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Eur J Clin Microbiol Infect Dis. 2012 Jul;31(7):1389-98. doi: 10.1007/s10096-011-1454-0. Epub 2011 Oct 31.

Empirical therapy with ceftazidime combined with levofloxacin or once-daily amikacin for febrile neutropenia in patients with neoplasia: a prospective comparative study.

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Department of Medicine, University Hospital of Heraklion, Heraklion, Crete, Greece.


Combination antimicrobial therapy represents common practice in the treatment of febrile neutropenia aiming to broaden the antimicrobial spectrum against Gram-negative pathogens. We did a prospective, non-randomized, comparative study to evaluate ceftazidime plus either levofloxacin or once-daily amikacin as empirical regimens for febrile neutropenia in patients with solid tumor or hematopoietic neoplasm in a region of high baseline resistance prevalence. We included 285 febrile neutropenic episodes in 235 individual patients. One hundred forty-eight cases received levofloxacin and 137 received amikacin, both in combination with ceftazidime. More cases in the levofloxacin than the amikacin group had underlying hematological malignancy; most other characteristics of the two groups were well balanced. Nephrotoxicity requiring treatment discontinuation occurred in one case in the amikacin group. No difference in clinical success (79.7% vs. 80.3%, p>0.99) or all-cause mortality (12.8% vs. 11.7%, p=0.86) was noted between the levofloxacin and the amikacin groups, even after adjustment for the independent predictor variables for each endpoint. Sepsis at presentation, presence of localizing symptoms/signs of infection, and isolation of a non-susceptible Gram-negative pathogen independently predicted both clinical success and all-cause mortality. Additionally, underlying solid tumor independently predicted clinical success, while poor prognosis of the underlying neoplasia and skin/soft tissue infection independently predicted mortality. Ceftazidime plus levofloxacin had similar effectiveness to ceftazidime plus amikacin as empirical regimens for febrile neutropenia. Nephrotoxicity with once-daily amikacin was minimal. Inappropriate empirical therapy was associated with worse prognosis.

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