Monotherapy with piperacillin/tazobactam versus cefepime as empirical therapy for febrile neutropenia in pediatric cancer patients: a randomized comparison

The purpose of this study was to compare the efficacy, safety, and cost of piperacillin/tazobactam with cefepime monotherapy in children with febrile neutropenia. A prospective randomized study in children and adolescent with cancer was conducted. Patients were randomly assigned to receive either 80 mg/kg piperacillin/10 mg/kg tazobactam every 6 h (maximum 4.5 g/dose) or cefepime 50 mg/kg every 8 h (maximum 2 g/dose). Treatment modification was defined as all the changes in the empirical antimicrobials after the first 96 h. Overall treatment success was defined as cure of febrile episode with or without modification. Cost of hospitalization, antimicrobial drugs, and supportive therapy were calculated. Fifty febrile netropenic episodes (25 in the piperacillin/tazobactam group, 25 in the cefepime group) in 27 pediatric cancer patients were evaluated. The groups were comparable in terms of age, gender, body weight, primary diagnosis, disease status, initial neutrophil count, and duration of neutropenia. Microbiologically and clinically documented infection rate was 46%. There was no infection-related mortality in the study period. The treatment success of initial empirical therapy without modification was not different in the 2 groups (56% in piperacillin/tazobactam group and 48% in cefepime group). Anti-anaerobic drugs were added more frequently in the cefepime group. Duration of fever, neutropenia, treatment, and cost of therapy were not different in the treatment groups. Piperacillin/tazobactam monoterapy is as effective as cefepime monotherapy in febril neutropenia of pediatric cancer patients.     

Management of febrile neutropenia in pediatric oncology patients: a Canadian survey

BACKGROUND: Traditionally, febrile neutropenia in pediatric oncology patients has been managed aggressively with hospital admission and intravenous antibiotics. Recent studies suggest that less intensive interventions are effective for selected children. Study of Canadian practice patterns may help better understand the current context of care for these patients. PROCEDURE: We carried out a cross-sectional mailed survey of the 17 tertiary pediatric centers in Canada. A 36-item questionnaire gathered information on oncology department characteristics, the existence of protocols for management of febrile neutropenia, use of outpatient therapy or early discharge, criteria used to identify patients at low risk, and opinions of oncologists. RESULTS: A total of 16 (94%) completed questionnaires were returned, reflecting a treatment population of approximately 2,100 children with febrile neutropenia/year. Three out of seventeen centers carry out exclusively traditional management. The remaining 14 offer modified treatment for low risk children. The majority (n = 10) carry out an early discharge approach. Two thirds of the episodes of febrile neutropenia are treated this way with good results. The rest (n = 4) implement complete outpatient management. Approximately 120 patients benefit from this annually, with a reportedly high success rate. Most specialists agreed on the benefits of decreased hospitalization for children with cancer. However, about half considered the level of evidence is not sufficient to fully implement complete outpatient management. CONCLUSIONS: Variations in the treatment of pediatric febrile neutropenia have been extensively implemented across Canada. However more evidence, ideally in the form of multicenter clinical trials, appears to be needed to further safely modify practice.     

An analysis of the resource use and costs of febrile neutropenia events in pediatric cancer patients in Australia

Background

Febrile neutropenia (FN) in children with cancer generally requires in-hospital care, but low-risk patients may be successfully managed in an outpatient setting, potentially reducing the overall healthcare costs. Updated data on the costs of FN care are lacking.

Methods

A bottom-up microcosting analysis was conducted from the healthcare system perspective using data collected alongside the Australian PICNICC (Predicting Infectious Complications of Neutropenic sepsis In Children with Cancer) study. Inpatient costs were accessed from hospital administrative records and outpatient costs from Medicare data. Costs were stratified by risk status (low/high risk) according to the PICNICC criteria. Estimated mean costs were obtained through bootstrapping and using a linear model to account for multiple events across individuals and other clinical factors that may impact costs.

