Overprescribing of antibiotics for self-limiting chest infection and cough is due in part to a lack of clear, authoritative evidence of the efficacy or otherwise of antibiotics in this situation. There is also considerable patient pressure to prescribe, which has undoubtedly been fuelled by GPs' own prescribing habits.
The SIGN Guideline on Community Management of Lower Respiratory Tract Infection (LRTI) in Adults, launched last month, sets out to address this problem.
The guideline covers epidemiology, severity assessment, investigations, immunisation and other issues. For most GPs, however, antibiotic prescribing for LRTI is the area where clear guidance backed by good evidence has traditionally been lacking. As always, clinical judgement is paramount, but this guideline provides a good steer for reasonably evidence-based decision making in this situation.
When I was invited to join the SIGN group to develop a guideline for use in this extremely common clinical situation in primary care, I saw it as an opportunity to establish some sorely needed facts. If there is evidence it should be readily available to guide our judgement in a more logical and consistent manner.
The Guideline Development Group consisted of GPs, microbiologists, respiratory nurses, a patient group representative and consultants in respiratory medicine, public health and infectious diseases.The SIGN executive searched the literature and provided management support and facilitation.
The group identified key words that the SIGN researchers could use to identify relevant papers. This resulted in a large volume of literature which had to be whittled down. We did this by splitting into small groups to tackle separate aspects of the guideline.
The resulting papers were then appraised using standard methodological checklists and their conclusions considered as evidence that could form the basis of recommendations. These recommendations are graded from A to D according to the supporting evidence levels (Figure 1, below).
|Figure 1: Key to evidence statements and grades of recommendations|
A national open meeting with 150 representatives of the relevant specialties allowed wider consultation and advice, as did displaying the draft on the SIGN website. A draft was also sent to a panel of independent expert referees.
The guideline does not apply to children under 16 years of age, to patients with asthma, lung cancer, cystic fibrosis, bronchiectasis or tuberculosis, or to those with HIV infection or who are otherwise significantly immunocompromised.
One of the first difficulties related to the definition of LRTI. In practice it is difficult to distinguish upper from lower respiratory symptoms, and not all lower respiratory tract symptoms relate to an identifiable infection.
Another problem that soon became apparent was the diagnosis of pneumonia, for which radiography is the gold standard. As X-rays are rarely available in general practice, reliance must be placed on the presence or absence of new focal signs on auscultation. This is somewhat imprecise, but can probably be lived with in the pragmatic world of primary care.
For the purpose of the guideline, patients with lower respiratory symptoms and signs are divided into three groups:
- Non-pneumonic LRTI
- Exacerbations of chronic obstructive pulmonary disease (COPD)
- Community-acquired pneumonia.
Patients in all groups should be assessed for features of severity (see Figure 2, below) and comorbidity, which may alter management.
|Figure 2: Features of severity in lower respiratory tract infection*|
*Items in bold are the most important
This category applies to patients who have been previously well with no chest signs. (New focal chest signs would classify them as having pneumonic involvement and therefore as community-acquired pneumonia.) These patients represent the majority of those with ´chest colds° who, in the past, may have been treated with antibiotics.
Many will have viral infections; some will have Mycoplasma pneumoniae, Bordetella pertussis or Chlamydia pneumoniae. Streptococcus pneumoniae and Haemophilus influenzae may be present but could represent secondary infection.
Investigations are not usually helpful in these patients.
Antibiotics lead to no or minimal advantage whether or not the sputum is purulent.
Exacerbations of COPD
This category is self-explanatory, and although there is no agreement on the precise definition of an exacerbation, for practical purposes an increase in dyspnoea, sputum volume and purulence, with or without upper respiratory tract symptoms, can be used.
Unlike patients with non-pneumonic LRTI, sputum purulence is relevant in these patients. Indeed, a British primary care study found that green sputum correlated highly with bacterial infection and that patients without purulence improved without antibiotics.1
Bacteria are isolated in 40-60% of acute exacerbations. Most are H. influenzae, Str. pneumoniae or Moraxella catarrhalis. Haemophilus is found in about 50%.2-15
- Sputum culture is controversial but may be helpful in reducing antibiotic prescribing if the results can be obtained quickly enough. This is not usually the case and therapy must be empirical.
- Chest X-ray is not usually useful acutely but should be considered later in smokers or if recovery is not satisfactory.
- Pulmonary function tests. A severely impaired FEV1 is more likely to be associated with resistant organisms and may therefore influence choice of antibiotic.16-17 Peak flow is not helpful.
- Pulse oximetry aids the detection of hypoxia and may therefore be of value.18 Oximeters are being used by GPs involved in prehospital immediate care, but are not widely used otherwise in primary care at present.
Patients with significant airway obstruction and an increase in breathlessness and sputum purulence should be treated with an antibiotic.19-21 An aminopenicillin, macrolide or a tetracycline is recommended.
