Naturally-occurring beta-lactamase inhibitors with antibacterial activity.


Sir: A number of important pathogens which are resistant to penicillins and cephalosporins owe their resistance to the production of a fi-lactamase. If this fl-lactamase could be inhibited adequately in vivo it would be expected that infections caused by such organisms could be successfully treated with the penicillins and cephalosporins now already available . We now wish to report the isolation of certain naturally-occurring substances which are potent 13-Iactamase inhibitors and which also possess antibacterial activity . These substances, designated MM 14151, MM 4550 and MM 13902 (Belgian Patents 827,926, 827,331 and 827,332) are produced by certain cultures of Streptomyces and were detected in fermentation broths using the following test . Agar plates were prepared containing benzylpenicillin at a concentration of 10 ug/ml and seeded with a strain of Klebsiella aerogenes NCTC 418 (ATCC 15380) which owes its penicillin resistance to the production of 3lactamase. Broth samples for test were placed in holes cut in the agar and the plates incubated overnight. Samples containing a diffusible /3lactamase inhibitor gave rise to zones of inhibition resulting from the protection of the penicillin present in the agar. In the absence of any /3-lactamase inhibitor, bacterial growth occurred as a result of the inactivation of the penicillin by the jl-lactamase produced by the organism. MM 14151 is produced by Streptomyces clavuli-

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@article{Brown1976NaturallyoccurringBI, title={Naturally-occurring beta-lactamase inhibitors with antibacterial activity.}, author={Amy G Brown and Darren Butterworth and Madeline L. Cole and G Hanscomb and Jennifer D. Hood and Chris L. Reading and George N Rolinson}, journal={The Journal of antibiotics}, year={1976}, volume={29 6}, pages={668-9} }