Unexplained shortness of breath Collapse New onset atrial \201 brillation Signs consisten t with right heart failure Pleural effusion CLINICAL FEATURES 407 Examination of a patient with PE \200 \200 \200 \200 \200 \200 May be normal Tachycardia and tachypnoea are common Atrial \201 brillation Reduced chest movement (due to pain) Pleural rub Classically loud P2 and splitting of the second heart so und, with a gallop rhythm (acute right heart strain) Hypoxia (with hypocapnia due to hyperv entilation, and an increased alveolar \200\223arterial gradient), but PaO2 may be in the no rmal range in young healthy individuals Low-grade fever Signs of DVT (common, in around 25% ) Right heart failure \200\224low cardiac output and raised JVP with reduced BP and perfusi on pressure \200 \200 CHAPTER 39 Pulmonary thromboembolic disease 408 Diagnosis of acute PE The diagnosis of a pulmonary embolism can be dif \201 cult and invol ves a clinical assessment of probability. This takes risk factors, clinical presenta- tion, and clinical signs into account. Investigations are then performed, that may add weight to the clinical decision, rather than being stand-alone diag- nostic tests. Therefore the est imation of the pre-test clinical probability of PE is of vital importance in interpreting t he results of the tests performed. Pre-test clinical probability scoring systems One exampl e is the BTS pre-test clinical probability scoring system, shown in the box below. A standard assessment of pre-test clinical probability might include: \200 (a) Patient has clinical features compatible with PE: \200 \200 \200 Plus 2 other fac tors: \200 \200 (a) plus 1 and 2: HIGH pre-test clinical probability (a) plus 1 or 2: I NTERMEDIATE pre-test clinical probability (a) alone: LOW pre-test clinical probability raised respiratory rate haemoptysis pleuritic chest pain 1. Absence of another reasonable clinical explanation 2. Presence of a major risk factor (s ee box, p 426) \200 \200 The Wells and Geneva pre-test probability scores are similar to the above, but include sepa rate scores for clinical features such as heart rate, haemoptysis, and blood gas estimates (Geneva). Local scoring systems may be in place. These scoring systems should always be use d with the D-dimer result. D-dimer has an important role in diagnosing and excluding PE, an d should only be used with a pre-test clinical probability assessment following careful cli nical evaluation by an experienced clinician. D-dimers are sensi- tive for thromboembolism, but not speci \201 c. They are rarely in the normal range in cases of acute thromboemboli sm, but are not a valid screening test for PE alone. D-dimers are generated as a result of \201 brinolysis, which occurs in many clinical situations, including sepsis, post surgery , pneumonia, neoplasia, in \202 ammatory disease, pregnancy, and advanced age. \200 Only a normal result (which excludes PE) is of clinical value \200 An abnormal result (howeve r high) does not necessarily imply a signi \201 cantly increased probability of PE The sen sitivity ranges from 87% to 99%, depending on the assay used (ELISA (Vidas) or red cell agg lutination (SimpliRED)). Speci \201 city is poorer, around 60 \200\22370% (so a large numb er of false positives) The different assays have different performance characteristics and these should be known before incorporating them into diagnostic algorithms DIAGNOSIS OF ACUTE PE 409 D-dimer testing for excluding PE has been validated as an out-patient test, but not in in-p atient groups A low or intermediate pre-test clinical probability score, combined with a ne gative D-dimer has a 92% sensitivity at excluding PE Modi \201 ed Geneva score Age >65 years 1 point Previous DVT or PE 3 points Surgery or fracture within 1 month 2 points Active malignancy 2 points Unilateral lower limb pain 3 points Haemoptysis 2 points Heart rate 75 \200\22394 bpm 3 points Heart rate >95 bpm 5 points Pain on limb palpation & unilateral oedema 4 points Low probability 0 \200\2233 points Intermediate probability 4 \200\22310 points High probability \211 11 points D-dimer test interpretation \200 A negative D-dimer test reliably excludes PE in patients with a low (SimpliRED) or intermed iate pre-test clinical probability (Vidas). These patients do not need further imaging A ne gative test is unhelpful in those with a high clinical probability and therefore should not be done in this situation A positive result needs further investigation, but does not nece ssarily imply PE The D-dimer becomes less useful the longer the period spent in hospital (i .e. increasing false positives), due to clot formation at vene- puncture sites, venous stas is due to bed rest, etc. Assessment and documentation of pre-test clinical probability in PE is paramount. This enab les accurate clinical assessment, and may obviate the need for imaging. An alternative explanation should be