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PubMed1972

Carbenicillin indanyl sodium, an orally active derivative of carbenicillin.

Carbenicillin indanyl sodium, an orally active derivative of carbenicillin, is active against a broad spectrum of bacterial species. Although the ester has in vitro antimicrobial activity per se when evaluated in Brain Heart Infusion broth, the in vivo antibacterial activity seen in mice and rats reflects primarily the efficient hydrolysis of the ester to carbenicillin. With an acute systemic infection in mice as a test system, orally administered carbenicillin indanyl sodium protected mice against lethal infections produced by Escherichia coli, Salmonella choleraesuis, Pasteurella multocida, Proteus vulgaris, Staphylococcus aureus, and Streptococcus pyogenes. The dose that protected 50% of the animals against each of these infections was comparable to that of parenteral carbenicillin. Against experimental urinary-tract disease in rats produced by E. coli, P. vulgaris, and Pseudomonas aeruginosa, it was again observed that carbenicillin indanyl sodium provided activity comparable to that of parenterally administered carbenicillin.

Animals↗

PubMed1982

Carbenicillin prodrugs: kinetics of intestinal absorption competing degradation of the alpha-esters of carbenicillin and prediction of prodrug absorbability from quantitative structure-absorption rate relationship.

The intestinal absorption of alpha-esters of carbenicillin disodium, carbenicillin phenyl sodium, and carbenicillin indanyl sodium was investigated using the in situ rat intestinal recirculating method. In the in situ intestinal lumen at pH 7, two prodrugs were rapidly converted to poorly absorbable carbenicillin, possibly by the action of intestinal nonspecific esterase in competition with the slow absorption of prodrugs. At pH 5, the reduced action of esterase and the increased absorption rate after 3 hr resulted in 50 and 60% absorption of carbenicillin phenyl sodium and carbenicillin indanyl sodium, respectively. The absorption rate constants determined for both prodrugs were in good agreement with the prediction from the quantitative structure-absorption rate relationship derived from the two-compartment aqueous diffusion model.

Animals↗

PubMed1986

Latamoxef versus carbenicillin plus gentamicin or carbenicillin plus mecillinam in leukopenic, febrile patients with solid tumors.

Sixty-six febrile episodes associated with leukopenia were observed in 56 patients with solid tumors, WBC less than 1.5 X 10(9)/l and temperature greater than or equal to 38.5 degrees C. Stratification to antibiotic treatment regimen was made with regard to prior cis-dichlorodiamineplatinum (cis-platinum) treatment or not. Patients who had received no cis-platinum were randomized between carbenicillin 10 g every 8 h plus gentamicin 80 mg every 8 h or latamoxef 2 g every 8 h (group I). Patients having received cis-platinum were treated with carbenicillin 10 g every 8 h plus mecillinam 800 mg every 8 h or latamoxef 2 g every 8 h (group II). The first dose of latamoxef was preceded by 10 mg of vitamin K i.v. In group I, clinical response was observed in 10 of 19 febrile episodes (52.6%) treated with carbenicillin plus gentamicin and in 10 of 14 (71.4%) treated with latamoxef (p greater than 0.05). In group II, 6 of 14 febrile episodes treated with carbenicillin plus mecillinam responded (42.9%) while 11 of 19 (57.9%) responded to latamoxef (p greater than 0.05). No bleeding due to antibiotic treatment was observed. No statistical difference between standard antibiotic therapy and latamoxef was seen in this subset of patients.

Adult↗

PubMed1973

Comparison of colistin-carbenicillin, colistin, and carbenicillin in Pseudomonas sepsis in monkeys.

Intravenous inoculation of 6.2 x 10(10) to 6.7 x 10(10)Pseudomonas aeruginosa organisms into rhesus monkeys 5 days after intratracheal inoculation of 2.0 to 2.5 mg of vincristine sulfate resulted in fatal sepsis in 8 of 10 untreated monkeys. When similarly infected monkeys were treated intramuscularly with 2.5 mg of colistin or 50 mg of carbenicillin per kg per day, all three monkeys in each treatment group survived; one of three monkeys receiving both antibiotics at the above doses died. Six of seven monkeys treated with 1.25 mg of colistin per kg per day and three of seven treated with 25 mg of carbenicillin per kg per day died; four of nine monkeys receiving both antibiotics at these doses died. A combination of the data obtained at both dose levels tested shows that 6 of 10, 3 of 10, and 5 of 12 monkeys, respectively, died after treatment with colistin, carbenicillin, and the colistin-carbenicillin combination. Antibacterial activity of serum from both infected and normal monkeys was not appreciably different when the two antibiotics were given singly or in combination. Under the conditions of this study and with the doses employed, the response of monkeys treated with the antibiotic combination did not differ significantly from that of monkeys treated with a single agent.

