Once Daily Oral Ofloxacin in COPD Exacerbation Requiring Mechanical Ventilation
Abstract & Commentary
Synopsis: This report found that ofloxacin was beneficial in the treatment of acute exacerbations of chronic obstructive pulmonary disease requiring mechanical ventilation. Ofloxacin reduced hospital death, need for additional antibiotic therapy, hospital length of stay, and duration of mechanical ventilation.
Source: Nouira S, et al. Lancet. 2001;358:2020-2025.
Chronic obstructive pulmonary disease (COPD) is a worldwide problem with significant economic and public health implications. Although antibiotics are frequently used in patients with COPD exacerbation, there is limited evidence to support this practice. Because of the increasing antibiotic resistance among respiratory pathogens to ampicillin, doxycycline, and trimethoprim-sulfamethoxazole, fluoroquinolones have been advocated as one alternative. Most therapeutic trials with fluoroquinolones have been done in moderate exacerbations of COPD and little is known about their efficacy in severe COPD exacerbations.
Nouira and associates performed a prospective, randomized, placebo-controlled trial in 2 medical intensive care units (MICU) in Tunisia. Patients 40 years of age or older admitted to the MICU for acute exacerbations of COPD requiring mechanical ventilation within the first 24 hours of admission were randomized to receive either enteral ofloxacin 400 mg every day or placebo. Death in hospital and the need for additional antibiotic therapy were the main study outcomes. Secondary outcomes included duration of mechanical ventilation and hospital stay.
There were 5 times more deaths in the placebo group than in the ofloxacin group (22% vs 4%; absolute risk reduction 17.5%; 95% CI, 4.3-30.7%; P = 0.01). All deaths occurred after the seventh day of MICU admission. Additional antibiotics were needed more frequently in the placebo group than in the ofloxacin group (35% vs 6%; absolute risk reduction 28.4%; 95% CI, 12.9-43.9%; P < 0.0006). The combined frequency of hospital death or need for additional antibiotics was significantly decreased in the ofloxacin group compared with the placebo group (11% vs 57%; absolute risk reduction 45.9%; 95% CI, 29.1-62.7%, P < 0.0001). Duration of mechanical ventilation and hospital stay was significantly shorter in the ofloxacin group than in the placebo group (absolute difference, 4.2 days; 95% CI, 2.5-5.9 days and 9.6 days; 95% CI, 3.4-12.8 days, respectively). Ofloxacin was well tolerated with no significant differences in the side effect profile compared to placebo.
Comment by David Ost, MD, and Aamir Awan, MD
There are few placebo-controlled trials of antibiotic treatment in patients with acute exacerbations of COPD. A meta-analyses of 9 placebo-controlled trials1 suggested that the available evidence for antibiotic use in acute exacerbation of COPD was inconclusive. The current study focused on patients with severe COPD exacerbations requiring mechanical ventilation without evidence of pneumonia. Patients were not taking antibiotics prior to admission. Ofloxacin was effective in reducing mortality, the need for additional antibiotic therapy, duration of mechanical ventilation, and hospital stay.
On analyzing the data, all deaths occurred after the seventh day of MICU admission. Patients receiving ofloxacin were less likely to develop ventilator-associated pneumonia (VAP) than those on placebo. In the placebo group, most episodes of VAP occurred within the first week after admission to MICU, whereas all episodes in the ofloxacin group occurred after this (mean 7.2 ± 2.2 days, range, 4-11 vs mean 10.6 ± 2.9 days, range 9-14; P = 0.04).
One hypothesis would be that the mortality rate was higher in patients who developed early-onset VAP and ofloxacin reduced mortality by reducing the frequency of this complication. Another possibility is that some of these patients may have had early community-acquired pneumonia at the time of intubation, and that this was treated effectively with ofloxacin, accounting for the survival benefit. Overall, however, this study strengthens the usual practice of using antibiotics in acute severe exacerbations of COPD. Whether antibiotics and fluoroquinolones in particular offer any benefit for mild-to- moderate exacerbations requires further investigation.
Reference
1. Saint S, et al. JAMA. 1995;273:957-960.
Dr. Awan is a Fellow in Pulmonary and Critical Care Medicine, North Shore University Hospital, Manhasset, NY.
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