sought when PE is excluded. CHAPTER 39 Pulmonary thromboembolic disease 410 Investigations \200 ECG Non-speci \201 c changes are frequent. Most commonly sinus tachycardia. Atrial \201 brillation, right bundle branch block, anterior T-wave inversion (indicating R ventricular strain) are common. The S1Q3T3 pattern is uncommon CXR A good quality departmental CXR is r equired. No speci \201 c fea- tures are characteristic in PE, but it may reveal another pa thology. Small effusions are present in 40% (80% are exudates, 20% transudates). Focal in \201 ltrates, segmental collapse, and a raised hemi-diaphragm can also occur Arterial blood gas may be normal, especially in the young and healthy. Hypoxia and hypocapnia, due to hyp erventilation, with an increased A \200\223a gradient are more common D-dimer (see p 408) T roponin and natriuretic peptides are sensitive markers of right ven- tricular dysfunction a nd early data suggest a raised troponin predicts poorer prognosis CTPA is the gold standard investigation, and is now recommended as the initial imaging technique in suspected non-ma ssive PE. It has a sensitivity of >95%, and may enable an alternative diagnosis to be made if PE is excluded. Advances in imaging mean that a 16-slice multi-detector row scanner can image the entire chest with resolution approaching 1 mm, requiring a breath-hold of less th an 10 s. Emboli can be detected in sixth-order pulmonary vessels, which are so small that t heir clinical relevance is uncertain. CTPA should be performed within 1 h in suspected mass ive PE, and within 24 h of suspected non-massive PE. The sensitivity and speci \201 city o f CTPA depends on the location of the emboli, with lower sensitivity for clot con \201 ned to the segmental or sub-segmental pulmonary vessels compared with more central clot. CTPA needs specialist reporting. \200 In those with a high clinical probability but negative CTPA the options are: \200 PE has been excluded, stop anticoagulation, or Perform further imaging (leg ultrasound, con ventional pulmonary angiogram, venous phase CT to include the legs) In one large prospective multicentre study, with all patients investigated with CTPA and le g ultrasound, those with negative tests and low or intermediate clinical probability were n ot anticoagulated. Only 0.2% had a de \201 nite PE after 3 months of follow-up. Those with negative tests but high clinical probability were investigated further, and PE was identi \201 ed in 5% (Musset D et al. Lancet 2002; 360: 1914). A volume of 100 \200\223150 ml contrast media is required for CTPA, which poses a substanti al risk of nephropathy (in patients with renal insuf \201 ciency and diabetes) and sometim es \202 uid overload (patients with impaired left ventricular function). In these patient s, leg ultrasound and/or isotope lung scanning might be safer \201 rst line investigation s. INVESTIGATIONS 411 Isotope lung scanning (ventilation/perfusion or V/Q scan) \200\224mostly now superseded by CTPA. Some units may just perform the Q (perfusion) part of the scan. May be useful as a \201 rst-line imaging investigation in patients with a normal CXR and with no concurrent ca rdiopulmonary disease, in whom a negative scan can reliably exclude a PE. Scans are reporte d as low, intermediate, or high probability, and the report \200\231s meaning must be inter preted in light of the pre-test clinical probability score. Further imaging is necessary fo r those in whom: \200 \200 The scan is indeterminate There is a discordant scan result and clinical probability. The clinical signi \201 cance of the V/Q scan report is: \200 \200 Normal = no PE Low or intermediate pre-test clinical probability plus low probability scan = PE excluded High pre-test clinical probability plus high probability scan = PE diag- nose d Any other = need further imaging. Other imaging techniques \200 Leg ultrasound \200\224around 70% of patients with a proven PE have a proximal DVT; hence l eg imaging can be used as an alternative to lung imaging in those with clinical DVT. A sing le examination is not adequate to exclude subclinical DVT (venography is more sensitive). I t is safe to withhold anticoagulation in patients with suspected DVT and a single negative leg ultrasound, but these data cannot yet be extrapolated to those presenting with suspecte d PE. If a leg ultrasound is positive in a patient with clinical features of PE, this exclu des the need for further imaging. Up to 50% of patients with a clinically obvious DVT will have a high-probability V/Q scan Conventional pulmonary angiogram is available in a few spe cialist centers only, where catheter fragmentation of large clots may be of therapeutic ben e \201 t. Now mostly superseded by CTPA CT venography is an emerging area. It can be combi ned with CTPA to image the pelvic leg veins simultaneously Echocardiogram is diagnostic in sub-massive and massive PE. The transoesophageal route is more sensitive, enabling visualiz ation of intrapulmonary and intracardiac clot. May give prognostic information Transthoraci c ultrasound is used uncommonly. May show peripheral infarcts with peripheral pulmonary emb oli. CHAPTER 39 Pulmonary thromboembolic disease 412 22 Management of acute massive PE Acute massive PE has a mortality of 20%. 