Empiric Therapy for Cancer Patients: Comparative Study of Ticarcillin-Tobramycin, Ticarcillin-Cephalothin, and Cephalothin-Tobramycin

Abstract

Three combinations of antibiotics (cephalothin-tobramycin, cephalothinticarcillin, and ticarcillin-tobramycin) were administered empirically to 186 patients with cancer who were suspected of having a life-threatening infection. In approximately one-half of these patients, gram-negative infection was documented bacteriologically and consisted of septicemia in 50% of these patients. The three antimicrobial regimens were similarly effective and resulted in a favorable clinical response in approximately 55% of the patients. The administration of the cephalothin-tobramycin combination was associated with a significantly higher frequency of nephrotoxicity than that of the other two regimens.In patients with cancer, especially when neutropenia is present, gram-negative bacterial infections are a major cause of death (1,8). Under these clinical circumstances, various antimicrobial regimens have been recommended; among them are the combinations of carbenicillin with gentamicin (15), carbenicillin with cephalothin (12), cephalothin with gentamicin (7), and multiple drug regimens including car-benicillin, cephalothin, and gentamicin (9) or carbenicillin, cephalothin, gentamicin, methicillin, and clindamycin (17).In the present study we have compared the combination of ticarcillin with cephalothin (Tic-Cef) to that of ticarcillin with tobramycin (Tic-Tob) and of cephalothin with tobramycin (Cef-Tob). Ticarcillin Therapy with Tic-Cef, Tic-Tob, or Cef-Tob was chosen at random using a table of randomized numbers. Therapy was started without waiting for the isolation and identification of the offending microorganisms. Ticarcillin (10 g) and cephalothin (3 g) were given intravenously, three times daily, over a period of 20 min, each drug being dissolved in 100 ml of 5% dextrose. Tobramycin was given intramuscularly (except in thrombopenic patients) three times daily; the dosage was calculated to represent a total daily dose of approximately 4.5 mg/kg; when given intravenously, tobramycin was dissolved in 100 ml of 5% dextrose and administered over a 20-min period.

Synergy Between Ticarcillin and Tobramycin Against Pseudomonas aeruginosa and Enterobacteriaceae In Vitro and In Vivo

“…In clinical studies, Klastersky et al (8) have reported better responses in cancer patients treated with combinations of antibiotics, including ticarcillin + tobramycin, that were synergistic than with nonsynergistic combinations. More recently, Parry and Neu (16) found that ticarcillin + tobramycin compared favorably with ticarcillin alone, or with ticarcillin + gentamicin, in eradicating P. aeruginosa from the sputum of patients with cystic fibrosis.…”

Attenuation of experimental tobramycin nephrotoxicity by ticarcillin

“…In 262 patients given an aminoglycoside plus ticarcillin, definite nephrotoxicity occurred in 8 patients (3.1%); in 126 patients given an aminoglycoside plus cephalothin, definite nephrotoxicity occurred in 23 patients (18.3%). Two prospective studies in neutropenic cancer patients found definite nephrotoxicity in 2 and 6% of the febrile neutropenic patients given either carbenicillin or ticarcillin with an aminoglycoside (10,11). A protective effect of the penicillin therapy can only be inferred, as treatment protocols did not include a group of patients that received an aminoglycoside only.…”

“…This concept is consistent with a previous report which showed that the simultaneous administration of carbenicillin in rats reduced the nephrotoxicity of gentamicin (4). Furthermore, febrile neutropenic cancer patients have exhibited a low frequency of nephrotoxicity after treatment with an aminoglycoside plus an antipseudomonal penicillin (10,11,22). The relative paucity of studies and the potential clinical benefit of reduced aminoglycoside nephrotoxicity prompted the current experiments.…”

Clinical Evaluation of Combination of Cefmetazole and Piperacillin in the Treatment of Infections in Patients with Acute Leukemia

“…Various antimicrobial regimens have been used, including the combination of an anti-pseudomonal penicillin, ami noglycoside and cephalosporin [Bloom field and Kennedy. 1974;Klastersky et al, 1971Klastersky et al, , 1974Klastersky et al, , 1975Middleman el al., 1972;Schimpffet al, 1971;EROTC Internation al Antimicrobial Therapy Project Group, 1978]. In spite of such advances in anti microbial therapy, infection remains one of the major problems.…”