VENTILATOR-ACQUIRED PNEUMONIA (VAP) 441 Non-bronchoscopic airway sampling, e.g. blind bronchial sampling of lower respiratory tract secretions, is less sensitive and speci \201 c than bronchoscopic sampling. It does not n eed an expert operator, and is cheaper Serial sampling is favored in some units. Regular no n-invasive serial airway sampling may aid early diagnosis of VAP. It needs careful interpre tation, as the microbiology of the respiratory tract changes over time in critically ill me chanically ventilated patients Tracheal aspiration samples are easy to obtain, but non-spec i \201 c in diagnosing VAP, as upper airway colonization is very common Additional sources of fever are common in ventilated patients, including infected lines, si nusitis, urinary tract infection, and pseudomembranous colitis, and may warrant further inv estigation. Antibiotic treatment Problems with the emergence of resistant bacteria mean that empirical treatment with antibiotics is used less com- monly. Local policies are often in place and a dvice should always be sought from microbiology. The most common drug resistant pathogens a re P. aeruginosa, MRSA, Acinetobacter spp. and Klebsiella spp. Delay in com- mencing antibi otics is associated with a poorer outcome. Risk factors for resistant organisms include: \200 \200 \200 \200 \200 Hospitalization in the previous 90 days Nursing home residence Current hospital admission > 5 days Mechanical ventilation >7 days Prior broad-spectrum antibiotic use (e.g. third-gener ation cephalo- sporin) High frequency of local antibiotic resistance. Antibiotics should be chosen on the basis of: \200 \200 \200 Recent antibiotic treatment Local policy and known local \202 ora Culture data. Antibiotics should cover anaerobes and MRSA, Legionella (if long hospital stay), Pseudomona s aeruginosa, and Acinetobacter. Length of treatment depends on the clinical response. Patients with P. aeruginosa infection have been shown to have a greater risk of recur- rence following discontinuation of antibi otics at 8 days. Failure to respond should lead to a change of antibiotics, and a search fo r additional infection or another cause for the radiographic in \201 ltrate. Further cultu res should be sent. CHAPTER 40 Respiratory infection: bacterial 442 Aspiration pneumonia De \201 nition Pneumonia that follows the aspiration of exogenous mat erial or endogenous secretions into the lower respiratory tract. Epidemiology Aspiration pn eumonia is the commonest cause of death in patients with dysphagia due to neurological diso rders and is the cause of up to 20% of pneumonias in nursing home residents. It occurs in a bout 10% of patients admitted to hospital with a drug overdose. Pathophysiology Micro-aspir ation is common in healthy individuals, but for an aspiration pneumonia to occur, there mus t be compromise of the normal defenses protecting the lower airways (i.e. glottic closure, cough re \202 ex), with inoculation of the lower respiratory tract of a signi \201 cant a mount of material. Most pneumonias are a result of aspiration of micro- organisms from the oral cavity or nasopharynx. Situations predisposing to aspiration pneumonia \200 Reduced conscious level (cough re \202 ex and impaired glottic closure) \200 \200 \200 \200 \200 Dysphagia \200 \200 Alcohol Drug overdose Post-seizure Post-anesthesia Massive CVA Motor neuron disease Following a neurological event; those with impaired swallow re \202 e x post-CVA are seven times more likely to develop a pneumonia than those in whom the gag re \202 ex is unimpaired Upper gastrointestinal tract disease \200 \200 Surgery to the stomach or esophagus Mechanical impairment of glottic or cardiac sphincter c losure, e.g. tracheostomy, nasogastric feeding, bronchoscopy Pharyngeal anesthesia Increased re \202 ux \200 Large volume vomiting \200 Large volume nasogastric feed \200 Feeding gastrostomy \200 Recumbent position Nursing home residents \200 The risk of aspiration is lower in those without teeth, who receive aggressive oral hygiene There is a higher incidence of silent aspiration in the otherwise healthy elderly High cor relation between volume of aspirate and the risk of developing pneumonia. This page intentionally left blank CHAPTER 40 Respiratory infection: bacterial 444 Aspiration pneumonia: clinical features Three pulmonary syndromes result from aspiration. T he amount and nature of the aspirated material, the site and frequency of the aspiration, a nd the host \200\231s response to it will determine which pulmonary syndrome occurs. 