brl-28500 and Leukemia

The empirical use of antibiotic treatments is widely accepted as a means to treat cancer patients in chemotherapy who have fever and neutropenia. Intravenous monotherapy, with broad spectrum antibiotics, of patients with a high risk of complications is a possible alternative.. We conducted a prospective open-label, randomized study of patients with lymphoma or leukemia who had fever and neutropenia during chemotherapy. Patients received either monotherapy with ticarcillin/clavulanic acid (T) or ceftriaxone plus amikacin (C+A).. Seventy patients who presented 136 episodes were evaluated, 68 in each arm of the study. The mean neutrophil counts at admission were 217cells/mm(3) (T) and 201cells/mm(3) (C+A). The mean duration of neutropenia was 8.7 days (T) and 7.6 days (C+A). Treatment was successful without the need for modifications in 71% of the episodes in the T group and 81% in the C+A group (p=0.23). Treatment was considered to have failed because of death in two episodes (3%) in the T group and three episodes (4%) in the C+A group, and because of a change in the drug applied in one episode in the T group and two episodes in the C+A group. Overall success was 96% (T) and 93% (C+A). Adverse events that occurred in group T were not related to the drugs used in this study.. In pediatric and adolescent patients with leukemia or lymphoma, who presented with fever and neutropenia, during chemotherapy, ticarcillin/clavulanic acid was as successful as the combination of ceftriaxone plus amikacin. It should be considered an appropriate option for this group of patients at high risk for infections.

Topics: Adolescent; Amikacin; Bacterial Infections; Brazil; Ceftriaxone; Child; Child, Preschool; Clavulanic Acids; Drug Therapy, Combination; Epidemiologic Methods; Female; Fever; Humans; Infant; Leukemia; Lymphoma, Non-Hodgkin; Male; Neutropenia; Ticarcillin; Treatment Outcome

Alerted by a high incidence of positive autologous controls in pretransfusion compatibility testing for patients with acute leukemia, we retrospectively analysed 59 cases of severe hemoblastoses undergoing myelosuppressive treatment. Seventeen (29%) of these patients had a positive direct antiglobulin test (DAT) with the following characteristics: the test was of the IgG and/or C3d type in all but two cases, which reacted with polyvalent antiglobulin sera only; the reaction was very weak throughout; very high concentrations of monospecific sera were needed to elicit positive reactions; free antibodies were never detected in the patients' serum; the eluates of the patients' red cells were non-reactive against a very large panel of test erythrocytes. All these criteria suggested a non-immunologic absorption of proteins under the influence of drugs such as cephalosporins and clavulanic acid. Timenten (ticarcillin and clavulanic acid) was found to be the only common drug which had been administered to the majority of the patients with a positive DAT: 15 of the 17 patients with a positive DAT (88%) had received Timenten against 19 of 42 patients (45%) with negative DAT. 44% of all the patients receiving Timenten thus had a positive DAT, whereas only 8% of the patients without this drug reacted in this way. These data document the role of clavulanic acid in the development of a positive DAT. The literature and our experience show that this kind of unspecific binding of proteins to the red cell membrane is not associated with increased hemolysis. Knowledge of the phenomenon, however, is important for differential diagnosis of anemias and interpretation of difficulties arising during pretransfusional compatibility testing.

Topics: Acute Disease; Adolescent; Adult; Aged; Antibody Affinity; Blood Grouping and Crossmatching; Child; Clavulanic Acids; Complement C3; Coombs Test; Drug Therapy, Combination; Erythrocyte Membrane; Female; Humans; Immunoglobulin G; Isoantibodies; Leukemia; Male; Middle Aged; Myelodysplastic Syndromes; Penicillins; Retrospective Studies; Ticarcillin

Timentin (5.2 g tds) and tobramycin (40 mg tds) were administered to 51 patients (22 male, 29 female, age range 17-72, mean age 40.4) with acute leukaemia, chronic myeloid leukaemia in blastic crisis, severe aplastic anaemia and acute agranulocytopenia. All patients had neutropenia (PMN less than 1000/mm3) and fever (greater than 38 degrees C). Febrile episodes consisted of 22 proved septicaemias due to Gram-positive organisms (Staphylococcus aureus, S. epidermidis, enterococcus) in 11 cases and to Gram-negative organisms (Escherichia coli, Pseudomonas aeruginosa, Alkaligenes faecalis, Serratia marcescens, Klebsiella pneumoniae) in 10 cases. One patient had a polymicrobial infection (P. aeruginosa, S. aureus, non-haemolytic streptococcus). Twenty-nine infections were diagnosed only clinically. The mean duration of treatment was 11.1 days (range 4-20 days). Eighty-seven per cent of evaluable febrile episodes improved. Among 11 infections due to Gram-positive cocci, eight (72%) resolved, and in nine (90%) of ten cases due to Gram-negative bacilli success was obtained. The polymicrobial infection also resolved. In only four patients were mild side effects seen, e.g. exanthema, pruritus, phlebitis: renal toxicity was not observed. These data suggest that the combination of Timentin and tobramycin is an effective and safe empirical antibiotic regimen in febrile neutropenic patients.

Topics: Adolescent; Adult; Aged; Agranulocytosis; Anemia, Aplastic; Bacteria; Bacterial Infections; Clavulanic Acids; Drug Combinations; Drug Evaluation; Drug Therapy, Combination; Female; Fever; Humans; Leukemia; Male; Middle Aged; Neutropenia; Penicillin Resistance; Penicillins; Ticarcillin; Tobramycin

Timentin (ticarcillin + clavulanic acid) combined with an aminoglycoside usually netilmicin, was given to 33 children with neutropenic haematological malignancies. The combination of Timentin and aminoglycoside was effective treatment in 27 (87%) of 31 febrile episodes. There were four failures and three results which could not be interpreted. Bacteriological investigations were positive in 13 patients, three strains were resistant to ticarcillin but all were sensitive to Timentin. Clinical success, based upon reduction of fever within 48 h of treatment, was identical whether an organism was isolated or not. The combination of Timentin plus aminoglycoside was very successful and represents one of the best combinations available for empirical treatment for febrile neutropenic children.

Topics: Adolescent; Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Clavulanic Acids; Drug Combinations; Drug Evaluation; Drug Therapy, Combination; Female; Fever; Humans; Infant; Leukemia; Male; Neoplasms; Neutropenia; Penicillins; Ticarcillin