Pulmonary Infections PDF

Pulmonary infections Eric Harp, DO 1 Learning objectives 1. Describe the general mechanisms underlying pneumonia 2. Describe general clinical presentation, pathophysiology, most common etiologies and potential complications of community acquired pneumonia 3. Describe general clinical presentation, p...

Pulmonary infections Eric Harp, DO 1 Learning objectives 1. Describe the general mechanisms underlying pneumonia 2. Describe general clinical presentation, pathophysiology, most common etiologies and potential complications of community acquired pneumonia 3. Describe general clinical presentation, pathophysiology and most common etiologies of viral pneumonia 4. Describe general clinical presentation and setting, pathophysiology and most common etiologies of atypical pneumonia 5. Describe risk factors, clinical setting and most common etiologies of healthcare associated pneumonia 6. Describe general clinical presentation and setting, pathophysiology of pneumonia due to opportunistic infections 7. Describe the general treatment strategy of pneumonia 8. Describe the diagnosis of community acquired pneumonia including use of laboratory tests 9. Describe management decisions regarding community acquired pneumonia including Site of care Antibiotics selection 10. Describe the rationale and use of procalcitonin and lactate in the workup and management of pneumonia 11. Describe the rationale behind and examples of empiric treatment of community acquired pneumonia 12. Describe selected and emphasized clinical examples regarding treatment of resistant organisms 13. Describe osteopathic considerations in patients who present with symptoms attributable to lower respiratory infections 2 Infections Respiratory tract infections are more frequent than those involving any other system Largest number of lost workdays Vast majority are of upper respiratory tract infections caused by viruses (rhinitis-common cold, pharyngitis-sore throat) Bacterial, viral, mycoplasmal, and fungal infections of the lung (pneumonia) account for an enormous amount of morbidity Responsible for large number deaths in the United States 3 United States mortality 4 Pneumonia Broadly defined as any infection of the lung parenchyma Can result when systemic resistance lowered chronic diseases, immunologic deficiencies, treatment with immunosuppressive agents, and leukopenia local defense mechanisms impaired Local pulmonary defense mechanisms may be compromised by many factors: Loss or suppression of cough reflex result of altered sensorium (ie-coma), anesthesia, neuromuscular disorders, drugs, or chest pain any of which may lead to aspiration of gastric contents Dysfunction of the mucociliary apparatus cigarette smoke inhalation of hot or corrosive gases viral diseases genetic defects of ciliary function (ie-immotile cilia syndrome) cystic fibrosis 5 Pneumonia Local pulmonary defense compromised continued: Accumulation of secretions Examples: cystic fibrosis bronchial obstruction Interference with phagocytic and bactericidal activities of alveolar macrophages alcohol, tobacco smoke, inhaled antigens (silica), anoxia, or oxygen intoxication Pulmonary congestion and edema 6 Pneumonia Classified based on etiologic agent (if known) if no pathogen can be isolated (occurs in about 50% of cases), by the clinical setting in which the infection occurs narrows list of suspected pathogens provides guide for empirical antimicrobial therapy seven distinct clinical settings (“pneumonia syndromes”, shown) implicated pathogens are fairly specific to each category 7 Robbins and Cotran. Pathologic Basis of Disease. Tenth Edition. Table 15.7 Pneumonia Pneumonia syndromes, continued 8 Pneumonia pneumonia Community acquired typical atypical chronic pneumonia Healthcare associated Hospital-48 hours after admission Viral pneumonia 9 Typical community-acquired pneumonia A leading cause of death in the United States Majority (> half) are caused by bacteria Viral pneumonias are less common, sometimes considered “atypical” COVID-19-notable exception to historical impact of viral pneumonia Most often due to Streptococcus pneumoniae (50–75% of cases) “Old man’s friend”-Osler Common cause of hospital death 10 Typical community-acquired pneumonia Community-acquired refers to lung infection in otherwise healthy individuals that is acquired from the normal environment Example: in the community, not necessarily from the community Most often due to Streptococcus pneumoniae (50–75% of cases) Streptococcus pneumonia lives in nasopharynx of asymptomatic patients Often follows viral infection (upper or lower respiratory infection) Affected patients are often: compromised (already somewhat sick) elderly debilitated 11 Typical community-acquired pneumonia Pathophysiology Mechanism: Aspiration of oropharyngeal contents (ie-during sleep)-most common cause Inhalation of aerosol droplets containing bacteria hematogenous spread mostcommoy Involving either or both lower lobes and right middle lobe is most common to preach Gram stain -numerous Gram-positive lancet-shaped diplococci with tapered ends pointing to each other -also described as cocci in pairs or short chains Optochin sensitive (vs viridans) Bacteria invade lung parenchyma Cause alveoli to be filled with an inflammatory exudate, thus causing consolidation consolidation (“solidification”) Lobar pneumonia 12 Goljan. Rapid Review Pathology. Figure 17-4 Typical community-acquired pneumonia Two patterns of anatomic distribution: (lobular) bronchopneumonia patchy consolidation but may still “appear” to be within a lobe or lobes more common lobar pneumonia consolidation of a large portion of a lobe or of an entire patterns may overlap patchy involvement may become confluent, producing lobar consolidation same organisms may produce either pattern depending on patient susceptibility Pattern is less important than identification of the causative agent and determination of the extent of disease 13 Robbins and Cotran. Pathologic Basis of Disease. Tenth Edition. Figure 15.32 Typical community-acquired pneumonia bronchopneumonia lobar pneumonia consolidation of a large portion of a lobe or of an entire lung patchy consolidation good bod 14 Robbins and Cotran. Pathologic Basis of Disease. Tenth Edition. Figure 15.33-34 Robbins Atlas of Pathology. Fourth Edition. Figure 5.69 Typical community-acquired pneumonia Bronchopneumonia patchy consolidation often centered on bronchioles Inflammation involves bronchioles and surrounding alveoli areas of inflammation can be bilateral, involve multiple lobes, and lung bases pattern more common in susceptible populations very young, old, terminally ill variation in causative organisms: Strep pneumonia Hemophilus influenza Pseudomonas aeruginosa 15 Robbins Atlas of Pathology. Fourth Edition. Figure 5.65 Typical community-acquired pneumonia Lobar pneumonia consolidation of lobe or of entire lung Streptococcus pneumoniae most commonly (up to 95%)(shown) Klebsiella pneumoniae 16 Robbins and Cotran. Pathologic Basis of Disease. Tenth Edition. Figure 15.34 Typical community-acquired pneumonia Pathophysiology Classic phases of lobar pneumonia Congestion Edema, vascular congestion, hyperemia No fibrin nets (contribute to organization and consolidation) Red hepatization Involves neutrophils and hemorrhage (A, as shown) Early organization of exudate (B) Gray hepatization Involves degradation of red blood cells Advanced organizing pneumonia Exudate (neutrophils, edema fluid and blood) have been converted to fibromyxoid masses rich in macrophages and fibroblasts (C) Resolution 17 Robbins and Cotran. Pathologic Basis of Disease. Tenth Edition. Figure 15.35 Typical community-acquired pneumonia Clinical presentation Sudden onset of high fever with productive cough Chest pain Chills, can have rigors (shaking chills) Tachycardia and tachypnea Confusion (particularly in elderly) May be described as “change in cognitive or mental status” Memory Communication and language Ability to focus and pay attention Reasoning and judgment Visual perception https://www.cdc.gov/pneumococcal/about/symptoms-complications.html 18 Typical community-acquired pneumonia Clinical presentation Physical exam signs of consolidation (representing exudative fluid in alveolar airspaces) Dullness to percussion Increased vocal tactile fremitus Sound is transmitted well through alveolar consolidations Late inspiratory crackles Bronchial breath sounds bronchophony and egophony www.learningradiology.com 19 www.radiopaedia.org Typical community-acquired pneumonia Clinical workup Chest radiograph Patchy infiltrates (bronchopneumonia) or lobar consolidation Affected lung adjacent lung imaging demonstration of infiltrate required for diagnosis could be computed tomogram or ultrasound Laboratory findings* Positive Gram stain Sputum specimen Sensitivity~80% Neutrophilic leukocytosis on CBC Left shift (release of immature granulocytes) Blood cultures sometimes positive *may not always be performed Robbins Atlas of Pathology. Fourth Edition. Figure 5.69-70 20 Typical community-acquired pneumonia Complications Fibrous scarring Pleural adhesions Empyema trapped focus of acute inflammation between pleura layers Sepsis Abscess (shown) Collection of neutrophils and necrotic, degenerated material Associated with aspiration Commonly involves right middle lobe May involve a mixed flora containing both anaerobic and aerobic oral flora Early antibiotic intervention hopes to prevent Robbins Atlas of Pathology. Fourth Edition. Figure 5.73 21 Abscess Pulmonary abscess: local suppurative process that produces necrosis Can be multiple, as shown (white-yellow round lesions) Clinical features which may be suggestive of abscess: cough, fever with copious amounts of foul-smelling purulent or sanguineous sputum fever, chest pain, weight loss imaging needed Can mimic carcinoma Especially squamous cell (cavitation) Most commonly involves: aerobic and anaerobic streptococci Staphlococcus aureus other gram-negative organisms mixed infections often with inhalation of foreign material oral cavity anaerobic organisms Bacteroides, Fusobacterium, and Peptococcus genera 22 Robbins and Cotran. Pathologic Basis of Disease. Tenth Edition. 