1. Chemical pneumonitis This is aspiration of substances toxic to the lower airways, in the absence of bacterial infection. This causes a chemical burn of the tracheobronchial tree causing an intense parenchymal in \202 ammatory reaction, with release of in \202 ammatory mediators, that may lead to ARDS . Animal studies show that an inoculum with a pH <2.5, of relatively large volume (about 25 mL in adults) is needed to initiate an in \202 ammatory reaction. Animal models show rapi d pathological changes within 3 min, with atelectasis, pulmonary haemor- rhage, and pulmona ry oedema. (This was \201 rst described by Mendelson, referring to the aspiration of ster ile gastric contents and its toxic effects. The original case series was in obstetric anest hesia.) Clinical features \200 \200 \200 Rapid onset of symptoms, with breathlessness (within 1 \200\2232 h) Low-grade fever Severe hypoxaemia and diffuse lung in \201 ltrates involving dependent seg- ments CXR changes wit hin 2 h. Treatment \200 If aspiration is observed \200\224suction and/or bronchoscopy to clear aspirated secretions or food. This may not prevent chemical injury from acid, which is similar to a \202 ash burn Support of cardiac and respiratory function \200\224with intravenous \202 uids, oxyg en ventilation Steroids \200\224controversial. No bene \201 t has been shown in human s tudies, but there is some evidence to support their early use in ARDS Antibiotics \200\224u sually given, even in the absence of evidence of infection, because secondary bacterial inf ection is common, and may be a contributing or primary factor in the aspiration. Acid-damag ed lung is more susceptible to the effects of secondary bacterial infection; up to 25% will develop secondary bacterial infection. Activity against Gram-negative and anaerobic organi sms is needed, e.g. cefuroxime plus metronidazole, or penicillin plus clindamycin. 2. Bacterial infection Aspiration of bacteria normally resident in the upper airways or sto mach. The normal bacterial \202 ora are anaerobes, in a host susceptible to aspiration, a nd less virulent than the bacteria causing CAP. ASPIRATION PNEUMONIA: CLINICAL FEATURES 445 Clinical features depend on the infecting organism: \200 Cough, fever, purulent sputum, b reathlessness \200 The process may evolve over weeks and months, rather than hours \200 May be more chronic, with weight loss and anemia \200 Absence of fever or rigors \200 Foul smelling sputum \200 Periodontal disease \200 Involvement of dependent pulmonary l obes \200 Anaerobic bacteria are more dif \201 cult to culture, so may be present, but n ot identi \201 ed in microbiological culture May present with later manifestations, e.g. e mpyema, lung abscess. Major pathogens are Peptostreptococcus, Fusobacterium nucleatum, Prevotella, and Bacteroide s spp. Mixed infection is common. Treatment \200 Antibiotics, to include anaerobic cover, e.g. co-amoxiclav or metronida- zole plus penicill in Swallow assessment/neurological review if no obvious underlying cause found. 3. Mechanical obstruction Aspiration of matter that is not directly toxic to the lung may l ead to damage by causing airway obstruction or re \202 ex airway closure. Causative agents include: \200 \200 \200 \200 \200 Saline Barium Most ingested \202 uids, including water Gastric contents with a pH >2.5 Me chanical obstruction, such as occurs in drowning, or those who are unable to clear a potent ial inoculum, e.g. neurological de \201 cit, impaired cough re \202 ex, reduced conscious level Inhalation of an object, with the severity of the obstruction depending on the size and site of the aspirated particle. This is commoner in children, but does occur in adults, e.g. teeth, peanuts. Treatment \200 \200 Tracheal suction No further treatment is needed if no CXR in \201 ltrates. CHAPTER 40 Respiratory infection: bacterial 446 Lung abscess: clinical features De \201 nition A localized area of lung suppuration leadin g to necrosis of the pulmonary parenchyma, with or without cavity formation. Lung abscesses may be single or multiple, acute or chronic (>1 month), primary or secondary . They may occur spontaneously, but, more com- monly an underlying disease exists. Lung abs cess is now rare in the devel- oped world, but has a high mortality of 20 \200\22330%. They are most common in alcoholic men aged >50. Pathophysiology Most are the result of aspirati on pneumonia. Predisposing factors for abscess are those for aspiration pneumonia (p 442). \200 \200 \200 \200 \200 Dental disease Impaired consciousness \200\224alcohol, post-anesthesia, dysphagia Diabetes Bronchial carcinoma (with bronchial obstruction) Secondary to pneumonia (cavitation occurs in about 16% of Staphylococcus aureus pneumonia) Immunocompromise \200\224abscesses due to Pneumocystis jiroveci (PCP), Cryptococcus neoformans, Rhodococcus species, and fungi in HIV positive patients Septic embolization (right heart endocarditis due to Staphylococcus aure us in intravenous drug abusers). The bacterial inoculum reaches the lung parenchyma, often in a dependent lung area. Cavitat ion occurs when parenchymal necrosis leads to commu- nication with the bronchus, with the e ntry of air and expectoration of necrotic material, leading to the formation