Background Information of the Condition
Acute bacterial sinusitis is a common, usually self-limited condition often associated with allergies and environmental irritants, as well as co-infection with viruses and fungi. Acute bacterial sinusitis is 200 times less common than viral rhinosinusitis. Symptoms and signs suggesting bacterial, as opposed to viral sinusitis include purulent nasal discharge in combination with facial pain and maxillary toothache, facial swelling and tenderness. Most diagnoses are based on history and physical examination as opposed to laboratory cultures and sinus xrays, which are considered unreliable.
Drug (Product Monograph)
Category: Levofloxacin is a fluoroquinolone class, broad-spectrum antibacterial agent. It is the L- isomer of the racemate, ofloxacin.
Mechanism of Action: Levofloxacin exerts its action by inhibiting the bacterial topoisomerases II (DNA gyrase) and topoisomerases IV, which interferes with DNA replication, transcription, repair, and recombination.
Indications: indicated for the treatment of adults with upper and lower respiratory tract, urinary tract infections, and infections of skin/skin structure.
Dose & Duration: The recommended dose for levofloxacin is 500mg i.v./oral once daily for 10-14 days (normal course of therapy) or 750mg i.v./oral once daily for 5 days (short-course therapy).
Methodology of Systematic Review
In double blind randomized controlled trials (DB RCTs), does levofloxacin (normal or short-course of therapy) provide a significant therapeutic advantage in terms of mortality or morbidity when compared to other fluoroquinolones or other classes of antibacterial agents in the treatment of adult patients ≥ 18 years of age with acute bacterial sinusitis?
Assessment principles: Double blind randomized controlled trials comparing levofloxacin to other fluoroquinolones or other classes of antibacterial agents in adult patients with acute bacterial sinusitis will be critically appraised. Therapeutic impact will be assessed according to the following hierarchy of health outcomes – mortality; non-fatal serious adverse events; quality of life; withdrawals due to adverse events; clinical response rates (clinical resolution of signs and symptoms of infection); microbiological response rates (bacteriological eradication of causative pathogen); and other adverse events (e.g. allergic reactions).
Search strategy: Databases searched: Medline, EMBASE and Cochrane Library (from 1966 to February 2008); the manufacturer’s submission, and references of review articles. Key search words included: “levofloxacin,” or “Levaquin,” “randomized controlled trial,” and “sinusitis.”
No DBRCT was identified comparing levofloxacin to other fluroquinolones. Three DBRCTs in adult patients with acute bacterial sinusitis lasting for 7 to 28 days, compared oral levofloxacin 500mg daily for 10-14 days to a single dose of oral azithromycin 2000mg (Murray et al 2005); oral cefdinir 600mg daily for 10 days (Henry et al 2004); and to oral clarithromycin 1000mg daily for 10-14 days (Lasko et al 1998).
Based on three DBRCTs in 1045 randomized adult patients with acute bacterial sinusitis lasting for 7 to 28 days, oral levofloxacin 500mg daily for 10-14 days was not significantly different from a single dose of oral azithromycin 2000mg (Murray et al 2005), oral cefdinir 600mg daily for 10 days (Henry et al 2004), or oral clarithromycin, 1000mg daily for 10-14 days (Lasko et al 1998) in terms of clinical response (as defined by the individual trial) and total withdrawals.
One trial (Murray et al) reported on mortality and serious morbidity. Total mortality, non-fatal serious adverse events and withdrawals due to adverse events were not significantly different between levofloxacin and azithromycin. None of the trials reported on bacteriological response. Murray et al and Henry et al did not report on total adverse events. Total adverse events were not significantly different between levofloxacin and clarithromycin treatment groups in the Lasko et al trial
In DB RCTs, Levofloxacin does not differ significantly compared to other fluoroquinolones or other classes of antibiotics in clinically relevant outcomes for the treatment of adult patients with acute bacterial sinusitis.
- Product Monograph: Levofloxacin (Levaquin™). Antibacterial Agent. Janssen-Ortho Inc., July 16, 2007.
- eCPS (electronic Compendium of Pharmaceuticals and Specialties), Mar. 2008
- Murray, J.J., Emparanza, P., Lesinskas, E., Tawadrous, M. et al. Efficacy and safety of a novel, single-dose azithromycin microsphere formulation versus 10 days of levofloxacin for the treatment of acute bacterial sinusitis in adults. Otolaryngology – Head and Neck Surgery, 133(2): 194-201, 2005.
- Henry, D.C., Kapral, D., Busman, T.A. and Paris, M.M. Cefdinir versus levofloxacin in patients with acute rhinosinusitis of presumed bacterial etiology: a multicenter, randomized, double-blind study. Clinical Therapeutics, 26(12): 2026-2033, 2004.
- Lasko, B., Lau, C.Y., St-Pierre, C., Reddington, J.L. et al. Efficacy and safety of oral levofloxacin compared with clarithromycin in the treatment of acute sinusitis in adults: a multicentre, double-blind, randomized study. The Journal of International Medical Research, 26: 281-291, 1998.