was found to be coupled to the presence of beta-lactamase. One strain contained a beta-lactamase characterized as a class IV beta-lactamase, whereas the other 14 strains possessed a class HI (TEM-like) beta-lactamase. The specific activity of the class IV beta-lactamase against mecillinam was 55%, and those of the class III beta-lactamases were 180% of the specific activities against benzylpenicillin. In view of this high beta-lactamase sensitivity of mecillinam, the minimal inhibitory concentrations were lower than might be expected. However, after enzymatic hydrolysis of mecillinam, no antibacterial activity was found. At increasing salt or buffer concentrations the minimal inhibitory concentrations of mecillinam increase to a varying extent for all strains, independently of betalactamase production. This study indicates that the increase in miniimal inhibitory concentration is dependent on the salt concentration. The study also shows that this increase is not due to salt-mediated hydrolysis or to stimulation either of beta-lactamase activity or of beta-lactamase production. To explain the difference between ampicillin and mecillinam resistance in the beta-lactamase-positive strains, a hypothetical model is presented and discussed.Mecillinam (6-beta-amidinopenicillanic acid) shows a remarkably high activity against gramnegative bacteria, whereas its activity against staphylococci and streptococci is relatively low (6). At low concentrations of this antibiotic Escherichia coli becomes spherical; at higher concentrations (>10 ,tg/ml) cells tend to lyse (7). Previous studies of this antibiotic include antibacterial activity (2, 6), mechanism of action (4,7,8,12), and emergence of resistance (1,3,7).Three factors may contribute to bacterial resistance to beta-lactam antibiotics: (i) the specific antibiotic susceptibility of the target, (ii) the specific penetration barrier function of the cell wall, and (iii) the presence of a beta-lactamase (penicillin amido-beta-lactamhydrolase, EC 3.5.2.6). A combination of these factors may occur.In vitro Enterobacteriaceae may readily become resistant to mecillinam (2). During successive passages in media containing mecillinam, an Aerobacter aerogenes strain developed resistance to mecillinam more rapidly than against ampicillin, cloxacillin, or cephazolin (11). Crossresistance between mecillinam and ampicillin is minimal (1). These data and the fact that the spontaneous mutation frequency from mecillinam-susceptible to -resistant strains is quite high (10-5 to 10-4) for beta-lactamase-negative E. coli (3) strongly suggest that these kinds of mecillinam resistance are all due to chromosomal mutations of the mecillinam target or of other components of the cell wall.Richmond showed that a number ofpenicillins were impeded in penetrating the periplasmic space of E. coli UB 1005, whereas a penetration barrier...

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A combination of amoxicillin and clavulanic acid in the treatment of respiratory tract infections caused by amoxicillin-resistant haemophilus influenzae

Beeuwkes¹,

Rutgers²

1981

Infection

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This study was undertaken to evaluate the efficacy of a fixed combination of amoxicillin and clavulanic acid in 33 patients with chronic or recurrent respiratory tract infections (R.T.I.), mainly bronchitis. In two patients bronchopneumonia was diagnosed, and in one cystic fibrosis. The patients were treated with 750 mg of the drug combination (500 mg amoxicillin/250 mg clavulanic acid) t. i. d. for seven or ten days. Good clinical success was obtained in 17 patients and a clear improvement in another eight. The most frequently isolated micro-organism was Haemophilus influenzae; of the 22 strains isolated, 20 were resistant to 2 mg/l amoxicillin but sensitive to the combination of 2 mg/l amoxicillin and 1 mg/l clavulanic acid. Side-effects were reported in nine patients; two patients discontinued treatment for this reason. Amoxicillin/clavulanic acid is a useful therapeutic addition to the existing forms of treatment for amoxicillin-resistant respiratory tract infections.

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Synergy of mecillinam and clavulanic acid with other beta-lactam antibiotics

Cited by 6 publications

References 20 publications

‘β-Lactams’ as β-lactamase inhibitors

‘β-Lactams’ as β-lactamase inhibitors

Effect of beta-lactamase and salt on mecillinam susceptibility of enterobacterial strains

A combination of amoxicillin and clavulanic acid in the treatment of respiratory tract infections caused by amoxicillin-resistant haemophilus influenzae

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