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

Abstract

The in vitro activities of the new ureidopenicillins piperacillin, mezlocillin, azlocillin, and Bay k 4999 were compared with those of ampicillin and ticarcillin against 336 Enterobacteriaceae, 109 nonfermenters, 55 Neisseria, and 28 Haemophilus influenzae isolates. Bay k 4999 displayed the largest spectrum of activity and had lower minimal inhibitory concentrations than any of the other penicillins against all of the species tested. Piperacillin showed the same spectrum but was slightly less active than Bay k 4999; it was slightly more effective than mezlocillin against Enterobacteriaceae and fully as active as azlocillin against Pseudomonas. All ureidopenicilins were substantially more active than ampicillin and ticarcillin. Isolates highly resistant to ampicillin or ticarcillin were also less susceptible to the ureidopenicillins.The broad-spectrum penicillins ampicillin (AMP) and carbenicillin have been used extensively in the treatment of severe infections with gram-negative bacilli. However, their spectrum is limited, and carbenicillin has to be administered in large doses to be effective against Pseudomonas aeruginosa. Ticarcillin (TIC) is about twice as active as carbenicillin (5). Substitution of the a-amino group of AMP with substituted ureum side chains produced a new family of penicillins, the ureidopenicillins, with a broader spectrum of activity, including activity against P. aeruginosa. The first member of this group, BL-P1654, was four-to eightfold more active than carbenicilhin against P. aeruginosa (3), but its use has been discontinued because of renal toxicity. A more complex ureidopenicillin, azlocillin (AZL) has about the same spectrum of activity (4,9). 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. After identification by standard criteria, the following species and numbers of bacteria were examined: Escherichia coli (51); Klebsiella pneumoniae (52) (29), and Neisseria gonorrhoeae (26).Within each species all strains were isolated from different patients.Antibiotics

Comparative Activity of N‐Formimidoyl Thienamycin with Third Generation Cephalosporins and Ureido Penicillins against Multiple Resistant Serratia marcescens

“…While the ureidopenicillins reportedly are more active than carbenicillin and ampicillin against S. marcescens (7,10,21), this finding could not be supported in the present study. Cefoperazone was the least active third generation cephalosporin studied since it exhibited the highest mean MIC (25.09.ug/ml) and showed a striking inoculum effect on bacteriological activity.…”

Comparative activity of mezlocillin, penicillin, ampicillin, carbenicillin, and ticarcillin against gram-positive bacteria and Haemophilus influenzae

“…(1,3,5,12). Previous reports indicate that mezlocillin, unlike other anti-Pseudomonas penicillins, retains a high degree of potency against gram-positive organisms and Haemophilus influenzae (5,6,(10)(11)(12). However, most of those studies focused primarily upon groups A and D streptococci and staphylococci, and many did not simultaneously evaluate other penicillins.…”

Piperacillin pharmacokinetics in pediatric patients

“…It is more active on a weight basis against most strains of gram-negative enteric organisms than are carbenicillin, ticarcillin, and azlocillin (3,7,16,18). It is particularly more active against strains of Pseudomonas aeruginosa than are carbenicillin, ticarcillin, or mezlocillin (3,7,16,18). Piperacillin appears to be a clinically useful antibiotic in adults (13,17), but its pharmacokinetics have not been evaluated in pediatric patients.…”