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.