Community Acquired Pneumonia (CAP)

Community Acquired Pneumonia (CAP) The following guidelines have been developed to aid clinicians in the investigation and management of patients with CAP at the Royal Liverpool University Hospital (RLUH). Please note that these guidelines do not apply to patients with: - Exacerbations of COPD - Bronchiectasis - Hospital Acquired Pneumonia (HAP) - Aspiration pneumonia - Confirmed or suspected immunocompromised status, such as those patients with HIV infection, or those receiving immunosuppressive drugs, including high dose systemic corticosteroids. When signs of sepsis are evident, the inclusion of Gram-negative cover should be considered. Patients who are systemically unwell with signs of sepsis should receive a dose of Gentamicin in addition to standard therapy, if the diagnosis of CAP is in any doubt. Background The incidence of CAP requiring hospitalisation in the UK varies with age, from 0.3 per 1000/yr in the 18-39 age group to 13 per 1000/yr in those >55 yrs. The overall mortality rate is ~ 6-12%, but >30% in severe CAP. An organism can be identified in research studies in ~ 70% of cases: the commonest pathogen is Streptococcus pneumoniae. The prevalence of penicillin resistance with pneumococci in Merseyside is ~4%, only half of which is high level. At the RLUH in 2009-2010, only 0.5% of S. pneumoniae isolates from sputum were fully resistant to Penicillin. Diagnosis and severity assessment Patients may be defined as having Community-acquired pneumonia if: They present with at least one symptom of lower respiratory tract infection and There are either signs consistent with consolidation or radiological changes consistent with pneumonia, and this has developed in the community or within 48 hours of hospital admission, with no hospital in-patient treatment during the preceding 30 days A normal CXR does not automatically exclude a diagnosis of CAP. However, a normal CXR in the absence of local chest signs makes CAP unlikely. 1

If the patient has CAP, assess the severity using the CURB-65 score (0-5), which is a prospectively validated predictor of severity and mortality, but which does not replace clinical judgement. Score 1 for each criterion met: Confusion- new mental confusion with abbreviated mental test score of 8 or less Urea >7mmol/l Respiratory rate 30/min Blood pressure -systolic <90 mm Hg and/or diastolic 60mm Hg 65 age 65 years Patients with a score of 0-1 are considered to be Mild and can be managed as an outpatient (mortality <3%). A score of 2 indicates Moderate severity (mortality 9%) and patients should be admitted to hospital. A score 3 indicates Severe CAP (mortality >30%) and patients should be assessed for HDU or ITU (see below). The CURB-65 score should be interpreted in conjunction with clinical judgment. The following are additional adverse prognostic features, which may be indicative of greater disease severity than reflected by the CURB-65 score: - Hypoxemia (SpO 2 <92% or PaO 2 < 8 kpa) regardless of FiO 2 - Bilateral or multilobar involvement on CXR - White cell count <4 or >20 - Presence of significant co-morbidities Remember to ask about occupation, pets, illicit drugs, sexual and travel history where appropriate Investigations All patients should have the following investigations on admission: Blood Tests - FBC - U+Es - Glucose - LFTs - CRP Chest X-ray 2

Microbiological Tests (Table 1, Appendix) Microbiological investigation is not routinely required in cases of Mild CAP (CURB-65 score 0 or 1) - Sputum should be sent for culture in: - patients with Moderate CAP (CURB-65 score 2) if purulent and patients have not already received antibiotic therapy - all cases of Severe CAP - cases where there is a failure to improve on apparently appropriate therapy Sputum culture for Legionella may be requested when there are specific clinical or epidemiological grounds for suspicion - Blood cultures should be sent in all cases of moderate or high severity (CURB-65 2), before antibiotic treatment is commenced. - Urine should be sent for Legionella and pneumococcal antigen testing in severe cases admitted to ITU (do not request urine culture and sensitivity). Legionella antigen testing should also be considered when specific risk factors are identified, or during outbreaks. Requests for antigen testing not pertaining to ITU patients, should be discussed with a Microbiologist. - Nose/throat swabs in viral transport medium for Mycoplasma pneumoniae and Chlamydia pneumoniae PCR tests should be considered in patients with: - severe CAP unresponsive to first antibiotic regimen or - strong suspicion of atypical pathogen on clinical, radiological or epidemiological grounds. When requesting PCR ensure the date of onset of respiratory symptoms is on the request form. - Respiratory virus PCR tests of respiratory tract specimens (nose/throat swabs in viral transport medium) should be requested during a seasonal epidemic or pandemic of influenza, - HIV testing should be offered to all patients with CAP under the age of 70 years. HIV testing should be considered and offered to patients over the age of 70 on a case by case basis. - Atypical serology is no longer recommended other than in certain exceptional circumstances. Such requests should be discussed with a Clinical Microibiologist. 3

