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 The complement \201 xation test (CFT) is the commonest serological assay and is regarded as the gold standard. Culture of Mycoplasma pneumoniae is not generally available Chlamydia \200 Chlamydial antigen can be detected by DIF in respiratory samples or by CFT Others \200 In \202 uenza A and B, adenovirus, respiratory syncytial virus. Coxiella burnetii indirect immuno \202 uorescence antibody test CHAPTER 40 Respiratory infection: bacterial 428 CAP: management General management \200 Oxygen Hypoxia is due to V/Q mismatching, as blood \202 ows through unventilated lung. Ai m for oxygen saturation >92%. If there is severe concomitant COPD, controlled oxygen therap y and close monitoring of blood gasses are mandatory. A rising CO2 in a patient without pri or respiratory disease may indicate they are tiring, and need respiratory support \200\224d iscuss with ITU early Non-invasive ventilatory support A number of studies demonstrate bene \201 cial effects of NIV in severe CAP. However, following initial improvement in physiol ogical parameters, >50% of patients subse- quently deteriorate, requiring intubation. A hig her initial respira- tory rate (>30) is associated with failure of non-invasive ventilatory support (CPAP or bi-level ventilation). NIV may have a place in the management of severe C AP, but should only be used in a high dependency setting, with very close observation Fluid s Assessment of volume status by JVP (with or without central venous access) and blood pres sure is paramount. Encourage oral \202 uids. Intravenous \202 uids may be needed if vol ume depleted and severely unwell. Monitor urine output Analgesia Paracetamol or NSAIDs init ially if required. Paracetamol also has an antipyretic role Nutrition Nutritional status is important to the outcome, and nutri- tional supplements may be of bene \201 t in prolonge d illness. Poor nutri- tional status may increase the risk of acquiring pneumonia Physiothe rapy is of no proven bene \201 t in acute pneumonia. Additional treatments Bronchoscopy May be helpful, especially after intubation on ITU, to s uction retained secretions, particularly if these are causing lobar collapse, to obtain fur ther samples for culture, and to exclude an endobronchial abnormality. Steroids There is some evidence that these are of bene \201 t in severe bacterial pneumoni a. Monitoring Temperature, respiratory rate, heart rate, blood pressure, mental status, oxy gen saturation, and inspired oxygen concentration should be monitored twice daily, and more often in the severely ill. ICU admission Those ful \201 lling criteria for severe CAP on admission, or who fail to respond rapidly to treatment, should be considered for transfer f or close monitoring, either to a high dependency unit or to ICU. Persisting hypoxia (PaO2 \211 8 kPa), acidosis, hypercapnia, hypotension, or depressed conscious level, despite maxi mal therapy, are indications for assisted ventilation. CPAP may be of bene \201 t whilst a waiting for the arrival of the anesthetist (although this may just be a more effective way of deliv- ering 100% oxygen). CAP: MANAGEMENT 429 When to discuss patient with CAP with ITU \200 \200 \200 \200 Always sooner rather than later Respiratory failure (PaO2 <8 kPa) despite high \202 ow ox ygen Tiring patient, with a rising CO2 Worsening metabolic acidosis, despite antibiotics an d optimum \202 uid management Hypotension despite adequate \202 uid resuscitation. CHAPTER 40 Respiratory infection: bacterial 430 CAP: antibiotics \200 Most antibiotics are used empirically at diagnosis of CAP in the absence of microbiological information. The clinical scenario also guides antibiotic choice, such as the addition of anaerobic cover in an alcoholic who has a high chance of aspiration Severity assessment gui des antibiotic therapy and the method of antibiotic administration Local protocols and anti biotic resistance