An open-label randomised clinical trial was designed to compare the efficacy and tolerance of
levofloxacin and
ciprofloxacin plus
phenethicillin for the prevention of
bacterial infections in patients with high-risk
neutropenia, and to monitor the emergence of antimicrobial resistance. Adult patients (n = 242) scheduled to receive intensive treatment for haematological
malignancies were assigned randomly to receive oral prophylaxis with either
levofloxacin 500 mg once-daily (n = 122), or
ciprofloxacin 500 mg twice-daily plus
phenethicillin 250 mg four-times-daily (n = 120). The primary endpoint was failure of prophylaxis, defined as the first occurrence of either the need to change the prophylactic regimen or the initiation of intravenous broad-spectrum
antibiotics. This endpoint was observed in 89 (73.0%) of 122
levofloxacin recipients and in 85 (70.8%) of 120
ciprofloxacin plus
phenethicillin recipients (RR 1.03, 95% CI 0.88-1.21, p 0.71). No differences were noted between the two groups with respect to secondary outcome measures, including time to endpoint, occurrence of
fever, type and number of microbiologically documented
infections, and administration of intravenous
antibiotics. A questionnaire revealed that
levofloxacin was tolerated significantly better than
ciprofloxacin plus
phenethicillin. Surveillance cultures indicated the emergence of viridans group (VG) streptococci resistant to
levofloxacin in 17 (14%) of 122
levofloxacin recipients; in these cases, the prophylactic regimen was adjusted. No bacteraemia with VG streptococci occurred. It was concluded that
levofloxacin and
ciprofloxacin plus
phenethicillin are equally effective in the prevention of
bacterial infections in neutropenic patients, but that
levofloxacin is tolerated better. Emergence of
levofloxacin-resistant VG streptococci is of concern, but appears to be a manageable problem.