brl-28500 and Neutropenia

We evaluated the efficacy of ticarcillin-clavulanic acid plus amikacin (TCA) with ceftazidime plus amikacin (CFA) as empiric therapy of fever in acute leukemia in a total of 127 episodes. The overall success rate of the therapy (survival) was 93% in TCA group and 92% in CFA group. Success without therapy modifications (afebrile at 72 hours) was 39% for TCA, 31% for CFA; success with modifications was 55% and 61% respectively. Failure (death due to documented or presumed infection) was 6% for TCA and 8% for CFA. Differences were not statistically significant. The success without modifications was higher in the group of patients with fever of unknown origin (FUO) than in documented infections (DI), mainly with CFA. No differences were documented in the resistance rate and in clinical outcome during severe neutropenia (ANC <100 microl). In our experience TCA is as effective as CFA as first-line treatment in severe neutropenic patients with acute leukemia, although in both regimens patients with DI are likely to require modifications in treatment.

Topics: Adult; Aged; Amikacin; Ceftazidime; Chi-Square Distribution; Clavulanic Acids; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Fever; Follow-Up Studies; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Neutropenia; Probability; Prospective Studies; Risk Assessment; Survival Rate; Ticarcillin; Treatment Outcome

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

Topics: Adult; Agranulocytosis; Amikacin; Bacterial Infections; beta-Lactamase Inhibitors; Child; Clavulanic Acids; Clinical Trials as Topic; Drug Therapy, Combination; Fever; Fever of Unknown Origin; Humans; Netilmicin; Neutropenia; Penicillins; Retrospective Studies; Sepsis; Ticarcillin; Tobramycin

The efficacy of ticarcillin and clavulanic acid (Timentin) was assessed in a regimen combined with tobramycin in febrile episodes in neutropenic patients. After randomization, 151 patients were assessable following treatment with either Timentin and tobramycin or piperacillin and tobramycin. The overall success rate was 70% in the Timentin and tobramycin group and 71% when piperacillin and tobramycin were given: when no infection could be demonstrated efficacy was 73% in the Timentin group, 65% when only clinical or radiological evidence of infection was present and 63% with conclusive microbiology. The figures in the groups treated with the piperacillin-containing regimen were 83%, 79%, and 50% respectively. There was no significant difference between the treatment groups. In septicaemic patients, the Timentin regimen was effective in 55% of cases, while the piperacillin group was successful in 40%. Timentin is a useful addition to the agents suitable for the treatment of febrile neutropenic patients.

Topics: Adolescent; Adult; Aged; Bacteria; Bacterial Infections; Clavulanic Acids; Clinical Trials as Topic; Drug Combinations; Drug Therapy, Combination; Female; Fever; Humans; Male; Middle Aged; Neutropenia; Penicillin Resistance; Penicillins; Piperacillin; Random Allocation; Sepsis; Ticarcillin; Tobramycin

A series of cases of piperacillin-tazobactam (P/T)-associated neutropenia has been observed recently in children in our center. Because neutropenia was seldom observed in children treated with ticarcillin-clavulanic acid (T/C), we conducted a study to determine if there is an increased risk of neutropenia in children exposed to P/T in comparison with T/C.. Medical records of subjects aged <18 years who received at least 1 dose of P/T or T/C between 1 January 2008 and 30 June 2011 were reviewed.. Two hundred ninety-nine episodes of treatment (65 P/T, 234 T/C) met inclusion criteria. Among those episodes, 213 had data allowing complete white blood cell count analysis and were included in the final analysis. Thirteen cases of neutropenia were observed during the study period. The average time to onset was 17.6 days and all patients were aged <13 years. Seven cases (10.8%) occurred in the P/T group and 6 (2.6%) in the T/C group (unadjusted odds ratio, 4.59; 95% confidence interval, 1.48-14.17). Although a statistically significant correlation was observed between age, treatment duration, and total dose and the development of neutropenia (r = -0.121, P = .037; r = 0.267, P < .001; r = 0.260, P < .001, respectively), this was not the case for sex, indications, neutrophil count at initiation, and concomitant drug treatments.. Although our results need to be confirmed, they suggest that children receiving long courses of therapy (>2 weeks) with P/T may be at increased risk of neutropenia, compared with T/C.

Topics: Adolescent; Anti-Bacterial Agents; Child; Child, Preschool; Clavulanic Acids; Cohort Studies; Female; Humans; Infant; Male; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Risk Assessment; Ticarcillin

To assess the clinical efficacy of ticarcillin, with clavulanic acid, and gentamicin, we conducted a prospective one year study of febrile episodes in neutropenic children. Seventy-five episodes were evaluated in 42 children. The response rate was 32% during persistent neutropenia, whilst another third of episodes responded with neutrophil recovery. Positive blood cultures occurred in 21 episodes and 20 of 24 micro-organisms belonged to the 'community' flora, i.e. organisms carried by healthy people (Streptococcus pneumoniae, Staphylococcus aureus, Branhamella catarrhalis and Escherichia coli). The route of pathogenesis was endogenous in 76% of the patients. There was a substantial superinfection-related morbidity (14%) and mortality (7%), related to emergence of resistance during and after parenteral antibiotic administration. The poor clinical response, combined with emergence of resistance, lead to the conclusion that this combination is of limited value as a first line regimen for neutropenic patients.

Topics: Child; Child, Preschool; Clavulanic Acids; Drug Resistance, Microbial; Drug Therapy, Combination; Fever; Gentamicins; Humans; Neutropenia; Remission Induction; 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