Prevention How does HAP arise? HAP to occur microbial pathogens \201 rst need to enter an d then colonize the lower respiratory tract (LRT). Host defenses must then be overcome befo re invasion and infection can ensue. Aspiration of oropharyngeal pathogens represents the m ain route by which bacteria enter the LRT. Oropharyngeal colonization by Gram-negative path ogens upon hospital admission is an independent risk factor for the develop- ment of HAP. General strategies to prevent HAP Most of the strategies that have been studied relate to V AP. \200 Avoid intubation and mechanical ventilation. Consider non-invasive ventilation. In intubate d patients, reduce the likelihood of aspiration of oropharyngeal pathogens by (a) maintaini ng endotra- cheal tube cuff pressures between 25 \200\22330cm water and (b) limiting the us e of sedatives and paralytic agents which depress cough. Avoid nursing the patient in a sup ine position. In one RCT, the risk of HAP was decreased 3-fold when ICU patients were manag ed in the semi-recumbent position (30 \200\22345 ) compared to the supine position. Enco urage oral feeding whenever possible. Enteral feed- ing increases the risk of aspiration of gastric contents although a clear association with HAP has not been demonstrated. If nutri tional supplementation is required, enteral feeding carries fewer risks than parenteral fee ding. Fig. 8.2.1 MRSA pneumonia in a patient on ICU. SDD has been less effective. Many units remain concerned regarding the selection of MDR pat hogens through the routine adoption of SDD. Antibiotic treatment: principles \200 Antibiotic choices are based on the likelihood of MDR pathogens causing the episode of HAP being treated and not based on the severity of disease. Locally relevant microbiological da ta relating to (a) the range of potential pathogens and (b) antimicrobial resistance patter ns are essential to guide local empirical antibiotic choices. A 7-day course of antibiotics is usually adequate unless the patient is not responding to treatment. AUTHOR \200\231S TIP A high standard of infection control (e.g. hand washing) is as importa nt as other measures through reducing environmental sources of infection and the transfer o f pathogens between staff and patients. Importance of optimal empirical treatment Inappropriate empirical antibiotic therapy in ICU patients with nosocomial pneumonia has been shown to be associated with increased mortalit y in various studies. This excess mortality is evident despite antibiotic switching accordi ng to microbiology results, emphasizing the importance of optimal treatment from the outset in these already critically ill patients. Advocates of broad spectrum combination antibiot ics as \201 rst-line empirical therapy, instead of second-line therapy as traditionally e mployed cite reasons related to: \200 \200 Stress bleeding prophylaxis and HAP Antihistamines and antacids are associated with an incr eased risk of HAP in patients managed on ICUs. Sucralfate, which does not decrease intragas tric acidity nor alter gastric volume, has been associated in some trials with a lower inci dence of VAP compared to antacids or antihistamines. In one large trial, sucralfate was ass ociated with an increased risk of clinically signi \201 cant gastrointestinal bleeding com pared to antacids or antihistamines. \200 increasing antibiotic resistance; and the recognition of the importance of optimal (ie. app ropriate and early) empirical therapy. Combination therapy: effect on resistance \200 Animal studies report less emergent antibiotic resistance in Pseudomonas aeruginosa using c ombination antibiotic therapy. There are limited data from human clinical trials demonstrat ing this effect. Where stress ulcer prophylaxis is indicated, sucralfate is prefered to reduce the risk of V AP , but sucralfate should only be used in patients with low to moderate risks of bleeding. Antibiotics and selective decontamination The use of antibiotics for the selective decontam ination of the digestive tract (SDD) has been associated with decreased rates of HAP and in creased ICU survival. In ICUs with endemically high levels of antibiotic resistance, Combination therapy: effect on ef \201 cacy No clinical trial has demonstrated an improved prognosis with combination empirical antibiotic therapy versus monotherapy. CHAPTER 8.2 Hospital-acquired pneumonia 175 Further reading Bonten MJ, Bergmans DC, Ambergen AW, et al. Risk factors for pneumonia, and colonization of respiratory tract and stomach in mechanically ventilated ICU patients. Am J Respir Crit Care Med 1996; 154(5): 1339 \200\22346. Antibiotic duration and emerging resistance The emergence of MDR pathogens in the ICU is as sociated with the volume of antibiotics used. Optimizing the dura- tion of antibiotic treat ment (and hence antibiotic volume) helps limit antibiotic resistance. In a