cefamandole and Neutropenia

Fourty-two febrile episodes of 32 patients with hematologic disease during neutropenia were treated with two randomly assigned antibiotic combinations of either piperacillin plus gentamicin or piperacillin plus aztreonam. Eleven of the 22 febrile episodes treated with piperacillin plus gentamicin and 12 of the 20 febrile episodes treated with piperacillin plus aztreonam responded. Addition of cefamandole to non-responders improved the outcome in 2 of the 16 febrile episodes. Mean nadir leucocyte count, age, sex, and underlying disease were not significantly different in both groups. Side effects were tolerable in both groups, although 1 patient treated with piperacillin plus gentamicin showed severe renal impairment. Piperacillin plus aztreonam is as effective as piperacillin plus gentamicin as an empiric antibiotic combination in the treatment of febrile episodes with hematologic disease during neutropenia.

Topics: Adolescent; Adult; Aged; Anemia, Aplastic; Aztreonam; Bacterial Infections; Cefamandole; Drug Therapy, Combination; Female; Fever; Gentamicins; Humans; Leukemia; Lymphoma; Male; Middle Aged; Neutropenia; Piperacillin; Prospective Studies

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

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

Cephalosporin antibiotics cause a variety of hematologic disturbances in man, the pathogeneses and hematopathology of which remain poorly characterized. There is a need for a well-defined animal model in which these blood dyscrasias can be studied. In four subacute toxicity studies, the intravenous administration of cefonicid or cefazedone to beagle dogs caused a dose-dependent incidence of anemia, neutropenia, and thrombocytopenia after 1-3 months of treatment. A nonregenerative anemia was the most compromising of the cytopenias and occurred in approximately 50% of dogs receiving 400-500 mg/kg cefonicid or 540-840 mg/kg cefazedone. All three cytopenias were completely reversible following cessation of treatment; the time required for recovery of the erythron (approximately 1 month) was considerably longer than that of the granulocytes and platelets (hours to a few days). Upon rechallenge with either cephalosporin, the hematologic syndrome was reproduced in most dogs tested; cefonicid (but not cefazedone)-treated dogs showed a substantially reduced induction period (15 +/- 5 days) compared to that of the first exposure to the drug (61 +/- 24 days). This observation, along with the rapid rate of decline in red cell mass parameters of affected dogs, suggests that a hemolytic component complicated the red cell production problem and that multiple toxicologic mechanisms contributed to the cytopenia. We conclude that the administration of high doses of cefonicid or cefazedone to dogs can induce hematotoxicity similar to the cephalosporin-induced blood dyscrasias described in man and thus provides a useful model for studying the mechanisms of these disorders.

Topics: Anemia; Animals; Cefamandole; Cefazolin; Cefonicid; Cephalosporins; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Female; Hematologic Diseases; Male; Neutropenia; Thrombocytopenia