Moxifloxacin for community acquired pneumonia

12 Nov 2008 Moxifloxacin for community acquired pneumonia

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Posted at 16:21h in Drug Assessments by

Background Information of the Condition

Pneumonia is the leading cause of death from infection, particularly among elderly and hospitalized patients.1 Diagnosis is based on history, co-morbidities, physical findings, and a chest x-ray. S. pneumoniae accounts for up to 50% of community-acquired pneumonia caused by bacteria.2

Drug (Product Monograph)3, 4

Category: Moxifloxacin is a member of the fluoroquinolone class of antibiotics.

Mechanism of Action: Moxifloxacin exerts its action by inhibiting the bacterial topoisomerases II (DNA gyrase) and topoisomerases IV which interferes with bacterial DNA replication, transcription, repair, and recombination.

Indications: Moxifloxacin is indicated for the treatment of adults with upper and lower respiratory tract, skin/skin structure, and intra-abdominal infections.

Dose & Duration: the recommended dose is 400mg i.v./oral once daily for 10 days in outpatients and 7-14 days in hospitalized patients.

Methodology of Systematic Review

Research Question:

In double blind randomized controlled trials (DB RCTs), does moxifloxacin 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 with community acquired pneumonia?

Assessment principles: Double blind randomized controlled trials comparing moxifloxacin to other fluoroquinolones or other classes of antibacterial agents in adult patients with community acquired pneumonia were critically appraised. Therapeutic impact was 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 (clinical resolution of signs and symptoms of infection), microbiological response (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: “moxifloxacin/fluoroquinolones,” or “Avelox,” “randomized controlled trial,” and “pneumonia.”

Search Findings:

Six DBRCTS met the inclusion criteria. Two trials compared moxifloxacin to levofloxacin (Anzueto et al 2006 and Kobayashi et al 2005)5, 6, three trials to amoxicillin (Jardim et al 2003, Petitpretz et al 2001, and Torres et al 2003)7, 8, 9 and two trials to clarithromycin (Torres et al 2003 and Hoeffken et al 2001).9, 10

Summary of Results:

Moxifloxacin compared to other fluoroquinolone antibiotics

Two double blind RCTs in 703 patients found no significant difference in mortality, non-fatal serious adverse events, clinical or bacteriological response, total withdrawals, total adverse events or withdrawals due to adverse events. Anzueto et al 20065 compared IV moxifloxacin 400mg daily for ≥ 2 days then oral moxifloxacin 400mg daily after improvement for 7-14 days to IV levofloxacin 500mg daily for ≥ 2 days then oral levofloxacin 250-500mg daily after improvement for 7-14 days, and Kobayashi et al 20056 compared oral moxifloxacin 400mg daily for 10 days to oral levofloxacin 500mg daily for 10 days.

In the Anzueto et al trial5, there was a significant improvement in the rate of “clinical recovery” (defined as the resolution of or reduction in acute signs and symptoms of infection) in patients receiving moxifloxacin after 3 to 5 days of therapy (moxifloxacin group an ARR = 8%, NNT = 13), but not at test of cure (5-21 days post therapy). Total adverse events, reported as treatment-emergent adverse events, were significantly higher with moxifloxacin (moxifloxacin group an ARI = 11%, NNT = 9)5.

Moxifloxacin compared to other classes of antibiotic drugs

Four double blind RCTs in 1504 patients compared oral moxifloxacin 400mg daily for 10 days (Torres et al 2003 trial: 5-15 day duration) 9 to either amoxicillin 500mg t.i.d. for 10 days (Jardim et al 2003)7, amoxicillin 1000mg t.i.d. for 10 days (Petitpretz et al 2001)8, clarithromycin 500mg b.i.d for 10 days (Hoeffken et al 2001)10 or amoxicillin 1000mg t.i.d. for 5-15 days (Torres et al 2003)9 versus clarithromycin 500mg b.i.d. for 5-15 days (Torres et al 2003)9. In the Torres et al and Hoeffken et al trials, no significant differences were found in mortality, non-fatal serious adverse events, clinical response, total withdrawals, withdrawals due to adverse events, and total adverse events. Bacteriological response was not significantly different in the Hoeffken et al trial and was not reported by Torres et al. Jardim et al showed no significant differences in terms of mortality, withdrawals due to adverse events, clinical or bacteriological response. Petitpretz et al showed no significant differences in mortality, non-fatal serious adverse events, or clinical or microbiological response. The Jardim et al and Petitpretz al trials did not report total withdrawals, or total adverse events. Non-fatal serious adverse events were not reported in the Jardim et al trial.

Conclusion

In double blind randomized controlled trials, moxifloxacin does not differ significantly compared to other fluoroquinolones or other classes of antibiotics in clinically relevant outcomes for the treatment of adult patients with community acquired pneumonia.

References

  1. Mandell, L., Bartlet, J., Dowell, S. et al. Update of practice guidelines for the management of community acquired pneumonia in immunocompetent adults. Clinical Infectious Diseases, 37: 1405-1433, 2003.
  2. Guideline for the Diagnosis and Management of: Community Acquired pneumonia: adult (2008 update). Toward Optimized Practice (TOP) Program, formerly the Alberta Clinical Practice Guidelines by the Alberta Medical Association.
  3. Product Monograph: Moxifloxacin hydrochloride (Avelox®). Antibacterial Agent. Bayer Inc., Feb. 15, 2007.
  4. eCPS (electronic Compendium of Pharmaceuticals and Specialties), Mar. 2008
  5. Anzueto, A., Niederman, M.S., Pearle, J., Restrepo, M.I. et al. Community-acquired pneumonia recovery in the elderly (CAPRIE): efficacy and safety of moxifloxacin therapy versus that of levofloxacin therapy. Clinical Infectious Diseases, 42: 73-81, 2006.
  6. Kobayashi, H., Aoki, N., Niki, Y., Watanabe A. et al. Phase III double-blind comparative study of BAY 12-8039 (moxifloxacin) versus levofloxacin in patients with community-acquired pneumonia. Japanese Journal of Chemotherapy, 53 (suppl. 3): 27-46, 2005 (Japanese language).
  7. Jardim, J.R., Rico, G., de la Roza, C., Obispo, E. et al. A comparison of moxifloxacin and amoxicillin in the treatment of community-acquired pneumonia in latin america: results of a multicenter clinical trial. Archivos de Bronconeumologia, 39(9): 387-393, 2003.
  8. Petitpretz, P., Arvis, P., Marel, M., Moita, J. et al. Oral moxifloxacin vs high-dosage amoxicillin in the treatment of mild-to-moderate, community-acquired, suspected pneumococcal pneumonia in adults. Chest, 119(1): 185-195, 2001.
  9. Torres, A., Muir, J-F., Corris, P., Kubin, R. et al. Effectiveness of oral moxifloxacin in standard first-line therapy in community-acquired pneumonia. European Respiratory Journal, 21: 135-143, 2003.
  10. Hoeffken, G., Meyer, H.P., Winter, J., and Verhoef, L. The efficacy and safety of two oral moxifloxacin regimens compared to oral clarithromycin in the treatment of community-acquired pneumonia. Respiratory Medicine, 95: 553-564, 2001.
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