Answer 5: Summary of clinical studies investigating 750mg dose

20 June, 2018

 

In a sentinel clinical trial, Dunbar and colleagues compared the efficacy of a 750-mg, 5-day course of levofloxacin with a conventional levofloxacin regimen, 500 mg for 10 days, for mild-to-severe CAP (6). In this multicenter, randomized, double-blind, prospective study as 750 mg once daily for 5 days) was as effective as 500 mg once daily for 10 days. In the clinically evaluable population, the clinical success rates were 92.4% for the 750 mg group and 91.1% for the 500 mg group. Of note, cures were obtained in 90.9% of patients with pneumococcal pneumonia and 100% of patients with Legionella pneumonia in the 750 mg group while the microbiological eradication rates were 93.2% and 92.4% in the 750 mg and 500 mg groups, respectively.

Of great significance, a higher percentage of patients in the 750 mg arm exhibited resolution of fever by Day 3 compared with those in the 500 mg arm. In addition, clinical signs such as measured temperature, production of purulent sputum, chills and shortness of breath all resolved more quickly with the high dose short-course levofloxacin therapy (7).

The incidence of any possible adverse events was similar in both groups, with 58% of the 750mg group and 60% of the 500mg group reporting more than one treatment-emergent adverse event. The actual drug-related adverse events were much lower for both groups at 7% and 6%, respectively (6). The most common adverse events were insomnia, constipation, nausea, and diarrhea. A subset analysis of this study investigated responses of 177 elderly patients aged greater than 65 years. (8). Eighty patients with a mean age of 73 years received 750 mg and 97 with a mean age of 76 received 500 mg. The overall clinical success rates were comparable between the two groups, being 89% in the 750 mg and 91.9% in the 500 mg arm. The incidence of treatment-emergent adverse events did not differ between the two study groups. The most significant finding from these studies is that the higher-dose, shorter course therapy was not only effective, but, more importantly, resulted in faster resolution of symptoms.