of an air \202 uid level. Bronchial obstruction leads to atelectasis with stasis and subsequent infec tion, which can predispose to abscess formation. Presentation \200 \200 \200 \200 \200 \200 Often insidious onset Productive cough, haemoptysis Breathlessness Fevers Night sweats Non- speci \201 c feature of chronic infection \200\224anemia, weight loss, malaise (especially in the elderly) Foul sputum or purulent pleural \202 uid. Lemierre \200\231s syndrome (necrobacillosis) Jugular vein suppurative thrombophle- bitis. This is a rare pharyngeal infection in young adults, most commonly due to the anaerobe Fuso bacterium necrophorum. It presents with a clas- sical history of painful pharyngitis, in th e presence of bacteraemia. Infection spreads to the neck and carotid sheath, often leading to thrombosis of the internal jugular vein. This may not be obvious clinically (neck vein U SS or Doppler may be needed). Septic embolization to the lung with subse- quent cavitation leads to abscess formation. Empyema and abscesses in the bone, joints, liver, and kidneys c an complicate. This page intentionally left blank CHAPTER 40 Respiratory infection: bacterial 448 Lung abscess: diagnosis The diagnosis is usually made from the history along with the appea rance of a cavity with an associated air- \202 uid level on CXR. Investigations \200 Microbiological culture, ideally before commencing antibiotics. Useful to exclude tuberculo sis \200 Blood cultures \200 Sputum or bronchoscopic specimen (BAL or brushings rarely needed) Transthoracic percutaneous needle aspiration (CT- or ultrasound- guided) may provid e samples. Risk of bleeding, pneumothorax, and seeding of infection to pleural space, if ab scess not adjacent to the pleura In practice, blood cultures and sputum microbiology usually suf \201 ce. Samples are usual ly only obtained by more invasive means if appropriate antibiotics are not leading to an ad equate clinical response. \200 Imaging \200\224exclude aspirated foreign body, underlying neoplasm, or bronchial stenosis and obstruction \200 CXR may show consolidation, cavitation, air- \202 uid level (if the patient is unwell, the CXR is likely to be taken in a semi-recumbent position, so an air- \202 uid level may not be visible). 50% of abscesses are in the posterior segment of the right upper lobe, or the apical basal segments of either lower lobe CT is useful if the diagnosis is in doubt and c annot be con \201 rmed from the CXR appearance, or if the clinical response to treatment i s inadequate. It can also help to de \201 ne the exact position of the abscess (which may be useful for physiotherapy, or if surgery is being considered \200\224rarely needed) CT also is useful to differentiate an abscess from a pleural collection \200\224a lung absc ess appears as a rounded intrapulmonary mass, with no compres- sion of adjacent lung, with a thickened irregular wall, making an acute angle at its contact with the chest wall. An em pyema typically has a \200\230lenticular \200\231 shape and compresses adjacent lung, whic h creates an obtuse angle as it follows the contour of the chest wall. CT can determine the presence of obstructing endobronchial disease, due to malignancy or fo reign body, and may be useful in de \201 ning the extent of disease in a very sick patient who has had signi \201 cant haemoptysis. Even with CT, differentiating an abscess from a cavitating malignancy can be very dif \201 cult (no radiological features differentiate th em). LUNG ABSCESS: DIAGNOSIS 449 Microbiology Commonly mixed infection, usually anaerobes. \200 The most common organisms are those colonizing the oral cavity and gingival crevices \200 \224Peptostreptococcus, Prevotella, Bacteroides, and Fusobacterium spp Aerobes \200\224Stre ptococcus milleri, Staphylococcus aureus, Klebsiella spp., Streptococcus pyogenes, Haemophi lus in \202 uenzae, Nocardia Non-bacterial pathogens are also reported \200\224fungi (Aspe rgillus, Cryptococcus, Histoplasma, Blastomyces) and Mycobacteria Opportunistic bacteria, Aspergillus. infections in immunocompromised \200\224Nocardia, Myco- Differential diagnosis of a cavitating mass, with or without an air- \202 uid level \200 \200 \200 \200 Cavitating carcinoma \200\224primary or metastatic Cavitatory tuberculosis Wegener \200\231 s granulomatosis Infected pulmonary cyst or bulla (can produce a \202 uid level, usually thinner walled) Aspergilloma Pulmonary infarct Rheumatoid nodule Sarcoidosis Bronchiectasis . \200 \200 \200 \200 CHAPTER 40 Respiratory infection: bacterial 450 Lung abscess: management Antibiotics to cover aerobic and anaerobic infection, including -lactamase inhibitors, e.g. co-amoxiclav and clindamycin. Long courses are needed. Risk of Clostridium dif \201 cile diarrhea. \200 \200 \200 Infections are usually mixed, therefore antibiotics to cover these Metronidazole to cover a naerobes No data to guide length