Table 1: Microbiological investigation of CAP Summary of recommended microbiological investigations in immunocompetent patients according to severity Severity Investigations Comments CURB-65 score 0-1 No microbiological investigation routinely recommended Requests for PCR testing respiratory pathogens, and urine antigen testing, may be considered where there is a specific clinical or epidemiological reason CURB-65 score 2 Blood cultures recommended Urinary antigen testing may be arranged if clinical or Discuss with Medical Microbiologist (x 4425 or bl epidemiological suspicion 4415) Sputum for MC&S recommended, especially if purulent or no response to prior antibiotic therapy Upper respiratory tract sample for Mycoplasma/Chlamydophila/ Legionella PCRs Bronchial washings / Broncho-alveolar lavage Pleural fluid (when available) Discuss with Medical Microbiologist (x 4425 or bl 4415) Will be tested in full whenever received and clinical details indicate a diagnosis of CAP ITU patients Management Blood cultures Urinary antigen testing for Legionella, Strep pneumoniae Sputum for MC&S Respiratory sample for Mycoplasma/Chlamydophila/ Legionella PCRs Bronchial washings / BAL Pleural fluid (when available) recommended Initial Management Monitor pulse, BP, temperature, mental status, MEWS and SpO 2 at least twice daily, and at least 6-hourly in the severe group (more frequently if required) Commence Oxygen supplementation to keep PaO 2 >8 kpa and SpO 2 >92%. Correct any volume deficit with appropriate crystalloid and /or colloid and monitor hydration status and urine output carefully. (For weight-based fluid prescribing schedule refer to separate guideline on the hospital intranet). Prophylaxis of venous thromboembolism with low molecular weight Heparin should be considered for all patients who are not fully mobile (and recorded on ICE) Consider analgesia for pleuritic chest pain 4

Select an appropriate antibiotic regimen according to Table 2 Management of severe pneumonia Consider the possibility of Gram-negative septicaemia, particularly if sepsis is evident and if the diagnosis of CAP is in doubt. Treatment with IV Gentamicin (5mg/kg stat) in addition to standard antibiotic therapy, or treatment for Sepsis of unknown origin with Tazocin + Gentamicin, is recommended in such cases. Patients with Severe CAP (CURB-65 3) have a high mortality risk and their management must include: - Administration of first dose of antibiotics intravenously, as soon as possible - Consideration of notification to ITU or CCOT (see below) - Blood cultures - Urgent Pneumococcal and Legionella Antigen testing - Triage to either Respiratory Department (Wards 6X or 6Y) or Infectious Diseases (Wards 3X or 3Y). ** Patients with Severe CAP should not be managed on wards other than Respiratory or Infectious Diseases wards, unless under exceptional circumstances** Cases of severe CAP require senior medical review (Consultant or SpR) as soon as possible, and again within 12 hours. Further senior review should continue at least 12 hourly until there is evidence of clinical improvement. Consider referral for Critical Care Assessment if: - FiO 2 of 60% or greater is required to maintain O 2 sats >92% - multilobar or bilateral lung changes on a chest X-Ray - serious co-morbidities - circulatory collapse and/or organ dysfunction secondary to Systemic Inflammatory Response Syndrome (SIRS) Treatment escalation: If a patient is failing to respond to first-line treatment, a decision to escalate antibiotic treatment to IV Tazocin (4.5g TDS) plus IV Clarithromycin (500mg BD) can be considered at Consultant or SpR/ST3 or above level. [Please note that Tazocin is a Penicillin: Patients with Penicillin allergy who fail to respond to first-line antibiotics should be discussed with Medical Microbiology or Infectious Diseases] 5