1. Oxygen \200 \224100%, via non-rebreathe mask 2. IV access. Send baseline bloods, including clotting. Pe rform ECG 3. Analgesia if required; consider opiates 4. Management of cardiogenic shock \200\224 \202 uids and inotropes may be required in sub-massive or massive PE to maintain right ventricular \201 lling 5. Start IV heparin unless active GI bleeding or intracerebral hemorrhage: \200 \200 \200 Bolus dose 5000 \200\22310 000 units or 80 IU/kg Maintenance infusion of 1300 IU/h or 18 un its/kg/h Adjust infusion rate until APTT is 1.5 \200\2232.5 \227 control. Check APTT4 \200 \223 6 h after initial bolus and 6 \200\22310 h after any dose change. When APTT is in the therapeutic range, check it daily 6. Investigation to con \201 rm PE depends on the clinical state of patient. Ideally perfo rm urgent echocardiogram and if this is non-diagnostic, perform a CTPA, but not delaying fo r more than 1 h. It may, however, be unwise to move a sick patient to the radiology departm ent for a CTPA. If there is circulatory collapse and the patient is peri-arrest and PE is t he most likely cause, con \201 rmation of the diagnosis should not be sought, but treatmen t prioritized. Remember aortic dissec- tion, cardiac tamponade, and acute MI can mimic PE 7. Thrombolysis if collapsed or hypotensive, if no active GI bleeding or intracerebral hemorrhage: \200 \200 Alteplase 100 mg over 2 h given peripherally Or streptokinase 250 000 units in 30 min with 100 000 units/h for 24 h (plus hydrocortisone to prevent further circulatory instability) O r urokinase 4400 IU/kg in 10 min and 4400 IU/kg/h for 12 h Stop the heparin during thrombol ysis and restart afterwards In cardiac arrest due to suspected massive PE, 50 mg IV altepla se immediately may be life-saving \200 \200 8. Consider liaising with cardiothoracic center to consider embolectomy, particularly if thrombolysis is contraindicated. Low molecular weight heparin (LMWH) is as effective as standard unfrac- tionated intravenou s heparin, and should be given to patients with inter- mediate or a high pre-test clinical probability prior to imaging. Unfractionated heparin should be considered in massive PE (fa ster onset of action) as a \201 rst dose bolus prior to commencement of LMWH. Oral antico agulation should only be commenced once PE is proven, after initial heparin treatment. Targ et INR 2.0 \200\2233.0 (when achieved, heparin can be stopped). Some centers now advocate o ut-patient anticoagulation for PE, as well as DVT. Recent data suggest that this is as safe as in-patient anticoagulation, in a carefully selected population, in centers with a well- established out-patient DVT service. Length of warfarin anticoagulation \200 \200 Temporary risk factor: 4 \200\2236 weeks. This is an area of some debate First episode of i diopathic PE: 3 months is currently recommended, though some still advocate 6 months warfar in treatment INVESTIGATIONS 413 Recurrent idiopathic PE: no guidelines exist; length of treatment depends on individual cir cumstances, with risk of bleeding balanced with risk of recurrent event, and often long-ter m anticoagulation Persisting risk factors: lifelong anticoagulation may be recommended Side-effects \200 \200 The risk of bleeding increases with age and concurrent illness Higher bleeding rate with co ncomitant aspirin use, and previous gastrointestinal bleed Risk of bleeding relates to dura tion and intensity of anticoagulation. Thrombolysis There is emerging evidence to support t he use of throm- bolysis in certain subgroups of patients with PE; however, this is a contr o- versial area, and the risk/bene \201 t analysis of this treatment must always be carefu lly considered. Massive PE causing circulatory collapse. Current BTS guidelines (2003) supp ort the use of early thrombolysis in massive PE. In practice, throm- bolysis is usually giv en to the acutely unwell/peri-arrest patient, when the history and physical \201 ndings a re suggestive of massive PE, in the absence of another reasonable explanation. There is rar ely time for imaging or inves- tigations in this situation. Non-massive PE is more controve rsial. Some evidence now supports the use of intravenous alteplase in addition to IV hepari n in the treatment of haemodynamically stable submassive PE, in association with pulmonary hypertension or right ventricular dysfunction. Current BTS guidelines rec- ommend thromboly sis only for patients with clinically massive PE. Increasing evidence suggests that individ uals with a large clot volume, in the absence