cefamandole and Agranulocytosis

A prospective randomised study was conducted comparing the efficacy and toxicity of the antibiotics ticarcillin and cefamandole (TC) with or without tobramycin (TCT) in 100 febrile neutropenic patients with solid tumours undergoing conventional chemotherapy. In this study, neutropenia less than 100/microliter was noted in 31% of 106 evaluable infectious episodes and neutrophil counts less than 1,000/microliter persisted for a median 4 days. Infection was microbiologically documented in 42% of episodes (bacteremia 24%) with gram-negative organisms responsible for 63% of bacterial isolates. Overall, 65% of episodes responded to TC and 76% to TCT (p greater than 0.05). Patients with initial shock bacteremia, pulmonary infection, or gram-negative sepsis responded relatively poorly. Neutrophil nadir and pathogen susceptibility did not influence outcome. Antibiotic toxicity was minimal with no tobramycin-related nephrotoxicity. These results are broadly comparable to those observed with leukemic patients, but the relatively short duration of neutropenia in the solid-tumour patients appears to minimize the need for additional antibiotics provided there is adequate antimicrobial coverage with the initial choice of antibiotics.

Topics: Adult; Aged; Agranulocytosis; Antineoplastic Agents; Cefamandole; Female; Humans; Infections; Male; Middle Aged; Neutropenia; Penicillins; Prospective Studies; Random Allocation; Ticarcillin; Tobramycin

A combination of tobramycin sulfate and cefamandole nafate was used as initial empiric therapy for the treatment of 71 evaluable febrile (temperature greater than 38.5 degrees C) episodes in 64 (neutrophils, less than 1,000/microL) adult patients with cancer and granulocytopenia. Carbenicillin sodium or ticarcillin disodium was substituted for cefamandole in patients with Pseudomonas infections and in patients in whom the initial regimen was unsuccessful. Twenty-nine episodes were randomized to receive tobramycin by continuous infusion, while 42 were randomized to receive tobramycin by interrupted infusion. Twenty-seven (79%) of the 34 documented infections responded to the initial empiric antibiotic combination, ten (83%) of 12 being given continuous infusion and 17 (77%) of 22 being given interrupted infusion of tobramycin. Nephrotoxic reaction occurred in 7% of patients treated with continuous infusion and 15% treated with interrupted infusion, mostly patients older than 60 years. Tobramycin, by either continuous or interrupted infusion, plus cefamandole is safe and efficacious empiric therapy for infections in patients with cancer and granulocytopenia.

Topics: Adult; Aged; Agranulocytosis; Bacterial Infections; Blood Urea Nitrogen; Cefamandole; Clostridium Infections; Creatinine; Drug Administration Schedule; Drug Therapy, Combination; Ear Diseases; Female; Humans; Infusions, Parenteral; Kidney Diseases; Male; Middle Aged; Neoplasms; Pseudomonas Infections; Tobramycin

A prospective, randomized study was performed to compare the efficacy and safety of mezlocillin plus sisomicin (Regimen A) and cefamandole plus tobramycin (Regimen B). Sixty-one episodes of documented infections were treated in 49 adult myelosuppressed cancer patients. About two-thirds of the patients treated with either regimen responded to this antibacterial therapy. The patients failing to respond to the initial therapy were treated with additional antibiotics, either with the empiric Regimen C (cefotaxime plus amikacin plus azlocillin) or with antibiotics selected on the basis of bacteriological results (Regimen D). With these schedules, the over-all response rate was increased to about 90%. The data suggest that febrile granulocytopenic cancer patients may profit from this empiric and sequential antibiotic treatment.

Topics: Adult; Aged; Agranulocytosis; Anti-Bacterial Agents; Bacterial Infections; Cefamandole; Clinical Trials as Topic; Drug Therapy, Combination; Humans; Leukemia; Lymphoma; Mezlocillin; Middle Aged; Neoplasms; Penicillins; Prospective Studies; Random Allocation; Sisomicin; Tobramycin

The in vitro activity of four cephalosporins was compared with their effects in an experimental thigh infection (cefuroxime and cefamandole against Escherichia coli and cefamandole, ceftriaxone, and ceftazidime against Klebsiella pneumoniae) in granulocytopenic mice. The effect in vitro (ER) was defined as the difference between the growth rate without antibiotic and the growth rate at the steepest part of a 3-h growth curve in the presence of an antibiotic. The relation between concentration and ER was described with the Hill equation. Using pharmacokinetic parameters of the plasma concentrations in vivo and those of the Hill equation the corresponding time course of ER was calculated and by integration with respect to time (0tERdt), an estimate was obtained of the effect on bacteria. For all four antibiotics this estimate was significantly correlated with the actual values of the effect in vivo (EN), defined as the difference in numbers of bacteria between controls and antibiotic-treated animals at 4 h.

Topics: Agranulocytosis; Animals; Cefamandole; Ceftazidime; Ceftriaxone; Cefuroxime; Cephalosporins; Disease Models, Animal; Escherichia coli; Escherichia coli Infections; Klebsiella Infections; Klebsiella pneumoniae; Mice; Protein Binding; Specific Pathogen-Free Organisms

The experience with empirical antimicrobial therapy of septicemia and febrile episodes in pediatric neutropenic patients was analyzed retrospectively. Between January 1985 and March 1988 in 49 patients 77 episodes were observed. Bacteremia was found in 15 (20%), culture proven localized bacterial infection in 11 (14%) and clinically diagnosed bacterial infection was found in 7 (9%) of the febrile episodes. Thus, 33 (43%) documented bacterial infections were observed. For initial therapy a combination of aminoglycoside plus 2nd/3rd generation cephalosporin (60%) or aminoglycoside plus piperacillin (30%) was usually chosen. Both regimens were equally effective. 52% and 56%, respectively, were sufficiently treated with the initial regimen. 95% of all episodes resolved completely, the mortality rate was 5%. Central venous catheters remained in situ in 84% of the cases. The period of time necessary for recovery of granulopoiesis had an influence on the therapy success.

Topics: Adolescent; Agranulocytosis; Antineoplastic Agents; Cefamandole; Cefotaxime; Child; Child, Preschool; Drug Therapy, Combination; Female; Fever of Unknown Origin; Gentamicins; Humans; Infant; Infusion Pumps; Leukocyte Count; Male; Neoplasms; Neutropenia; Piperacillin; Sepsis

Clinical studies on cefamandole were carried out with the following results. (1) Cefamandole was administered 100 mg/kg/day (q.i.d.) by intravenous route to 29 cases of children. In 10 out of 29 cases bacteriological effect was observed. Bacteriological response was effective in 8 cases (80.0%). Clinical responses were effective in 27 cases (93.1%). (2) As to adverse reactions, granulocytopenia and elevation of S-GOT, S-GPT developed in each two cases.

Topics: Agranulocytosis; Alanine Transaminase; Aspartate Aminotransferases; Cefamandole; Cephalosporins; Child; Child, Preschool; Female; Humans; Infant; Infusions, Parenteral; L-Lactate Dehydrogenase; Male; Respiratory Tract Infections; Urinary Tract Infections