patterns may also guide choice. Liaise closely with microbiologist. General points \200 Early administration of antibiotics is associated with an improved outcome Antibiotics give n before admission can in \202 uence the results of subsequent microbiological investigati ons, but this should not delay antibiotic administration in the community if the patient is unwell It is vital that there is no delay in the administration of the \201 rst antibiot ic dose in patients admitted to hospital. The admitting doctor should oversee its administr ation. IV antibiotics will be needed in 30 \200\22350% of patients admitted to hospital. Co nsider IV antibiotics if: \200 Severe pneumonia \200 Loss of swallow re \202 ex \200 Impaired absorption \200 Impaired conscious level Oral antibiotics should be used in tho se with community-managed pneumonia, or those with non-severe hospital-managed pneumonia, w ith no other contraindications. Add anaerobic antibiotic cover, e.g. metronidazole if possi ble aspiration pneumonia in an unconscious patient, or if suspicion of a lung abscess on CX R/CT Switch from IV to oral antibiotics as soon as possible, usually when a patient has sho wn clear response to treatment, with a normal temperature for 24 h A switch to oral co-amox iclav, and not an oral cephalosporin is recommended after treatment with IV cephalosporin F or those treated with benzylpenicillin plus levo \202 oxacin, a switch to oral levo \202 oxacin oral amoxicillin is recommended Length of treatment There is no evidence to guide treatment length, but consensus suggests \200 \200 \200 5 \200\2237 days \200\224non-severe, uncomplicated pneumonia 10 days \200\224severe microbi ologically unde \201 ned pneumonia 14 \200\22321 days \200\224if Legionella, staphylococca l disease, Gram-negative suspected Consult local antibiotic guidelines; concern regarding i ncreasing rates of Clostridium dif \201 cile has lead to reduced antibiotic course length and alternative empirical antibiotic choice in some centers. There is no evi- dence that an y speci \201 c antibiotic (other than clindamycin) is more likely to cause C. dif \201 ci le than any other CAP: ANTIBIOTICS 431 Table 40.1 Suggested initial antibiotics for CAP treatment Preferred treatment Alternative (if intolerant of or allergic to preferred treatment) Community treatment Amoxicillin 500 mg \200\2231 g tds PO Erythromycin 500 mg qds PO or clarithromycin 500 mg bd PO Hospital treatment: not severe pneumonia Erythromycin 500 mg qds PO or clarithromycin 500 mg bd PO or levo \202 oxacin 500 mg od PO or moxi \202 oxacin 400 mg OD Oral Amoxicillin 500 mg \200\2231 g tds PO erythromycin 500 mg qds PO or clarithromycin 500 m g bd PO Levo \202 oxacin 500 mg od IV If intravenous treatment needed Ampicillin 500 mg qds IV or benzylpenicillin 1.2 g qds IV plus erythromycin 500 mg qds IV o r clarithromycin 500 mg bd IV Levo \202 oxacin 500 mg bd IV plus benzylpenicillin 1.2 g qds IV Hospital treatment: severe pneumonia Co-amoxiclav 1.2 g tds IV or cefuroxime 1.5 g tds IV or cefotaxime 1 g tds IV or ceftriaxon e 2 g od IV plus erythromycin 500 mg qds IV (or clarithromycin 500 mg bd IV) New \202 uoroquinolones Moxi \202 oxacin is licensed in the UK for the treat- ment of no n-severe CAP. It is not available for IV use. It has equivalence to the other oral antibiot ics used in CAP, but is not recommended for \201 rst- line treatment for CAP for communit y use, given the current low level of pneumococcal resistance in the UK. Levo \202 oxacin is available in oral and IV preparations, and is licensed for severe CAP. In the future, ot her \202 uo- roquinolones, e.g. gema \202 oxacin and gati \202 oxacin, are likely to ex tend the choice of oral antibiotics for CAP when they are licensed in the UK. The ketolides (e.g. telithromycin) are novel macrolides, with ef \201 cacy against penicillin- and eryt hromycin-resistant pathogens. Antibiotic resistance Surveillance studies suggest