of treatment. Common practice would be 1 \200\2232 weeks i ntravenous treatment, with a further 2 \200\2236 weeks oral antibiotics, often until out-pa tient clinic review. Drainage Spontaneous drainage is common, with the production of purulent sputum. This can b e increased with postural drainage and physiotherapy. \200 \200 No data to support use of bronchoscopic drainage Percutaneous drainage with radiologically placed small percutaneous drains for peripheral abscesses may be useful in those failing to respond to antibiotic and supportive treatment. These are usually placed under ultrasound guidance (though are rarely indicated). Surgery is rarely required if appropriate antibiotic treatment is given. It is usually rese rved for complicated infections failing to respond to standard treatment after at least 6 w eeks of treatment. May be needed if: Very large abscess (>6 cm diameter) Resistant organisms Hemorrhage Recurr ent disease Lobectomy or pneumonectomy is occasionally needed if severe infection with an a bscess leaves a large volume of damaged lung that is hard to sterilize. \200 \200 \200 \200 Complications Hemorrhage (erosion of blood vessels as the abscess extends into the lung par enchyma). This can be massive and life- threatening (see p 43), and is an indication for ur gent surgery. If slow to respond, consider: \200 Underlying malignancy \200 Unusual microbiology, e.g . mycobacterium, fungi \200 Immunosuppression \200 Large cavity (>6 cm) may rarely requ ire drainage \200 Non-bacterial cause e.g. cavitating malignancy, Wegener \200\231s granu lomatosis Other cause of persistent fever, e.g. Clostridium dif \201 cile diarrhea, antibi otic-associated fever. Prognosis 85% cure rate in the absence of underlying disease. Mortality is reported as high as 75% in immunocompromised patients. The prognosis is much worse in the presence of under lying lung disease, with increasing age and large abscesses (>6 cm) with Staphylococcus aur eus infection. This page intentionally left blank CHAPTER 40 Respiratory infection: bacterial 452 Nocardiosis De \201 nition Nocardia are Gram-positive, partially acid-fast, aerobic bacill i that form branching \201 laments. They are found in soil, decaying organic plant matter , and water, and have been isolated from house dust, garden soil, and swimming pools. Infec tion typically follows inhalation, although percutaneous inoculation also occurs. The Nocar dia asteroides species complex accounts for the majority of clinical infections. Consider Nocardia infection when soft tissue abscesses and/or CNS manifestations occur in t he setting of a pulmonary infection. The com- bination of respiratory, skin, and/or CNS inv olvement may lead to a misdiagnosis of vasculitis, and the respiratory manifestations may m imic cancer, tuberculosis, or fungal disease. Epidemiology Nocardia occurs worldwide and the frequency of subclin- ical exposure is unkno wn. Clinically apparent infection is rare, and usually occurs in patients with immunocompro mise (hematological malignancy, steroid therapy, organ transplant, diabetes, alcoholism, an d HIV infection, especially IV drug users) or pre-existing lung disease (particularly pulmo - nary alveolar proteinosis, tuberculosis). Infection also occurs in apparently healthy peo ple (10 \200\22325% of cases). Nosocomial infection and disease out- breaks have been repor ted. Clinical features Pulmonary disease \200 \200 The lung is the most common site of involvement Patients typically present with productive cough, fever, anorexia, weight loss, and malaise; dyspnoea, pleuritic pain, and haemoptysis may occur, but are less common Empyema occurs in up to a fourth of cases, and direct intra thoracic spread causing pericarditis, mediastinitis, rib osteomyelitis, or SVCO is also rep orted Extrapulmonary disease \200 \200 Dissemination from the lungs occurs in 50% of patients Central nervous system is the most c ommon site of dissemination, occurring in 25% of pulmonary nocardiosis cases. Single or mul tiple abscesses occur, and may be accompanied by meningitis Other sites include the skin an d subcutaneous tissues, kidneys, bone, joints and muscle, peritoneum, eyes, pericardium, an d heart valves. Investigations \200 Identi \201 cation by smear and culture is the principal method of diagnosis. Nocardia gro w on routine media usually within 2 \200\2237 days, although more prolonged culture (2 \200 \2233 weeks) may be required Direct smear of appropriate specimens (e.g. aspirates of absce sses, biopsies) is highly sensitive and typically shows Gram-positive beaded branching \201 laments, which are usually acid-fast on modi \201 ed ZN stain. Examination of BAL \202 uid may also be diagnostic NOCARDIOSIS 453 Sensitivity testing of isolates and identi \201 cation to species level is done by referen ce laboratories Biopsies typically show a mixed cellular in \201 ltrate; granulomata