Treatment of common lower respiratory tract infections

Summary
Antibiotics do not help the many lower respiratory infections which are caused by viruses. While acute bronchitis often does not require antibiotic therapy, antibiotics can be given to patients with acute exacerbations of chronic bronchitis. The indications for treatment are increased dyspnoea, and an increase in the volume or purulence of the sputum. The treatment of bacterial pneumonia is selected by considering the age of the patient, the severity of the illness and the presence of underlying disease. Amoxycillin and doxycycline are suitable for many of the lower respiratory tract infections seen in general practice.

Introduction
An important consideration in the treatment of a patient with a lower respiratory tract infection is to decide if an antibiotic is required at all. Many infections are viral and symptomatic treatment only is required. If an antibiotic is required, the choice of drug will depend on the site of infection, the severity of illness, the age of the patient, the presence of any other underlying diseases, history of drug reactions and the likely compliance of the patient.

Acute bronchitis
This is almost always due to a viral infection and therefore does not require antibiotic therapy. Antibiotics are only considered if there is a bacterial super infection. This is suggested by the patient's symptoms getting worse, often with the development of fever and an increase in the amount and purulence of the sputum. In these circumstances, the patient should be treated as for an acute exacerbation of chronic bronchitis.

Acute exacerbations of chronic bronchitis
This is an area of some controversy. Early trials did not show any significant benefit from antibiotics, although there was a trend in their favour. More recent trials which have addressed some of the problems of the previous trials have shown a significantly better outcome in the treatment group. The largest study showed that antibiotic treatment was associated with a significantly higher success rate than the placebo group, with an overall failure rate of 29% in the treatment group and 42% in the placebo group.¹ This response was further analysed according to the number of symptoms present. Significant improvement was obtained with antibiotics if the patient had two of the following:

• increased dyspnoea
• increased sputum volume
• increased purulence

A meta-analysis² also found a small, but statistically significant, improved outcome in the patients given antibiotics.

It is reasonable to start antibiotics when a patient fulfils the criteria mentioned above. In many infections, a culture provides useful information for choosing an antibiotic, but this can be misleading in patients with acute on chronic bronchitis. The respiratory tract of these patients is usually colonised with one or more of the recognised respiratory tract pathogens, Streptococcus pneumoniae, Haemophilus influenzae , and Moraxella catarrhalis. Although these organisms can cause infections, a positive sputum culture in isolation is not an indication for commencing therapy. The only benefit from culture is to identify the presence of a coloniser, and hence a potential cause of infection, which is resistant to one of the usual antibiotics used in the respiratory tract. I generally perform cultures only if the patient has a poor response to treatment.

So what is the best treatment? The ninth edition of the Antibiotic Guidelines³ recommends either amoxycillin or doxycycline as initial therapy. Either of these will be effective against most of the causative bacteria, although amoxycillin may fail in patients with a beta lactamase-producing organism. Approximately 20% of Haemophilus influenzae and almost 100% of Moraxella catarrhalis produce a beta lactamase. If one of these organisms has colonised the respiratory tract, if the clinical response is slow or the patient has a severe exacerbation, an alternative drug should be chosen. The alternatives that have the required spectrum of activity and that are not affected by beta lactamases are roxithromycin, cefaclor and amoxycillin/potassium clavulanate. I would choose roxithromycin as both cefaclor and amoxycillin /potassium clavulanate cost slightly more.

Pneumonia
Although the diagnosis of community-acquired pneumonia is made on clinical and radiographic grounds, the same information cannot be used to establish the identity of the causative agent. For many years, the empirical choice of antibiotic for the initial treatment of pneumonia has been 'organism based'. This assumed that the clinical and radiographic appearances of disease caused by the different pathogens were sufficiently distinct as to be easily recognised.

For example, an acute illness characterised by fever, productive cough with blood-stained sputum, signs of lobar consolidation and a neutrophilia has been considered diagnostic for Streptococcus pneumoniae infection. A dry cough, low grade fever, extra pulmonary symptoms and diffuse infiltrates on chest X-ray were considered indicative of an infection due to Mycoplasma pneumoniae, Chlamydia pneumoniae or Legionella spp. While this may be true for many patients, there is unfortunately much overlap. Well-controlled studies in which clinical or radiographic parameters have been used to predict the microbial aetiology show a correct prediction in less than 50% of cases.⁴

A different approach to selecting the initial empirical therapy is necessary. The most useful approach is to identify the risk factors contributing to morbidity and mortality and then select empirical therapy accordingly.⁵ The most important predictors of patient morbidity and mortality are

• age
• the presence of underlying disease
• severity of illness.

Age
This is important for two reasons.

• Patients over 60 years of age have a significantly higher mortality and should be treated more vigorously, with hospitalisation being considered at an earlier stage than for a younger patient.
• There is an association of particular pathogens with different age groups. Streptococcus pneumoniae is more common in the elderly, although it does occur in all age groups, while Mycoplasma pneumoniae is much more common in the 20-40 age group.