that the U K prev- alence of penicillin resistant S. pnemoniae is now about 20%. Macrolide resistant o rganisms may be as high as 25 \200\22330%. Worldwide prevalence of pneumococcal resistance to \202 uoroquinolones is low, at <2%, though this has increased substantially in some co untries (e.g. Hong Kong) in recent years (because of the spread of a \202 uoroquinolone r esistant clone). CHAPTER 40 Respiratory infection: bacterial 432 CAP: treatment failure A CRP that does not fall by >50% at 4 days suggests either treatment failure, or the development of a complication such as a lung abscess or empyema. Causes of failure to improve \200 \200 Slow clinical response, particularly in the elderly patient Incorrect initial diagnosis \200 \200 \200 \200 \200 Pulmonary thromboembolic disease Pulmonary oedema Bronchial carcinoma Bronchiectasis Also c onsider eosinophilic pneumonia, foreign body aspiration, alveolar hemorrhage, cryptogenic o rganizing pneumonia, vasculitis or connective tissue disease, drug-induced lung disease Rev iew the history, examination, and radiology Consider repeat imaging, e.g. CT chest \200 Secondary complication \200 Pulmonary, e.g. parapneumonic effusion (occurs in 36 \200\22357%, most resolve spontaneousl y, thoracentesis is recommended), empyema, abscess formation, ARDS Extrapulmonary, e.g. sep ticaemia, metastatic infection (e.g. menin- gitis, endocarditis, septic arthritis), sequela e of initial insult, e.g. renal failure, myocardial infarction Inappropriate antibiotics or unexpected pathogen \200 Review dose, compliance, and route of administration. Send further microbiological specimen s Review microbiological data, exclude less common pathogens, e.g. Legionella, Mycoplasma, staphylococcal disease Pathogen may be resistant to common antibiotics; 10% of CAP will hav e a mixed infection Consider tuberculosis, fungal infection Impaired immunity \200 \200 \200 Systemic, e.g. hypogammaglobulinaemia, HIV infection, myeloma Local, e.g. bronchiectasis, a spiration, underlying bronchial carcinoma Overwhelming infection CAP: TREATMENT FAILURE 433 Table 40.2 Recommended antibiotic treatment of speci \201 c causative organisms Pathogen Preferred antibiotic Alternative antibiotic Streptococcus pneumoniae Erythromycin 500 mg qds PO or clarithromycin 500 mg bd PO or cefuroxime 0.75 \200\2231.5 g tds IV or cefotaxime 1 \200\2232 g tds IV or ceftriaxone 2 g od IV Amoxicillin 500 mg \200\2231 g tds PO or benzylpenicillin 1.2 g qds IV Mycoplasma pneumoniae and Chlamydia pneumoniae Tetracycline 250 \200\223500 mg qds PO, or \202 uoroquinolone PO or IV Erythromycin 500 mg qds PO/IV or clarithromycin 500 mg bd PO or IV Erythromycin 500 mg qds or clarithromycin 500 mg bd, both PO or IV Chlamydia psittaci and coxiella burnetii Tetracycline 250 \200\223500 mg qds PO or 500 mg bd IV Fluoroquinolone PO or IV Legionella sp. Clarithromycin 500 mg bd PO, or IV rifampicin 600 mg od or bd, PO or IV Haemophilus in \202 uenzae Cefuroxime 750 mg \200\2231.5 g tds IV or cefotaxime 1 \200\2232 g tds IV or ceftriaxone 2 g od IV or \202 uoroquinolone PO or IV Non-lactamase producing amoxicillin 500 mg tds PO or ampicillin 500 mg qds IV Lactamase pro ducing co-amoxiclav 625 mg tds PO or 1.2 g tds IV Gram-negative enteric bacilli Fluoroquinolone IV or imipenem 500 mg qds IV or meropenem 0.5 \200\2231.0 g tds IV Cefuroxime 1.5 g tds or cefotaxime 1 \200\2232 g tds IV or ceftriaxone 1 \200\2232 g od IV Pseudomonas aeruginosa Cipro \202 oxacin 400 mg bd IV or piperacillin 4 g tds plus gentamicin or tobramycin (NB t herapeutic drug monitoring) Cipro \202 oxacin 500 \200\223750 mg bd PO ceftazidime 2 g tds IV plus gentamicin or tobra mycin (NB therapeutic drug monitoring) Staphylococcus aureus Non-MRSA Teicoplanin 400 mg bd IV rifampicin 600 mg od or bd PO/IV linezolid 600 mg bd PO/IV \202 ucloxacillin 1 \200\2232 g qds IV rifampicin 600 mg od/bd, PO, or IV MRSA vancomy cin 1 g bd (NB therapeutic drug