large prospectiv e study of patients with VAP in 51 ICUs in France randomized to 8 versus 15 days of antibio tics: \200 Chastre J, Wolff M, Fagon JY, et al. Comparison of 8 vs 15 days of antibiotic therapy for v entilator-associated pneumonia in adults: a randomized trial. Jama 2003; 290(19): 2588 \200 \22398. No significant differences were noted in (a) 28-day mortality (18.8% vs 17.2% respectively) or (b) microbio- logically documented recurrent pulmonary infection (28.9% vs 26% respecti vely, 2.9% difference; 90% con \201 dence interval (CI) \210\2223.2 to 9.1). MDR pathogen s were implicated less frequently when recurrent infection occurred (42% vs 62% respectivel y, p=0.038). In a subgroup of patients with Pseudomonas aeruginosa infection (a third of pa tients in each arm), recurrent pulmonary infection was more common in the 8-day group compa red to the 15-day group (40.6% vs 25.4% respectively, p=0.09). Cook D, Guyatt G, Marshall J, et al. A comparison of sucralfate and ranitidine for the prev ention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. Can adian Critical Care Trials Group. N Engl J Med 1998; 338(12): 791 \200\2237. de Jonge E, Schultz MJ, Spanjaard L, et al. Effects of selective decon- tamination of diges tive tract on mortality and acquisition of resistant bacteria in intensive care: a randomiz ed controlled trial. Lancet 2003; 362(9389): 1011 \200\2236. Drakulovic MB, Torres A, Bauer TT, et al. Supine body position as a risk factor for nosocom ial pneumonia in mechanically ventilated patients: a randomized trial. Lancet 1999; 354(919 3): 1851 \200\2238. Driks MR, Craven DE, Celli BR, et al. Nosocomial pneumonia in intubated patients given sucr alfate as compared with antacids or histamine type 2 blockers. The role of gastric coloniza tion. N Engl J Med 1987; 317(22): 1376 \200\22382. Which antibiotic to choose? Early-onset HAP, no risk factors for resistance In HAP caused b y non-MDR pathogens, monotherapy with a limited spectrum antibiotic directed against the mo st likely pathogens is adequate: \200 Gastinne H, Wolff M, Delatour F, et al. A controlled trial in intensive care units of selec tive decontamination of the digestive tract with nonabsorbable antibiotics. The French Stud y Group on Selective Decontamination of the Digestive Tract. N Engl J Med 1992; 326(9): 594 \200\2239. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171(4): 388 \200\223416. no prior antibiotics \200\223 consider co-amoxilas or cefuroxime; prior antibiotics \200 \223 consider cefotamine, ceftriacene, a \202 urosamine or pipenacillin/tazobactam. Neuhauser MM, Weinstein RA, Rydman R, et al. Antibiotic resist- ance among gram-negative ba cilli in US intensive care units: impli- cations for \202 uoroquinolone use. Jama 2003; 2 89(7): 885 \200\2238. Late-onset HAP, risk factors for resistance \200 Wunderink RG, Rello J, Cammarata SK, et al. Linezolid vs vancomy- cin: analysis of two doub le-blind studies of patients with methicil- lin-resistant Staphylococcus aureus nosocomial pneumonia. Chest 2003; 124(5): 1789 \200\22397. MDR pathogens are likely to be implicated but the range of pathogens and their susceptibili ty patterns are highly variable. Antimicrobial choice should be based on local data of prev alent pathogens. Wherever possible antibacterial manotherapy should be used instead of comb ination therapy. In most instances, antimicrobials used should be active against Pseudomona s aeruginosa. If MRSA infection is suspected, either vancomycin or linezolid should be adde d. AUTHOR \200\231S TIPS \200 Empirical antibiotic treatment should be reviewed after 48 \200\22372 hours in the light of microbiology results and patient progress. Narrow spectrum antibiotics should be used as s oon as appropriate. Avoid using an antibiotic the patient has been exposed to recently. Ide ally, avoid using the same class of antibiotic as other patients in the same unit. Individu alizing empirical antibiotic treatments leads to increased antibiotic heterogeneity within a unit which may in turn reduce pressure on emergent resistance within a unit. Linezolid ha s antitoxin properties as well as antibacte- rial properties. In comparison to vancomycin i n MRSA pneumonia, it has also been shown in one analysis to offer significantly higher clin ical cure rates (59% vs 35.5% respectively, p<0.01) and higher survival rates (80% v 63.5% respectively, p=0.03) A ATALLA & D DERRY 176 8.3 Aspiration syndromes De \201 nition Aspiration is the inhalation of material into larynx, lower airways, or lun gs and typically requires a defect in swallow or protective airways defenses. Consequences are in \202 u- enced by volume and nature of material aspirated. Not all aspiration will r esult in pneumonia. such protective re \202 exes which predisposes to aspiration. Bedside assessment of swallo w as performed by speech and language therapists