Properties of MM 13902 and other carbapenem antibiotics in vitro and in vivo.

The carbapenem antibiotics, which include the olivanic acids and the thienamycins, have a broad-spectrum of antibacterial activity but only thienamycin itself shows appreciable activity against Pseudomonas aeruginosa. The zwitterionic nature of thienamycin was reproduced in the olivanic acid series by preparing the deacetyl derivatives of MM 17880 and MM 22380--compounds NA 26975 and NA 26978. The latter derivative showed antipseudomonas activity and had an antibacterial spectrum similar to thienamycin itself. In contrast the O-sulfated analogue, NA 26975, was no more active than the parent compound against P. aeruginosa. Both deacetyl compounds were more stable than the parent natural products to a mouse kidney enzyme preparation and gave higher urinary recoveries in the mouse. Pharmacokinetic studies with MM 13902 in various animal species showed that the compound was rapidly eliminated from the blood and gave only low urinary recoveries. Similar findings were observed also in human volunteers given MM 13902. The nephrotoxicity reported for thienamycin/MK 0787 in the rabbit was not seen with the olivanic acids MM 13902, MM 17880, MM 22382 and MM 22383 when tested under the same conditions.