Concentration of pefloxacin in feces during infection prophylaxis in neutropenic patients

Abstract

Pefloxacin (400 mg twice daily) was administered orally for infection prophylaxis in neutropenic patients. Diffusible fecal pefloxacin concentration was determined by bioassay during 24 neutropenic periods. The median diffusible fecal pefloxacin concentration was 187 g/g. This concentration was comparable with those found in volunteers following oral and intravenous administration of pefloxacin (400 mg twice daily) (median of 171 and 155 g/g, respectively). From this study, it is concluded that pefloxacin administered orally results in a predictable high diffusible fecal concentration which leads to effective elimination of susceptible aerobic gram-negative bacilli from the colonic flora.Fluorinated carboxyquinolones are widely used for infection prophylaxis in patients with severe neutropenia (2, 4). These agents have a broad spectrum of activity against aerobic gramnegative bacilli (GNB) (including Pseudomonas aeruginosa) and are effective in preventing infections by gram-negative organisms (1,5,7,(10)(11)(12)18).Long-term prophylaxis of infection in patients with neutropenia may be achieved by elimination of potentially pathogenic aerobic flora from the digestive tract (3). In order to be effective, antibiotics used for decontamination of the digestive tract must reach high and predictable concentrations in the bowel (15). It has been suggested that nonabsorbable antimicrobial agents are required for this purpose (4). In volunteers, however, we observed high antimicrobial activity of pefloxacin in feces after oral (almost complete resorption) and intravenous administration of pefloxacin (16,17).In the present study, we investigated the diffusible fecal concentration of pefloxacin and eradication of GNB from feces in neutropenic patients following oral administration. We compare these results with those of similar previous studies in healthy volunteers following oral and intravenous administration (16,17).During 24 periods of chemotherapy-induced neutropenia, prophylactic antibiotics, including pefloxacin (400 mg twice a day [BID] orally), fluconazole (50 mg orally), amphotericin B (450 mg BID orally), and trimethoprim (2%, as nasal ointment), were given to decontaminate the digestive tract.All 13 patients (median age, 51 years; range, 49 to 76 years) were treated for a hematologic malignancy, and median duration of neutropenia (Ͻ500 neutrophils per l) was 16 days (range, 9 to 35). During the prophylaxis, no salads were permitted. Fecal samples were taken at admission and twice weekly to determine the diffusible pefloxacin concentration and to perform viable counts of aerobic GNB.The diffusible fecal concentration of pefloxacin was determined by an agar diffusion method. An undiluted aliquot of feces was put in a well (depth, 5 mm; diameter, 7 mm; volume, 0.77 ml) in a solid medium of Iso-Sensitest agar (300 ml; Oxoid, Basingstoke, United Kingdom) seeded with a strain of Escherichia coli (ATCC 25922). The MIC of pefloxacin for this strain is 0.25 g/ml. The diameters of the inhibition zones were compared with t...

Emergence of fluoroquinolone-resistant Escherichia coli in fecal flora of cancer patients receiving norfloxacin prophylaxis

“…Our results differ from those of previous studies, which found that fluoroquinolone prophylaxis leads to marked reduction and often complete elimination of members of the family Enterobacteriaceae from fecal flora, with little or no emergence of fluoroquinolone resistance (3,11,22,25). This difference may be explained in part by the fact that our study was conducted in a community in which the incidence of quinolone use is high and the prevalence of quinolone resistance appears to be increasing (21).…”

Antibiotic prophylaxis for bacterial infections in afebrile neutropenic patients following chemotherapy

“…The comparison is between three options:no antibiotic prophylactic regimens, vancomycin or ciprofloxacin and amoxicillin-clavulonic acid. However, it is not randomised Reuter 2005 Not an RCT, a prospective observational study Risi 1998 A review article Schaison 1991 A study of febrile neutropenia Solano 2005 Not a randomised trial - a prospective study of prophylaxis compared with historical controls Spanik 1998 A retrospective trial Takemoto 1990 A randomised controlled trial but for febrile neutropenia Timmer-Bonte 2005 A randomised controlled trial, but the intervention was granulocyte colony-stimulating factor and both arms received prophylactic antibiotics Tjan Heijnen 2002 A letter relating to another trial Tunkel 2002 A review article Van De Leur 1995 A study which evaluates antibiotic concentration in faeces, but not in neutropenics, not a RCT Viscoli 2001 A review article Viscoli 1998 A review article Viscoli 2002 A review article von Baum 2006 Controlled before and after observational study of prophylaxis but not randomised von Minckwitz 2008 This study compared four consecutive cohort studies of patients receiving chemotherapy for breast cancer, it was not randomised. The 4 methods of neutropenia prophylaxis administered were : ciprofloxacin alone vs figrastim vs. pegfilgratim vs pegfilgradtim+ciprofloxacin Wade 1981 A retrospective study…”

Comparable Bioavailability and Disposition of Pefloxacin in Patients with Cystic Fibrosis and Healthy Volunteers Assessed via Population Pharmacokinetics

“…Likewise, pefloxacin is more lipophilic than ciprofloxacin and fleroxacin which further contributes to the complete bioavailability of pefloxacin. A major part of pefloxacin is recovered in feces [16] and pefloxacin reaches high concentrations in this matrix [64,65]. While these data show that pefloxacin is present at considerable concentrations in the gut and ultimately in feces, they also suggest that reabsorption of pefloxacin is less than 100%.…”