Table 2: Empirical antibiotic therapy in CAP (record indication, CURB-65 Score & stop date on drug chart) IV Gentamicin (5mg/kg stat) should be added if the patient is septic and the diagnosis of CAP is equivocal Severity Location of treatment Antibiotic of choice Alternative Regime (Penicillin allergy) Mild (i.e. CURB-65 score 0-1) Home Amoxicillin PO 500mg TDS for 7 days Clarithromycin PO 500mg BD for 7 days Mild (i.e. CURB-65 score 0-1) Hospital (for other reasons e.g. social) Amoxicillin PO 500mg TDS for 7 days (give IV if unable to tolerate oral route) Clarithromycin PO 500mg BD for 7 days (give IV if unable to tolerate oral route). Moderate (i.e. CURB-65 score 2) Hospital (9% mortality) Amoxicillin PO 500mg TDS for 7 days AND Clarithromycin PO 500mg BD for 7 days Clarithromycin PO 500mg BD for 7 days (give IV if unable to tolerate oral route). OR (Give IV if unable to tolerate oral route). PO Doxycycline 200mg loading dose then 100mg BD Severe (i.e. CURB-65 score 3-5; MEWS 3 or based on clinical judgement) Hospital and HDU review if appropriate ( 30% mortality) Benzylpenicillin IV 2.4g QDS AND Clarithromycin 500mg IV BD Treatment duration 7-10 days, with step-down to PO Amoxicillin 500mg TDS and Clarithromycin 500mg BD if no pathogen identified Teicoplanin 800mg IV OD (give loading dose of 1.2g if >70kg) AND Clarithromycin 500mg IV BD. Discuss with microbiology if in doubt Treatment duration 7-10 days if no pathogen identified The antibiotic regimen may be modified when microbiology results become available, as outlined in Table 3. When no positive cultures have been obtained, treatment is according to the CURB-65 score: 7 days for non-severe and 7-10 days for severe pneumonia (may be extended further according to clinical judgment). Drug safety warning: Concomitant use of macrolide antibiotics (such as Clarithromycin) and statins may increase the risk of myopathy, and should be avoided. Statins should be stopped for the duration of treatment with clarithromycin. Macrolides should also be used with caution in patients with a predisposition to QT interval prolongation (e.g. concomitant use of other drugs which prolong QT interval). 6

Reviewing the antibiotic regimen All prescriptions for intravenous antibiotic treatment should be reviewed at least every 24 hours. The following features indicate response to treatment and step down to oral antibiotics can be considered. Resolution of fever for > 24 hours No cardiovascular instability Clinically hydrated, taking oral fluids and no concerns over absorption Resolution of tachypnoea and hypoxaemia Improving white cell count Table 3: Recommended antibiotic choices after pathogen identification Pathogen Preferred Alternative Duration (days) S pneumoniae Amoxicillin 500 mg-1g TDS PO or Benzylpenicllin1.2-2.4g QDS IV Clarithromycin 500 mg BD or Cefuroxime 750 mg 1.5g TDS IV 5-7 M pneumoniae and C pneumoniae C psittaci and C burnetti Legionella spp H influenzae Clarithromycin 500 mg BD, PO or IV Doxycycline 200mg loading dose then 100 mg BD Fluoroquinolone (PO or IV) (Consider addition of Rifampicin in severe cases) Amoxicillin 500 mg TDS PO or IV (if sensitive) Doxycycline 200 mg loading dose then 100mg BD orally Clarithromycin 500 mg BD, PO or IV Clarithromycin 500 mg BD PO or IV (Consider addition of Rifampicin in severe cases) Ceftriaxone 1g OD IV (If severe Penicillin allergy discuss with Microbiology or ID) 14 14 14-21 Gram negative enteric bacilli Depends on sensitivity results 14-21 P aeruginosa Piperacillin/Tazobactam 4.5g TDS Ciprofloxacin 400 mg BD IV 14-21 or 500mg BD PO S aureus (non MRSA) 14-21 Flucloxacillin 1-2g QDS IV + Rifampicin 600 mg OD or BD, PO or IV Teicoplanin 800 mg OD iv + Rifampicin 600 mg OD or BD, PO or IV 7 Failure to respond to treatment Patients failing to improve should be reviewed by a senior clinician (preferably Respiratory or Infectious Diseases). Review antibiotic dosage, compliance and whether absorption may be impaired. When patients with severe pneumonia are not improving within 24 hours of the initiation of appropriate antibiotic therapy, substitution of IV Benzylpenicillin with IV Tazocin should be considered. 7

