key: cord-0041922-oxdsfxya authors: Meisner, Sarah title: Recommended management of lower respiratory tract infections date: 2008-10-03 journal: nan DOI: 10.1002/psb.285 sha: 03d0fad6e48fb005f164fee1177d1cb1e17662e6 doc_id: 41922 cord_uid: oxdsfxya Lower respiratory tract infections comprise a wide range of pathologies and causative pathogens that require differentiating in order to administer the most appropriate treatment. Our Drug review discusses the current recommended management of LRTIs in the community, followed by sources of further information in Resources. Copyright © 2008 Wiley Interface Ltd L ower respiratory tract infections (LRTIs) cover a broad spectrum of pathological processes and aetiologies, including acute and chronic bronchitis, bron-chiolitis and acute and chronic pneumonia, as well as pleural effusions, empyemas and lung abscesses. The latter three conditions will usually be managed in hospital initially, and treatment will depend on the microbiology. In complicated pneumonias, eg in immunosuppressed or HIV-infected individuals, and in chronic lung conditions such as cystic fibrosis, decisions on antibiotic therapy should be made by the specialist physician looking after the patient in conjunction with a microbiologist, virologist or infectious disease physician. This review concentrates on the LRTIs that are seen and managed by GPs. Appropriate patient selection for treatment and the correct use of agents are important, not only in optimising therapy for the individual patient but also in order to keep emergence of resistance and side-effects to a minimum. 1 The decision to prescribe and the choice of antibiotic used has never been more important than now with the rise in prevalence of aggressive strains of Clostridium difficile. The indication for antibiotic use in LRTIs and the type of antibiotic used will depend upon the diagnosis and severity of the disease, which may give clues to the likely aetiology. The British Thoracic Society (BTS) have recently published guidelines on the assessment and management of cough in children, which doctors may find useful in assisting them to differentiate between infective and noninfective causes. 3 Other factors to be considered in choosing an antibiotic are the spectrum of activity of the drug, the local resistance pattern, the side-effect profile, contraindications, interactions with other drugs that the patient may be taking (see Table 1 ; refer to the BNF for a comprehensive list), tolerability (including the frequency of dosing) and the cost. Community-acquired pneumonia (CAP) is an LRTI with lung parenchymal involvement. CAP affects 5-11 per 1000 of the population per year, with a greater proportion affected at the extremes of age. Diagnosis of CAP in the community relies on clinical features. Patients may present with some of the following features: cough, fever, sputum production (may be purulent or blood stained), dyspnoea, pleuritic chest pain and localised chest signs. Older patients may present with nonrespiratory symptoms such as confusion, falls or worsening of a chronic illness, and may not have a fever. Very young patients may also present with nonspecific symptoms such as abdominal pain. Disease severity should be assessed in order to decide whether the patient requires hospital admission. Various severity indices have been produced, but one of the simplest is the CURB-65 severity score summarised in the 2004 update of the 2001 BTS guidelines. 3 This has been adapted to the CRB-65 score (see Figure 1 ) for use in the community where a blood urea is not generally available at the time of initial assessment. Using the CRB-65 score, patients are at low risk of death if they have no core prognostic features, and can therefore be considered for treatment at home. If there are more than two core features, mortality rises steeply and management in hospital is recommended. In intermediate groups scoring 1 or 2, clinical judgement should be used taking into account the patient's wishes and social circumstances. Co-existent disease or the presence of confusion -as defined by a Mini-Mental State Examination (MMSE) test score of ≤8/10 or new disorientation in time, place or person -in the patient should prompt consideration of hospitalisation. Status should be reviewed regularly. • allopurinol -risk of rash with ampicillin and amoxicillin eg amoxicillin • oral contraceptive pill -possible decreased efficacy of combined oral contraceptive (COC) • warfarin -increased anticoagulant effect • antiarrhythmics -increased risk of arrhythmias and other • antiepileptics -inhibition of metabolism of macrolides carbamazepine, phenytoin and possibly sodium valproate • antihistamines -risk of hazardous arrhythmias with terfenadine • anxiolytics -inhibition of metabolism resulting in an increased sedative effect, eg midazolam • cimetidine -increased toxicity of macrolide, eg deafness • warfarin -increased anticoagulant effect • antiepileptics -increased metabolism of doxycycline with carbamazepine, phenytoin and some other antiepileptics • calcium salts and dairy products -reduced absorption of tetracyclines (less marked with doxycycline and minocycline) • iron and zinc -reduced absorption of both the metal and the tetracycline • COC -possible decreased efficacy of COC • warfarin -possible increased anticoagulant effect • antacids -decreased absorption of quinolones • metal salts, eg iron, zinc and calcium -reduced