Activity of a-Phenoxyalkyl Penicillins Against Sensitive and Resistant Staphylococci

While studying the antimicrobial activity of a large number of synthetic penicillins, it became apparent that members of the α-phenoxyalkyl penicillin series were displaying significant activity against penicillinase-producing resistant staphylococci. Preliminary microbiological data and methods of synthesis of a number of such penicillins have been reported 1 , 2 . A detailed study was done on certain members of this series of penicillins using both sensitive and resistant staphylococci in an attempt to delineate the extent of the activity and relate some of the properties of the penicillins to the structure. Comparisons of these penicillins were made with penicillin G and dimethoxyphenyl penicillin, the former being penicillinase sensitive and the latter extremely penicillinase resistant 3 . Studies were also carried out to determine the in vivo effectiveness of the different penicillins in curing penicillin-sensitive and penicillin-resistant Staphylococcus aureus infections in mice.

Materials and methods. The penicillins used in this study were alkyl derivatives of phenoxymethyl penicillin substituted in the a position. The side chains of the penicillins studied are shown in Table I together with the side chains of controls, benzylpenicillin (penicillin G) and dimethoxyphenyl penicillin. The last was used as the monohydtate of the sodium salt. All the other penicillins were potassium salts. Benzylpenicillin (penicillin G), α-phenoxyethyl penicillin (phenethicillin), dimethoxyphenyl penicillin V) were obtained from commercial sources, the first 3 being Bristol Laboratories production lots, the last one a Lilly product. The other penicillins were synthesized by the Organic Chemistry Dept. of Bristol Laboratories.

Cultures were maintained on porcelain beads 4 , on nutrient agar slants, or frozen in milk suspension. The inoculum used for determination of the minimum inhibitory concentration was prepared by overnight incubation of a bead or a loopful from a slant culture in heart infusion broth. Standard 2-fold serial dilution technics in heart infusion broth (Difco) or in heart infusion mixed 1 : 1 with pooled filter-sterilized human serum were used. Usually, the overnight culture was diluted 10⁴, but other dilutions were also used as noted below.