has high sensitivity and speci \201 city. Video \202 uoroscopy facilitates dynamic assessment as well as allowing identi \201 cati on of structural lesions seen with more traditional contrast swallowing studies. Technicium labeled colloids may be instilled down nasogastric (NG)/gastros- tomy (PEG) feeding tubes to demonstrate re \202 ux and aspi- ration. However all of these techniques are limited by the fact that aspiration may not occur consistently. Various tests have been used to ident ify gastric contents in sputum: food dyes; glucose dipsticks after high sugar feeds; amylas e and lipid laden macrophages. Of these methylene blue dye added to NG or PEG feeds has fou nd most wide- spread use. Distinction of aspiration from mere gastro- oesophageal re \202 ux may be dif \201 cult without bronchoscopic sampling. Mucosal oedema or erythema at bron choscopy are further pointers to gastric aspiration. Certain presentations should increase the suspicion of aspiration, including indolent anaerobic pneumonias, lung abscesses and re current pneumonias. Epidemiology Incidence of aspiration pneumonia is unknown as cases classi \201 ed as CAP m ay result from silent or unwitnessed aspiration. Estimates suggest aspiration accounts for 5 \200\22310% of CAP and up to 20% of pneumonias in care home residents. KEY FACTS A high index of suspicion is required in cases of com- munity and hospital acquir ed pneumonia. Diagnosis of aspiration has implications for acute treat- ment and management of future risk. Pathophysiology Radionucleotide studies have suggested that up to half of healthy adults ha ve micro-aspiration during sleep without apparent adverse effect. Development of pathologic al con- sequences is in \202 uenced by: \200 integrity of protective upper airways defenses: cough re \202 ex, mucocillary transportati on; integrity of host immune response: cellular immunity, nutritional status; nature and vo lume of material aspirated; extent of lung affected; colonization of aspirate and bacterial virulence. \200 \200 Aspiration of saliva may have signi \201 cant pathological con- sequences as colonization of the oropharynx by virulent bacteria is common in hospitalized or elderly institutional- ised patients. Speci \201 c factors increasing risk of aspiration \200 Neurological: reduced GCS including alcohol and drug intoxication, sedating drugs and gener al anesthesia; impaired swallow post stroke; motor neuron disease with bulbar involvement. Gastrointestinal: vomiting; gastro-oesophageal re \202 ux; gastric distension, gastropares is with residual volumes \211 150ml; oesophageal malignancies; upper gastrointesti- nal su rgery. Mechanical: physical defenses bypassed by tracheostomy or endotracheal intubation. I ncreasing age: swallowing re \202 ex is prolonged; gastro- oesophageal junction incompeten ce increases. Bacterial virulence of oral secretions: poor oral hygiene, periodontal infect ions, bronchiectasis. Fig. 8.3.1 Middle and left lower lobe consolidation in patient with systemic sclerosis. Vid eo \202 uoroscopy demonstrated \200\230silent \200\231 aspiration without protective coug h re \202 ex. Radiological distribution is in dependant parts of the lung. After the age of 15 the right main bronchus is more verti- cal, but until this age both lower lobes are equally affected by aspiration. If aspiration occurs when patients are recumbent, then superior segments of the lower lobes or posterior segment of upper lobes may be affected. Aspiration pneumonias are frequently polymicrobial, re \202 ecting the spectrum of pathogens found in oropharyn- geal secretions. Anaerobic bacteria are rarely identi \201 ed in sputum due to dif \201 culties with their culture, but the pres- ence of Staphylococcus aureus or Gram-negative ba cilli should heighten suspicions of aspiration. Streptococcus pneumoniae may be present in oropharyngeal secretions, so its identi \201 cation in CAP does not exclude the possibilit y of aspiration. Diagnosis of aspiration May be problematic when aspiration is not witnessed as presentation s are varied and there is no universally applica- ble test to con \201 rm diagnosis. A hig h index of suspicion is essential particularly in those at increased risk. Persistent throa t clearing, hoarseness and problems chewing food may be useful signs. Cough while eating or drinking is not a sensitive symptom, as it is often the lack of CHAPTER 8.3 Aspiration syndromes 177 Aspiration syndromes Aspiration may lead to various syndromes depending on the substance as pirated; whether inert, caustic, particulate or contaminated with pathogenic organisms. so most clinicians give empirical antibiotics. These should be stopped if patient improves rapidly. The majority of patients show prompt and complete reso- lution. Deterioration may be due to development of sec- ondary infection in 25% or ARDS. Fibrosis or