occur rarely, and may result in misdiagnosis as tuberculosis or histoplasmosis CXR and CT may de monstrate parenchymal in \201 ltrates, single or multiple nodules (sometimes with cavitati on), or features of pleural infection Sputum smear is usually unhelpful. Sputum culture has a greater yield, but Nocardia growth may be obscured in mixed cultures. The signi \201 - cance of Nocardia growth on sputum culture in asymptomatic patients is unclear; it may repr esent contamination or colonization in the setting of underlying lung disease Blood culture s are almost always negative, although Nocardia bacter- aemia may occur in the setting of p rofound immunocompromise Consider MRI of the brain to exclude asymptomatic CNS involvement in patients with pulmonary nocardiosis. Management \200 \200 Discuss treatment with an infectious diseases specialist Drug treatment choices include sul phonamides/co-trimoxazole, mino- cycline, imipenem, cefotaxime, ceftriaxone, or amikacin. S ulpha drugs, in particular co-trimoxazole, have traditionally been the mainstay of therapy. Imipenem and amikacin combination therapy has been shown to be active in vitro and in anim al models, and is recommended for pulmonary nocardiosis and for very ill patients. Extended spectrum cephalosporins such as ceftriaxone and cefotaxime have the advantages of good CNS penetration and low toxicity Optimal treatment duration is unclear: typically given for 6 months in non-immunocompromised patients, and for 12 months or longer for CNS involvement o r immunocompromised patients Surgery may be required for abscess drainage. Prognosis Clinical outcome is dependent on the site and extent of disease and on underlying host factors. Disease remissions and exacerba- tions are common. Cure rates are approximat ely 90% in pleuropulmonary disease, and 50% in brain abscess. Mortality of Nocardia infecti on is gener- ally low, although it approaches 50% in cases of bacteraemia. Further information Saubolle MA, Sussland D. Nocardiosis: review of clinical and laboratory experience. J Clin Microbiol 2003; 41: 4497 \200\223501 Lerner PI. Nocardiosis. Clin Inf Dis 1996; 22: 891 \200\223905 CHAPTER 40 Respiratory infection: bacterial 454 Actinomycosis De \201 nition Actinomycosis is caused by a group of anaerobic Gram- positiv e bacilli, of which Actinomyces israelii is the commonest. These organisms are present in t he mouth, gastrointestinal tract, and vagina. Clinical infection may follow dental procedur es or aspiration of infected secretions. Infection is slowly progressive and may disseminat e via the bloodstream or invade tissue locally, sometimes resulting in sinus tract formatio n. Consider this diagnosis particularly in patients with pulmonary disease accompanied by soft tissue infection of the head and neck. The diagnosis of actinomycosis is often unsuspected , and the clinical and radiological features may mimic cancer, tuberculosis, or fungal dise ase. Epidemiology Actinomycosis is rare. It can occur at any age, and is more common in men. Pre disposing factors include corticosteroid use, chemotherapy, organ transplant, and HIV infec tion. Clinical features Thoracic disease Thoracic disease occurs in about 15% of cases. Symptoms of pulmonary involvement are non-speci \201 c, and include cough, chest pain, haemoptysis, fever, anorexia, and weight loss. Chest wall involvement may occur, with sinus formation o r rib infection, and empyema is common. Mediastinal involvement is documented. Extrathoraci c disease Soft tissue infection of the head and neck, particu- larly the mandible, is the c ommonest disease presentation (about 50% of cases). Discharging sinuses may form. Other ext rathoracic disease sites include the abdomen (particularly the ileocaecal region), pelvis, liver, bone, and CNS (manifest as single or multiple abscesses). Investigations \200 CXR and CT appearances are variable, including masses (sometimes with cavitation), parenchy mal in \201 ltrates, consolidation, mediastinal disease, and/or pleural involvement Diagno sis is based on the microscopy and anaerobic culture of infected material. Warn the microbi ology laboratory if the diagnosis is suspected, as speci \201 c stains and culture conditi ons are required. Examination of infected material may reveal yellow \200\230sulfur granul es \200\231 containing aggregated organisms. Sample sputum, pleural \202 uid, and pus fro m sinus tracts; inoculate into anaerobic transportation media, and rapidly transportation t o lab. Endobronchial biopsies have a low sensitivity. Most infections are polymicrobial, wi th accompanying aerobic or anaerobic bacteria. ACTINOMYCOSIS 455 Management \200 \200 Discuss treatment with an infectious diseases specialist Drug treatment choices include pen icillin, amoxicillin, clindamycin, or erythromycin. Administration should initially be intr avenous. Optimal treatment duration is unclear (typically