Comparison of the In Vitro Activity of Bay k 4999 and Piperacillin, Two New Antipseudomonal Broad-Spectrum Penicillins, with Other β-Lactam Drugs

Abstract

with other fl-lactam antibiotics, including carbenicillin, azlocillin, mezlocillin, benzylpenicillin, ampicillin, and cefoxitin, against a wide range of gram-positive and -negative organisms. Bay k 4999 and piperacillin were extremely active against Pseudomonas aeruginosa (50% inhibited by 2 ,ig/ml), being about 16-fold more active than carbenicillin. Bay k 4999 was the most active drug against Escherichia coli (50% inhibited by 0.5 ,tg/ml) and Klebsiella spp. (50% inhibited by 2 jig/ml). Piperacillin and Bay k 4999 were equally active against Proteus spp., and piperacillin had high activity against Bacteroides fragilis (50% inhibited by between 1 and 2 ,tg/ml).Broad-spectrum penicillins with antipseudomonal activity have been widely used in the treatment of severe sepsis. Carbenicillin (CAR), the first member of this group, must be administered in large doses, because its activity against Pseudomonas aeruginosa is poor in comparison with its activity against the Enterobacteriaceae. Ticarcillin may be considered to be a modest advance over carbenicillin (8). Azlocillin (AZ) and mezlocillin (MEZ) are two new a-aminosubstituted penicillins with broad spectra and increased antipseudomonal activity (1, 5). Piperacillin (PIP) (6) is another member of this structurally related group of penicillins and has the formula sodium 6[D-(-) -a-(4-ethyl-2,3-dioxo-1-piperazinyl carbonyl amino)-a-phenyl-acetamido] penicillanate. Bay k 4999 (BAY) has the formula 6[D -2 -(3 -furfurylidenamino -2 -oxoimidazolidine -1-carboxamido) -2-(4-hydroxyphenyl)-acetamido] penicillanic acid (Fig. 1) RESULTSThe results given in the tables refer to the 103-CFU/p1 inoculum unless otherwise stated.

Comparison of the Activities of the New Ureidopenicillins Piperacillin, Mezlocillin, Azlocillin, and Bay k 4999 Against Gram-Negative Organisms

“…The MIC and MBC of BAY in Mueller-Hinton broth have been determined with five selected strains of K. pneumoniae, E. coli, Proteus mirabilis, and P. aeruginosa with inocula of 103, BAY was the most active member of the ureidopenicillin group but also displayed a bimodal distribution pattern of susceptibility and a strong inoculum effect at 107 CFU/ml with some species, as was shown previously for other ureidopenicillins (1,2,7,8). The presumption that ureidopenicillins are unstable to ,B-lactamases has been confirmed in vitro: indeed, MEZ, AZL, and PIP were found to be almost as susceptible as AMP and carbenicillin to different types of ,B-lactamase (2).…”

“…The chemically related mezlocillin (MEZ) (1,9) is less active against P. aeruginosa but has highly increased activity against Enterobacteriaceae. Piperacillin (PIP) (2,6,7), another ureidopenicillin, displays high activity against nearly all gram-negative bacilli, including Pseudomonas; the new compound Bay k 4999 (BAY), chemically related to AZL and MEZ (8), is reported to combine the high activity of AZL against Pseudomonas with the high activity of MEZ against Enterobacteriaceae. The purpose of this study is to compare the in vitro activities of the ureidopenicillins PIP, MEZ, AZL, and BAY with each other and with the reference antibiotics AMP and TIC.…”

Comparative In Vitro Appraisal of Piperacillin, Including Its Activity Against Salmonella typhi

“…In general the effect of the inoculum size on MICs and MBCs was similar to that reported by other workers (2,7,11,20,22,23). With our gram-negative bacteria, the 105-CFU/ml inocula resulted in MICs consistently higher than those observed with 106 CFU/ml, but the differences were less pronounced than those reported by some other authors (2,7,11,22).…”

“…With our gram-negative bacteria, the 105-CFU/ml inocula resulted in MICs consistently higher than those observed with 106 CFU/ml, but the differences were less pronounced than those reported by some other authors (2,7,11,22). Wise et al were able to correlate the markedly increased MICs dependent on heavy inocula with,-lactamase production (23). In the case of our f8-lactamaseproducing S. aureus isolates, the effect of a heavy inoculum on the piperacllin as well as the carbenicillin and ampicillin MICs was considerably greater than that observed with gram-negative isolates.…”

In Vitro Activity of Furazlocillin (Bay k 4999) Compared with Those of Mezlocillin, Piperacillin, and Standard Beta-Lactam Antibiotics

“…Two other new penicillins, azlocillin and mezlocillin, compare favorably with carbenicillin and ampicillin against Escherichia coli, Klebsiella, Enterobacter, Citrobacter, Acinetobacter, and Serratia (4). Furazlocillin (Bay k 4999) is the latest member of the expanded-spectrum penicillins (10). The compound appears to be more potent than azlocillin, mezlocillin, and piperacillin against many gramnegative bacilli, including Klebsiella, indole-positive Proteus, and Enterobacter (H. Grimm, Program Abstr.…”