absorption of quinolones • NSAIDs -possible increased risk of convulsions • theophylline -possible increased risk of convulsions • warfarin -increased anticoagulant effect • some of the newer fluoroquinolones, eg moxifloxacin, have an increased risk of arrhythmias with a number of drugs (see BNF) Drug Important interactions Table 1 . Some of the more commonly encountered drug interactions to be considered in patients taking antibiotics for the treatment of LRTIs information is frequently unhelpful in predicting the aetiology. Even when microbiology results are available, the delay in obtaining results and the limitations of the available diagnostic tests in identifying the aetiological agent make empirical treatment necessary (see Table 2 ). Differentiation of pneumonia caused by 'typical' and 'atypical' pathogens on clinical grounds alone has been shown to be unreliable. The latest BTS guidelines 3 suggest that microbiology tests are of low sensitivity, particularly in patients with nonsevere CAP and no co-morbid disease. Although Legionella and pneumococcal antigen testing kits are now available and have considerably greater sensitivity than blood or sputum cultures, their routine use in patients at low risk is felt not to be cost effective. The extent of microbiological investigations in patients with nonsevere CAP should be guided by clinical and epidemiological factors and by the response to previous antibiotic therapy. 3 Point-of-care tests are available for influenza (A and B). Specificity is generally excellent but sensitivity may be as low as 50-74 per cent. These rapid tests allow a diagnosis of influenza to be made within 10-30 minutes, such that timely prescription of antivirals can be made and/or the clinician may feel more confident about not prescribing antibiotics. 4 Streptococcus pneumoniae is the major cause of CAP, accounting for over a third of cases in the community. 3 More unusual forms of pneumonia to consider are Pneumocystis jirovecii (previously known as Pneumocystis carinii) pneumonia in patients with HIV and other forms of immunosuppression -seen much less frequently these days because of the use of prophylactic co-trimoxazole, TB in those with a more chronic pneumonia, and rare fungal and bacterial forms of pneumonia in those who have travelled. We need to remain alert to emerging causes of pneumonia such as avian influenza (bird flu) and severe acute respiratory syndrome (SARS). These should be considered in all patients presenting with a fever, cough or shortness of breath who have a relevant travel or contact history. 5, 6 Infection control issues will need to be addressed in these patients and an expert should be consulted in cases fitting the diagnostic criteria. Pneumonia in children has a slightly different epidemiological pattern. Neonates may develop pneumonia from organisms acquired from the mother's genital tract such as Group B Streptococcus, Gram-negative organisms and Chlamydia trachomatis. These children will usually be admitted to hospital for treatment. In one-month to four-year-old children most cases of CAP are viral in origin, eg respiratory syncytial virus (RSV), influenza, parainfluenza, rhinovirus, adenovirus and the newly recognised metapneumovirus. 7 These are generally self-limiting and do not require antibiotics. Bacterial pneumonias in this age group are predominantly due to Strep. pneumoniae, whereas in the over-fours Strep. pneumoniae and M. pneumoniae are the most frequently isolated organisms. 8 Resistance Concerns exist over the growing number of resistant bacteria, in particular Strep. pneumoniae, H. influenzae and methicillin-resistant Staph. aureus (MRSA). Penicillin-resistant Strep. pneumoniae is of concern, especially as resistance is frequently linked to macrolide resistance. Penicillin resistance in Strep. pneumoniae varies widely between countries, communities and groups of patients within those communities. The latest Heath Protection Agency data for England, Wales and Ireland demonstrates penicillin resistance of 1. Empirical treatment in the community is based on the fact that Strep. pneumoniae remains the leading cause of CAP. Prudent use of antibiotics is important in order to treat infections appropriately to curb the growing problem of antimicrobial resistance and to minimise side-effects and maximise compliance. Once a decision is made to treat, local resistance patterns must be taken into account. BTS recommendations are based on current practice and experience and take into account the cost, tolerability, safety and side-effect profile of the drugs currently available. As yet, the incidence of highly penicillin-resistant strains of Strep. pneumoniae in most areas of the UK is sufficiently low to allow amoxicillin to remain the first-line therapy for adults and for children under five years of age -provided that the patient has not just returned from an area where the incidence is much greater. Note, however, that the latest BTS guidelines recommend adequate dosing with amoxicillin (500mg-1g three times daily) to cover intermediate-resistant strains. 3, 10 Macrolides such as erythromycin are the secondline agents of choice if there are contraindications to amoxicillin or the patient fails to tolerate it. They are also the first-line agents in children over five years in whom M. pneumoniae is common. 