Alternative diagnoses, such as pulmonary embolism, pulmonary oedema and underlying malignancy, should be considered, as should the possibility of sepsis arising from an alternative focus of infection. Other predisposing conditions might include aspiration, endobronchial obstruction (e.g. by inhaled foreign body), and bronchiectasis. The possibility of infection with rarer causative organisms, such as Mycobacterium tuberculosis or Legionella pneumophila, should be considered, as should the possibility of a previously undiagnosed immunosuppressive condition. Such patients may need to undergo further investigation, such as bronchoscopy and lavage. It may be appropriate to repeat the CXR to look for evidence of complications (e.g. development of empyema or lung abscess) see below. Monitoring for complications Repeat CRP and CXR and further investigations should be considered, in the light of any new information after the clinical review. - Parapneumonic effusion All patients should be referred to Respiratory Medicine for consideration of pleural ultrasound, thoracocentesis ± insertion of intercostal drain (ICD) - Empyema Diagnostic aspiration should be arranged, and fluid samples sent separately to Biochemistry (for ph, LDH and glucose measurement), and Microbiology (for culture & sensitivity testing). Turbid appearance, pus cells in pleural fluid on Gram stain or ph < 7.2, indicate pleural infection and necessitate early and effective pleural drainage with an ICD. Please refer to Respiratory Medicine. - Lung abscess Consider possibility of lung abscess in the event of slow clinical recovery. Raises possibility of less usual respiratory pathogens, including anaerobes, S aureus, gram negative enteric bacilli, and Strep milleri. May also be seen in influenza outbreaks. Consider poor dentition as possible predisposing factor in these patients. Management of community-acquired pneumonia during influenza outbreaks (see Department of Health guidelines) A patient with uncomplicated influenza admitted to hospital for other reasons and who has no risk factors for severe disease does not routinely require antibiotic therapy. The use of antibiotics should be reviewed daily. Prophylactic or prolonged use of antibiotics for pneumonia may increase the risk of late superinfection with resistant organisms, which is often associated with rapid deterioration. Patients with pre-existing co-morbidities (such as chronic lung, heart, renal, liver or neuromuscular disease and immunosuppression) who are therefore at high risk of severe disease and complications, and who present with an influenza-like illness, should be strongly considered for antibiotics in addition to antiviral treatment 8

Most patients with non-severe influenza-related pneumonia can be treated with oral antibiotics (e.g. PO doxycycline, co-amoxiclav or clarithromycin for 5-7 days). Antibiotics should ideally be administered within four hours of admission. Patients with severe influenza-related pneumonia should be treated promptly with parenteral antibiotics - IV co-amoxiclav plus clarithromycin is first line; IV Cefuroxime may be used instead of co-amoxiclav in penicillin-allergic patients. Discuss with Medical Microbiology or Infectious Diseases if in doubt. Antiviral treatment of patients with influenza or influenza-like illness is covered by a separate guideline. Follow Up Clinic review should be arranged for all patients at 4 to 6 weeks, and should include a follow-up CXR. Influenza and pneumococcal vaccination should be considered for patients who have been treated for CAP, based on current Department of Health guidelines Smoking cessation advice should be offered to all patients with CAP who are current smokers References British Thoracic Society. Guidelines for the management of community acquired pneumonia in adults: update 2009 Update. Thorax 2009; 64 (Suppl III):iii1-iii55 (available at http://www.brit-thoracic.org.uk) Department of Health influenza guidelines (2009) http://www.dh.gov.uk 9

Appendix: Algorithm for Microbiological Investigation of CAP 10