title: 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.
abstract: 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 neutropenia episodes (granulocyte count, <500/mm(3)) compared to a standard regimen and to clarify whether ciprofloxacin administration may be switched to 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 administration 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 intravenously 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 frequencies were 48.3% (57 of 118 patients) versus 49.6% (56 of 113 patients), respectively, in a per-protocol analysis (P values for one-sided equivalence, 0.0485 and 0.0516, respectively; delta = 10%), with no significant differences among patients with bacteremia and other microbiologically or clinically documented infections and fever of unknown origin. For 82 (66.1%) patients, it was possible to switch from parenteral ciprofloxacin to the oral ciprofloxacin, and the response was successful for 61 (74.4%) patients. The efficacies of the regimens against streptococcal bacteremias were 16.6% (one of six patients) for the ciprofloxacin group and 33.3% (one of three patients) for the combination group (it was not statistically significant), with one breakthrough streptococcal bacteremia observed among the ciprofloxacin-treated patients. Adverse events were mostly self-limited and were observed in 27 (20.6%) ciprofloxacin-treated patients and 26 (19.7%) patients who were receiving the combination. This study demonstrates that high-dose ciprofloxacin given intravenously for at least 3 days and then by the oral route is therapeutically equivalent to the routine regimen of intraveneous ceftazidime plus amikacin even in febrile patients with severe neutropenia (polymorphonuclear leukocyte count, <100 mm(3)). However, it is very important that before an empirical therapy is chosen each hospital determine bacteriologic predominance and perform resistance surveillance.
authors.affiliation: 4th Department of Internal Medicine, Greece. hgiama@ath.forthnet.gr
authors.forename: H
authors.initials: H
authors.lastname: Giamarellou
authors.forename: H P
authors.initials: HP
authors.lastname: Bassaris
authors.forename: G
authors.initials: G
authors.lastname: Petrikkos
authors.forename: W
authors.initials: W
authors.lastname: Busch
authors.forename: M
authors.initials: M
authors.lastname: Voulgarelis
authors.forename: A
authors.initials: A
authors.lastname: Antoniadou
authors.forename: E
authors.initials: E
authors.lastname: Grouzi
authors.forename: N
authors.initials: N
authors.lastname: Zoumbos
mesh_terms: D000284:Administration, Oral; D000380:Agranulocytosis / Q000188:drug therapy* / Q000401:mortality; D000583:Amikacin / Q000009:adverse effects / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D002442:Ceftazidime / Q000009:adverse effects / Q000627:therapeutic use*; D002511:Cephalosporins / Q000627:therapeutic use; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005334:Fever / Q000209:etiology; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D002511:Cephalosporins; D002939:Ciprofloxacin; D000583:Amikacin; D002442:Ceftazidime