11 Many people favour clarithromycin over erythromycin because of its better GI tolerance. Azithromycin is another alternative to erythromycin. Macrolides are also the treatment of choice in people with pneumonia proven to be due to 'atypical' organisms, and are routinely added to the treatment regimen in hospitalised patients with moderately severe pneumonia. Tetracyclines are not recommended as empirical therapy in the UK, mainly because of concerns over inadvertent prescribing in children and pregnant women. Treatment may be rationalised if a specific pathogen is identified or if sensitivities are at variance with the empirical regimen. This should be guided by local microbiological advice. Patients should improve on appropriate therapy within 48 hours. It is therefore important to review them at this stage or earlier. If they have failed to improve they should be considered for addition of an agent to cover atypical organisms if not already on one, and for radiography and/or hospital admission. 10 Over the last few years several new drugs with greatly improved bioavailability and tolerability have become available for use in the treatment of CAP. The fluoroquinolones, eg moxifloxacin (Avelox) and levofloxacin (Tavanic), which have antistreptococcal activity, have both an excellent antimicrobial spectrum -they are active against atypical pathogens and Legionella species as well as the common 'typical' organisms -and advantageous pharmacodynamic characteristics. With the increasing prevalence of penicillin-and macrolide-resistant pneumococci they may well have a place in therapy. However, due to concerns over the rapid development of fluoroquinolone resistance in pneumococci and other organisms, these newer fluoroquinolones should be considered only when first-line agents have been ineffective and when the causative agent, if identified, is known to be sensitive. 3 There are additional concerns in that fluoroquinolones appear to be a significant risk factor in precipitating C. difficile infections caused by the hypervirulent 027 strain. 12 Although these data were largely based on ciprofloxacin use, it is likely that the newer fluoroquinolones will have a similar effect. Quinolones are not recommended for use in the under-18s except on the advice of a paediatrician or microbiologist. Widespread use of the newer macrolides, eg azithromycin, is not being encouraged as yet. There is evidence that delays in antibiotic administration in patients with pneumonia adversely affect mortality. For patients who need to go to hospital, particularly those who are severely ill or in whom delays in transfer of two or more hours are likely, antibiotics should be commenced by the GP as soon as possible. If parenteral penicillin G is available, it www.prescriber.co.uk Prescriber 19 September 2008 29 LRTIs should be given (1.2g benzylpenicillin im or iv). If not, oral amoxicillin 1g (or oral er ythromycin 500mg if penicillin sensitive) should be commenced. 13 It is important that antibiotics are administered in a high enough dose and for a sufficient duration that the patient does not relapse after stopping the therapy and that antibiotic resistance does not develop. This needs to be balanced with the risk of side-effects, particularly the risks of C. difficile infection. The cur-rent BTS guidelines recommend a 7-10 day course of antibiotics for CAP. Some preliminary data suggest that courses as short as three days may be adequate; this is not yet endorsed, but may well be in the future. 14, 15 Emphasis needs to be placed on primary prevention of LRTIs. Influenza vaccination has been shown to reduce hospital admissions, death rates from pneumonia and flu, prevent pneumonia and decrease outpatient visits for all respiratory conditions in over-65s and patients with chronic disease. Vaccination should be offered on an annual basis to: all those aged 65 or over; all those six months of age or over and in a clinical risk group; individuals in long-stay residential or care facilities where rapid dissemination with a high morbidity and mortality is likely if influenza were introduced; and carers of individuals whose welfare would be at risk if the carer were to fall ill. Please refer to updates from the Chief Medical Officer for more details (www.dh.gov.uk/en/Publicationsand statistics/Lettersandcirculars/Professionalletters/ Chiefmedicalofficerletters/DH_073581). Influenza vaccine is contraindicated in those with severe allergy to eggs. 16 In at-risk persons of 13 years or older who have not been vaccinated, and in institutionalised individuals, when influenza A or B is known to be circulating in the community, oseltamivir may be used for postexposure prophylaxis within 48 hours of exposure. 5 Pneumococcal vaccine should also be offered to selected individuals. The pneumococcal polysaccharide vaccine (PPV) is recommended for all those of 65 years and over, and those between 2 and 65 years with risk factors of invasive pneumococcal disease. This includes individuals with asplenia or functional asplenia, chronic renal, heart, lung and liver disease, diabetics treated with insulin or hypoglycaemic agents, immunosuppression, cochlear implants and CSF leaks. Since September 2006 immunisation with the pneumococcal conjugate vaccine (PCV) has been recommended in the under twos, the schedule being a dose at 2, 4 and 13 months, with a catch-up regimen for anyone who has missed earlier doses. Immunisation should not be given to those who have had a confirmed anaphylactic reaction to a previous dose or to any of the components of the vaccine. 