Community Acquired Pneumonia Prof. Dr. Çağrı BÜKE Yeditepe University Medical Faculty Infectious Diseases and Clinical Microbiology

CAP Ç. BÜKE Community-acquired pneumonia is responsible for great Mortality Morbidity High costs Suspected CAP is defined by acute symptoms and presence of signs of lower respiratory tract infection (LRTI) without other obvious cause For Definitive diagnosis of CAP new pulmonary infiltrate on chest radiograph is needed

Signs and Symptoms for CAP Ç. BÜKE Signs and Symptoms for CAP Dyspnoea Cough Fever New focal chest signs In elderly people, clinical presentation can have less evident; An altered state of consciousness, gastrointestinal discomfort, and fever can be absent Diagnosis is frequently delayed

Signs and symptoms for CAP Ç. BÜKE Signs and symptoms for CAP For some pathogens, unusual clinical presentations can be seen; Pneumonia due to Legionella spp.; can present with headache, confusion, diarrhoea, and clinical manifestations of hyponatraemia Pneumonia due to Mycoplasma pneumoniae; can be associated with upper respiratory involvement (otitis, pharyngitis), skin changes (Stevens-Johnson-like syndrome), and haemolytic anaemia.

Differential diagnosis of CAP Ç. BÜKE Differential diagnosis of CAP Many diseases and syndromes have clinical signs and symptoms that can mimic pneumonia Delays in correct diagnoses of CAP increase the risks of poor outcomes In patients with not-severe CAP, the main differential diagnosis is upper respiratory tract infection In these cases, clinicians should rely on; 1) clinical evaluations (including manifestations of LRTI, 2) focal chest sounds, exclusion of other possible diagnosis) and 3) point-of-care tests (eg, C-reactive protein [CRP])

Differential diagnosis of CAP Ç. BÜKE Differential diagnosis of CAP Patients with severe CAP; should be monitored for other life-threatening disorders Differentiation of pneumonia from non-infectious disorders such as acute heart failure is occasionally difficult Prompt start of antibiotic treatment is recommended Biomarkers (eg, procalcitonin [PCT]) can help; In the early differentiation from heart failure Avoiding antibiotic misuse

Recurrent pneumonia Ç. BÜKE In patients with recurrent pneumonia, underlying diseases should be suspected such as; Lung cancer Metastasis Tuberculosis Foreign bodies Hypersensitivity pneumonitis Unknown immunosuppressed status

Epidemiology Ç. BÜKE Worldwide incidence 0.5-1.1% annually in Europe The rate is increasing with age 6/1000 patients 16-59 years 20/1000 patientrs 60-74 years 34/1000 patients over 75 years Incidence in Turkey The patients admitted to primary health care institutions with pneumonia symptoms is 2.8% /year Cause of hospitalisation due to CAP is 1.9% /year

Ç. BÜKE Epidemiology Short-term mortality (in-hospital and 30 day mortality) for Hospitalised patients ranges from 4·0% to 18·0% Patients in intensive care, this rate can reach 50% Costs related to CAP are high Only few approaches (such as reducing the length-of-stay, adequate use of antibiotics, and the introduction of vaccines) have reduced these costs so far

Causative pathogens Ç. BÜKE Streptococcus pneumoniae is the main pathogen that causes CAP worldwide, independent of age In Europe, nearly 35% of cases, worldwide it is about 27.3% The introduction of the conjugated pneumococcal vaccine in children has decreased the incidence of the invasive penicillin-R cases; but infections with serotypes not affected by the vaccine have increased About 90 distinct pneumococcal serotypes have been identified throughout the world

Causative pathogens Ç. BÜKE The polysaccharide vaccine consists of purified capsular polysaccharides from the 23 serotypes causing about 90% of invasive pneumococcal infection in industrialized countries. Pneumococcal conjugate vaccines contain polysaccharides from 13 serotypes covering 65–80% of serotypes associated with invasive pneumococcal disease among young children in western industrialized countries.

Causative pathogens Ç. BÜKE Other frequent causes include Haemophilus influenzae, which accounts for 12% (2·4–44·9%) of cases Atypical bacteria (including Mycoplasma, Chlamydia, and Legionella spp), which caused 22% of cases In adults, viruses, particularly influenza, rhinovirus, and coronaviruses, cause a third of cases of pneumonia

Pathophysiology Ç. BÜKE In healthy individuals, many microorganisms colonise the nasopharynx and oropharynx Microaspiration of contaminated secretions can cause infections in the lower airways The glottal reflexes, the presence of complement proteins and immunoglobulins, the secretion of peptides with antimicrobial activities, and the inhibition of bacteria binding all protect the lower airways The healthy microbiota of the upper airway also exert protection effects

Pathophysiology Ç. BÜKE In healthy individuals, many microorganisms colonise the nasopharynx and oropharynx The use of broad-spectrum antibiotics can modify the microbiota and predispose to infection The interactions between the virulence of the pathogens, the amount of inoculum, and the innate and adaptive immune responses determine the development of pneumonia

Ç. BÜKE Risk factors All individuals are at risk for development of pneumonia However, some individuals are more prone to pneumonia than are others due to intrinsic and extrinsic factors New findings have revealed individual genetic variability in the predisposition to the development of pneumonia and its clinical presentation Specific variants of the FER gene are associated with a reduced risk of death in patients with sepsis due to pneumonia TLR6 polymorphism is associated with increased risk of Legionnaires’ disease