Animals↗

PubMed1980

Carbenicillin-trimethoprim/sulfamethoxazole versus carbenicillin-gentamicin as empiric therapy of infection in granulocytopenic patients. A prospective, randomized, double-blind study.

The results of therapy with carbenicillin plus trimethoprim-sulfamethoxazole (C-T/S) were compared to those obtained with carbenicillin plus gentamicin (C-G) in a prospective double-blind study of empiric antibiotic therapy in granulocytopenic patients. Patients were stratified into two groups: favorable-prognosis, group 1 (carcinoma, lymphoma, multiple myeloma), or unfavorable-prognosis, group 2 (acute leukemia, bone marrow transplantation), based on anticipated duration of granulocytopenia. Over-all, empiric antibiotic trials were more often successful (P = 0.004) in group 1 (55 of 62 patients or 89 per cent) than in group 2 (42 of 64 patients, 66 per cent)mwithin group 1, there was a favorable outcome in 30 of 32 (94 per cent) C-T/S trials and in 25 of 30 (83 per cent) C-G trials (P = 0.25); within group 2, there was a favorable outcome in 23 of 30 (77 per cent) C-T/S trials and in 19 of 34 (56 per cent) C-G trials (P = 0.14), Combined results in both groups indicated a higher proportion of favorable outcome in C-T/S trials (53 of 62, 85 per cent) than in C-G trials (44 of 64, 69 per cent). Further analysis (Manetl-Naenszel test) showed the over-all difference in outcome to be significant (P = 0.049), but the general applicability of this result may be limited by the rather low incidence of gram-negative bacterial infections in this study. There was no difference between the treatment regimens in antibiotic toxicity, and serious superinfection occurred only in group 2 patients (21 per cent of trials), equally divided between treatment arms. Initial protocol dosing achieved target plasma levels of trimethoprim (3 to 8 micrograms/ml) or gentamicin (4 to 10 micrograms/ml) in 57 of 68 (84 per cent) C-T/S trials compared to 21 of 60 (35 per cent) C-G trials.

Adult↗

PubMed1973

Comparison of gentamicin, carbenicillin and gentamicin, and carbenicillin in Pseudomonas sepsis in monkeys.

Intravenous inoculation of 6.0 x 10(10)Pseudomonas aeruginosa organisms into rhesus monkeys 4 days after intratracheal inoculation of 2.5 mg of vincristine sulfate resulted in fatal sepsis in all of three untreated control monkeys. After intramuscular administration of either 2.5 mg of gentamicin or 50 mg of carbenicillin per kg per day, three of four monkeys in each group survived. When both antibiotics were given at the same dose but in separate sites, six of eight monkeys survived. Antibacterial activity of serum from infected monkeys or normal monkeys was not appreciably different when the two antibiotics were combined. Under the conditions of this study, there was no apparent difference in response of monkeys treated either with gentamicin or carbenicillin alone or with the combination of the two antibiotics.

Animals↗

PubMed1969

In vitro susceptibility of Pseudomonas aeruginosa to carbenicillin and the combination of carbenicillin and gentamicin.

One hundred and eleven strains of Pseudomonas aeruginosa isolated from clinical material were studied for susceptibility to carbenicillin. Of the strains, 80% were inhibited by 125 mug/ml or more. The combination of carbenicillin and gentamicin was shown to have inhibitory and bactericidal synergistic effect on 15 of 16 strains of P. aeruginosa tested. There was poor correlation between the single-disc sensitivity method and the tube dilution method.

Drug Synergism↗

PubMed1983

Tobramycin and carbenicillin compared with gentamicin and carbenicillin in the treatment of infection with Pseudomonas aeruginosa in adult patients with cystic fibrosis.

Treatment with gentamicin or tobramycin given intravenously with carbenicillin is compared in the treatment of bronchopulmonary infection in older patients with cystic fibrosis. All patients improved on both regimens and there was no observed difference in the two treatments. Pseudomonas aeruginosa could still be isolated from the sputum 3 months after completion of treatment with both treatments. No toxic or allergic side-effects were noted.

Adolescent↗

PubMed1979