Comparative Activity In Vitro of Ticarcillin, BL-P1654, and Carbenicillin

Abstract

The activity of ticarcillin, BL-P1654, and carbenicillin was compared in vitro using a microtiter tube dilution test in Mueller-Hinton broth against 50 recent clinical isolates each of Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella species, Enterobacter species, Proteus species, and Pseudomonas aeruginosa. Bactericidal end points were determined using a modified Steers replicator. Ticarcillin was generally two to four times more active against all organisms tested except S. epidermidis against which BL-P1654 was most active. Median minimum inhibitory concentrations in micrograms per milliliter were for S. aureus: ticarcillin (6.2), carbenicillin (12.5), BL-P1654 (25); for S. epidermidis: BL-P1654 (1.6), ticarcillin (3.2), carbenicillin (3.2); for E. coli: ticarcillin (3.2), BL-P1654 (6.2), carbenicillin (6.2); for Klebsiella sp.: >100 for all three drugs; for Enterobacter sp.: ticarcillin (3.2), carbenicillin (6.2), BL-P1654 (12.5); for Proteus sp.: ticarcillin (1.6), carbenicillin (1.6), BL-P1654 (3.2); for P. aeruginosa: ticarcillin (31), BL-P1654 (62), carbenicillin (125). Bactericidal end points were dependent on both the drug and the species but were in general no more than twofold more than the minimum inhibitory concentration with the exception of BL-P1654 against P. aeruginosa. BL-P1654 was bactericidal for only 60% of the strains tested at a concentration of 500 gg/ml.Carbenicillin has been found, in the years since its introduction, to be a remarkably useful drug in certain patients with infections caused by Pseudomonas aeruginosa, Serratia marcescens, and other selected susceptible pathogens. However, the emergence of carbenicillin-resistant strains and the risk of electrolyte and coagulation problems associated with high-dose therapy of sytemic infections have limited its clinical use.BL-P1654 is the sodium salt of 3-guanylureido-phenyl-acetamino-penicillanic acid, with a spectrum similar to that of carbenicillin. BRL-2288, ticarcillin, is the disodium salt of a-carboxy-3-thienylmethyl penicillin, also with a spectrum similar to that of carbenicillin. We compared the in vitro activity of these three drugs against a number of recent clinical isolates.MATERIALS AND METHODS Fifty isolates each of Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella species, Enterobacter species, Proteus species, Pseudomonas aeruginosa, and 10 isolates of enterococci were studied. The organisms were isolated in the Clinical Microbiology Laboratory of Colorado General Hospital, University of Colorado Medical Center, having been recovered from specimens of blood, urine, sputum, and other infected sites submitted from patients and were identified by standard methods under the direction of L. Barth Reller. Minimum inhibitory concentrations were carried out using microtiter tube dilution tests in Mueller-Hinton broth, adding 0.05 ml of a 10-4 dilution of an overnight Mueller-Hinton broth culture of each organism to be tested to 0.05 ml of diluted antibiotic in a micr...

Therapy of Experimental Pseudomonas Endocarditis with High-Dose Amikacin and Ticarcillin

“…We have examined the efficacy and tox icity of high-dose amikacin regimens plus ticarcillin in experimental tricuspid valve PA IE, in hopes of taking advantage of the superior in vitro activity of ticarcillin (ver sus carbenicillin) aginst PA [9], and the possibly higher therapeutic: toxic ratio of amikacin (versus gentamicin or tobramy cin) [15]. The present study demonstrated several interesting findings: (1) amikacinticarcillin regimens are effective in experi mental right-sided PA endocarditis; (2) high-dose amikacin regimens demonstrat ed no enhanced efficacy over standarddose regimens; (3) no increase in nephro toxicity was seen with use of the high-dose amikacin regimens, and (4) there was no demonstrable difference in posttherapy vegetation cultures with high-dose com pared to standard-dose amikacin regi mens.…”

Randomised study of ticarcillin, cefamandole with or without tobramycin in febrile, neutropenic patients with solid tumors

“…Ticarcillin is a more potent antipseudomonal agent than carbencillin when tested in vitro [13], and has clinical efficacy comparable to that of piperacillin in conjunction with an aminoglycoside in febrile neutropenic cancer patients [5]. Cefamandole Recognising the potentially broad-spectrum efficacy of the combination of ticarcillin and cefamandole, this prospectively randomised study was undertaken to define -~~ Most previous reports contained a majority of leukemic patients, whereas solid-tumour patients represent an Older and more heterogenous group, generally with From the Department of Clinical Oncology, Royal North Shore Hosbrief periods of moderate neutropenia following myelo-pital of Sydney, st. Leomrds whether the addition of tobramycin influenced efficacy and toxicity in a population of febrile neutropenic patients with solid tumours.…”

“…Ticarcillin is a more potent antipseudomonal agent than carbencillin when tested in vitro [13], and has clinical efficacy comparable to that of piperacillin in conjunction with an aminoglycoside in febrile neutropenic cancer patients [5]. Cefamandole has valuable activity against Klebsiella species; Staphylococcus aureus; and isolates of Enterobacter species, Serratia marcescens, and Escherischi coli resistant to earlier cephalosporins [ 141.…”