Laboratory Studies witha NewBroad-Spectrum Penicillin, Pirbenicillin

Pirbenicillin {6-[D-2-phenyl-2(N-4-pyridylformimidoylaminoacetamido)-acetamidol-penicillanic acid} showedbroad-spectrum antibacterial activity invitro andalsointhetreatment ofexperimental infections after parenteral administration tomice.Against Pseudomonas aeruginosa, a three- tofourfold potency advantage overcarbenicillin was seen bothinvitro andinvivo. Theinvitro antibacterial spectrumofpirbenicillin includes Escherichia coli, Serratia, Citrobacter, andEnterobacter isolates, against whichitexhibited minimal inhibitory concentration values comparable tothose ofcarbenicillin. However, miceinfected withE.coli andSerratia were protected atdosesofpirbenicillin that were twotofourtimeslower thanthose required ofcarbenicillin. Pirbenicillin was more active thancarbenicillin against gram-positive bacteria, especially Streptococcus faecalis. Itwas less active thancarbenicillin against Proteus spp. andwas inactive against ampicillin-resistant E.colistrains. Pirbenicillin was bactericidal atconcentrations generally equal tooronlytwofold higher thantheminimal inhibitory concentration. Withappropriately bufferedmedia,pirbenicillin demonstrated eight- andfourfold betterminimal bactericidal concentration values towards Pseudomonas isolates thanthoseof carbenicillin andticarcillin, respectively. Thediscovery ofcarbenicillin, withitsextended spectrum ofclinical activity, hasencouraged thesearch formorepotent members inthepenicillin series. Laboratory studies presented inthiscommunication demonstrate thatpirbenicillin (Fig. 1)hascertain potency advantages overcarbenicillin inbothinvitro andinvivostudies. Pirbenicillin iscurrently undergoing clinical evaluation asa broadspectrum chemotherapeutic agent. MATERIALSAND METHODS