monitoring) CHAPTER 40 Respiratory infection: bacterial 434 CAP: follow-up CXR resolution Radiographic improvement lags behind clinical improvement. Th ere is no need to repeat a CXR before hospital discharge in those who have made a satisfact ory clinical recovery. \200 In one study of CAP, complete radiographic resolution occurred after 6 weeks in 74% of pati ents, but only in 51% at 2 weeks Radiographic resolution is slower in the elderly, those wi th multilobe involvement at presentation, smokers, and hospital in-patients Legionella and pneumococcal pneumonia are slower to resolve (may take 12 weeks or more). CXR follow-up is recommended around 6 weeks after CAP: \200 \200 In all patients with persisting symptoms or clinical signs In all patients at higher risk o f underlying lung malignancy, i.e. smokers and those over the age of 50. This is to exclude an underlying condition that may have led to CAP, such as lung cancer. F urther investigations, such as bronchoscopy, should be considered at this time in patients with persisting symptoms and/or a persistently abnormal CXR. \200 One study showed lung cancer is diagnosed on follow-up in 17% of smokers aged over 60 treat ed for CAP in the community Other studies have shown a prevalence of lung cancer of 11% in current and ex-smokers aged over 50, who are in-patients with CAP and who undergo bronchosc opy prior to discharge. Vaccination In \202 uenza vaccination This reduces hospital deaths from pneumonia and in \202 uenza by about 65% and respiratory deaths by 45%. It also leads to fewer hospital admi ssions. Recommended for \200\230high-risk \200\231 individuals \200 \200 \200 \200 \200 \200 \200 \200 Chronic lung disease Cardiac, renal, and liver disease Diabetes Immunosuppression due to di sease or treatment Those aged over 65 Long-stay residential care Health care workers Contra indicated in people with hen egg hypersensitivity (the virus is cultured in chick embryos). The vaccination contains both A and B subtype viruses and provides partial protection again st in \202 uenza illnesses. It is modi \201 ed annually, based on recent viral strains. T he protection rate from in \202 uenza by vaccination is over 75% for in \202 uenza A and 51 \200\22397% for in \202 uenza B. Antibody levels appear to reduce about 6 years after v accination. CAP: FOLLOW-UP 435 Pneumococcal vaccination Recommended for: \200 \200 \200 \200 Asplenic individuals (including coeliac disease and sickle cell disease) Chronic renal, car diac, and liver disease Diabetes Immunode \201 ciency or immunosuppression (due to disease , including HIV infection, or drugs). It should not be given during acute infection or in pregnancy. Re-immunization is contraind icated within 3 years. Further information British Thoracic Society Guidelines for the management of community acq uired pneumonia in Adults. Thorax 2001; 56(S): VI An updated version of the 2001 guidelines is on the BTS website: http://www.brit-thoracic.o rg. uk/c2/uploads/MACAPrevisedApr04.pdf Thomas MF. Community acquired pneumonia. Lancet 2003; 362: 1991 \200\2232001 CHAPTER 40 Respiratory infection: bacterial 436 Hospital-acquired pneumonia: clinical features De \201 nition New radiographic in \201 lt rate in the presence of evidence of infection (fever, purulent sputum, leucocytosis) with o nset at least 72 h after hospital admission. It represents around 15% of hospital-acquired infec- tions. Most occur outside the ICU, but those at highest risk are mechani- cally vent ilated patients. Hospital-acquired pneumonia is expensive and prolongs the hospital stay. I t requires different antibiotic treatment to community-acquired pneumonia, and is the leadi ng cause of death from hospital-acquired infection. It is also known as nosocomial pneumoni a. Pathophysiology Hospital-acquired pneumonia occurs from haemato- genous spread of organi sms, aspiration of infected upper airway secretions, or from the inhalation of