bronchiectasis m ay complicate long term recovery. Foreign body aspiration Consequences are in \202 uenced by size of particles, volume and c omposition of foreign matter aspirated. Even when not directly toxic to the lungs damage ma y occur through airways obstruction: \200 Aspiration pneumonia Particles large enough to cause proximal obstruction may result in asphyxiation and rapid d eath (caf coro- nary syndrome). Smaller particles may cause lobar/(sub)segmental col- lap se or atelectasis. Partial obstruction may result in gas trapping which is only visible on expiratory radiographs. Still smaller particles may result in formation of intersti- tial g ranulomata. These may mimic miliary tuberculosis, cause hypercalcaemia and progress to pulm onary \201 brosis. Aspiration of vegetable or mineral oil (as in laxatives) may cause lip oid pneumonia with persistent consolida- tion or irregular mass lesions mimicking lung canc er. Large volume \202 uids may cause asphyxia due to laryn- gospasm (near drowning). Refl ex bronchospasm and \202 eeting hypoxaemia may progress to pulmonary oedema. Foreign body aspiration Chemical pneumonitis Fig. 8.3.2 Aspiration syndromes. Distinction may be made between the inflammatory response seen with a chemical pneumonitis, the infective response to introduction of pathogens and the mechanical effect of foreign b ody aspiration. These processes are not mutually exclusive but represent a spectrum of lung injury and may evolve with time. Although dif \201 cult, distinction between syndromes ma y prompt maneuvers to clear par- ticulate matter from airways or permit avoidance of unnec- essary antibiotics. Management \200 Immediate airways clearance maneuvers involving subdiaphragmatic abdominal thrusts (Heimlic h) back blows or tracheal suction. Secondary bacterial infection may occur particularly if clearance is delayed. Recovery may be complicated by localized bronchiectasis. Aspiration pneumonia \200 Chemical pneumonitis \200 Aspiration of colonized oropharyngeal and gastric secre- tions may result in pneumonia. Pne umonia may develop acutely after an infected aspira- tion; a secondary pneumonia may compli cate in \202 amma- tion or obstruction by non-infected aspirates. Likelihood of infection is in \202 uenced by volume aspirated and degree and virulence of bacterial contamination; more virulent pathogens require smaller aspirates. Less virulent organisms produce an indo lent infection typi \201 ed by gradual onset, non-speci \201 c systemic symp- toms of mal aise and weight loss, low grade fever and anemia. CXR may show a rounded area of consolida- tion, demonstrate cavitation or pleural involvement at presentation. Misdiagnosis of lung cancer can occur, particularly if there is mediastinal lymphadenopathy, indeterminate bronc hoscopic or sputum cytology, when further invasive investigation are limited by poor perfor mance status. Aspiration of gastric contents, often witnessed and usu- ally sterile, dispersed and rapidl y neutralized. Gastric contents rapidly incite an in \202 ammatory response causing atelec tasis, peribronchial hemorrhage and oedema within minutes and CXR changes within 2 hours. H ypoxaemia exacerbated by reflex bronchospasm, impaired surfactant activity and VQ mismatch cause intrapulmonary shunting. Fever/leucocytosis may be present in absence of infection. S everity related to volume (>20 ml) and pH (<2.5). \200 Management \200 \200 Immediate suction of airways. Supportive measures including ventilatory support with high P EEP; avoidance of \202 uid overload. No evidence of bene \201 t from: \200 \200 \200 Corticosteroids \200\223 may increase risk of secondary infection. Large volume lavage \200\223 as acid is promptly neutralized. Bronchoscopy \200\223 unless aspirate heavily co ntaminated with particulate matter. KEY FACTS \200 Anaerobes are dif \201 cult to culture by standard means. Their presence in aspiration pne umonias should be assumed. Clinical deterioration after 24 \200\22348 hours may suggest dev elopment of secondary infection. Broadening spec- trum of antibiotics to cover Staphylococc us (MRSA) and Gram-negative bacilli should be considered. Antibiotics are not mandatory. Data suggests prophylaxis does not reduce the risk of subseq uent superadded bacte- rial infection (tends to occur after 2 \200\2235 days) and may incre ase selection of resistant organisms. However distinction between in \202 ammatory respons e and infection is dif \201 cult A ATALLA & D DERRY 178 Microbiology \200 Body position: elevation of head of bed, ensuring sitting position while feeding and for 2 hours subsequently. Compensatory feeding strategies and training in chewing and swallowing maneuvers to modify risk. Liquid thick- eners reduce risk in those with neurogenic aspirati on. Minimize sedation and optimize anti-epileptic medications Enteral tube feeding is often used