of haemodynamic compromise, have better clini cal outcomes with throm- bolysis. This is due to the prevention of chronic thromboembolic d isease, as larger clot volume is a risk factor for this. More data is required. Contraindic ations None absolute; rarely a consideration in the life- threatening situation. Risk of ma jor hemorrhage is 3 \200\2234 times that of heparin, with a higher incidence of bleeding in the elderly. Active bleeding or recent intracerebral bleed are contraindications. Embolect omy Rarely done, and only in life-threatening massive PE. Options include surgical embolect omy (few regional centers only) and mechanical clot fragmentation via right heart catheteri zation. IVC \201 lter placement There is little evidence to show improved survival or red uction in recurrent PE rate with IVC \201 lters, and changing to low molecular weight hep arin may be as effective. IVC \201 lters may, however, be indicated in: \200 \200 \200 \200 Acute VTE in patients with an absolute contraindication to anticoagulation Patients with ma ssive PE who survive (a second PE may be fatal) Recurrent VTE despite adequate anticoagulat ion Post-pulmonary thromboendarterectomy in pulmonary hypertension. Further information Konstantinides S et al. Heparin plus alteplase compared with heparin al one in patients with sub- massisve pulmonary embolism. NEJM 2002; 347: 1143 \200\22350 CHAPTER 39 Pulmonary thromboembolic disease 414 Special circumstances Pregnancy and thromboembolic disease \200 The incidence of DVT PE in pregnancy is 1 in 1000, rising to 2 in 1000 in the puerperium . The risk of PE in pregnancy is greater with increasing maternal age and with increasing g estational age. More PEs occur during pregnancy than after delivery. There is a 20 \200\223 30 times increased risk with Cesarean section, compared with normal vaginal delivery. PE is one of commonest causes of maternal death in pregnancy (1/100 000 pregnancies) D-dimers ar e raised in the normal pregnancy and so are usually unhelpful in the investigation of throm boembolic disease The CTPA whole-body radiation dose is 2 \200\2234 mGy, with an absorbed d ose to the fetus of 0.01 mSv. This equates to a risk of fatal cancer to age 15 of <1 in 1 m illion. The absorbed dose to the breast is 10 mSv (higher in pregnancy). CTPA increases the lifetime breast cancer risk in premenopausal women from 10% to 11.4%, with an even higher risk in pregnancy The V/Q scan whole-body radiation dose is 1.5 \200\2232 mGy, with an abso rbed dose to the fetus of 0.12 mSv. This equates to a risk of fatal cancer to age 15 of 1 i n 280,000. The absorbed dose to the breast is 0.28 mSv The overall radiation risk depends o n the gestation of the fetus and the metabolic activity of the pregnant breast tissue. Ther e is considerable debate as to which imaging technique is best in pregnancy, in terms of ra diation risk to both the mother (including breast tissue) and the fetus. The lowest overall risk favors a Q scan as the \201 rst-line investigation, especially as this young health y population are likely to have normal lungs. Some experts suggest a leg ultrasound \201 rst (see p 64) In those with antenatal thromboembolic disease, low molecular weight heparin (LMWH) is used. Close to delivery, this is changed to unfrac- tionated heparin, as it is e asier to monitor and to reverse its effects. It is unclear whether heparin should be stoppe d or the dose reduced at the time of delivery. LMWH levels can be monitored with anti-Xa le vels There are case reports of successful thrombolysis, catheter-directed thrombolysis, and embolectomy in massive PE, but no relevant trials Warfarin is teratogenic and is contraind icated in pregnancy, although it is safe in breast-feeding Anticoagulation should be contin ued for 6 weeks after delivery or 3 months following initial episode, whichever is longer. SPECIAL CIRCUMSTANCES 415 Thromboembolic disease and the oral contraceptive pill/HRT \200 The OCP, pregnancy, and hormone replacement therapy (HRT) increase the risk of PE, but the incidence of fatal PE is low \200\224estimated at 1/100 000 OCP users, with a median age of 29 Risk of fatal PE is twice as high amongst those taking third-generation pills Previous history of DVT or PE is a contraindication to the OCP Meta-analyzes show a relative risk of VTE of 2.1 in HRT users, which is highest in the \201 rst year of use. \200 Flight prophylaxis for thromboembolic disease \200 For patients with high risk of a PE, i.e. previous VTE, within 6 weeks of surgery, or curre nt malignancy, the 1997 BTS Guidelines recommend low-dose aspirin, low molecular weight hep arin, or formal anticoagula- tion (INR 2 \200\2233) prior to \202 ying For those with mod erate or low risk, graduated or compression stockings with or without pre- \202 ight aspir in is suggested. Future developments Thrombolysis Further research is ongoing regarding the use