bacteria fro m contaminated equipment. Aspiration is thought to be the most important cause. Around 45% of normal people aspirate during sleep, and this is increased in hospital in-patients (who may be more frail) and in those with chronic disease. These patients \200\231 upper airways become colonized with Gra m-negative bac- teria (in up to 75% within 48 h of admission) and this proportion is even h igher in those who have received broad-spectrum antibiotics. In addi- tion, the severely il l may have impaired host defenses, making them more susceptible to hospital-acquired pneumo nia. Alteration in the gastric pH with illness, and various drugs, means that the gastroint estinal tract is no longer sterile, thereby providing a potential source of bacterial infec tion. A cerebrovascular event and reduced conscious level are the major risk factors for as piration. Risk factors for nosocomial pneumonia \200 \200 \200 \200 \200 \200 \200 \200 \200 Age >70 Chronic lung disease and/or other comorbidity (especially diabetes) Reduced conscio us level/cerebrovascular accident Chest/abdominal surgery Mechanical ventilation Nasogastri c feeding Previous antibiotic exposure Poor dental hygiene Steroids and cytotoxic drugs. HOSPITAL-ACQUIRED PNEUMONIA: CLINICAL FEATURES 437 Risk factors for speci \201 c organisms Streptococcus pneumoniae and Haemophilus in \202 uenza Increased risk in trauma. Staphylococcus aureus Increased risk in ventilated neurosur gical patients (especially closed head injury), blunt trauma, and coma. Pseudomonas aerugin osa Increased risk with intubation >8 days, COPD, prolonged antibiotics. Acinetobacter spp. Increased risk with prolonged ventilation and previous broad spectrum antibiotics. Anaerob ic bacteria Increased with recent abdominal surgery, aspiration. Clinical features It prese nts typically with: \200 \200 \200 \200 \200 Fever Productive cough Raised in \202 ammatory parameters New CXR in \201 ltrate Deterior ation in gas exchange. Diagnosis is often a clinical one, and identi \201 cation of the infecting agent can be di f \201 cult, especially if the patient has already received broad spectrum antibiotics. Investigations \200 \200 \200 \200 \200 CXR usually shows a non-speci \201 c in \201 ltrate Blood, sputum, and pleural \202 uid should be cultured Arterial blood gas to determine severity Renal and liver function tests to assess other organ dysfunction Serological tests are of little use in nosocomial pneumo nia. CHAPTER 40 Respiratory infection: bacterial 438 Hospital-acquired pneumonia: management Severity assessment The CURB or CURB-65 pneumonia s everity score (see p 180) for community-acquired pneumonia has not been vali- dated in hosp ital-acquired pneumonia, but may be useful in guiding the treatment needed. Microbiology \200 \200 About 50% are mixed infections 30% are due to aerobic bacteria alone (most commonly Gram-ne gative bacilli and Pseudomonas) Anaerobes alone are found in about 25% Pseudomonas aerugino sa and Staphylococcus aureus are common causes Peptostreptococcus, Fusobacteroides, and Bac teroides species are commonly isolated, as well as Enterobacter spp., Escherichia coli, Ser ratia marcescens, Klebsiella, and Proteus spp. Acinetobacter is a new emerging pathogen MRS A is increasing in prevalence Viruses are recognized as causes. \200 \200 \200 \200 Management \200 Patients developing pneumonia within 48 h of arrival in hospital can be treated with standa rd community-acquired pneumonia antibiotics (see p 430), as the pneumonia is likely to be d ue to bacteria acquired in the community Patients developing pneumonia more than 48 h after hospital admission need antibiotics to cover different organisms Intravenous, prolonged tr eatment is usually needed, with cover for Gram-negative anaerobic bacteria. This is best do ne by using a second-generation cephalosporin, e.g. cefuroxime 750 mg \200\2231.5 g tds, wi th an aminoglycoside, e.g. gentamicin 7 mg/kg