British Journal of Hospital Medicine Management of community-acquired pneumonia – essential tips for the physician on call --Manuscript Draft-- Manuscript Number: Full Title: Management of community-acquired pneumonia – essential tips for the physician on call Article Type: Education and training Corresponding Author: Jeremy S. Brown Centre for Inflammation and Tissue Repair London, UNITED KINGDOM Corresponding Author Secondary Information: Corresponding Author's Institution: Centre for Inflammation and Tissue Repair Corresponding Author's Secondary Institution: First Author: Jeremy S. Brown First Author Secondary Information: Order of Authors: Jeremy S. Brown Malcolm Avari Order of Authors Secondary Information: Abstract: Community-acquired pneumonia (CAP) is a common clinical problem requiring admission to hospital, with a particularly high incidence in the elderly population and those with significant comorbidities. Diagnosis is made on the combination of a short history of respiratory symptoms and systemic ill-health with new examination and / or radiological features of consolidation. Multiple other infective and non-infective conditions can mimic CAP, leading to misdiagnosis in 5-17% of cases. The CURB-65 scoring can identify high-risk CAP patients, but is insensitive at identifying patients requiring intensive care support and needs to be combined with clinical markers of potential severity. Both high admission levels of C-reactive protein and its failure to decline by >50% by day 4 after admission are associated with higher risk of complications, need for ventilation or inotropic support, and mortality. Empirical antibiotic therapy for most patients admitted to hospital is combination of a ß-lactam and a macrolide. Short-courses of antibiotics do not result in significantly different outcomes to longer courses unless the patient has developed complications such as a complex parapneumonic effusion. Implementation of a CAP care bundle into clinical practice has been demonstrated to improve mortality, and should be a high priority for all acute hospitals. Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation text and tables and figure Click here to access/download;Anonymous manuscript;Management of pneumonia BJHM submitted Management of community-acquired pneumonia – essential tips for the physician on call Malcolm Avari1, Jeremy S Brown2* 1Department of Respiratory Medicine, University College London Hospitals Trust, 235 Euston Road, London NW1 2BU, United Kingdom 2UCL Respiratory, Department of Medicine, University College London, Rayne Institute, 5 University Street, London WC1E 6JF, United Kingdom. *Corresponding author: Phone: +44 20 3108 7728 E-mail: [email protected]. Word count: 2865 (max 3000) Key words: community-acquired pneumonia; CURB-65; C-reactive protein; resistant organisms; care bundles Abstract Community-acquired pneumonia (CAP) is a common clinical problem requiring admission to hospital, with a particularly high incidence in the elderly population and those with significant comorbidities. Diagnosis is made on the combination of a short history of respiratory symptoms and systemic ill-health with new examination and / or radiological features of consolidation. Multiple other infective and non-infective conditions can mimic CAP, leading to misdiagnosis in 5-17% of cases. The CURB-65 scoring can identify high-risk CAP patients, but is insensitive at identifying patients requiring intensive care support and needs to be combined with clinical markers of potential severity. Both high admission levels of C-reactive protein and its failure to decline by >50% by day 4 after admission are associated with higher risk of complications, need for ventilation or inotropic support, and mortality. Empirical antibiotic therapy for most patients admitted to hospital is combination of a ß-lactam and a macrolide. Short-courses of antibiotics do not result in significantly different outcomes to longer courses unless the patient has developed complications such as a complex parapneumonic effusion. Implementation of a CAP care bundle into clinical practice has been demonstrated to improve mortality, and should be a high priority for all acute hospitals. Key points: Accurate interpretation of the chest radiograph is key to identifying potential differential diagnoses and complications of CAP. The CURB-65 scoring system is an essential management tool for CAP but is insensitive at identifying severe cases requiring intensive care treatment, and needs to be combined with a clinical assessment of physiological markers of severity. Failure of the admission C-reactive protein level to fall by <50% at day 4 is associated with higher risk of mortality, complications and invasive ventilation / inotrope use. The outcomes of short-course and long-course antibiotic treatments for CAP patients are similar. CAP mortality can be reduced by establishing appropriate systems of care to ensure care bundles are adhered to. Introduction and background on pneumonia Pneumonia occurs when the alveoli become infected with microorganisms, causing a local and systemic inflammatory response that results in the alveoli filling with exudative fluid and inflammatory cells. It is this local alveolar inflammatory reaction to the infection which leads to consolidation, the clinical hallmark of pneumonia. Extensive consolidation compromises gas exchange and can lead to life-threatening hypoxia (Quinton et al. 2018). Pneumonia is classified according to the patient’s location when they acquired the infection. Community- acquired pneumonia (CAP) occurs when infection is acquired outside the hospital and is by far the commonest type of pneumonia. CAP has an overall incidence estimated between 1.5 and 14 cases per 1000 person-years depending on geographical location, the season (with a distinct increase in winter in the UK) and characteristics of the population (Prina et al. 2015). Hospital acquired pneumonia (HAP) is pneumonia acquired 48 hours after admission to hospital or within 14 days after discharge from hospital. Ventilator acquired pneumonia (VAP) is a subset of HAP affecting patients 48 hours after endotracheal intubation (Jean et al. 2020). This classification allows clear communication between clinicians about the patient’s condition, but importantly also ensures the correct empirical antibiotic therapy is chosen as the potential infecting microorganisms vary between CAP, HAP and VAP. Pneumonia developing in patients with a severe degree of immunosuppression such as chemotherapy- induced neutropenia, after organ transplantation, or in patients with advanced Human Immunodeficiency Virus (HIV) infection are considered separately due to the extensive range of potential causative microorganisms (Di Pasquale et al. 2019). Pneumonia is one of the most commonly encountered respiratory infection accounting for approximately 230,000 deaths in Europe (29,000 in the UK) per year, and in the UK is responsible for more hospital admissions than any other lung disease (Chalmers et al. 2017; Marshall et al. 2018). For CAP patients admitted to hospital the 30-day mortality rate is between 5-15% (Chalmers et al. 2017). The incidence of pneumonia is increasing over time, and at present Europe spends €5.7 billion per year on inpatient care and half a billion on outpatient care for patients with pneumonia (Chalmers et al. 2017). The incidence of CAP and risk of death are related to age, sex and the presence of comorbidities (Prina et al. 2015; Luna et al. 2016). CAP is commoner in older adults with approximately 45% of cases in the over 65 years age group (Cillóniz et al. 2018), and the incidence is also higher in males than in females (Prina et al. 2015). The exponential increase in CAP incidence after 65 years of age is partially due to the presence of comorbidities associated with CAP, but is also probably related to immunosenescence – the decreased efficacy of the adaptive and innate immune systems with increasing age (Cillóniz et al. 2018). The mortality of CAP is also higher in patients with more than one comorbidity and some specific comorbidities eg cardiac failure (20.5%) compared to patients with chronic obstructive pulmonary disease (COPD) (8.1%) (Luna et al. 2016). This article will explore the diagnostic features of CAP, some of the potential traps for misdiagnosis, the recognition of possible complications and patients with severe disease, and discuss some of the important issues when selecting appropriate antibiotic treatment. Diagnosis of CAP and diagnostic pitfalls To make a diagnosis of CAP requires evidence of new lung consolidation (eg dyspnoea, pleuritic chest pain, signs of consolidation, and / or air space shadowing on the chest radiograph) associated with evidence of a significant inflammatory response (eg a fever, tachycardia, and raised C-reactive protein or erythrocyte sedimentation rate) (Lim et al. 2009). However, these features also occur in many other less common conditions. Although a pyrexia and raised biomarkers such as C-reactive protein may suggest an infective aetiology, they are not specific for infectious causes of inflammation (Black 2016) and are often abnormal in non- infective causes of lung inflammation. Perhaps 5-17% of patients admitted to hospital with a diagnosis of CAP actually have non-infectious mimics of CAP (Black 2016), the correct diagnosis of which will enable the patient to receive appropriate treatment. An important clinical point is that CAP will usually present with