to reduce risk of aspi- ration, but feed can still be aspirated if gastro-oesophageal re \202 ux occurs. More importantly it offers no protection against aspiration of orophar yngeal secretions. NG tube position should be regularly reassessed. Gastric residual should be checked during feeding (4-hourly with rate reduced if residual >50ml). NG tubes impair lower oesophageal sphincter (LOS) function. Prokinetics (e.g. metoclopramide) stimulate gas tric emptying and increase LOS tone. Despite theo- retical bene \201 ts, trials have not s hown clinical advantage of continuous over bolus feeding, of jejunal over gastric feeding, or of small bore tubes over large. Oral hygiene measures: aggressive oral care, treatment o f dental infections, avoidance of dehydration. There is no bene \201 t from medications wh ich dry up secretions such as anticholinergics and antihistamines. Angiotensin converting e nzyme inhibitors (ACEi) inhibit breakdown of substance P causing both increase cough sensit ivity (potential bene \201 t rather than annoying side- effect) and improved swallowing re \202 ex in the elderly. Reduced pneumonia in stroke patients treated with ACEi, suggests bene \201 t particularly in silent aspirators. If aspiration is severe and persistent, lar yngectomy to separate tracheobronchial tree and GI tract may be necessary. Spectrum of pathogens is wide and in \202 uenced by poor dental hygiene (so edentulous pat ients at less risk), pre- vious antibiotic use and hospitalization. Aspiration in hospitali zed patients more frequently involves Gram-negative organisms and Staphylococcus aureus. Ga stric contents rendered less acidic by proton pump inhibitors or NG feeding are at increase d risk of coloni- sation by enteric bacilli. Anaerobes such as Bacteriodes, Peptostreptococ cus and Fusobacterium, though dif \201 cult to culture, are thought to be implicated in ov er half of cases of aspiration pneumo- nia. These are more likely when there is foul sputum , parenchymal necrosis and abscess formation. \200 Management \200 Antibiotics; choice in \202 uenced by probable spectrum of pathogens and risk of antibioti c resistance. Historically, high-dose penicillin had good activity against anaerobes, but r esistant organisms are increasingly seen, hence combination with beta-lactamase inhibitors (e.g. co-amoxyclav). Metrondazole has activity against certain anaerobes, but should not be used as monotherapy because of its lack of activity against microaerophilic streptococci. Clindamycin has rapid action and low failure rates. Its use is limited by frequency of deve lopment of Clostridium dif \201 cule diarrhea particularly in the aspiration-prone elderly . Newer quinolones (levo \202 oxacin, moxi \202 oxacin) currently still have broad spectr um including good anaerobic cover. Restricted use of chloramphenicol due to risk of serious hematological side effects is likely to help main- tain bacterial sensitivity to this pote nt antibiotic. The increasing prevalence of MSRA and pseudomonas in hospital acquired aspir ation requires further extension of antibiotic coverage. Combination therapy is increas- in gly appropriate. Optimum duration is unclear \200\223 typically 7 \200\22310 days is used, but longer courses needed for more aggressive patho- gens or complications such as lung ab scess or empyema. Further reading Johnson LJ, Hirsch CS. Aspiration pneumonia: recognizing and man- aging a p otentially growing disorder. Postgraduate Medicine 2003; 113: 99 \200\223102. Marik PE, Kaplan D. Aspiration pneumonia and dysphagia in the elderly. Chest 2003; 124: 328 \200\223336. Sasaki H, Sekizawa K, Uania M, et al. New Strategies for Aspiration Pneumonia. Internal Medicine 1997; 36: 851 \200\223855. KEY FACT Enteral feeding offers many advantages but does not protect against aspiration of oral secretions Prevention \200 \200 Education and counseling of patient and carers is essential. Foreign body aspiration is a l eading cause of accidental death of infants in the home; restricting access to such items i s key. Diagnosis can be dif \201 cult if the inhaled object is not radio-opaque. This page intentionally left blank L DOBSON 180 8.4 Lung abscess Epidemiology Since the introduction of penicillin in the 1940s the inci- dence has declined and the prognosis has improved. There remains a subgroup of elderly and immunocompromised patients in whom there is still signi \201 cant morbidity and mortality. Male predominance (2:1) with a peak incidence in the 4th and 5th decades. Incidence twice as common in immun ocompromised patients. more insidious or chronic picture. The most common symptoms are: cough (90%), fever (83%), putrid sputum (59%), chest pain (54%), weight loss (54%), night sweats (45%), and haemoptys is (31%). Examination Often unhelpful. Findings may be similar to those of pneu- monia or pleural eff usion, with dullness to