given for 6 \200\22312 months) Su rgery may be required for abscess drainage Monitor response to treatment with serial CT or MRI scans Treat any associated periodontal disease. \200 \200 Prognosis Disease relapse is common if prolonged treatment is not administered. Further information Mabeza GF, Mcfarlane J. Pulmonary actinomycosis. Eur Resp J 2003; 21: 5 45 \200\22351 CHAPTER 40 Respiratory infection: bacterial 456 Anthrax De \201 nition and epidemiology \200 Bacillus anthracis is an aerobic Gram-positive spore-forming bacterium that causes human di sease, principally following either inhalation or cutaneous contact. Spores can survive in soil for many years. Person- to-person transmission does not occur Considerable recent inte rest has focused on the use of anthrax in bioterrorism: \201 ve envelopes containing anth rax spores were sent through the US postal service in 2001 and there were 11 con \201 rmed cases of inhalational anthrax (including 5 deaths) and 7 con \201 rmed cases of cutaneous anthrax. A previous outbreak occurred in Sverdlovsk in the former Soviet Union in 1979, fo llowing the release of spores from a biological weapons plant, and resulted in 68 deaths An thrax infection also occurs very rarely in association with occupational exposure to Bacill us anthracis in animal wool or hides. The majority of occupational cases result in cutaneou s disease, and a diagnosis of inhalational anthrax strongly suggests a bioterrorist attack. Clinical features Inhalational anthrax \200 Incubation period is variable, although in the USA in 2001 it typically ranged 4 \200\2236 days following exposure from opening mail Patients typically experience a prodrome of \202 u-like symptoms such as fever and cough. Gastrointestinal symptoms (vomiting, diarrhea , abdominal pain), drenching sweats, and altered mental status are often prominent symptoms . Breathlessness, fever, and septic shock develop several days later. Haemorrhagic meningit is is a common complication Large haemorrhagic pleural effusions are a characteristic featu re. Cutaneous anthrax \200 Initial symptoms include itch and development of a papule at the infec- tion site. A necrot ic ulcer with a black center and often surrounding oedema subsequently develops. Systemic s ymptoms such as fever and sweats may be present. Investigations \200 Bacillus anthracis grows on conventional media, and is readily cultured if sampling precede s antibiotic treatment; a de \201 nitive diagnosis requires specialized laboratory tests, however Blood tests typically reveal leucocytosis Blood cultures are positive in nearly all cases of inhalational anthrax when taken prior to antibiotic treatment. Staining and cultu re of pleural \202 uid may be diagnostic CXR in inhalational anthrax classically shows a widened mediastinum; pleural effusions and pulmonary in \201 ltrates may be present. CT ma y also demonstrate mediastinal and hilar lymphadenopathy Gram stain and culture of the ulce r is usually diagnostic in cutaneous anthrax, although biopsy is sometimes required. \200 ANTHRAX 457 Management \200 Discuss with infectious diseases and public health specialists if the diagnosis is suspecte d Antibiotic treatment should be administered immediately after taking blood cultures. Rece nt recommendations are for initial treatment with either cipro \202 oxacin or doxycycline IV, in combination with 1 \200\2232 additional antibiotics (choices include clindamycin, va ncomycin, meropenem, or penicillin). Subsequent treatment should be with either cipro \202 oxacin or doxycycline orally for 60 \200\223100 days. Oral treatment alone may be suf \201 cient in cases of mild cutaneous disease Corticosteroid treatment should be considered in patients with menin- gitis, or severe neck or mediastinal oedema Supportive care, inclu ding ventilatory support, treatment of shock with intravenous \202 uids and/or inotropes, and chest tube drainage of large pleural effusions may be needed. Prognosis Inhalational anthrax is associated with a high mortality: 5 of the recent 11 case s in the USA died. The mortality of previously docu- mented cases has been even higher, per haps re \202 ecting a delay or lack of antibiotic treatment. Prophylaxis Recent USA recomm endations advise prophylaxis with oral cipro \202 oxacin or doxycycline for individuals co nsidered to have been exposed to anthrax spores in contaminated areas. A vaccine is availab le, although its value in post-exposure prophylaxis is unknown. CHAPTER 40 Respiratory infection: bacterial 458 Tularaemia De \201 nition and epidemiology Tularaemia is a rare zoonosis caused by infecti on with the Gram negative bacteria Francisella tularensis. Two major subspecies are describ ed: biovar tularensis (type A) is highly virulent and found in North America; biovar palaea rtica (type B) is less virulent, and found in Europe and Asia. Small mammals (particularly rabbits and