2021. Figure 3.15 Abscess Pathophysiology Potential underlying mechanisms: Aspiration of infective material (most common) Risk factors include: suppressed cough reflexes (acute alcohol intoxication, opioid abuse, coma, anesthesia, seizure disorders) severe dysphagia (neurologic deficits, esophageal disease), protracted vomiting poor dental hygiene Aspiration first causes pneumonia Progresses to tissue necrosis and formation of lung abscess (shown) 23 Robbins and Cotran. Pathologic Basis of Disease. Tenth Edition. Figure 15.36 Robbins Atlas of Pathology. Fourth Edition. Figure 5.76 Abscess Pathophysiology and potential mechanisms: Antecedent primary lung infection “postpneumonic” abscess formations associated with S. aureus, K. pneumoniae, and pneumococcus Cavitation common with Staph, as shown (upper right) bronchiectasis posttransplant or immunosuppressed at special risk Septic embolism infected emboli may arise from thrombophlebitis in any portion of the systemic venous circulation from the vegetations of infective bacterial endocarditis on the right side of the heart and lodge in the lung can be multiple, as shown (lower) 24 Robbins and Cotran. Pathologic Basis of Disease. Tenth Edition. Figures 3-15, 15.36 Abscess Pathophysiology contributing mechanisms: Neoplasia (obstruction from…) Can occur in bronchopulmonary segments obstructed by a primary or secondary malignancy (postobstructive pneumonia, as shown) Obstruction could lead to abscess is compromised typical a person Digumarthy, S; Shepard, J. Thoracic Radiology. 2010. Figure 13-12 B 25 Corrin, B. Pathology of the Lungs. 2011. Figure 12.1.9 atypical (community acquired) pneumonia “atypical” describes both the presentation and causative organism Most commonly caused by Mycoplasma pneumoniae 20% of cases “walking pneumonia” why healthy Young adults and pediatrics Common in communal settings and can spread (concern in dormitory, basic training, prisons) Peculiar associations: atypical gets pple Organism has no cell wall Patient may have cold agglutinins (IgM) Other pathogens Legionella (contaminated aerosolized water/air-conditioning, also immunocompromised) May see upper lobe involvement Chlamydophila pneumoniae Viruses: Respiratory syncytial virus, influenza adenovirus patchy reticulonodular opacities, especially seen in the perihilar lung Chlamydia trachomatis in newborns https://radiopaedia.org/cases/mycoplasma-pneumoniae-pneumonia Mycoplasma pneumonia 26 atypical pneumonia Clinical presentation Slower onset Insidious onset more insidious Low-grade fever Nonproductive cough (dry) Chest pain Flu-like symptoms versus typical which is: Rapid onset (more acute) High fever Productive cough -Myalgias less commonly reported Confusion in elderly Pharyngitis, laryngitis, myalgias, headache, arthropathy Less likely to show signs of consolidation on physical exam (or imaging, but can) Imaging shows patchy, perihilar reticulonodular opacities 27 atypical (community acquired) pneumonia “atypical” describes both the presentation and causative organism Summary features: Insidious, mild fever, dry cough Contracted by inhalation (droplet infection) Patchy interstitial pattern pneumonia (shown) Mononuclear infiltrate (ie-lymphocytes) Alveolar spaces usually free of exudate patchy reticulonodular opacities, especially seen in the perihilar lung Plain-film imaging (shown) Bilateral perihilar interstitial infiltrates Peribronchial/perivascular interstitial infiltrates reticular densities Laboratory findings: drows sick blond I was Leukocytosis Positive IgM serology for Mycoplasma IgMs can result in cold agglutination and possible hemolysis of red cells https://radiopaedia.org/cases/mycoplasma-pneumoniae-pneumonia 28 Mycoplasma pneumonia Community-acquired viral pneumonia Viral infections are common Can cause common “cold” or more severe lower respiratory tract infection Factors that may promote extension of infection to lung include: extremes of age malnutrition alcoholism underlying debilitating illnesses Viruses Influenza virus types A and B Orthomyxoviridae RNA core surrounded by a lipid envelope classified based on antigenicity of their hemagglutinin and neuraminidase surface glycoproteins Coronavirus respiratory syncytial viruses human metapneumovirus