35 Respiratory infections
Upper respiratory tract infections
Colds and flu
Viral URTIs causing coryzal symptoms, rhinitis, pharyngitis and laryngitis, and associated with varying degrees of systemic symptoms, are extremely common. These infections are usually caused by viruses from the rhinovirus, coronavirus, parainfluenza virus, respiratory syncytial virus, influenza virus and adenovirus families, although new viruses continue to be identified. For instance, in 2001, a novel respiratory pathogen was described that has become known as human metapneumovirus (hMPV). This causes a spectrum of respiratory illnesses particularly in young children, the elderly and the immunocompromised (Van Den Hoogen et al., 2001).
Influenza
National guidelines for the UK recommend NAIs should only be used when influenza is circulating in the community (which is carefully defined), and in patients who are both at risk of developing complications and can commence treatment within a defined time window of onset or exposure (NICE, 2008, 2009). Individuals at risk and eligible for treatment include those:
Pandemics (or global epidemics) of influenza A occur around every 25 years and affect huge numbers of people. The 1918 ‘Spanish flu’ pandemic is estimated to have killed 20 million people. Further pandemics have taken place in 1957–1958 (Asian flu), 1968–1969 (Hong Kong flu) and 1977 (Russian flu). An avian strain, H5N1, emerged in South East Asia in 2003 and is now considered endemic in many parts of South East Asia and remains a concern for public health (WHO, 2010).
The widespread use of NAIs during the 2009 pandemic brought its own problems. Resistance to oseltamavir emerged (Gulland, 2009), and some argued that the cure was worse than the disease (Strong et al., 2009). Further, a Cochrane review (Jefferson et al., 2009) found no good evidence that oseltamivir prevents secondary complications such as pneumonia, one of the main justifications for its widespread use in pandemic influenza. However, the relatively benign course of the 2009 pandemic should not provide false reassurance as to the risks associated with future pandemics.
Sore throat (pharyngitis)
Clinical features
In the UK, there has been a recent increase in rates of group A streptococcal infection. This includes invasive group A streptococcal infection (iGAS), associated with infection in normally sterile sites such as blood or tissue. The most common serotypes seen in England and Wales are emm 1, 3, and 89; emm 3 infections are associated with higher case fatality rates. The cause of the upsurge is unknown but may represent a natural periodic increase or alternatively excess transmission associated with high rates of influenza in 2008 (Lamagni et al., 2009).
Treatment
Treatment of viral sore throat is directed at symptomatic relief, for example with rest, antipyretics and aspirin gargles. Streptococcal sore throat is usually treated with antibiotics although the extent to which they shorten the duration of symptoms and reduce the incidence of suppurative complications is modest (Del Mar et al., 2004). Antibiotic treatment also reduces the incidence of non-suppurative complications so is likely to be of greater benefit where these are common. There is also an argument that treating to eradicate streptococcal carriage might reduce the risk of relapse or later streptococcal infection at other sites.
Broadly, there are three treatment strategies:
There is no correct approach and each has its advocates, although the problem of resistance has led to increasing pressure on prescribers to restrict empirical antibiotic use particularly for conditions such as pharyngitis that are frequently viral. The prevailing view is that antibiotics should not be routinely prescribed except where there is a high risk of severe infection, for instance, in immunocompromised patients (NICE, 2010).
Penicillins such as benzylpenicillin (penicillin G) or phenoxymethylpenicillin (penicillin V) have traditionally been regarded as the treatment of choice for streptococcal sore throat, but there is now convincing evidence that cephalosporins are more effective in terms of both clinical response and eradication of the organism from the oropharynx. This was summarised in a large meta-analysis of 40 studies in which 10-day courses of oral cephalosporins and penicillins were compared in the management of children with streptococcal pharyngitis (Casey and Pichichero, 2004). Bacteriological and clinical cure significantly favoured cephalosporins over penicillins, perhaps because penicillins are hydrolysed by β-lactamases produced by organisms such as anaerobes naturally resident in the oropharynx, whereas cephalosporins are not. The 10-day course length became accepted following earlier studies that compared the effect of different durations of penicillin treatment on bacteriological colonisation, but a recent systematic review (Atamimi et al., 2009) found comparable efficacy with shorter courses of newer antibiotics such as azithromycin.
Otitis media
Treatment
There has been much debate about whether or not antibiotics should be used for the initial treatment of acute otitis media. A meta-analysis combined seven clinical trials involving 2202 children and concluded that, although antibiotics confer a modest reduction in pain at 2–7 days, they do not reduce the incidence of short-term complications such as hearing problems and they do cause side effects (Glasziou et al., 2004). The benefit of antibiotic treatment may be greater in children under two than in older children (Damoiseaux et al., 2000), but in any case about 80% of cases treated without antibiotics will resolve spontaneously within 3 days. If antibiotic treatment is to be given, it should be effective against the three main bacterial pathogens: S. pneumoniae, H. influenzae and S. pyogenes. The streptococci are usually sensitive to penicillins, but these are much less active against H. influenzae, so the broader spectrum agents amoxicillin or ampicillin are preferred. These drugs have identical antibacterial activity, but amoxicillin is recommended for oral treatment since it is better absorbed from the gastro-intestinal tract. Patients with penicillin allergy may be treated with a later-generation cephalosporin (see later).
Pneumococcal conjugate vaccines, which are currently given routinely in the childhood vaccination schedule, may reduce the incidence of acute otitis media, although a recent review (Jansen et al., 2009) found only modest benefit. No benefit was found for influenza vaccination (Hoberman et al., 2003). Long-term antibiotic prophylaxis might have a role in some children (Leach and Morris, 2006), but any benefit has to be balanced against the risks.
Lower respiratory infections
Acute bronchitis and acute exacerbations of COPD
The importance of chronic bronchitis is that it renders the patient more susceptible to acute infections and more likely to suffer respiratory compromise as a result. These acute exacerbations of COPD are a frequent cause of morbidity and admission to hospital. An exacerbation is defined as ‘a sustained worsening of the patient’s symptoms from his or her usual stable state that is beyond normal day-to-day variations, and is acute in onset’ (NICE, 2004). Common symptoms include worsening breathlessness, cough, increased sputum production and change in sputum colour. It is important to remember that not all acute exacerbations of COPD have an infective aetiology since atmospheric pollutants are sometimes implicated.
Treatment
Despite the reservation that many cases are non-infective, current guidelines recommend that antibiotics are prescribed when an exacerbation is associated with more purulent sputum (NICE, 2004). There is no unequivocal evidence that one antibiotic is better than another, so recommendations for empiric treatment are based generally upon spectrum, side effects and cost. Most authorities favour either a tetracycline such as doxycycline or an aminopenicillin such as amoxicillin, since these agents cover most strains of S. pneumoniae and H. influenzae. Some people argue in favour of co-amoxiclav, which covers β-lactamase producing strains of H. influenzae and M. catarrhalis that are therefore resistant to amoxicillin, but this agent is more expensive and has a greater incidence of side effects. For penicillin-allergic patients for whom tetracyclines are contraindicated, neither the macrolide erythromycin nor the earlier oral cephalosporins such as cefalexin or cefradine are sufficiently active against H. influenzae for empiric use. However, both clarithromycin and newer oral cephalosporins such as cefixime are active against haemophili while retaining activity against pneumococci.