New Insights in the Treatment by Levofloxacin

20 June, 2018

Levofloxacin, the first recognized antipneumococcal fluoroquinolone, has been used for over a decade with excellent efficacy, tolerability and very low rates of resistance. Levofloxacin has exceptional bactericidal activity against key respiratory pathogens, including atypicals and drug-resistant isolates. It has excellent extra and intracellular penetration.

Levofloxacin is indicated for infections of the respiratory tract, skin and urinary system. New indications include a 750 mg dose for nosocomial pneumonia and complicated skin and skin structure infections, and a 500 mg dose for chronic bacterial prostatitis.

Clinical data confirms the efficacy of fluoroquinolones versus ceftriaxone with or without a macrolide, or amoxicillin/clavulanic acid with or without clarithromycin in the management of community-acquired pneumonia or CAP. Fluoroquinolones achieved equivalent or better clinical and bacteriological responses than comparator regimens.

The results of a large multi-center phase IV study support the use of levofloxacin for the treatment of CAP. The clinical success rate was 94%, bacterial eradication was 95.6%, and there was a low incidence of adverse events.

The first reported study assessing levofloxacin monotherapy versus ceftriaxone plus erythromycin in CAP patients at high risk of mortality, demonstrated a clinical response rate of 89% for levofloxacin compared to 83% for the comparator. Bacteriological response with levofloxacin was 87.7%.

Another study reviewed levofloxacin versus comparator regimens for the treatment of seriously ill patients with bacteremic pneumococcal pneumonia. Levofloxacin monotherapy achieved a 91% clinical response rate and 92% bacteriological eradication rate; 100% of drug-resistant Streptococcus pneumoniae isolates were eradicated.

International guidelines reflect the growing use of fluoroquinolones as first line therapy for CAP for both outpatients and inpatients. IDSA guidelines state that respiratory fluoroquinolones are appropriate monotherapy in the general ward. In ICU patients with no risk of pseudomonal infection, the combination of a beta-lactam plus an IV macrolide or fluoroquinolone is recommended.

Levofloxacin 500 mg once daily has been indicated for chronic bacterial prostatitis. It has been proven to be equivalent to ciprofloxacin 500 mg twice daily.

A 750 mg levofloxacin dose has been recommended where higher pharmacodynamic parameters are needed, such as for difficult-to-treat pathogens with higher MICs. A study investigating 750 mg levofloxacin for five days versus 500 mg once daily for 10 days, demonstrated that the high-dose, short-course regimen achieved comparable or better results for patients with CAP.

The high-dose, short-course regimen was shown to have excellent bacterial eradication rates, including 100% eradication of Legionella pneumophila.

Patients treated with the short-course, 750 mg dose reported more rapid resolution of fever and purulent sputum. This may be due to faster eradication of pathogens and may result in shorter hospital stay and reduced costs.

Another advantage of the 750 mg regimen was shorter parenteral therapy and faster switch to oral administration, with 7% more patients receiving oral therapy by day three on this regimen. This can potentially result in significant cost savings.

Not only is the 750mg levofloxacin dose associated with excellent clinical efficacy and shorter therapy, it also has been proven to be as well tolerated as 250 mg and 500 mg doses with a low rate of all common adverse events.

Compared to longer regimens, short-course, high-dose levofloxacin therapy results in equivalent clinical and microbiological efficacy, making it an effective treatment for mild to severe CAP. It is associated with more rapid resolution of symptoms and faster switch to oral therapy with equivalent safety.

Levofloxacin continues to be a very useful antimicrobial. Latest indications include a higher once daily dose targeting difficult-to-treat pathogens. Emerging data suggests the potential for shorter therapy, which may be associated with increased efficacy, while minimizing resistance and improving cost-effectiveness.