Diagnosis of pneumonia Ç. BÜKE Diagnosis of pneumonia Laboratory evaluation In patients who clinicians suspect to have community- acquired pneumonia, blood tests can provide information about the inflammatory state Leucocyte cell number and characteristics [neutrophilia] CRP Biomarkers can support clinicians in the differentiation of bacterial pneumonia from other disorders Antibiotic is encouraged PCT concentrations; higher than 0·25 μg/L; and is strongly encouraged, PCT concentrations higher than 0·5 μg/L

Diagnosis of pneumonia Ç. BÜKE Diagnosis of pneumonia Microbiological evaluation Microbiological evaluations are recommended for higher-risk patients such as those with; Severe CAP, Special disorders (eg, asplenia, immunosuppression, HIV infection, and alcohol abuse) Septic shock A risk of resistant pathogens Failure of the initial empirical treatment

Diagnosis of pneumonia Ç. BÜKE Diagnosis of pneumonia Microbiological evaluation Although a positive blood (or pleural fluid) culture test definitively identifies the pathogen responsible for pneumonia, A positive respiratory tract sample needs clinical interpretation because the microorganism can be present due to colonisation or be part of the healthy flora The collection of any sample after the administration of antibiotics increases the rate of false-negative results.

Diagnosis of pneumonia Ç. BÜKE Diagnosis of pneumonia Urinary antigens Urinary antigens are useful for the detection of all serotypes of S pneumoniae and For serogroup 1 of Legionella pneumophila (responsible for about 90% of legionella cases of CAP). Advantages of these tests are promptness (<15 min), reasonable accuracy, and the ability to detect the infection while the patient is receiving antibiotic therapy The urinary antigens have a sensitivity of 75% and a specificity of 97%

Diagnosis of pneumonia Ç. BÜKE Diagnosis of pneumonia Blood serology test Available for Chlamydia pneumoniae, M pneumoniae, and Legionella spp; however, their clinical usefulness is limited by the delay in the results and difficulty in interpretation PCR Available for bacterial causes related to Mycoplasma, Chlamydia, Streptococcus, and Legionella spp, which have to be done on bronchoalveolar lavage fluid or nasopharyngeal swabs PCR tests are available for several respiratory viruses

Diagnosis of pneumonia Ç. BÜKE Diagnosis of pneumonia Imaging Thoracic images are essential for several aspects of pneumonia management Chest radiograph has diagnostic accuracies of 75% for alveolar consolidation and 47% for pleural effusion CT is considering as the gold standard technique But CT has limitations that include increased cost, radiation exposure, and the impossibility of doing CT at the bedside Lung ultrasound is a useful method for pneumonia with a sensitivity of 94·0% (95% CI 92·0–96·0) and a specificity of 96·0% in adults

Management of pneumonia Ç. BÜKE Management of pneumonia Two questions need to be answered; Does the patient need to be admitted in the hospital and Should they be treated in intensive care Scores and biomarkers can assist the clinical judgment The Pneumonia Severity Index (PSI) and CURB-65 are the most frequently used scores Patients should be admitted to intensive care; when they require mechanical ventilation, vasopressors and have thrombocytopenia, hypothermia, and leucopenia

Ç. BÜKE - Confusion - Urea - Respiratory rate - Blood pressure - Age

Pneumonia severity index for CAP Ç. BÜKE Pneumonia severity index for CAP

Selection of antibiotics Ç. BÜKE Selection of antibiotics

Selection of antibiotics Ç. BÜKE Selection of antibiotics

Selection of antibiotics Ç. BÜKE Selection of antibiotics

Timing of antibiotic treatment Ç. BÜKE Timing of antibiotic treatment The first dose of antibiotics should be given as soon as possible after diagnosis of CAP The antibiotics should be started preferably within the first 4–8 h of hospital arrival In unstable patients with severe sepsis or septic shock, the time to the first dose is strongly associated with a reduction in mortality, and administration in the first hour after diagnosis is recommended

Respiratory support Ç. BÜKE Patients with acute respiratory failure due to pneumonia must be assessed early for a need for respiratory support and oxygen saturation is an important marker for outcome Patients with severe pneumonia are candidates for invasive mechanical ventilation, and a delay can lead to an increased mortality Patients with moderately severe disease can be cautiously managed with the use of non-invasive ventilation by trained staff

Antibiotic policy Ç. BÜKE When microbiological tests become available, it is important to re-evaluate antibiotic treatment Antibiotics should be adapted according to antibiogram results Narrowed according to the identified pathogen, and discontinued when a diagnosis of pneumonia is unlikely Most patients in hospital with CAP began treatment with an intravenous antibiotic A switch to oral therapy should be considered for patients who reach clinical stability

Duration of antibiotic therapy Ç. BÜKE Duration of antibiotic therapy 5 days of treatment should be given for low-severity pneumonia with clinical stability after 3 days of treatment 7 days should be given for severe pneumonia, which should be adapted depending on the improvements in symptoms and stability Biomarkers can be used to guide antibiotic duration. One-time PCT values lower than 0·25 μg/mL or a decrease from the peak by 80–90% are a strong indication that antibiotics should be discontinued

Prevention and vaccines Ç. BÜKE Prevention and vaccines Influenza vaccines are robustly associated with a reduced rate of pneumonia and better outcomes 30% reduction in the rate of pneumonia and influenza infection in individuals older than 65 years old Two vaccines are available for S pneumoniae: the pneumococcal polysaccharide vaccine and the pneumococcal conjugate vaccine

Prevention and vaccines Ç. BÜKE Prevention and vaccines By comparison with pneumococcal polysaccharide vaccine, the pneumococcal conjugate vaccine seems to induce a stronger and longer-lasting secondary immune response with booster effect The US Centers for Disease Control and Prevention recommended the administration of both pneumococcal conjugate vaccine-13 and pneumococcal polysaccharide vaccine-23 in series to all adults aged 65 years and older

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