Quantitative systematic review of randomised controlled trials comparing antibiotic with placebo for acute cough in adults

British Medical Journal, March 21, 1998 by Tom Fahey, Nigel Stocks, Toby Thomas

Introduction

Acute cough and respiratory tract infection are terms used to describe a wide variety of clinical syndromes. Symptoms range from cough without sputum to an illness characterised by expectoration of mucopurulent sputum, fever, general malaise, and dyspnoea,[1] but coughing is nearly always present[1- 4] Therefore, although the terms acute bronchitis, upper respiratory tract infection, common cold, and chest infection are used in a clinical context to define separate disease entities, they represent a range of respiratory tract infection whose symptoms, causative agents, and resolution vary.[1, 2]

Acute cough is a common reason for consulting a general practitioner. The fourth national morbidity survey in the United Kingdom found that the overall consultation rate for acute upper respiratory infections (code 465 of the international classification of diseases, ninth revision (ICD-9)) and acute bronchitis and bronchiolitis (ICD-9 code 466) was 772 and 719 per 10 000 person years at risk.[5]

The clinical syndrome of cough is nearly always preceded and associated with a viral nasopharyngitis.[1, 2] The causes of such infection are usually influenza virus, pare-influenza virus, respiratory syncytial virus, rhinovirus, coronavirus, and adenovirus.[2, 6, 7] Infection with non-viral organisms such as Bordetella pertussis, Mycoplasma pneumoniae, and Chlamydia pneumonia may also occur, some studies reporting a high prevalence of infection with Mycoplasma spp, particularly in young adults.[7, 8] Secondary bacterial infection occurs in a certain proportion of cases, usually with Haemophilus influenzae and Streptococcus pneumoniae.[1, 2, 7] Because bacteria are carried as normal resident flora in the upper respiratory tract, the aetiological role of bacteria cultured from sputum samples is unclear.[2] In a study based in the United Kingdom 25% of sputum culture samples from people being treated for acute bronchitis grew recognised or potential respiratory bacterial pathogens.[9] A community based longitudinal study in the United Kingdom showed that a potential pathogen was cultured in only 29% of cases, with viruses being identified more frequently than Mycoplasma spp and bacteria being identified least of all.[4] In a community based study in the United Kingdom of 206 patients with more severe respiratory tract infection (inclusion criteria were productive cough, focal signs on chest examination, and prescription of antibiotic) an aetiological diagnosis was established in 91 (44%) patients.[10) The most commonly identified pathogens were S pneumoniae (36%), H influenzae (10%), and influenza viruses (13%).[10] An accompanying editorial highlighted the difficulty in clinically differentiating between the more severe forms of bronchitis and pneumonia in the community."

Microbiological investigation of acute bronchitis is rare in general practice.[1, 9, 12] Differentiation between viral and bacterial infection is difficult on the basis of symptoms alone,[1] and therefore general practitioners have substantially different diagnostic and treatment thresholds for respiratory tract infection in the community.)[1, 12, 13]

Concern about the treatment of acute cough with antibiotics is not new.[14, 15] Review articles have questioned the value of antibiotic treatment for acute bronchitis and related conditions.[1, 16- 19] To our knowledge, the absolute risk of illness without antibiotic treatment, the likely benefits and risks of treatment, and the balance of risk and benefit for individual patients have not been measured. We therefore carried out a systematic review of randomised controlled trials to establish whether antibiotics are effective in the treatment of acute cough in the community.

Methods

Inclusion and exclusion criteria

We included studies of patients aged greater than 12 years who were attending a family practice clinic, community based outpatient department, or an outpatient department attached to a hospital. We included patients who complained of acute cough with or without purulent sputum that had not been treated in the preceding week with antibiotic. Patients with chronic obstructive airways disease were excluded. The included studies were prospective trials in which antibiotic was allocated by formal randomisation or by quasi-randomisation, such as alternate allocation to treatment and placebo groups. Only placebo controlled trials were included; comparative studies between different classes of antibiotics were excluded. Categorical and continuous outcomes were reported in the randomised controlled trials identified at the start of the review.[20- 28] Many different outcomes were reported in individual randomised controlled trials; we concentrated on the three most commonly reported outcomes: the proportion of subjects reporting productive cough, the proportion of subjects who had not improved clinically at re-examination, and the proportion of subjects who reported side effects from taking antibiotic or placebo.