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High-dose levofloxacin for the treatment of febrile neutropenia

Abstract number: 902_p1451

Kahn J.

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Background/Objective:

The variety of organisms isolated from febrile neutropenic patients (FNP) warrants empiric antimicrobial therapy broad enough to cover most clinically significant Gram positive and negative bacteria. In an adult, low-risk, subset of such patients, current IDSA guidelines include the option of giving ciprofloxacin (C) and amoxicillin-clavulanate (AC) jointly. Several features of the fluoroquinolone levofloxacin (L) make it an attractive potential monotherapy alternative to that of combination regimen. Its spectrum encompasses the same implicated pathogens, the serum and tissue levels achieved with the 750 mg dose exceed PD targets for those bacteria. It is administered orally once daily, and it has an extensive and reassuring tolerability and safety profile. We report here on two pilot studies using L in the management of FNP.

Methods:

Talcott IV out-patients were randomised to receive C 750 mg q12 h plus AC 875/125 mg po q12 h (following at least one IV dose each of ceftriaxone (CTX) 2 gms and amikacin (AK) 15 mg/kg) or L 750 mg po qd (poster presentation, ICID, 2002). More severely ill in-patients were randomised to cefepime (CP) 2 g iv q8 h or L 750 mg iv qd. Fever defervescence was the primary endpoint in both trials; secondary endpoints included safety and tolerability and microbiologic eradication.

Results:

In the outpatient study, the total defervescence in the L-treated patients (n = 27) was 74% compared with 63% of the comparator-treated patients (n = 19). The clinical cure rate at post therapy in the inpatient study was 72.7% for L-treated patients (n = 11) and 20.0% for the comparator-treated patients (n = 15). Adverse events were comparable between arms in both studies and none were considered to be drug-related.

Conclusion:

These limited data suggest that L 750 mg iv/po qd may offer a safe, effective, and convenient new option in the antimicrobial management of febrile neutropenia. Since fluoroquinolone agents are cidal in a concentration-dependent manner, higher doses have been thought possibly capable of retarding the emergence of resistance. Recent PD studies in vitro are lending experimental support to this hypothesis and give one more reason for considering this higher dose of L in the setting of febrile neutropenia. Based on these results, we propose additional full-scale studies of L 750 mg qd in FNP.

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Session Details

Date: 01/08/2007
Time: 00:00-00:00
Session name: XXIst ISTH Congress
Subject:
Location: Oxford, UK
Presentation type:
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