percussion and bronchial breathing if the abscess is close to the p leural surface. Clubbing is sometimes noted. Etiology This can be split into the following main groups: \200 Differential diagnosis \200 \200 \200 \200 \200 \200 \200 \200 Aspiration: (a) impaired consciousness (excess alcohol, epilepsy, Neoplastic (lung cancer or metastases). Vasculitis (Wegener \200\231s granulomatosis). Rheu matoid nodule. Pneumoconiosis (PMF, Caplans syndrome). Pulmonary infarction. Bullae, cysts or sequestration. Localized saccular bronchiectasis. Gas \202 uid level in esophagus, sto mach or bowel. anesthesia); (b) neuromuscular disease; (c) oesophageal pathology (stricture, hiatus hernia, acha- lasia). Bronchial obstruction (malignancy, in \202 ammation, foreign body). Pneumonia (e.g. Klebsi ella pneumoniae, Staphylococcus aureus). Blood-borne infection. Immunosuppressive states. Investigations Radiology \200 \200 Plain chest radiograph usually raises the possibility of a lung abscess. More common in rig ht lung (60 \200\22375% vs 25 \200\22340%) Involves those segments dependent in recumbency i.e. posterior segments of upper lobes and superior segments of lower lobes. CT scanning ca n aid diagnosis and differentiate between empyema and abscess. Abscesses typically have an irregular wall, indistinct outer margin, oval or round shape, make an acute angle with the chest wall and show no evidence of compression of the lung. Radiological studies of cavity behavior reveal that 13% will be gone in 2 weeks; 44% in 4 weeks; 59% in 6 weeks; and 70% i n 3 months. Microbiology Most lung abscesses are polymicrobial. Historically, with aspiration being the commonest aetiological factor, anaer- obic bacteria are the predominant organisms isolated . The spectrum of aetiological agents may however be evolving. A recent study noted the pre sence of anaerobes in only 31% of patients, with aerobes (in particular Klebsiella pneumoni ae 33%) being most common. This may be partly due to taxonomic changes, but predominantly r e \202 ects the changing patient demographics with a growing number of immunosuppressed pa tients. \200 Infectious causes of lung abscess \200 Bacteria (a) anaerobe fusobacteria Gram-negative bacilli (e.g. Prevotella) Gram-positive cocci (e.g. Peptostrepto coccus) Gram-negative (e.g. Klebsiella, Pseudomonas) Gram-positive (e.g. Staphylococcus aur eus) Blood sampling Raised in \202 ammatory markers are often present with a leu- kocytosis. Bl ood cultures may be useful. If chronic, anemia is frequently present. Microbiological sampling The polymicrobial nature of these infections and the varia- tions in antimicrobial susceptibility means that knowledge of the pathogens can optimize the choi ce of antibiotic. However it can be dif \201 cult to obtain a reliable specimen. (b) aerobes (c) Legionella pneumophila (d) Pseudomonas pseudomallei Fungal Coccidioidomycosis, Mucormyc osis, Sporotri- chosis, Cryptococcosis, Histoplasmosis, Blastomycosis, Aspergillosis Amoebi c. Mycobacteria. Actinomycocis/Nocardiosis. Echinococcosis. Sputum sampling \200 \200 Low diagnostic accuracy. Contamination by normal \202 ora in upper airways. Transtracheal aspiration \200 \200 \200 \200 \200 Old studies showed reported high accuracy (80%). Relied on concept of sterile bronchial tre e beyond vocal cords. Elevated concentrations of bacteria in lower airways, with- out clini cal signs of infection, has cast doubt on its use. Clinical features Symptoms Depending on the etiology of the abscess, symptoms can vary from being very acute (abrupt, short duration) to a Fibreoptic bronchoscopy. \200 \200 \200 Can rule out tumor, foreign bodies & other diagnoses. Underlying bronchial carcinoma (7 \200\22317.5%). Risks of sample contamination reduce accuracy. CHAPTER 8.4 Lung abscess 181 Percutaneous lung aspiration \200 \200 \200 \200 Suggested indications for surgery: \200 \200 \200 \200 \200 \200 haemoptysis malignancy chronicity (6 \200\2238 weeks without clear progress) persisting sep sis after 2 weeks despite antibiotics radiological signs of inadequate healing complication s - bronchopleural \201 stula, empyema Can be guided by Fluoroscopy, ultrasound or CT. High accuracy depending on modality (79 \200\22394%). Changes antibiotic regimen in up to 47% patients. Commonest complication pneu mothorax (14%). Treatment Antibiotics It is reasonable to proceed with empiric antibiotic therapy without p rior diagnostic investigations in those patients who have a classical clinical and radiogra phic presentation. \200 \200 \200 \200 Post-operative complications include empyema (10 \200\22329%) and a mortality rate (11 \200 \22316%). Outcome \200 Penicillin alone probably ineffective. Metronidazole not effective alone (50% response). Cl indamycin has been reported superior to penicillin. Beta lactam/beta lactamase inhibitor co mbinations are effective. Other