hares) acquire infection from arthropod bites and act as reservoirs; human infe ction follows inhalation, direct contact with infected rodents, ingestion of contaminated f ood, or arthropod bites. Tularaemia is most frequently encountered in rural areas, followin g activities such as farming and hunting, although laboratory workers are also at risk. The re has been considerable interest in the development of F. tularensis as a biological weapo n, and more recently concerns have arisen as to its possible use in bioterrorism. Clinical features Typically abrupt onset of fever, headache, dry cough and malaise. Development of a tender ulcer and regional lymphadenop- athy ( \200\230ulceroglandular tularaemia \200\231) around an infected arthropod bite is common. Tularaemia pneumonia following infection with type A is char- acterized by cough (productive or dry), breathlessness, and sweating, with often minimal signs on examination; may progress rapidly to respiratory failure and death. Symptoms of pneumonia are milder after infection with type B. Investigations \200 Serology is the principal method of diagnosis, although PCR-based techniques are increasing ly used F. tularensis may be identi \201 ed in culture of wound specimens, although the la boratory should be warned \200\224type A is suf \201 ciently virulent for some laboratorie s not to perform culture. Sputum cultures may be diagnostic CXR may demonstrate parenchymal in \201 ltrates, often progressing to lobar consolidation. Pleural effusions, hilar lymph adenopathy, and lung abscess may occur. Management \200 \200 Discuss treatment with an infectious diseases specialist Drug treatment choices include str eptomycin or gentamicin for 10 days. Doxycycline or chloramphenicol are alternatives, altho ugh treatment failure rates are higher and a course of 14 days is recommended In the settin g of a large-scale outbreak (e.g. following use in bioterrorism), doxycycline or cipro \202 oxacin may be used for treatment or following exposure. Prognosis Mortality is 1 \200\2232% from type A; type B is benign in humans. Further information Tarnvik A, Berglund L. Tularaemia. Eur Resp J 2003; 21: 361 \200\22373 This page intentionally left blank CHAPTER 40 Respiratory infection: bacterial 460 Melioidosis De \201 nition and epidemiology Melioidosis is caused by Burkholderia pseudoma llei, a Gram-negative bacillus that is found in soil and water in Southeast Asia, northern Australia, China, and India; clinical disease is par- ticularly common in Thailand, where i t may account for up to a third of all pneumonia deaths. Infection is thought to follow ent ry via skin abrasions or inhalation, and pneumonia is the most common clinical presentation . Most cases represent recent infection; reactivation of infection is rare but can occur ma ny years after exposure. Risk factors for melioidosis include diabetes, alcohol excess, ren al disease, and chronic lung disease (including cystic \201 brosis). Consider melioidosis in returning travelers from Asia or Australia with community-acquired pneumonia or a subacute/chronic \200\230tuberculosis- like \200\231 respiratory illness. Clinical features include: \200 Acute septicaemic melioidosis Patients present acutely unwell with a severe pneumonia and w idespread nodular consolidation on CXR, may progress rapidly to death Localized subacute me lioidosis Subacute cavitating lobar (often upper) pneumonia, mimicking tuberculosis Chronic suppurative melioidosis Chronic lung abscess empyema; suppurative infection may involve other organs, including skin, brain, joints, bones, liver, spleen, kidney, adrenal, prosta te, lymph nodes Diagnosis Identi \201 cation by culture is the principal method of diagnosis. Blood cul- t ures may be diagnostic; alert the laboratory to the possibility of this infec- tion. ELISAs are relatively insensitive. Management \200 B. pseudomallei is resistant to multiple antibiotics. Treat with high-dose IV ceftazidime o r meropenem for at least 10 \200\22314 days (longer if severe pulmonary disease or organ ab scesses), then oral antibiotic (e.g. co-trimoxazole alone or in combination with doxycyclin e) for at least 12 weeks to ensure eradication. Supportive care, with ITU admission for sep tic shock or severe pneumonia. Prognosis Documented mortality rates range 19 \200\22346%. Further information Currie BJ. Melioidosis: an important cause of pneumonia in residents of and travelers returned from endemic regions. Eur Resp J 2003; 22: 542 \200\22350 This page intentionally left blank CHAPTER 40 Respiratory infection: bacterial 462 Leptospirosis De \201 nition and epidemiology Leptospirosis is a zoonosis trans- mitted fr om water or soil contaminated with urine of infected animals (e.g. rats, dogs, cats, pigs, cattle, hamsters, bats) through skin abrasions or mucosa. Present worldwide, more common in tropical countries, but well described in UK. Individuals