BL-P1654: a Bacteriostatic Penicillin?

The response of Pseudomonas aeruginosa to carbenicillin, BL-P1654, and two cephalosporins (112384 and 112883) was evaluated by minimal inhibitory concentration determinations, [14C]leucine uptake studies, morphological studies of colonial growth, and mouse intraperitoneal inoculations. Spheroplast formation and bacterial lysis were not the early response; instead, cell division was inhibited and long filaments were formed. Spheroplast formation and bacterial lysis were not observed in the first 7 h of incubation in minimal inhibitory concentrations of antibiotic.

Section: Resultssupporting

confidence: 72%

“…Large discrepancies between the MIC and minimal bacterial concentration were reported for BL-P1654 (15,16). It was found that the killing curves ofP.…”

mentioning

confidence: 99%

Evaluation of Antibiotic Efficacy Using Electron Microscopy: Morphological Effects of Guanylureido Cephalosporin, Chlorobenzoylureido Cephalosporin, BL-P1654, and Carbenicillin on Pseudomonas aeruginosa

Ellis

Herron

Preston

et al. 1976

“…The mean MICs VOL. 14,1978 were: BAY, 0.5 ,ug/ml (range, 0.25 to 16 ,ug/ml); PIP, 1.0 jig/ml (range, 0.5 to 64 ,g/ml); CAR, 2.0 ,tg/ml (range, 1.0 to >1,024 ,ig/ml); AZ, 4 In Table 2 the activity of PEN against N.…”

Section: Resultsmentioning

confidence: 99%

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

Wise

Andrews

Bedford

1978

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.

“…DISCUSSION The use of CAR and TIC in the treatment of gram-negative infections, in particular P. aenugiosa, is well established. Unlike CAR and TIC, BL-P1654 was a substituted ampicillin or ureido-penicillin that had a marked antipseudomonal activity (8). The further evaluation of BL-P1654 has since been abandoned.…”

Section: Resultsmentioning

confidence: 99%

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

Wise

Gillett

Andrews

et al. 1978

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)