Monotherapy with intravenous followed by oral high-dose ciprofloxacin versus combination therapy with ceftazidime plus amikacin as initial empiric therapy for granulocytopenic patients with fever

The aim of the present study was to obtain clinical experience with the use of high-dose ciprofloxacin as monotherapy for the treatment of febrile neu tropenia episodes (granulocyte count, <500/mm(3)) compared to a standard re gimen and to clarify whether ciprofloxacin administration may be switched t o the oral route. In a prospective randomized study ciprofloxacin was given at 400 mg three times a day (t.i.d.) for at least 72 h followed by oral ad ministration at 750 mg twice a day (b.i.d). That regimen was compared with ceftazidime given intravenously at 2 g t.i.d. plus amikacin given intraveno usly at 500 mg b.i.d. The frequency of successful clinical response without modification at the end of therapy was almost identical for ciprofloxacin (50% [62 of 124 patients]) compared with that for ceftazidime plus amikacin (50.8% [62 of 122 patients]) in an intent to treat analysis; the frequenci es were 48.3% (57 of 118 patients) versus 49.6% (56 of 113 patients), respe ctively, in a per-protocol analysis (P values for one-sided equivalence, 0. 0485 and 0.0516, respectively; <delta> = 10%), with no significant differen ces among patients with bacteremia and other microbiologically or clinicall y documented infections and fever of unknown origin. For 82 (66.1%) patient s, it was possible to switch from parenteral ciprofloxacin to the oral cipr ofloxacin, and the response was successful for 61 (74.1%) patients. The eff icacies of the regimens against streptococcal bacteremias were 16.6% (one o f six patients) for the ciprofloxacin group and 33.3% (one of three patient s) for the combination group (it was not statistically significant), with o ne breakthrough streptococcal bacteremia observed among the ciprofloxacin-t reated patients. Adverse events were mostly self-limited and were observed in 27 (20.6%) ciprofloxacin-treated patients and 26 (19.7%) patients who we re receiving the combination. This study demonstrates that high dose ciprof loxacin given intravenously for at least 3 days and then by the oral route is therapeutically equivalent to the routine regimen of intraveneous ceftaz idime plus amikacin even in febrile patients with severe neutropenia (polym orphonuclear leukocyte count, <100 mm(3)). However, it is very important th at before an empirical therapy is chosen each hospital determine bacteriolo gic predominance and perform resistance surveillance.