Presence of underlying disease
The most common underlying condition of significance is chronic obstructive pulmonary disease. The airways are colonised with organisms such as Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis making infection with these organisms more likely. Similarly, patients with diabetes mellitus, alcoholism, renal disease, altered mental state, congestive cardiac failure, post-splenectomy state and a history of smoking are more predisposed to these pathogens.

Severity of illness
This can be defined as mild, moderate or severe. The patient with severe pneumonia can usually be recognised and sent rapidly to hospital for specialist care (Table 1). The patient with mild or moderate pneumonia requiring hospitalisation is perhaps harder to identify. Attempts have been made to identify risk factors which predispose to a complicated course. The presence of two or more of the 5 risk factors listed in Table 2 should lead to hospitalisation, while those patients with one or less risk factors could be given a trial of therapy at home.⁶

Choice of antibiotic
As patients are grouped by their risk factors, a stratified approach to the choice of empiric therapy can be made (Table3).

Group 1 includes younger patients with mild disease. They can be adequately treated with a drug that covers both Streptococcus Pneumoniae and Mycoplasma pneumoniae . The macrolides (erythromycin, roxithromycin) or doxycycline have the required spectrum for oral therapy. For moderate disease requiring parenteral therapy, intravenous penicillin (or cephalothin in the penicillin-allergic patient) should be used
in combination with a macrolide. The macrolide can often be given orally in these patients.

Group 2 includes older patients or those with pre-existing illnesses. As these patients are more likely to have infection with Haemophilus influenzae as well as Streptococcus pneumoniae, any antibiotic therapy should be aimed primarily against these organisms. For oral therapy, amoxycillin is suitable for most patients. However, as treatment failure may occur if the Haemophilus influenzae produces a beta lactamase, alternatives should be considered if the patient is known to be colonised with such an organism or if response to therapy is slow. Alternative drugs include roxithromycin, doxycycline, amoxycillin/potassium clavulanate or cefaclor. Penicillin when given parenterally achieves adequate tissue concentrations to treat non-beta lactamase-producing Haemophilus influenzae as well as Streptococcus pneumoniae and can therefore be used for those patients requiring parenteral therapy. However, in those patients where a beta lactamase-producing organism may be causing infection, therapy should be changed to a 'third generation' cephalosporin such as ceftriaxone or cefotaxime.

Group 3 patients require parenteral antibiotics that will cover all the possible causes including Legionella spp . At first a third generation cephalosporin should be combined with intravenous erythromycin. A subgroup of patients with underlying disease such as bronchiectasis have an increased risk of Pseudomonas aeruginosa infection. Their optimal therapy is an antipseudomonal beta lactam such as ceftazidime together with an aminoglycoside.

Patients in Groups 4 and 5 usually have a moderate to severe pneumonia requiring hospitalisation and specialist care.

The initial route of therapy will depend on the severity of illness, the ability of the patient to tolerate oral medication and the likely patient compliance. If the initial treatment is parenteral, transfer to oral therapy can be considered once the clinical condition has stabilised and the patient can tolerate oral fluids and has a temperature of <38oC for at least 48 hours. The choice of drug should be made on known susceptibilities if the causative organism has been identified or from the empirical drugs listed in Table 3. For those initially treated for severe pneumonia, a combination of an oral macrolide together with either amoxycillin/potassium clavulanate or cefaclor would be suitable.

Duration of treatment
The total length of therapy will depend on the clinical response, but is usually 5-10 days. For severe disease, therapy should be for 7-14 days, but prolonged therapy may be necessary if complications such as empyema or abscess formation occur. Treatment for Legionella should be for at least 14 days.

Prevention of respiratory tract infections
Some respiratory tract infections can be prevented by the use of vaccination. Pneumococcal polyvalent vaccine is recommended for those at risk i.e. asplenia, the immuno compromised (in particular, patients with HIV, nephrotic syndrome, multiple myeloma, lymphoma, Hodgkin's disease and organ transplantation), patients with chronic illness (cardiac, renal or pulmonary, diabetes and alcoholism), patients >50 years old from communities with high attack rates (Aboriginal and Torres Strait communities). Consideration should also be given to individuals over the age of 65. Revaccination after 5 years is only necessary in those at risk of severe life-threatening disease e.g. asplenia. Influenza vaccine is recommended for most of the patients listed above, but must be given on an annual basis. Diphtheria is a disease now rarely encountered. This, however, is dependent on maintaining an immune population, thus regular Adult Diphtheria Tetanus vaccination is required.

Summary
Acute exacerbations of chronic bronchitis and pneumonia are common illnesses in our community. Prescribing the appropriate antibiotic is important to obtain the optimal patient response. The antibiotics recommended have the required spectrum of activity for each of the settings described. Where more than one drug has been mentioned, preference should be given to the drug with the fewest adverse effects and lowest cost, and one which the patient is likely to take.

Further reading
Campbell GD. Overview of community-acquired pneumonia. Prognosis and clinical features. Med Clin North Am 1994;78:1035-48.