Antibiotics for Exacerbations of COPD

Clinical Question

Does routine use of antibiotics in patients with an exacerbation of chronic obstructive pulmonary disease (COPD) improve clinical outcomes?

Evidence-Based Answer

There is consistent evidence from a small number of studies that antibiotics significantly reduce mortality (number needed to treat [NNT] = 8) and treatment failure (NNT = 3) in more severely ill patients with COPD who are hospitalized because of an exacerbation. Two smaller studies found no benefit of antibiotics for patients with an exacerbation of COPD who were treated in the community setting.

Practice Pointers

Many acute exacerbations of COPD are caused by bacterial infection, but many are caused by viruses or are noninfectious. Although some studies have found the routine use of antibiotics beneficial in patients with COPD exacerbations, others have failed to find a benefit. Ram and colleagues identified 11 studies of patients with COPD who experienced an exacerbation and who were randomly assigned to receive an antibiotic or placebo. An exacerbation was defined as one or more of the following: increased sputum purulence or volume, increased shortness of breath, increased wheeze, chest tightness, or fluid retention. Only two of the studies included outpatients. Study quality was high.

Three studies involving a total of 298 hospital inpatients and using an objective definition of COPD found mortality rates of 3 percent in the antibiotic group and 15 percent in the placebo group (relative risk [RR] = 0.24; 95% confidence interval [CI], 0.1 to 0.57; NNT = 8). Results between studies were consistent and remained so when a fourth study conducted in an intensive care unit was added.

Another important outcome is treatment failure, generally defined as failure to improve, deterioration, or death during the study period. Six studies with a total of 705 patients reported this outcome, but there was significant variation (heterogeneity) between studies, with some showing improvement in patients taking antibiotics and others showing no benefit. After exploring the data for patterns, the authors found that antibiotics consistently reduced the likelihood of treatment failure in four studies with a total of 321 hospitalized patients (28 percent with treatment versus 58 percent with placebo [RR = 0.47; 95% CI, 0.36 to 0.62; NNT = 3]). However, the same was not true for the two outpatient studies with a total of 384 patients. In these studies, antibiotics did not reduce the likelihood of treatment failure (40 percent with antibiotics versus 35 percent with placebo [RR = 1.14; 95% CI, 0.88 to 1.48]). The antibiotics used in the studies were amoxicillin/clavulanate (Augmentin), trimethoprim/sulfamethoxazole (Bactrim, Septra), and amoxicillin.

The most widely used evidence-based guidelines recommend antibiotics for patients with COPD who have at least two of the following: increased dyspnea, increased sputum production, or increased sputum purulence.1,2

Antioxidants and Minerals for Age-Related Macular Degeneration

Clinical Question

Does supplementation with high doses of antioxidant vitamins and minerals slow the progression of age-related macular degeneration (ARMD)?

Evidence-Based Answer

Supplementation with a combination of vitamin C, vitamin E, beta-carotene, and zinc modestly reduces the progression of ARMD in patients with disease in one or both eyes. High-dose vitamin supplements should not be recommended for patients without ARMD because of the possible harmful effects of vitamin E and beta-carotene at high doses.

Practice Pointers

ARMD is the most common cause of blindness in industrialized countries, with up to one third of adults older than 75 years showing at least early signs of the disease. High doses of vitamin C, vitamin E, carotenoids, lutein, selenium, and zinc are increasingly being recommended to prevent or treat ARMD. However, some studies have shown that high doses of vitamin E and beta-carotene may increase all-cause mortality.1,2

Evans reviewed any randomized trial comparing antioxidant vitamins with placebo in patients with ARMD in one or both eyes. The primary outcome was visual acuity. Eight studies were included in the systematic review. Patients had a mean age of 70 years. Three of the trials studied zinc alone, two studied an antioxidant combination, one studied lutein, and one vitamin E. The vitamin E trial (Vitamin E, Cataract and Age-related maculopathy study [VECAT]) had 1,204 participants and followed patients for four years. The largest study (Age-Related Eye Disease Study [AREDS]), which compared zinc alone, an antioxidant combination, or both, with placebo, included 3,640 patients and lasted six years.3 The other six studies each had fewer than 200 patients and lasted for no more than two years; thus, most of the data come from the VECAT and AREDS trials.

The AREDS trial found that supplementation with vitamin C, vitamin E, zinc, and beta-carotene slows the progression of disease in patients with ARMD (relative risk = 0.68; 99% confidence interval, 0.49 to 0.93).3 The VECAT study included healthy older patients and found no visual benefit to supplementation with vitamin E (500 IU per day) after four years. Given the potential risks of vitamin E, it cannot be recommended to protect vision in patients without ARMD. The single study of lutein included 52 patients and found no effect on visual acuity.

Vitamin supplements for “eye health” are increasingly used by patients who may have a family history of ARMD but who do not have macular degeneration. It is important to warn patients about the potential harms of these supplements and the lack of known benefit.