Treatment of complicated urinary tract infection and acute pyelonephritis by short-course intravenous levofloxacin (750 mg/day) or conventional intravenous/oral levofloxacin (500 mg/day): prospective, open-label, randomized, controlled, multicenter, non-inferiority clinical trial

Abstract

ObjectiveTo compare the efficacy and safety of short-course intravenous levofloxacin (LVFX) 750 mg with a conventional intravenous/oral regimen of LVFX 500 mg in patients from China with complicated urinary tract infections (cUTIs) and acute pyelonephritis (APN). MethodsThis was a prospective, open-label, randomized, controlled, multicenter, non-inferiority clinical trial. Patients with cUTI and APN were randomly assigned to a short-course therapy group (intravenous LVFX at750 mg/day for 5 days) or a conventional therapy group (intravenous/oral regimen of LVFX at 500 mg/day for 7–14 days). The clinical, laboratory, and microbiological results were evaluated for efficacy and safety.ResultsThe median dose of LVFX was 3555.4 mg in the short-course therapy group and 4874.2 mg in the conventional therapy group. Intention-to-treat analysis indicated the clinical effectiveness in the short-course therapy group (89.87%, 142/158) was non-inferior to that in the conventional therapy group (89.31%, 142/159). The microbiological effectiveness rates were also similar (short-course therapy: 89.55%, 60/67; conventional therapy: 86.30%, 63/73; p > 0.05). There were no significant differences in other parameters, including clinical and microbiological recurrence rates. The incidence of adverse effects and drug-related adverse effects were also similar for the short-course therapy group (21.95%, 36/164; 18.90%, 31/164) and the conventional therapy group (23.03%, 38/165; 15.76%, 26/165).ConclusionPatients with cUTIs and APN who were given short-course LVFX therapy and conventional LVFX therapy had similar outcomes in clinical and microbiological efficacy, tolerance, and safety. The short-course therapy described here is a more convenient alternative to the conventional regimen with potential implication in anti-resistance and cost saving.Electronic supplementary materialThe online version of this article (doi:10.1007/s11255-017-1507-0) contains supplementary material, which is available to authorized users.

<p>Comparison of high-dose, short-course levofloxacin treatment vs conventional regimen against acute bacterial infection: meta-analysis of randomized controlled trials</p>

“…The similar results were found in the further subgroup analyses of CAP patients with pneumonia severity index class III and IV,6 aged ≥65 years,7 with atypical pathogens 8. In addition, a high-dose, short-course regimen was assessed in the setting of complicated urinary tract infection (cUTI), acute pyelonephritis (APN), and acute sinusitis 9–12. But so far, there is no systematic review and meta-analysis comparing the efficacy and safety of high-dose, short-course levofloxacin and comparators for treating acute bacterial infections.…”

“…Then 4,010 articles were screened after excluding 1,690 duplicated articles. Finally, seven RCTs5,9–12,14,15 fulfilling the inclusion criteria were included in this meta-analysis (Figure 1). All of studies were designed to compare the clinical efficacy and safety of high-dose, short-course levofloxacin with the conventional regimen for patients with bacterial infection (Table 1).…”

“…All of studies were designed to compare the clinical efficacy and safety of high-dose, short-course levofloxacin with the conventional regimen for patients with bacterial infection (Table 1). 5,9–12,14,15 During the initial enrollment, the high-dose, short-course regimen and conventional regimen were applied for 1,835 and 1,896 patients, respectively. All of them were multicenter studies.…”

“…Four studies were performed in the US,5,9–11 and three studies were conducted in China 12,14,15. Three studies5,14,15 focused on CAP, and three studies focused on cUTI and APN 9,10,12. Only one study investigated acute sinusitis 11.…”

“…Only one study investigated acute sinusitis 11. Except one study that used ciprofloxacin regimen as a comparator,9,10 the other six studies5,9,11,12,14,15 used levofloxacin 500 mg for 7–14 days for comparison. Figures 2 and 3 show the analyses of risk of bias.…”