The key to this category for the purpose of the guideline is the presence of new focal chest signs.
Many different organisms may be involved, particularly Str. pneumoniae (most frequently isolated in the community), M. pneumoniae, Staphylococcus aureus, H. influenzae, and influenza and other viruses.
- Sputum culture is useful for antibiotic sensitivities, and a Gram stain may provide a more rapid clue as to which organisms are involved.22,23 Initial empirical antibiotic choice can be modified following results of sputum analysis.
C-reactive protein, pulmonary function tests and chest X-ray were all considered, but were not felt to be useful routinely in acute community-acquired pneumonia. Chest X-ray should be considered in the convalescent period in smokers and those not progressing satisfactorily.
Surprisingly, the evidence for antibiotic therapy in pneumonia is of a low level, owing to the fact that trials would not now be ethical. It is taken for granted, therefore, that early administration of antibiotics in pneumonia is essential.24 An antibiotic that is effective against Str. pneumoniae such as an aminopenicillin or a macrolide is recommended.
In patients under 50 years of age M. pneumoniae should be considered, particularly in an epidemic year, if there are upper respiratory tract symptoms, headache or symptoms for more than a week. For these patients and those with chlamydial pneumonia, a macrolide or tetracycline should be used.
For patients with features of severity (see Figure 2,above) who are to be managed at home, a combination of an aminopenicillin and macrolide should be used.
In ill patients with pneumonia it may be advisable to consider a bolus of intravenous antibiotic prehospital admission, as used in cases of presumed bacterial meningitis.
The value of cough mixtures was assessed. Cough is a defence mechanism and its suppression may not be desirable in the context of infection. Studies of codeine, pholcodine and dextromethorphan tended to have very small patient numbers and mainly dealt with suppression of artificially induced cough.25-28 A few larger randomised controlled trials showed no benefit.29-30
It is generally accepted that expectorants and demulcents are ineffective.31 A Cochrane Review showed no benefit with ß2 agonists either.32
Advice on smoking cessation and prevention by pneumococcal and influenza vaccines was also considered in the guideline.
How will the guideline affect practice?
The sections of the guideline relating to exacerbations of chronic bronchitis and community-acquired pneumonia are probably non-controversial (see Figure 3 below), and I do not think most practitioners will find that implementation alters their current practice very much.
|FIgure 3: Quick Reference guide containing key points on the guideline (click here to download PDF of guideline from the SIGN website)|
|FIgure 3 (continued): Quick Reference guide containing key points on the guideline (click here to download PDF of guideline from the SIGN website)|
The management of non-pneumonic LRTI could be more problematic however.
Patients with LRTI who have been previously well and whose chests are clear should not be given antibiotics. Patients may find this difficult to accept if they are accustomed to getting a script.
Cough mixtures are also of no clinical benefit, so some necessarily time-consuming explanation will be required.
The guideline includes a patient leaflet, which should help to back up the advice given. Inevitably, some of these patients may feel quite ill and there will be a temptation to give an antibiotic to maintain goodwill. Of course, if the clinician feels that the patient is clinically ill a judgement would have to be made, particularly as the diagnosis of a more serious pneumonia hinges, to some extent, on the detection of new focal signs in the chest, which could easily be overlooked.
The majority of people with ´chest colds° are not ill, however, and it is important that practitioners are consistent in their adherence to the evidence, as giving a prescription at a later date easily undermines explanations of the lack of efficacy of antibiotics.
Under pressure of time and patient expectation it may appear easier to give an antibiotic, but this strategy will be counterproductive in the long term and will result in patients being given drugs they do not need, undermine later attempts to educate, increase prescription costs, and perpetuate the rise in antibiotic resistance in the community.
It is hoped that this guideline with its patient information leaflet will provide primary care physicians with the confidence and support to apply the evidence to clinical practice.
- Stockley RA, O°Brien C, Pye A, Hill SL. Relationship of sputum colour to nature and outpatient management of acute exacerbations of COPD. Chest 2000; 117: 1638-45.
- Leeder SR. Role of infection in the cause and course of chronic bronchitis and emphysema. J Infect Dis 1975; 131: 731-42.
- Murphy TF, Sethi S. Bacterial infection in chronic obstructive pulmonary disease. Am Rev Respir Dis 1992; 146: 1067-83.
- Gump DW, Phillips CA, Forsyth BR et al. Role of infection of chronic bronchitis. Am Rev Respir Dis 1976; 113: 465-74.
- Tager I, Speizer FE. Role of infection in chronic bronchitis. N Engl J Med 1975; 292: 563-71.
- Davies BI, Maesen FP, Teengs JP, Baur C. The quinolones in chronic bronchitis. Pharm Weekl Sci 1986; 8: 53-9.
- Basran GS, Joseph J, Abbas AM et al. Treatment of acute exacerbations of chronic obstructive airways disease - a comparison of amoxycillin and ciprofloxacin. J Antimicrob Chemother 1990; 26: 19-24.
