Empirical therapy with ceftazidime combined with levofloxacin or once-daily amikacin for febrile neutropenia in patients with neoplasia: a prospective comparative study.
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.
Department of Medicine, University Hospital of Heraklion, Heraklion, Crete, Greece.
G
G
Samonis
E
E
Koutsounaki
D E
DE
Karageorgopoulos
P
P
Mitsikostas
C
C
Kalpadaki
V
V
Bozionelou
I
I
Bompolaki
J
J
Sgouros
V
V
Taktikou
M E
ME
Falagas
D000368:Aged; D000583:Amikacin / Q000008:administration & dosage* / Q000009:adverse effects; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002442:Ceftazidime / Q000008:administration & dosage* / Q000009:adverse effects; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D005260:Female; D005335:Fever of Unknown Origin / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced; D064704:Levofloxacin; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications; D009503:Neutropenia / Q000150:complications; D015242:Ofloxacin / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D064704:Levofloxacin; D000583:Amikacin; D002442:Ceftazidime; D015242:Ofloxacin