16 Smoking should be discouraged. In cases of chronic pneumonia where a pulmonary parenchymal process has been present for weeks to months, other causes need to be considered including TB and a host of both infectious and noninfectious causes. 17 Exacerbations of infection in patients with cystic fibrosis should be treated in conjunction with the specialist involved in their care. The majority of empyemas are secondary to pneumonia, but can result from other causes such as trauma, oesophageal perforation or subdiaphragmatic infections, and the bacterial agent(s) isolated will depend upon the aetiology of the disease. This is a complex condition with a poor prognosis if missed or mismanaged. Patients with these conditions should be managed in hospital in the first instance. Acute exacerbations of chronic obstructive pulmonar y disease (AECOPD) are characterised by increased cough, sputum production, purulence of sputum, and dyspnoea in someone with a background of excessive cough productive of sputum on most days of more than three months of at least two consecutive years. Infections account for most exacerbations, but allergens, pollutants and irritants can also contribute. Despite the frequent viral aetiology, a meta-analysis of the literature on treatment of AECOPD favoured the use of antibiotics in patients with severe disease, although the benefit seen was small and could be attributed to the expected variation of peak expiratory flow rate (PEFR) results in patients. 18, 19 The largest study on the use of antibiotics in acute exacerbations demonstrated that patients with two or more of increased dyspnoea, increased sputum volume and sputum purulence improved significantly if given antibiotics compared to those on placebo. 20 Stratifying patients into risk groups has been suggested in order to minimise hospitalisation and target therapy more appropriately (see Table 4 ). In the lowerrisk groups narrower-spectrum antibiotics can be used first line, whereas for those in whom failure of antibiotic *people fitting into this category who have continuous sputum production all year round may also be colonised with coliform bacilli or pseudomonads, and this will need to be taken into account when choosing an antibiotic Lung function and other Aetiology Antibiotics Persistent symptoms considerations Table 4 . Stratification of patients with acute exacerbation of COPD (adapted from Wilson 21 and Grossman 22 ) therapy could have serious consequences, treatment should be directed against resistant organisms. 21, 22 Antibiotic therapy A fair percentage of H. influenzae (approximately 20 per cent in the UK in 2000) 6 and of M. catarrhalis (approximately 90 per cent) produce beta-lactamases and are subsequently resistant to beta-lactams, so in cases where antibiotics are indicated local sensitivity patterns must be taken into account (see Table 4 ). Since most H. influenzae are resistant to erythromycin and other macrolides, these are not recommended for treatment of exacerbations unless Chlamydophila or Mycoplasma are suspected. Patients who experience frequent exacerbations are more likely to have resistant organisms and may require broad-spectrum antibiotics. Recommendations regarding other aspects of patient management, eg indications for steroids or bronchodilators, can be found under chest infections on Clinical Knowledge Summaries (CKS). 8 Acute bronchitis is an inflammatory condition of the tracheobronchial tree characterised by a severe cough, frequently lasting several weeks. Patients may also have a fever, hoarseness, sputum production, dyspnoea or a wheeze, with a background of a preceding upper respiratory tract infection (URTI). Acute bronchitis is usually due to respiratory viruses, eg rhinovirus, coronavirus, influenza, parainfluenza, respiratory syncytial virus (RSV), adenovirus and, though rarely seen nowadays, measles. Nonviral causes include Bordetella pertussis, M. pneumoniae and C. pneumoniae. The role of Strep. pneumoniae and H. influenzae in acute bronchitis remains unclear -these organisms are commonly isolated from specimens, but this is likely to reflect the fact that they are normal commensals of the upper respiratory tract. Symptoms are worse in those exposed to cigarette smoke and other pollutants. Noninfectious conditions that may mimic acute bronchitis and should be considered include foreign body aspiration and malignancy. 23 In those at risk, TB should also be excluded. The majority of patients with acute bronchitis do not require anything other than symptomatic therapy, and antibiotics are not indicated for the majority of cases, even in the presence of purulent sputum. 8 Studies have suggested that up to one-fifth of adults with acute severe cough have pertussis. 24 Adults whose immunity to pertussis is waning are a major reservoir for B. pertussis. It is therefore important to consider this as a diagnosis in those with a persistent cough and to take a nasopharyngeal swab/aspirate for culture if indicated. Treatment for pertussis is 14 days of erythromycin and is primarily aimed at eliminating carriage. It is also effective in decreasing the duration and severity of disease in the catarrhal phase, but may not alter the course once patients are in the paroxysmal stage. Patients with acute bronchitis due to M. or C. pneumoniae should also receive antibiotics. Macrolides are the first-line therapy for these conditions. Tetracyclines can be used in the groups in which they are not contraindicated (children under eight years old and pregnant women). In patients with significant co-morbidity, first-line antibiotics are amoxicillin, erythromycin or tetracyclines. If patients do not respond to these, consider co-amoxiclav, tetracyclines, clarithromycin or azithromycin. 