In vitro evaluation of alaphosphin (Ro 03-7008) against Serratia marcescens

Alaphosphin (Ro 03--7008; S-alanyl-R-1-aminoethyl-phosphonic acid) proved active against most of 53 strains of Serratia marcescens tested. The majority of strains were inhibited by less than or equal to 64 micrograms/ml of the drug; concentrations of greater than or equal to 128 micrograms/ml of Ro 03--7008 were required for adequate killing of most of the assay strains. This drug revealed comparable in vitro activity, including killing kinetics, in a defined medium (RST2 broth) and in clean-voided urine specimens from human volunteers, but was antagonized by conventionally employed broth media, human serum, and human thoracic and abdominal fluids. The inoculum effect against the control Escherichia coli strain ATCC 25922 proved marked. The 'skipped tube (well) phenomenon' was encountered not uncommonly in microtiter broth susceptibility tests and in checkerboard combination assays. The combination of alaphosphin with either carbenicillin or a cephalosporin, i. e., cefamandole, yielded an additive effect against S. marcescens; in contrast, indifferent effects were observed when Ro 03--7008 had been combined with gentamicin, nalidixic acid, polymyxin B, and rifampin, respectively.