Due to the concentration-dependent action of levofloxacin, increasing the dose results in higher concentrations in both plasma and alveolar epithelial lining fluid as well as enhanced antibacterial activity. With resistance continuing to increase, regimens that provide an effective and well tolerated treatment while at the same time reducing overall drug exposure are being assessed. Chinese researchers compared a shorter duration of therapy using a high-dose regimen of levofloxacin (750 mg once daily, 5 days) versus standard (500mg once daily, 7-14 days)  for treating patients with mild to moderate CAP  (CURB-65 score 0-2).

457 patients were enrolled with 448 and 427 in the ITT and PP analyses, respectively. The mean duration of therapy in the short-course group was 4.86 days, compared to 10.35 days in the conventional group. The mean drug exposure was 3,641.4 and 5,169.6 mg in 750 and 500 mg groups respectively. The high-dose, short-course group achieved a clinical efficacy rate of 91.40% (202/221), which was non-inferior to the 94.27% (214/227) associated with the conventional regime. Both groups achieved a 100% bacterial eradication rate. There was no statistical difference in the incidence of drug-related adverse events between the two groups (18.42% and 13.54% in the short-course and conventional regimens, respectively).

This study demonstrated that a short-course, high-dose levofloxacin regimen is non-inferior to a longer duration of therapy associated with a much greater drug exposure in Chinese patients with CAP.  Researchers emphasised that the short-course regimen resulted in a 30% reduction in total drug exposure. This is likely to result in economic and healthcare resource savings. In addition, reducing total drug exposure is likely to reduce the growth of bacterial resistance.

PMID: 27746999

J Thorac Dis. 2016 Sep;8(9):2473-2484. doi: 10.21037/jtd.2016.08.30

Source: https://www.ncbi.nlm. nih.gov/pubmed/27746999?dopt=Abstract