of thrombol- ysis in non-massive PE and more data are likely in the next few years. Low-intensity warfarin therapy A reduced target INR of 1.5 \200\2232.0 may be used. A study of a cohort of patients treated for up to 4.3 years, following 6 months of standard warfar in therapy for idiopathic venous thromboem- bolism, led to a 48% reduction in recurrent VTE , major hemorrhage, or death compared with placebo (Ridker PM et al, NEJM 2003; 348: 1425). Further information BTS guidelines for the management of suspected acute pulmonary embolism . Thorax 2003; 58: 470 \200\22384 Goldhaber SZ. Seminar: pulmonary embolism. Lancet 2004; 363: 1295 \200\2231305 CHAPTER 39 Pulmonary thromboembolic disease 416 Rare causes Air embolism Air is found within the arterial or venous circulation. Small amou nts of air can be tolerated, but large amounts can lodge in the pulmonary vasculature and c ause mechanical obstruction and death. This is rare. Causes Neck vein cannulation, intrauterine manipulations (such as criminal abortion, where a frothy liquid is passed under pressure into the uterus), bronchial trauma, or barotrauma causing air to enter the pulmonary vein and left heart. Air in the left ventricle causes im pairment to venous \201 lling and subsequent poor coronary perfusion as air enters the co ronary arteries. Diagnosis Arterial air emboli may cause dizziness, loss of consciousness, and convulsions. Air may be seen in the retinal arteries or from transected vessels. Venous air emboli may c ause raised venous pressure, cyanosis, hypotension, tachycardia, syncope, and a \200\230mi ll-wheel \200\231 murmur over the praecordium. Treatment Patients should lie on their right side, with head down and feet up, to allow air to collect and stay at the cardiac apex. From here it can be aspirated via thoracotomy. Am niotic \202 uid embolism is estimated to occur in 1 in 25 000 \200\22380 000 live births. It is the third commonest cause of maternal death, and the most common cause of death in t he immediate post-partum period. Usually catastrophic, 80% of women die, 20 \200\22350% of these in the \201 rst hour. An anaphylactic-type response to amniotic \202 uid entering the circulation is seen. Amniotic \202 uid enters the circulation because of torn fetal mem- branes, which can occur in Cesarean section, uterine or cervical trauma, or uterine ru pture. It has a thromboplastic effect, causing disseminated intravascular coagulation and t hrombi to form in pulmonary vessels. Not all women react in this way to amniotic \202 uid . It is more common in older multiparous mothers, who have had short tumultuous labor, ofte n involving uterine stimulants. Clinically presents with sudden onset respiratory distress, hypoxia, bron- chospasm, cyanos is, cardiovascular collapse, pulmonary oedema, convul- sions, coma, and cardiac arrest. Coa gulopathy with intractable uterine bleeding and uterine atony is seen. Diagnosis is clinical. Fetal debris/cells can be identi \201 ed in blood sampled from the maternal pulmonary artery, but this is not pathognomonic. Treatment is supportive, whilst the thrombi clear from the maternal lungs. Maintain the cir culation with \202 uids and inotropes. Respiratory support with oxygen and ventilation ma y be needed. Correct coagulopathy with fresh frozen plasma and packed cells. Control placen tal bleeding. RARE CAUSES 417 Fat embolism Common pathological \201 nding following long bone fractures. Occurs especia lly with lower limb fractures \200\224pelvis and femur. Commoner in fractures that have not been immobilized. Can also occur after prosthetic joint replacement, cardiac massage, live r trauma, burns, bone marrow transplant, rapid high-altitude decompression, and liposuction . Generally occurs in the young and previously healthy. Presents 24 \200\22372 h post-fract ure. Marrow fat enters the circulation and lodges in the lungs, causing mechanical obstruct ion. Classically presents with hypoxia, coagulopathy, with a transient petechial rash on the nec k, axillae, and skinfolds, and neurological disturbance, such as confusion, disorientation, or sometimes coma. Stable patients may deteriorate with low-grade fever, petechial rash, h ypoxia, and confusion. Jaundice and renal dysfunction are possible. Diagnosis is usually made clinically in a patient with a lower limb fracture presenting wit h tachypnoea and hypoxia. Fat globules can be identi \201 ed in the urine. CXR shows bilat eral alveolar in \201 ltrates. ARDS can develop. Treatment is with early immobilization of fracture, \202 uid replacement, oxygen, and sup portive care. Septic, hydatid, and tumor emboli are also causes. Uterine leio- myosarcoma h as vascular tropism and can invade the inferior vena cava and obstruct the pulmonary arteri es. Teratomas can invade the IVC and pulmonary arteries. This page intentionally left blank 419 Chapter 40 Respiratory infection: bacterial