Comparative antibacterial properties in vitro of seven olivanic acid derivatives: MM 4550, MM 13902, MM 17880, MM 22380, MM 22381, MM 22382 and MM 22383.

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Abstract
Streptomyces olivaceus ATCC 31365 produces a family of novel .beta.-lactam antibiotics collectively referred to as the olivanic acids. Seven such compounds, MM 4550, MM 13902, MM 17880, MM 22380, MM 22381, MM 22382 and MM 22383 were identified which have the same carbapenem nucleus but with different side chains attached to the nucleus. The compounds with an (8S) hydroxyethyl substituent and cis-orientated .beta.-lactam protons, MM 22380 and MM 22382, and their sulfate esters, MM 17880 and MM 13902, are potent antibiotics with minimal inhibitory concentration values against gram-positive and gram-negative bacteria in the range 0.1-3.1 .mu.g/ml. The corresponding (8S) hydroxyethyl compounds with trans-.beta.-lactam protons, MM 22381 and MM 22383, also have broad-spectrum activity but are rather less potent than the cis-compound. In addition to their antibiotic activity, the olivanic acids inhibit a number of .beta.-lactamases and enhance the activity of .beta.-lactams such as amoxycillin against .beta.-lactamase-producing bacteria. Significant differences are observed in antibacterial activities and in .beta.-lactamase inhibition properties when the olivanic acids are compared with the related thienamycin antibiotics which have (8R) rather than (8S) stereochemistry and trans-.beta.-lactam protons.