Activity of Azlocillin and Mezlocillin Against Gram-Negative Organisms: Comparison with Other Penicillins

Abstract

The activities of azlocillin and mezlocillin were compared with those of carbenicillin, ticarcillin, and pirbenicillin against a wide range of gram-negative organisms. The tyvo new drugs were considerably more active than carbenicillin against Klebsiella species and Escherichia coli. Carbenicillin was twice as active against Proteus mirabilis as mezlocillin and four times as active as azlocillin. Against Pseudomonas aeruginosa, azlocillin was eight times as active as carbenicillin. Azlocillin and mezlocillin were twice as active as carbenicillin against Bacteroides fragilis, and these drugs showed a high degree of activity against Haemophilus influenzae and Neisseria gonorrhoeae.Carbenicillin (CAR) is an established antibiotic in the treatment of infections caused by Pseudomonas aeruginosa, Serratia marcescens, and the Proteus species. The practice of giving large amounts intravenously, which is occasionally associated with toxicity (4, 6), has prompted the search for drugs with a similar spectrum but greater activity. Two new penicillins, azlocillin (AZ) and mezlocillin (MZ), were investigated in this study. Both of these compounds can be considered as a amino-substituted ampicillins, as is pirbenicillin (PB) (2, 11). Their activity against a wide range of gram-negative organisms was studied. The two new drugs were compared with CAR, ticarcillin (TIC), PB, and, where appropriate, benzylpenicillin (PEN) and ampicillin (AMP). The production of fi-lactamase by certain strains was verified by the chromogenic cephalosporin method (7). The protein binding of CAR, AZ, and MZ in human serum was determined by an ultrafiltration method. The initial concentrations of each drug were 20 and 100 yg/ml. The ultrafiltrate was assayed against standards prepared in phosphate-buffered saline by using P. aeruginosa NTCC 10771 as indicator organism. RESULTSIn Fig. 1, 45 strains that were susceptible to CAR (MIC, <128 ,ug/ml) are shown. AZ and PB were approximately eight times as active as CAR. Figure 2 shows the activity against 17 strains that were resistant to CAR (MIC, al128 ,Lg/ml). All strains (other than those producing B8-lactamase) were susceptible to 16 ,tg or less of AZ per ml and to 64 ,ug of MZ per ml. For the two strains producing ,B-lactamase, the MICs of CAR, PB, and TIC were >1,024 ,ug/ml, and the MICs, of AZ and MZ were 256 and 512 ug/ml, respectively.The activities of the five drugs against different Enterobacteriaceae are shown in Fig. 3 through 7. MZ, TIC, and PB showed a similar degree of activity against Escherichia coli. Of the 12 strains of E. coli resistant to CAR (MIC, >128 ,ug/ml and known to be ,B-lactamase producers), a number were more susceptible to AZ, MZ, and PB. The spectrum of activity of the drugs against the Klebsiella species (Fig. 4) was variable, but a number of these organisms were susceptible to these three drugs, yet they were uniformly resistant to TIC and CAR. Against P. mirabilis (Fig. 5)

Comparative Study of Anti-Pseudomonas Activity of Azlocillin, Mezlocillin, and Ticarcillin

“…The MICs and MBCs of these agents for 20 strains of P. aeruginosa, the mean serum levels after intravenous infusion of 5 g of these drugs, and the inhibitory and bactericidal activities of serum obtained 1 and 6 h after onset of the infusion were similar. These findings are in accordance with those reported by others (5,8,9,12) who found a similar in vitro activity of mezlocillin and ticarcillin against P. aeruginosa; the concentration of mezlocillin that inhibited 75% of strains studied by others was quite similar to our findings. We also found a twofold difference between the MICs and MBCs of mezlocillin.…”

HR 756, a Highly Active Cephalosporin: Comparison with Cefazolin and Carbenicillin

“…HR 756 was also more active than the recent cephalosporins, cefuroxiime (2,5), cefoxitin (3), and cefamandole (2). In addition HR 756 has modest activity against P. aeruginosa, comparable to the a-amino-substituted penicillin mezlocillin (1,9). Other pathogens, often consid- Passage of a variety of strains on media containing HR 756 indicated that resistance could readily be induced in vitro and that this resistance was stable on serial transfer on antibioticfree media.…”

Mezlocillin Pharmacokinetics After Single Intravenous Doses to Patients with Varying Degrees of Renal Function

“…In vitro studies have shown this antibiotic to have a spectrum of activity encompassing that of the cephalosporins and penicillins, including activity against Escherichia coli, species of the Klebsiella-Enterobacter-Serratia group, Proteus, Pseudomonas, Haemophilus influenzae, and Neisseria gonorrhoea (3,16). It is more active than ampicillin, carbenicillin, and cephalothin against some gram-negative bacilli (17). It is also active against Streptococcus faecalis and other gram-positive bacteria which do not produce , 8-lactamase.…”