Community-acquired pneumonia (CAP) 420 CAP: clinical features 422 CAP: severity assessment 424 CAP: investigations 426 CAP: management 428 CAP: antibiotics 430 CAP: treatment failure 432 CAP: follow-up 434 Hospital-acquired pneumonia: clinical features 436 Hospital-acquire d pneumonia: management 438 Ventilator-acquired pneumonia (VAP) 440 Aspiration pneumonia 44 2 Aspiration pneumonia: clinical features 444 Lung abscess: clinical features 446 Lung absc ess: diagnosis 448 Lung abscess: management 450 Nocardiosis 452 Actinomycosis 454 Anthrax 4 56 Tularaemia 458 Melioidosis 460 Leptospirosis 462 CHAPTER 40 Respiratory infection: bacterial 420 Community-acquired pneumonia (CAP) Community-acquired pneumonia is a common disease, associ ated with signi \201 cant morbidity and mortality. De \201 nition A syndrome of infection that is usually bacterial with symp- toms and signs of consolidation of part(s) of the lun g parenchyma. This is different to bronchitis (see p 647). Epidemiology \200 CAP is the commonest infectious cause of death and the 6th leading cause of death in the UK and USA (with age-adjusted death rates of between 1 and 24/100 000) Up to 40% of UK adults with CAP require hospital admission. Hospital mortality varies between 5% and 12% A BTS mu lticentre UK study showed that 5 \200\22310% of patients with CAP require ICU admission Mor tality is up to 50% in those admitted to ICU CAP managed in the community has a mortality o f 1%. \200 Pathophysiology The lung and tracheobronchial tree are usually sterile below the level of t he larynx, so an infecting agent must reach this site via a breach in host defenses. This m ay be by micro-aspiration (which occurs in around 45% of healthy individuals overnight), ha ematogenous spread, direct spread from an adjacent structure, inhalation, or activation of previ- ously dormant infection. Etiology Broadly similar pathogens are seen in patients man aged in the community and in hospital. A single pathogen is identi \201 ed in 85% of cases . The proportion of cases with more than one pathogen is unknown. Risk factors for CAP \200 \200 Aspiration Typically caused by anaerobes and Gram-negative organisms Alcoholism and diabete s Typically associated with bacteraemic pneumococcal pneumonia. Anaerobes and mixed infecti ons are more common in alcoholics Oral steroids/immunosuppression Legionella infection may be more common Cigarette smoking is the strongest independent risk factor for invasive pneu mococcal disease in immunocompetent patients COPD Haemophilus in \202 uenzae and Moraxella catarrhalis are more common, and COPD is more common in those with bacterial pneumonia Nur sing home residents have an increased frequency of CAP, with aspiration, Gram-negative orga nisms, and anaerobes more common than in age-matched elderly people. Haemophilus in \202 u enzae is the most common causative organism. Mycoplasma pneumoniae and Legionella are less common. COMMUNITY-ACQUIRED PNEUMONIA 421 Organisms causing community-acquired pneumonia \200 Streptococcus pneumoniae (the pneumococcus) \200\224the most frequently identi \201 ed or ganism, commonest in winter, accounting for two-thirds of all cases of bacteraemic pneumoni a. Previous epidemics in the UK have been associated with overcrowding, e.g. in prisons \200\224 these are now very rare. Legionella pneumophilia \200\224most common in the autumn . 52% are travel-related. Epidemics occur related to water-containing systems in buildings, typically in the Mediterranean Staphylococcus aureus \200\224commonest in winter months. C oincident in \202 uenza infection in 39% of those requiring hospital admission and 50% of those admitted to ICU In \202 uenza \200\224annual epidemics in the winter months, complic ated by pneumonia in 3% of community cases. 10% of those admitted to hospital have coincide nt Staphylococcus aureus infection Mycoplasma pneumoniae \200\224epidemics occur every 4 or 5 years in the UK Chlamydia pneumoniae \200\224epidemics in the community; whether it has a direct pathogenic role, or is an associated infectious agent, is not clear Chlamydia psit taci \200\224infection acquired from birds and animals, with 20% of cases having a history of bird contact. Human-to-human spread may occur. Uncommon Coxiella burnetii (Q fever) \200 \224epidemics in relation to animal sources (usually sheep), but occupational exposure only present in 8%. Uncommon. See p 463 for zoonotic causes of community-acquired pneumonia CHAPTER 40 Respiratory infection: bacterial 422 CAP: clinical features \200 \200 \200 \200 \200 \200 Fever Cough Sputum Shortness of breath Pleuritic chest pain Non-speci \201 c features in t he elderly. May present \200\230off legs \200\231 or with confusion, in the absence of fev er. Examination \200 \200 \200 Raised respiratory rate (may be the only sign in the elderly) Tachycardia Localizing signs on chest examination. Reduced chest