oa Monotherapy Versus Combination Gram Negative Empiric Antibiotic Therapy For Febrile Neutropenia In Children With Cancer

Background: Children with cancer who are treated with intensive myelosuppressive chemotherapy or radiation therapy and develop neutropenia are at risk of developing life-threatening infections. In adult cancer patients with febrile neutropenia, some evidence suggests that there is no difference in efficacy between monotherapy and combination gram negative empiric antibiotic regimens. Outcomes of these different antibiotic regimens have not been compared in the pediatric population in North America. The objectives of this study were to compare the effectiveness and safety of a combination gram negative antibiotic regimen versus monotherapy in pediatric cancer patients with cancer and febrile neutropenia, and to describe the use of additional antimicrobial agents for those patients who did not respond to initial empiric therapy. Methods: A retrospective review of medical records of cancer patients who received empiric treatment for febrile neutropenia with piperacillin-tazobactam and gentamicin, and those who received monotherapy for febrile neutropenia with pipercillin-tazobactam was performed. Demographic information, drug therapy for febrile neutropenia, measures of renal function, daily peak temperature, other medications received (including antibiotics and antipyretics), and bacterial and fungal cultures were obtained from the patient's medical records using a standardized data collection form. Descriptive statistics were used to describe the study patient's demographic information. Difference in duration of fever and change in serum creatinine were assessed using the Wilcoxon Rank-Sum Test. Results: A total of 60 patients were included in this study. Mean duration of fever was 3.5 days in the combination treatment group and 3.1 days in the monotherapy group (p = 0.5). Both the combination and monotherapy groups had similar rates of adding vancomycin (17% vs. 13%). The monotherapy group received additional gram-negative coverage antibiotics more often (10%) than the combination group (0%). Antibiotics added included: gentamicin (0 combination group, 7% combination group), and ciprofloxacin (0 combination group, 3% monotherapy group). Piperacillin-tazobactam was changed to meropenem in 3% of the patients in the combination group and 7% of the monotherapy group, while 3% of the combination group patients were switched from piperacillin-tazobactam to ceftriaxone. Mean percent increase in serum creatinine was 25% in the combination group and 10% in the monotherapy group (p = 0.03). Conclusion: Empiric treatment of febrile neutropenia in children with cancer using a monotherapy regimen with piperacillin-tazobactam is as effective as the combination of piperacillin-tazobactam and gentamicin for reducing duration of fever. This therapeutic option however must be evaluated against local microbial resistance patterns and patient risk factors. Although statistically significant, the difference in change in serum creatinine between the two groups was not clinically significant.