title: Pharmacokinetics and effects on bowel and throat microflora of oral levofloxacin as antibacterial prophylaxis in neutropenic patients with haematological malignancies.
abstract: Gram-positive breakthrough infections pose a major drawback to the use of quinolones for antibacterial prophylaxis in neutropenic patients. Levofloxacin offers the advantage of an augmented Gram-positive spectrum and may potentially overcome this problem. In an open-label, clinical pilot study, we investigated the effects on throat and bowel microflora and pharmacokinetics of a once-daily oral dose of 500 mg levofloxacin, during neutropenia in 20 patients with haematological malignancies. Gram-negative bowel flora and Staphylococcus aureus were successfully eradicated. No Gram-negative infections occurred. Minimal inhibitory concentration values for viridans group (VG) streptococci tended to increase, in four patients over 8 mg/l, indicating resistance to levofloxacin. Four patients developed blood-stream infections with levofloxacin-resistant Gram-positive cocci. No significant changes in numbers of anaerobic microorganisms were observed. Pharmacokinetic parameters of levofloxacin, including the maximum serum concentration (C(max)), time to C(max) (T(max)), area under the concentration-time curve (AUC), volume of distribution at steady state (V(ss)/F) and clearance (CL/F) were not statistically different at first dose and during neutropenia. In conclusion, levofloxacin eradicates Gram-negative microorganisms and S. aureus and spares the anaerobic flora. Its pharmacokinetic profile is unaltered during neutropenia. However, prolonged administration of levofloxacin as antibacterial prophylaxis may be hampered by the emergence of levofloxacin-resistant VG streptococci.
authors.affiliation: Department of Haematology, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: G J
authors.initials: GJ
authors.lastname: Timmers
authors.forename: Y
authors.initials: Y
authors.lastname: Dijstelbloem
authors.forename: A M
authors.initials: AM
authors.lastname: Simoons-Smit
authors.forename: A J
authors.initials: AJ
authors.lastname: van Winkelhoff
authors.forename: D J
authors.initials: DJ
authors.lastname: Touw
authors.forename: C M J E
authors.initials: CM
authors.lastname: Vandenbroucke-Grauls
authors.forename: P C
authors.initials: PC
authors.lastname: Huijgens
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004064:Digestive System / Q000382:microbiology*; D024881:Drug Resistance, Bacterial; D005260:Female; D006090:Gram-Negative Bacteria / Q000187:drug effects; D016908:Gram-Positive Bacterial Infections / Q000517:prevention & control; D006095:Gram-Positive Cocci / Q000187:drug effects; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D064704:Levofloxacin; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000188:drug therapy* / Q000382:microbiology*; D015242:Ofloxacin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D010614:Pharynx / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D064704:Levofloxacin; D015242:Ofloxacin