od (unless renal impairment), with levels at 8 \200\22312 h, to determine dose interval Supportive treatment is also required, with oxyg en, \202 uids, and ventila- tion if necessary In penicillin-allergic patients clindamycin or cipro \202 oxacin can be used (as long as Streptococcus pneumoniae is not thought to b e the infecting agent). Levo \202 oxacin has better pneumococcal cover Complications of no socomial pneumonia are the same as for community-acquired pneumonia, including lung abscess and empyema. Drug fever, sepsis with multi-organ failure, and pulmonary embolus with secon dary infection are all more common in nosocomial pneumonia In this situation, chest ultraso und (to look for empyema) or CT scanning may demonstrate abscess, underlying tumor, or infe ction at extrathoracic sites. HOSPITAL-ACQUIRED PNEUMONIA: MANAGEMENT 439 Prognosis It has a high mortality, ranging between 20 and 50%. Prevention Meticulous hygien e and hand washing by medical staff, in addition to careful infection control measures have been shown to reduce hospital-acquired pneumonia. Post-operatively, early mobilization, careful cleaning and maintenance of respiratory equip ment, and pre-operative smoking cessation reduce infection rates. Some intensive care units use antibiotics to selectively decontaminate the gastrointestinal tract of Gram-negative b acilli. This has been shown to reduce infection rates, but there is no proven effect on mor tality or length of ITU admission. CHAPTER 40 Respiratory infection: bacterial 440 Ventilator-acquired pneumonia (VAP) De \201 nition Pneumonia in a mechanically ventilated patient, which develops 48 h after intubation. It has a prevalence of up to 65% in some uni ts. It is an independent predictor of mortality, and is the commonest nosocomial infection in ITU. Up to two-thirds of patients requiring mechanical ventilation for >48 h will develo p VAP. It has a mortality of 15 \200\22350%, increasing the length of ITU stay by an averag e of 6.1 days. The major cause is bacterial contamination of the lower respiratory tract from the aspirati on of oropharyngeal secretions, which is not pre- vented by cuffed endotracheal tube or tra cheostomy. Diagnosis is suggested by \200 \200 New or progressive CXR in \201 ltrate Associated with fever, high WCC, and purulent secret ions There are many non-infectious causes of fever and CXR in \201 ltrate in ITU patients, so t he diagnosis is not always straightforward. Differential diagnosis of fever and CXR in \201 ltrate in ITU \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 Chemical aspiration without infection Atelectasis ARDS Left ventricular failure PE with lun g infarction Pulmonary hemorrhage Cryptogenic organizing pneumonia (COP) Drug reaction Tumo r Lung contusion. Investigations \200 CXR often shows a non-speci \201 c in \201 ltrate, with air bronchograms being the best p redictor of the disease Airway sampling for microbiology \200 Bronchoscopic sampling Protected specimen brush (PSB) samples (with the tip of the bronchos cope placed opposite the ori \201 ce of an involved segmental bronchus, and the PSB advanc ed through its protective sheath into the airway) or BAL samples (from a sub- segmental bro nchus, with the end of the bronchoscope wedged into the airway, ideally >150 mL saline wash ) are the best methods to obtain lower airway samples with minimal contamination. VAP is di agnosed when an arbitrary threshold of organisms is grown on a BAL or PSB sample. The usual cut-offs are 1000 colony-forming units/mL (cfu/mL) for PSB samples, and >10,000 cfu/mL for BAL samples. The thresholds will vary from unit to unit, and the threshold for starting tr eatment will also vary. Quantitative culture of bronchopulmonary secretions leads to reduce d antibiotic use, and is associated with improved outcomes. Airway neutrophil counts may al so aid in making the diagnosis 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.