options include cephalosporins, macrolides, chloramphenicol , amoxicillin/metronidazole, imipenem and antipseudomonal penicillins. Published experience with newer antibiotics is limited. Patients should be treated for a period of 4 \200\2236 weeks although there have been no formal trials to support this. The \201 nal decision on duration should be made according to clinical and radiological response. On appropriate antibiotic therapy fever usually disap- pears within days (4 \200\2238 days) . Persistence beyond 2 weeks is unusual and suggests inadequate drainage. Conservative medi cal therapy proves effective in 80 \200\22390% of patients. Despite the introduction of mod ern techniques overall mortality still remains at up to 10% (compared with pre- antibiotic era of 30 \200\22340%). Mortality rates vary depending on the etiology e.g. 0 \200\2232% in non-immunocompromised patients vs 8% in immunocompromised patients. AIDS patients have bee n reported to have mortality rates of 28% and cure rates of only 36%. Drainage \200 Markers of poor outcome include: \200 \200 \200 \200 \200 Antibiotic therapy and physiotherapy are mainstays of treatment for most patients. Many spo ntaneously drain during the course of therapy via communication with the tracheobronchial t ree. Complicated abscesses may require tube drainage, and timing depends on the clinical st atus of the patient. advanced age/debilitation/malnutrition; HIV (and other immunosuppressive states); malignanc y; large cavity size (>6cm); duration of symptoms > 8 weeks. Intervention more likely to be required if: \200 \200 \200 \200 \200 Complications \200 \200 \200 \200 \200 Large cavity (>6cm). Necrotising pneumonia (multiple small abscesses). Elderly or immunocom promised patient. Bronchial obstruction. Aerobic bacterial pneumonia. Recurrent abscess (8%). Empyema (4%). Life threatening hemorrhage (4%). Embolic cerebral ab scess very rare. Longer term complications include aspergilloma and saccular bronchiectasis . Drainage can be achieved by: \200 Bronchoscopy: \200 \200 Further reading Davis B, Systrom DM. Lung abscess: pathogenesis, diagnosis and Debate about role. Value limited by the risk of spillage of abscess contents into the unaff ected bronchial tree. treatment. Curr Clin Top Infect Dis 1998; 18: 252 \200\223273. Hirshberg B, Sklair-Levi M, Nir-Paz R et al. Factors predicting mor- tality of patients wit h lung abscess. Chest 1999; 115: 746 \200\223750. External percutaneous drainage: \200 Preferred option, surgery frequently avoided (84%), marked improvement in sepsis indicators within 48 hours of drainage. Variety of imaging techniques reported ( \202 uoroscopy, ult rasound and CT scanning). Ultrasound provides more precise spatial localization, real-time images and no radiation dose. CT scanning is frequently used, provides better visualization of intrathoracic structures and is familiar with operators. Complication rate low (broncho pleural fistula, hemorrhage, empyema). Mansharamani N, Balachandran D, Delaney D et al. Lung abscess in adults: clinical compariso n of immunocompromised to non- immunocompromised patients. Resp Med 2002; 96: 178 \200\2231 85. Mwandumba HC, Beeching NJ. Pyogenic lung infections: factors for predicting clinical outcom e of lung abscess and thoracic empyema. Curr Opin Pulm Med 2000; 6: 234 \200\223239. Wang J-L, Chen K-y, Fang C-T et al. Changing bacteriology of adult community-acquired lung abscess in Taiwan: Klebsiella pneumo- niae vs anaerobes. Clin Infect Dis 2005; 40: 915 \200 \22322. Wiedemann HP, Rice TW. Lung abscess and empyema. Sem Thor Card Surg 1995; 7: 119 \200\223128. Surgery Surgery is now seldom required in the management of lung abscess (<10%). A MALIN 182 8.5 Nocardia and actinomycosis Nocardia Nocardia species are aerobic actinomycetes, branching beaded \201 lamentous bact eria which usually stain weakly acid fast. Nocardiosis results from opportunistic infection due to a variety of Nocardia spp. Infection is limited to the skin (subcutaneous or lympho cutaneous) in about 20% of cases. More invasive disease occurs in 80%, predominantly pulmon ary infection (40%), but also systemic disease with frequent cerebral abscess formation. Investigations Imaging Plain and CT chest imaging of pulmonary nocardiosis is protean and m ay show: \200 Mild subtle in \201 ltrates. \200 Reticular nodular shadowing \200\223 patchy or diffuse. \200 Lobar or multilobar consolidation. \200 Diffuse alveolar in \201 ltrates, especially in severe immuno- compromise (HIV with CD4 <200). Abscess formatio n. Irregular nodules. Cavitary disease. Effusions and empyema. Pulmonary TB-like appearance with calci \201 ed lesions. \200 \200 \200 \200 Fig. 8.5.1 Smear preparation of Nocardia asteroides. (See Plate 5.) Epidemiology Nocardia spp. are ubiquitous bacteria found in soil, water and vegetable matte r. Infection usually occurs by