most at risk in the UK include f armers, vets, sewage workers, returning travelers from the topics, military personnel, and canoeists. Incidence peaks in spring/summer. In the tropics, epidemics may occur following storms or \202 oods. Consider leptospirosis in all patients with diffuse alveolar hemorrhage, and in at-risk ind ividuals with pneumonia or ARDS. Clinical features Disease manifestations are highly variable, ranging from asymptomatic inf ection to multi-organ failure, pulmonary haemor- rhage, and death. Patients may present sol ely with pulmonary haemor- rhage, without other features of Weil \200\231s disease. Manifes tations include: \200 Acute (anicteric) leptospirosis Self-limiting \202 u-like illness; myalgia, rash and asep tic meningitis may occur Weil \200\231s disease (icterohaemorrhagic fever) Classic form of leptospirosis. Features include fever, myalgia, conjunctival hemorrhage, rash, jaundice/ he patic failure, renal failure, coagulopathy and thrombocytopaenia, shock, myocarditis/cardia c arrthymias Pulmonary disease Occurs in at least a third of hospitalized patients with acu te leptospirosis or Weil \200\231s disease. Manifestations include mild symptoms/signs (cou gh, wheeze, and crackles), pneumonia, pulmonary oedema secondary to myocarditis, and ARDS o r fulminant alveolar hemorrhage syndrome. Investigations \200 Serology con \201 rms the diagnosis and is performed in a single Leptospira Reference Unit in the UK. Both ELISA and microscopic agglutination tests may be performed CXR and CT typi cally demonstrate patchy consolidation and ground- glass shadowing, commonly bilateral with lower lobe predominance. Management \200 Discuss treatment with infectious diseases and renal specialists. Antibiotic choices includ e penicillin, ceftriaxone, or doxycycline Ventilatory support required for alveolar hemorrh age and ARDS Ensure adequate hydration; blood products may be required High-dose glucocorti coids are occasionally used, although there is no convincing evidence of bene \201 t. Plas ma exchange and desmopressin infusions have been tried. \200 \200 LEPTOSPIROSIS 463 Prognosis Acute leptospirosis typically resolves spontaneously after about 14 days. Severe pulmonary disease can progress very rapidly (over hours), with reported mortality rates app roaching 50%. Differential diagnosis of zoonotic microbial causes of community-acquired pneumonia (with e xposures) \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 Avian in \202 uenza virus (birds, animals) Bacillus anthracis (anthrax; animals) Brucellos is (animals) Chlamydia psittaci (psittacosis; poultry, birds) Coxiella burnetii (Q fever; p arturient cats, cattle, sheep, goats, rabbits) Cryptococcus neoformans (birds) Francisella tularensis (tularaemia; rabbits, cats, rodents) Hantavirus (rodents, the Americas) Histopla sma capsulatum (histoplasmosis; birds or bats, the Americas) Leptospirosis (water contamina ted with infected animal urine) Pasteurella multocida (pasteurellosis; animals, birds) Rick etsia rickettsii (Rocky mountain spotted fever; tick bite or exposure to tick-infested habi tats, USA) Yersinia pestis (pneumonic plague; rodents, cats) This page intentionally left blank 465 Chapter 41 Respiratory infection: fungal Aspergillus lung disease: classi \201 cation 466 Atopic allergy to fungal spores 467 Asthm a and positive IgG precipitins to Aspergillus 467 Bronchopulmonary aspergillosis 468 Invasi ve aspergillosis 470 Semi-invasive aspergillosis 472 Aspergilloma/mycetoma 474 Pneumocystis pneumonia (PCP): diagnosis 476 PCP: treatment 478 Endemic mycoses 480 Histoplasmosis 480 B lastomycosis 482 Coccidioidomycosis 483 Paracoccidioidomycosis 483 Other fungi: cryptococco sis 484 Candidal pneumonia 485 466 CHAPTER 41 Respiratory infection: fungal Aspergillus lung disease: classi \201 cation Types of disease Aspergillus fumigatus and ot her Aspergillus molds are ubiquitous fungi that can be isolated from the air in most houses , and this increases with increasing indoor humidity. Inhalation of spores (conidia) can pr oduce a range of diseases, some of which are related to each other, and some of which are n ot. The \201 nding of fungal hyphae (rather than just spores) in the sputum should provok e an assessment. Classi \201 cation 1. IgE-mediated allergic asthma inhaled Aspergillus spores. One of many common antigens provoking airway in \202 ammation and bronchospasm from 2. Exuberant IgE and IgG reaction to Aspergillus in the airways of (usually) asthmatics pro voking mucous plugging with distal consolidation that may \202 it from area to area. This is one of the causes of pulmonary eosi- nophilia 3. Allergic bronchopulmonary aspergillosis (APBA) A probable evolu- tion and progression of (2) in (usually) asthmatics with in \202 ammatory damage to the airways and resultant bro nchiectasis (but no actual invasion of Aspergillus into the airway walls)