Results

The total costs of FN care were significantly higher for FN events classified as high-risk ($17,827, 95% confidence interval [CI]: $17,193–$18,461) compared to low-risk ($10,574, 95% CI: $9818–$11,330). In-hospital costs were significantly higher for high-risk compared to low-risk events, despite no differences in the cost structure, mean cost per day, and pattern of resource use. Hospital length of stay (LOS) was the only modifiable factor significantly associated with total costs of care. Excluding antineoplastics, antimicrobials are the most commonly used medications in the inpatient and outpatient setting for the overall period of analysis.

Conclusion

The FN costs are driven by in-hospital admission and LOS. This suggests that the outpatient management of low-risk patients is likely to reduce the in-hospital cost of treating an FN event. Further research will determine if shifting the cost to the outpatient setting remains cost-effective overall.     

Experience with cefepime versus meropenem as empiric monotherapy for neutropenia and fever in pediatric patients with solid tumors

A prospective, open-label, randomized, comparative study in pediatric cancer patients was conducted to evaluate the efficacy and safety of cefepime and meropenem in the empiric therapy of febrile neutropenic patients. Febrile episodes were classified as microbiologically documented infection, clinical documented infection, or fever of unknown origin. Clinical response to therapy was classified as success or failure. In this period 37 children with solid tumors including lymphoma, 25 males, 12 females, had neutropenia on 65 occasions. Microbiologically documented infections occurred in 21 episodes (32.31%). Frequency of positive bacteria isolated was higher than gram-negative bacteria. There was no infection-related death. There were no statistical differences between the cefepime and meropenem groups for duration of fever or neutropenia, response rate, and necessity for modification. Cefepime appears to be as effective and safe as meropenem for empiric treatment of febrile episodes in neutropenic pediatric cancer patients.     

Single-daily ceftriaxone plus amikacin versus thrice-daily ceftazidime plus amikacin as empirical treatment of febrile neutropenia in children with cancer

OBJECTIVE: Empirical antibiotic treatment for febrile neutropenic patients has been the mainstay of treatment for many years. Beta-lactam antibiotics and aminoglycosides have been the most frequently used drug combination. The purpose of this study was to evaluate the efficacy, safety, tolerance and costs of single-daily ceftriaxone plus amikacin versus thrice-daily dose of ceftazidime plus amikacin. METHODOLOGY: One hundred and ninety-one episodes of fever and neutropenia in 128 patients from October 1997 to December 1998 were included in a prospective, open-label, single-centre study. Patients were randomly assigned to either treatment group and evaluated as successes or failures according to defined criteria. Daily assessments were made on all patients and all adverse events recorded. Univariate and multivariate analysis of outcomes and a cost analysis were carried out. RESULTS: There were 176 evaluable patient-episodes with 51.1% in the single-daily ceftriaxone-amikacin group and 48.9% in the ceftazidime-amikacin group. There were 50 positive blood cultures: 12 Gram-positive bacteria, 33 Gram-negative bacteria and five fungi. Pseudomonas aeruginosa (P. aeruginosa) accounted for 14% of total isolates. The overall success rate was 55.5% in the ceftriaxone group compared to 51.2% in the ceftazidime group (P = 0.56). Mean time to defervescence was 4.2 days in the single-daily group and 4.3 days in the thrice-daily group. There were nine infection-related deaths; five in the single-daily ceftriaxone group. The daily cost of the once-daily regime was 42 Malaysian Ringgit less than the thrice-daily regime. There was a low incidence of adverse effects in both groups, although ototoxicity was not evaluable. CONCLUSIONS: The once-daily regime of ceftriaxone plus amikacin was as effective as the 'standard' combination of thrice-daily ceftazidime and amikacin with no significant adverse effects in either group. The convenience and substantial cost benefit of the once-daily regime will be particularly useful in developing countries with limited health resources and in centres with a low prevalence of P. aeruginosa.