expansion on the affected side, with signs consistent w ith consolidation (reduced air entry, with bronchial breathing, reduced percussion note, in creased vocal resonance) and crackles. A normal chest examination makes the diagnosis unlik ely. Diagnosis of CAP is made on the basis of: \200 \200 \200 \200 \200 Symptoms and signs of an acute lower respiratory tract infection New focal chest signs New radiographic shadowing, for which there is no other explanation At least one systemic featu re (e.g. sweating, fevers, aches, and pains) No other explanation for the illness. Most helpful in diagnosis \200 \200 Fever, pleuritic pain, dyspnoea, and tachypnoea Signs on chest examination. Speci \201 c clinical features of pathogens The aetiological agent cannot be accurately pr edicted from the clinical features alone, although some features are more statistically lik ely with one pathogen than another. The exception to this is the presence of chest pain or fever (>39 C) in those admitted to ICU, which predicts a higher likelihood of streptococca l pneumonia. \200 Streptococcus pneumoniae Increasing age, comorbidity (especially cardiovascular), acute ons et, high fever, and pleuritic chest pain Bacteraemic Streptococcus pneumoniae Alcohol, diab etes, COPD, dry or no cough, female Legionella Younger patients, smokers, absence of comorb idity, more severe infection, neurological symptoms, evidence of multisystem disease (e.g. abnormal liver enzymes and raised creatine kinase) Mycoplasma pneumoniae Younger patients, prior antibiotics, less multisystem involvement, but extrapulmonary involvement including h aemolysis, cold agglutinins, hepatitis, skin and joint problems Staphylococcus aureus Recen t in \202 uenza-like illness Chlamydia psittaci Longer duration of symptoms prior to admis sion, headache. \200 CAP: CLINICAL FEATURES 423 Coxiella burnetii (Q fever) Dry cough, high fever, headache, male. animal exposure e.g. she ep and goats Klebsiella pneumoniae Low platelet count and leucopenia, male. Rare causes \200 \200 \200 Acinetobacter Older patients, history of alcoholism, high mortality Streptococcus milleri D ental or abdominal source of infection Streptococcus viridans Aspiration is a risk factor. CHAPTER 40 Respiratory infection: bacterial 424 CAP: severity assessment \200 CAP has a wide range of severity. An assessment of severity enables the most appropriate ca re to be delivered in the most appropriate clinical setting Early identi \201 cation of pa tients at high risk of death allows early decisions about hospital admission and possible n eed for assisted ventilation to be made Assessment of disease severity depends on the exper ience of the clinician; a number of predictive assessment models have been trialed. These s everity models should be regarded as adjuncts to clinical assessment, and regular reassessm ent of the disease is needed. Poor prognostic factors Those with two or more adverse prognostic factors are at high risk of death and should be managed as for severe CAP. \200 \200 \200 Age ( \211 65) Coexisting disease \200\224including cardiac disease, diabetes, COPD, stroke Respiratory rate \211 30/min \200\224this is one of the most reliable predictors of disea se severity Confusion \200\224abbreviated mental test score \211 8 Blood pressure \200\224 systolic \211 90 mmHg and/or diastolic \211 60 mmHg Hypoxaemia \200\224respiratory failur e with PaO2 <8 kPa and the need for assisted ventilation predicts mortality Urea \211 7 mm ol/L Albumin <35 g/L White cell count \200\224a WCC >20 or <4 x 109/L are both predictive R adiology \200\224bilateral or multilobe involvement. In patients admitted to ICU, progressi on of CXR changes is a poor prognostic marker Microbiology \200\224positive blood culture, whatever the pathogen isolated. \200 \200 \200 \200 \200 A commonly used severity assessment score is CURB or CURB-65, which aims to predict morbidi ty and mortality in CAP. The Pneumonia Severity Index (PSI) is an alternative, which may be more sensitive, but is much more complicated, and includes information on comorbid disease and laboratory tests before stratifying patients into 5 risk classes. Ewig \200\231s score is another severity assessment score. CURB-65 score core factors \200 \200 \200 \200 \200 Confusion \200\224new mental confusion de \201 ned (AMTS \211 8) Urea \200\224 \211 7 mm ol/L. Some scores omit this Respiratory rate raised \211 30/min Blood pressure \200\224sys tolic BP \211 90 and/or diastolic BP \211 60 65 age \211 65 The presence of the 4 \200\230core \200\231 CURB factors correlates with mortality: \200 4 factors present gives a mortality of 83%, 3 factors 33%, 2 factors 23%, 8% with one, and 2.4% in the presence of no core factors CAP: SEVERITY ASSESSMENT 425 Low risk of death: age <50, no coexisting disease, CURB score zero patients may be suitable for home treatment Pneumonia severity scores aim to contribute