8 Anti-influenza agents may be considered in those in whom a swift diagnosis is made. 11 Immunisation against influenza and pertussis as guided by current DoH recommendations (www.dh.gov.uk/en/Publicationsandstatistics/Letters andcirculars/Professionalletters/Chiefmedicalofficer letters/DH_073581) will reduce some of the burden of this disease, and discouraging smoking is another important preventive strategy. Bronchiolitis is an acute LRTI characterised by acute onset of wheeze, cough, rhinorrhoea, tachypnoea and respirator y distress, although it may manifest as lethargy, irritability, poor feeding and apnoeic episodes. RSV is the most important cause of bronchiolitis in infants and young children. Other aetiological agents include parainfluenza, adenovirus, rhinovirus and occasionally Mycoplasma. Many cases can be managed in the community, but children may need admission for greater supportive therapy, such as oxygen and intravenous hydration. Risk factors for more severe disease include cyanotic or complicated congenital heart disease, underlying pulmonary disease, prematurity and immunodeficiency due to underlying disease or therapy, and children falling into these categories should be admitted in most cases. Some ver y unwell children may be treated with antivirals, eg ribavirin (Virazole). The monoclonal antibody palivizumab (Synagis) has been used as a prophylactic agent. No vaccines are currently available to prevent RSV. Preventive measures should be taken to reduce the risk of exposure of these children to infected individuals. Particular attention should be paid to hand-washing to reduce transmission if someone in the household is suffering from a URTI. OPAT, which is well established in countries such as USA and Italy, is becoming increasingly widespread within the UK and Ireland and is already widely used by many respiratory departments to manage patients with cystic fibrosis and bronchiectasis. OPAT services are frequently overseen by infectious disease physicians and microbiologists and, in most cases, the care of the patient remains with the hospital rather than the GP. Appropriately selected patients who require, usually long, courses of intravenous therapy can be discharged to their normal place of residence. Antibiotics are administered by a trained district nurse or family member (sometimes the patient him/herself) via a line, and are usually given in the patient's residence, but sometimes at a local community hospital or surgery. This gives patients significantly more freedom and reduces their risks of hospital-associated problems such as infections, deep vein thromboses and institutionalisation. Although GPs are generally not primarily responsible for this aspect of patient care, they may occasionally become involved. They need to be alert to potential complications with the lines, eg infection or blockage, and side-effects from the antibiotics, which can include antibiotic fevers, blood disorders, eg neutropenia, deranged renal or liver function, as well as the possibility that the underlying infection has relapsed. In general referral should be directed back to the OPAT team or to the doctors with overall responsibility for the patient. With the increasing emphasis on out-of-hospital care, GPs should expect to be see more patients on intravenous therapy in the community in the future. 25 LRTIs encapsulate a wide range of pathologies caused by a broad spectrum of organisms and need differentiating in order to decide on the most appropriate empirical therapy. CAP is a common infection with significant mortality and, because of the proportion of cases that are due to Strep. pneumoniae, therapy should always include adequate cover against this organism. Most cases of acute bronchitis and exacerbations of COPD are viral in origin and do not require antibiotic therapy. However, certain groups of patients are more vulnerable and antibiotics may be warranted. Lung function, age and premorbid condition should be taken into account when assessing such patients. Preventive measures, such as immunisation against influenza and Strep. pneumoniae, should be considered in at-risk individuals, and smoking discouraged. With the increasing prevalence of hypervirulent strains of C. difficile and increasing rates of antimicrobial resistance, it has never been more important that antibiotics are used appropriately. Local policies should be used to ensure that empirical regimens take into account local resistance patterns. A risk/benefit analysis should be performed whenever antibiotics are prescribed and treatment regimens should be revised on the basis of culture results. Antibiotics should not be continued for longer than necessary. Standing Medical Advisory Committee. The path of least resistance. DoH, The Stationery Office Recommendations for the assessment and management of cough in children British Thoracic Society guidelines for the management of community-acquired pneumonia Point-of-care tests for lower respirator y tract infections Health Protection Agency. 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