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Abstract & Commentary
Synopsis: The administration of ofloxacin to patients requiring mechanical ventilation because of acute exacerbations of chronic bronchitis significantly improved outcomes.
Source: Nouira S, et al. Once daily oral ofloxacin in chronic obstructive pulmonary disease exacerbation requiring mechanical ventilation: A randomised placebo-controlled trial. Lancet. 2001;358:2020-2025.
Nouira and colleagues randomized 93 patients with chronic obstructive lung disease admitted to 2 Tunisian hospitals because of acute respiratory failure necessitating mechanical ventilation to receive either ofloxacin or placebo for 10 days. Among the reasons for exclusion from the study were recent (within 10 days) antibiotic use and radiographic evidence of pneumonia. None were receiving corticosteroids. Culture of respiratory secretions yielded "no growth" in 34 patients, while cultures from the other 55 patients yielded a total of 67 organisms. Haemophilus spp. accounted for 63% of the Gram-negatives isolated, while streptococci, 38% of which were Streptococcus pneumoniae, accounted for all but 1 of the Gram-positives. Two of 8 (25%) of the S pneumoniae were resistant to ofloxacin.
There was a decreased number of patients requiring treatment for pneumonia (presumably community acquired) in the first 3 days of hospitalization among the ofloxacin recipients. Nosocomial pneumonia developed after the third hospital day in 10 of 46 (21.7%) patients receiving placebo and 3 of 47 (96.4%) given ofloxacin (P = 0.03). The pathogens isolated from these patients were A baumanii (5), P aeruginosa (5), E cloacae (2), and K pneumoniae (1). The duration of both mechanical ventilation and of hospital stay was significantly reduced in the ofloxacin recipients. Finally, the in-hospital mortality was 4% in those randomized to receive ofloxacin and 22% in those assigned placebo (absolute risk reduction 17.5%; 95% CI 4.3-30.7%; P = 0.01).
Comment by Stan Deresinski, MD, FACP
Despite their widespread use for this purpose in the United States, the role of bacteria and of antibiotic therapy in acute bacterial exacerbations of chronic bronchitis has remained controversial. In one study, protected brush specimens obtained by bronchoscopy in 54 patients with acute exacerbation of chronic bronchitis requiring intubation obtained within 24 hours after admission yielded no growth in one half.1 Furthermore, with the exception of fever, the severity of exacerbation was the same in those with and without positive cultures and, among those with positive cultures, the administration of appropriate antibiotic therapy did not affect outcome.
However, a meta-analysis of placebo-controlled trials found a small but statistically significant improvement due to antibiotic therapy in patients with exacerbations of COPD.2 The authors of that study pointed out that, although the benefit appeared small, it may be of clinical significance, especially in patients with severe underlying airways disease. It should also be noted that these studies examined were performed prior to the availability of the "respiratory quinolones." The fluoroquinolone used in the trial reviewed here is also not among the most potent against respiratory pathogens. In fact, although the number of pneumococcal isolates in this study was only 8, 2 of these were resistant to ofloxacin.
It is possible that antibiotics may provide benefit by mechanisms independent of their antibacterial effect. Thus, both macrolides and fluoroquinolones have been reported to have immunomodulatory activity.3-5 Most likely, these are not independent benefits; the presence of bacterial pathogens in the sputum of patients with exacerbations is associated with increased sputum concentrations of proinflammatory cytokines.6
Among the apparent benefits from antibiotic therapy in the study reviewed here were a reduced number of both early (first 3 days) and late pneumonia. The pneumonias occurring in the first 3 days were presumably community acquired and the administration of ofloxacin most likely prevented the progression of early inapparent pneumonia to a stage at which it became apparent on plain chest radiography. This interpretation is consistent with a previous study demonstrating that plain radiography missed almost one third of pneumonias detectable by high resolution computerized tomography.7 More extensive reporting of microbiological data may have helped to assess this hypothesis. In contrast, the reduction in incidence of later pneumonias was most likely the result of effective prophylaxis.
This trial appears to clearly demonstrate that antibiotic administration is beneficial to patients with ABECB who are ill enough to require assisted ventilation. Further studies are necessary to confirm this observation and to more clearly define the role of antibiotic therapy in patients with less severe illness.
Dr. Deresinski, Clinical Professor of Medicine, Stanford; Director, AIDS Community Research Consortium; Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, is Editor of Infectious Disease Alert.
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6. Khan AA, et al. Antimicrob Agents Chemother. 2000; 44:3169-3173.
7. Syrjala H, et al. Clin Infect Dis. 1998;27:358-363.