inhalation, aspiration into the lung, direct inoculation of the skin or possibly from contaminated food via gastrointestinal tract. Hospital transmissi on has occurred in transplant and oncology units. Globaly, the N. asteroides complex accoun ts for up to 90% of pulmonary and disseminated infections. N. brasiliensis is a common caus e of skin mycetomas. N. farcinica, linked to hand transmission by anaethestists, has been a ssociated with sternotomy wound infection. Incidence has been estimated as 500 \200\2231000 cases a year in the USA with a steady increase due to the increased number of immunocompro mised individuals. Signi \201 cant under-report- ing is likely. Infection is three times m ore common in men. Fig. 8.5.2 CXR showing overwhelming pulmonary nocardiosis. Microbiology Sputum, BAL or other samples should be sent for pro- longed culture. Speci \201 c molecular tests can be employed to distinguish species, particularly N. farcinia, a species associated with disseminated disease which may be resist- ant to co-trimoxazole. Pathology Biopsy material is usually suppurative with numerous poly- morphonucleocytes, but can be granulomatous with an absence of epithelioid cells but multinucleate giant cells ca n be found. History and examination Clinical presentation varies widely and depends both on the site of infection and host response. Pulmonary nocar- diosis may present as an acute pyogenic infe ction mimick- ing pneumonia or as a chronic insidious disease mimicking pulmonary tuberculo sis, lung cancer or more rarely, aspergillosis and actinomycosis. Systemic infection and CN S involvement occur more frequently in those with severe immunocompromise. Infection also o ccurs in those with intact immunity and is usually focal such as following an inoculation i njury of the skin. Management Patient \200\231s management must be individualized and take into account clinic al presentation and in vitro antibiotic sensitivi- ties. Empirical treatment prior to labor atory results should include trimethoprim-sulphamethoxazole (with a second agent in those w ith signi \201 cant immunocompromise or sys- temic/ CNS involvement). Other agents include : carbapen- ems, amikacin, minocycline, cephalosporins or linezolid. AUTHOR \200\231S TIP Consider nocardiosis if unexplained in \201 ltrates/infec- tion in: \200 \200 \200 \200 Prognosis Outcome is determined by the site of infection and coex- istent co-morbidity. Cut aneous infection is the most benign. Even uncomplicated pulmonary nocardiosis has a mortali ty of 10%. Patients with advanced immunocompromise have a worse outcome. HIV infection. Solid organ transplant recipients. Lymphoreticular malignancy. Other causes of immunocompromise \200\223 high dose cor- ticosteroid use, alcoholism and diabetes. Alve olar proteinosis. CHAPTER 8.5 Nocardia and actinomycosis 183 Key points \200 Other investigations \200 Leukocytosis. \200 Culture from sputum, bronchial washings or biopsy material (needs anaerobic culture). Histology from lung biopsy or resected lung. Consider nocardiosis if spread to CNS or contiguous structures with soft tissue swellings o r \201 stulas. Culture samples require prolonged incubation \200\223 alert laboratory if nocardiosis possible. Species identi \201 cation in a Reference Laboratory will assist an tibiotic choice. Pathology \200 \200 \200 Actinomyces israelii commonest cause. See chronic in \202 ammatory and granulation tissue. Occasional multinucleate giant cells containing sulfur granules. Untreated disease may pro gress to: \200 \200 Actinomycosis De \201 nition An uncommon chronic suppurative infection caused by the genus , Actinomyces. These are slow-growing branching Gram-positive bacteria which form mycelia ( mass of branching, thread-like hyphae) similar to fungi. Unlike Nocardia spp., they are not acid fast. Characteristically they invade locally, forming external sinuses which discharg e sulfur granules. Multiple abscesses. Draining sinuses. Management \200 Penicillin is the treatment of choice but can also use ceftriaxone or a carbapenem. Treatme nt duration of 10 days with recent infections but need longer if \201 brosis present. Con sider co-infection. Epidemiology Actinomyces are common non-virulent oral saprophytes frequently found in assoc iation with dental infection. Spread may occur by local invasion through damaged mucosa or following surgery or trauma. Sites of infection include: 55% Cervicofacial (direct invasion ) 15% Thorax (aspiration) Abdomen (ingestion) 20% Other organs \200\223 bone, brain, skin 10% Key points \200 Despite forming mycelia, not a fungus and treated with penicillin. May mimic lung cancer or any abscess-forming organism. May co-exist with lung cancer or any abscess-forming organis m. May see sinus formation with purulent discharge of sulfur granules. Thoracic actinomycosis History and examination \200 \200 