X2.2.3 Antibiotics for treatment of exacerbations

Exacerbations with clinical signs of infection (increased volume and change in colour of sputum and/or fever, leukocytosis) benefit from antibiotic therapy (Isada CM and Stoller JK, 1994),(Siafakas NM and Bouros D, 1998),(Anthonisen et al., 1987, Patel et al., 2002, Seemungal et al., 2001) [evidence level II]

Bacterial infection may have either a primary or secondary role in about 50% of exacerbations of COPD. (Macfarlane et al., 1993),(Wilson, 1998),(Miravitlles et al., 1999),(Patel et al., 2002) Haemophilus influenzae, Streptococcous pneumoniae and Moraxella catarrhalis are most commonly involved.(Macfarlane et al., 1993),(Soler et al., 1998),(Murphy et al., 1999) Mycoplasma pneumoniae and Chlamydia pneumoniae have also been reported. (Macfarlane et al., 1993),(Mogulkoc et al., 1999) As lung function deteriorates (FEV₁ < 35%), Pseudomonas aeruginosa and Staphylococcus aureus may be encountered. (Macfarlane et al., 1993), (Soler et al., 1998),(Miravitlles et al., 1999) Multi drug resistant Ps. aeruginosa is associated with 6 fold increased risk of death (Montero et al., 2009) [evidence level III-2].

Two systematic reviews have found similar benefits for antibiotic treatment over placebo in severe acute exacerbations requiring hospitalisation, despite including different studies. Ram et al (Ram et al., 2006), including mostly hospital-based studies, found a significant decrease in mortality (RR 0.23, 95% CI 0.10 to 0.52) with a NNT of 8 (95% CI 6 to 17). Puhan et al (Puhan et al., 2007) also found a decrease in mortality of their sub-group analysis of severe exacerbations requiring hospitalisation (OR 0.20, 95% CI 0.06 to 0.62) with a NNT of 14 (95% CI 12 to 30). Both systematic reviews also found a significant decrease in treatment failure. Although Puhan did not combine the results of adverse drug effects due to heterogeneity, Ram found antibiotic treatment increased adverse events, most notably diarrhoea (RR 2.86, 95% CI 1.06 to 7.76) with a NNH of 20 (95% CI 10 to 100). The effect of antibiotics in the general practice setting is unclear. Puhan found no significant benefit for treatment failure in mild and moderate exacerbations treated outside the hospital setting (OR 0.81, 95% CI 0.55 to 1.18). (Puhan et al., 2008) Mild to moderate exacerbations were defined as those requiring outpatient treatment.

El Moussaoui et al (El Moussaoui et al., 2008) conducted a systematic review of 21 randomised controlled trials of antibiotics in acute exacerbations of chronic bronchitis and COPD. There were similar rates of clinical or bacteriological cure with short courses (≤ 5 days) and longer courses of antibiotics [evidence level I]. A related systematic review (Falagas et al., 2008) found that patients receiving short courses experienced fewer adverse effects than those receiving longer courses. It would be necessary to treat 26 (95%CI 15 to 134) patients with short course antibiotics to prevent one adverse effect. However the antibiotics evaluated were late generation cephalosporins, macrolides and fluoroquinolones, which are not those recommended in Australia.

Therapeutic guidelines: antibiotic (Therapeutic Guidelines Limited, 2000) recommend the use of oral agents such as doxycycline or amoxycillin (alternatively, erythromycin or roxithromycin). If patients do not respond, or if resistant organisms are suspected, amoxycillin–clavu­lanate should be prescribed. If pneumonia, pseudomonas or staphylococci is suspected, appropriate antibiotics should be used.

Typically, a course of treatment should be over seven to 10 days. A response is usually seen within three to five days, and a change of antibiotic should be considered if the response is unsatisfactory. If parenteral administration was commenced, oral treatment should be substituted within 72 hours. An historical population-based cohort study (Roede et al., 2008) [evidence level III-2] found that co-treatment of an acute exacerbation with oral glucocorticoids and oral antibiotics significantly increased the time to subsequent exacerbations (median 312 versus 418 days, p<0.001 to next compared to oral glucocorticoids alone).

Radiologically proven pneumonia in patients with COPD, especially in those who have been frequently hospitalised, may not be restricted to the above organisms. Gram- negative organisms, Legionella spp. and even anaerobic organisms may be responsible. Initial empiric antibiotic therapy should be tailored according to clinical and radio­graphic criteria.