to, rather than supersede, a clinical judgment; they include a potential over-emphasis on age. Abbreviated mental test score (1 point per question, max = 10) Age Date of birth Time (to n earest hour) Year Hospital name Recognition of 2 people (e.g. nurse, doctor) Recall address Date of First World War Name of monarch Count backwards 20 to 1 CHAPTER 40 Respiratory infection: bacterial 426 CAP: investigations General investigations are aimed at con \201 rming the diagnosis, asse ssing disease severity, guiding appropriate treatment, assessing the presence of underlying disease, enabling identi \201 cation of complications, and moni- toring progress. \200 Oxygenation assessment Those with an oxygen saturation of <92% on admission or with feature s of severe pneumonia should have arterial blood gasses measured. The inspired oxygen conce ntration must be documented CXR \200 Consolidation, most commonly in the lower lobes. Also interstitial in \201 ltrates and cav itation Multilobe involvement, more common in bacteraemic pneumo- coccal infection Pleural effusion, more common in bacteraemic pneumococcal infection Lymphadenopathy, uncommon, but most likely with mycoplasma infection Multilobe involvement, cavitation, or spontaneous pne umothorax suggest Staphylococcus aureus infection Upper lobe preponderance suggests Klebsie lla CT chest Unlikely to add additional information. May be useful if the diagnosis is in doubt or the patient is severely ill and failing to respond to treatment in order to exclude abs cess formation, empyema, under- lying malignancy, or other interstitial disease process. Bl ood tests \200 FBC \200\224a white cell count (WCC) >15 x 109 suggests bacterial (particularly pneumococca l) infection. Counts of >20 or <4 indicate severe infection Deranged renal and liver functi on tests can be indicative of severe infection, or point to the presence of underlying dise ase. LFTs may be abnormal, particularly with right lower lobe pneumonia. A raised urea is a marker of more severe pneumonia Metabolic acidosis is associated with severe illness C-rea ctive protein may be useful in management, with high levels being a more sensitive marker o f infection than the white cell count or temperature. Serial measures may be useful in asse ssing response to treatment. \200 Microbiological investigations The microbiological cause for CAP is not found in 25 \200 \22360% of patients and therefore often does not contribute to patient management. Microbio logical investigations can help to aid selection of optimal antibiotics, hence limiting ant ibiotic resistance and the possible problems of Clostridium dif \201 cile associated diarr hea. They also inform public health or infection control teams, aiding in the monitoring of pathogen trends causing CAP over time. CAP: INVESTIGATIONS 427 Blood cultures Recommended for all patients with CAP, ideally before antibiotics are starte d. About 10% of patients with CAP will have positive blood cultures. The early availability of blood culture results (within 24 h of admission) improves outcome. Sputum culture and s ensitivity Useful for those patients who have failed to improve with empirical antibiotic t reatment, and in those with non-severe pneumonia admitted to hospital who are expectorating purulent samples and have not received prior antibiotics. Also useful in severe pneumonia. Not routinely recommended for those treated in the community. Sputum examination is recomm ended for possible tuberculosis in those with weight loss, a persistent cough, night sweats , and risk factors for TB, e.g. ethnic origin, social deprivation Pleural \202 uid (if pr esent) for M, C, & S and pH to exclude empyema (see p 354) Viral and atypical pathogens In severe CAP only Serological testing Paired samples (from within 7 days of the onset of the illness, repeated 7 \200\22310 days later) should be tested together, in those with severe CAP, and in those unresponsive to B-lactam antibi- otics. They are unlikely to guide initia l treatment though. \200 Speci \201 c serological tests \200 Pneumococcal pneumonia \200 Urinary antigen (SpUA) has a sensitivity of 100% and speci \201 city of 60 \200\22390% for invasive pneumococcal disease, and should be tested in all patients with severe CAP Legionnaires \200\231 disease A number of immunological tests exist to aid in the prompt an d accurate diagnosis of Legionella pneumophilia: \200 Urinary antigen detection is about 70% sensitive and about 90% speci \201 c for serogroup A, and rapid results can be obtained early. A positive urinary antigen test correlates with subsequent ITU admission Direct immuno \202 uorescence tests (DIF) \200\224Legionella pne umophilia can be detected on bronchial aspirates Culture is 100% speci \201 c (sputum, end otracheal aspirate, BAL, pleural \202 uid, lung) Serology \200\224antibody levels and PCR are also available Mycoplasma pneumonia \200 