- Aldons PM. A comparison of clarithromycin with ampicillin in the treatment of outpatients with acute bacterial exacerbation of chronic bronchitis. J Antimicrob Chemother 1991; 27: 101-8.
- Bachand RT Jr. A comparative study of clarithromycin and penicillin VK in the treatment of outpatients with streptococcal pharyngitis. J Antimicrob Chemother 1991; 27: 75-82.
- Lindsay G, Scover HJ, Carnegie CM. Safety and efficacy of femafloxacin versus ciprofloxacin in lower respiratory tract infections: a randomized, double-blind trial. J Antimicrob Chemother 1992; 30: 89-100.
- Neu HC, Chick TW. Efficacy and safety of clarithromycin compared to cefixime as outpatient treatment of lower respiratory tract infections. Chest 1993; 104: 1393-9.
- Grayston JT. Infections caused by Chlamydia pneumoniae strain TWAR. Clin Infect Dis 1992; 15: 757-63.
- Nenning ME, Shinefield HR, Edwards KM et al. Prevalence and incidence of adult pertussis in an urban population. JAMA 1996; 275: 1672-4.
- Sethi S, Murphy TF. Bacterial infection in chronic obstructive pulmonary disease in 2000: a state-of-the-art review. Clin Microbiol Rev 2001; 14: 336-63.
- Sethi S. Etiology and management of infections in chronic obstructive pulmonary disease. Clin Pulmon Med 1999; 6: 327-32.
- Eller J, Ede A, Schaberg T et al. Infective exacerbations of chronic bronchitis: relationship between bacteriologic aetiology and lung function. Chest 1998; 113: 1542-8.
- Miravitlles M, Espinosa C, Fernandez-Laso E et al. Relationship between bacterial flora in sputum and functional impairment in patients with acute exacerbations of COPD. Study group of Bacterial Infection in COPD. Chest 1999; 116: 40-6.
- Mower WR, Sachs C, Nicklin EL et al. Effect of routine emergency department triage pulse oximetry screening on medical management. Chest 1995; 108: 1297-302.
- Anthonisen NR, Manfreda J, Warren CP et al. Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. Ann Intern Med 1987; 106: 196-204.
- Sethi S, Murphy TF. Bacterial infection in chronic obstructive pulmonary disease in 2000: a state-of-the-art review. Clin Microbiol Rev 2001; 14: 336-63.
- Niroumand M, Grossman RF. Airway infection. Infect Dis Clin North Am 1998; 12: 671-88.
- Parry CM, White RR, Rideway ER et al. The reproducibility of sputum gram film interpretation. J Infect 2000; 41: 55-60.
- Bartlett JG, Breiman RF, Mandell LA, File TM Jr. Community-acquired pneumonia in adults: guidelines for management. The Infectious Diseases Society of America. Clin Infect Dis 1998; 26: 811-38.
- BTS Guidelines for the Management of Community Acquired Pneumonia in Adults. Thorax 2001; 56: 1-64.
- Empey DW, Laitinen LA, Young GA et al. Comparison of the antitussive effects of codeine phosphate 20 mg, dextromethorphan 30 mg and noscapine 30 mg using citric acid-induced cough in normal subjects. Eur J Clin Pharmacol 1979; 6: 393-7.
- Karttunen P, Tukiained H, Silvasti M, Kolonen S. Antitussive effect of dextromethorphan and dextromethorphan-salbutamol combination in healthy volunteers with artificially induced cough. Respiration 1987; 52: 49-53.
- Grattan TJ, Marshall AE, Higgins KS, Morice AH. The effect of inhaled and oral dextromethorphan on citric acid induced cough in man. Br J Clin Pharmacol 1995; 39: 261-3.
- Edwards GF, Lewis HE, Stafford D. The effect of pholcodine with and without an antihistamine on cough and expectoration. Br J Dis Chest 1977; 71: 245-52.
- Eccles R, Morris S, Jawad M. Lack of effect of codeine in the treatment of cough associated with acute upper respiratory tract infection. J Clin Pharm Ther 1992; 17: 175-80.
- Freestone C, Eccles R. Assessment of the antitussive efficacy of codeine in cough associated with common cold. J Pharm Pharmacol 1997; 49: 1045-9.
- British Medical Association, Royal Pharmaceutical Society of Great Britain. British National Formulary 42. London: The Association, The Society; 2001. [cited on 22 April 2002]. Available from url: http://www.bnf.org
- Sheikh A, Nolan D, Greenstone M. Long-acting beta-2-agonists for bronchiectasis (Cochrane Review). In: The Cochrane Library, Issue 1, 2002. Oxford:Update Software.
SIGN guideline no. 59 Community Management of Lower Respiratory Tract Infection in Adults is available on the SIGN website www.sign.ac.uk and can be downloaded free of charge.