adenovirus rhinoviruses rubeola varicella 29 Community-acquired viral pneumonia Pneumonia associated viruses produce disease through similar general mechanisms Tropisms allow attachment to and entrance into respiratory lining cells Viral replication and gene expression leads to cytopathic changes cell death secondary inflammation (ie-COVID-19) Resulting damage can impair local pulmonary defenses ie-mucociliary clearance May predispose to bacterial superinfections often more serious than the viral infection itself 30 Community-acquired viral pneumonia Pathophysiology of inflammation and cell death from viral pneumonia Virus infection inhibits sodium channels produces electrolyte and water shifts can lead to fluid accumulation in the alveolar lumen Cells die by Findings are in keeping with atypical pneumonia Reticulonodular opacities, bilateral, lower lobes Can be severe lead to acute lung injury (COVID pneumonia shown) inhibition of host cell messenger RNA translation activation of caspases leading to apoptosis Death of epithelial cells exacerbates the fluid accumulation Release of “danger signals” that activate resident macrophages 31 https://radiopaedia.org/articles/covid-19-summary?lang=us Community-acquired viral pneumonia Pathophysiology of inflammation and cell death from viral pneumonia infected epithelial cells release a variety of inflammatory mediators interstitial pneumonitis, patchy hyaline membranes and prominent intraalveolar edema from viral pneumonia chemokines and cytokines activate nearby pulmonary endothelium and serve as chemoattractants for neutrophils some cases may cause sufficient lung injury to produce acute respiratory distress syndrome-acute lung injury (severe COVID reactions) patient is at risk for superimposed bacterial pneumonia 32 Zander. Pulmonary Pathology. Second Edition. Figure 13.3. 2018 Community-acquired viral pneumonia Pathologic findings Gross (and clinical) mucosal hyperemia and swelling overproduction of mucus secretions swollen mucosa and viscous exudate may plug the nasal channels, sinuses, or the Eustachian tubes, leading to secondary bacterial infection virus-induced tonsillitis causing lymphoid hyperplasia plugging of small airways may give rise to focal lung atelectasis severe widespread plugging of secondary and terminal airways by cell debris, fibrin, and inflammatory exudate may can lead to organization and fibrosis if prolonged 33 Community-acquired viral pneumonia Pathologic findings Histology lymphocytes predominant inflammatory pattern is interstitial involving alveolar walls septa and interstitium are widened and edematous invaded by mononuclear inflammatory infiltrate of lymphocytes ( ), macrophages, and occasionally plasma cells COVID-19 can cause acute lung injury (diffuse alveolar damage-associated histology) Robbins Atlas of Pathology. Fourth Edition. Figure 5.76 viral infection 34 Community-acquired viral pneumonia Influenza Orthomyxoviridae single-stranded RNA Influenza type A major cause of pandemic and epidemic influenza infections major virulence factors: hemagglutinin and neuraminidase proteins both are proteins embedded in the influenza lipid bilayer RNA viral envelope hemagglutinin involved in viral attachment neuraminidase facilitates release of newly formed virions Oseltamivir, neuraminidase inhibitor 35 Community-acquired viral pneumonia Human Metapneumovirus paramyxovirus most common in young children, elderly adults, and immunocompromised patients 5-10% of pediatric hospitalizations 12-20% of outpatient pediatric visits of children suffering from acute respiratory tract infections Human Coronaviruses Most cause mild cold-like upper respiratory tract infections SARS-CoV-2 binds to ACE2 protein in lower respiratory cells susceptible patients, typically older individuals with comorbid conditions host immune response and locally released cytokines can lead to acute lung injury and ARDS (shown) 36 Zander. Pulmonary Pathology. Second Edition. Figure 13.4. 2018 Community-acquired viral pneumonia Clinical features extremely varied often occurs as upper respiratory tract infections or called “chest cold” often few localizing symptoms cough may be absent most conserved features: perihilar peribronchial thickening and interstitial infiltrates fever, headache, and myalgia spirometry and blood gases (if performed) often look worse than patient edema and exudation often cause ventilationperfusion mismatch leading to hypoxemia most resolve spontaneously without any lasting sequelae Imaging: bilateral perihilar peribronchial thickening and interstitial infiltrates 37 Case courtesy of Assoc Prof Craig Hacking, Radiopaedia.org, rID: 74252 Healthcare-associated pneumonia Former names include hospital-acquired or nosocomial Clinical and laboratory diagnosis No classic radiologic appearance Risk factors: Pseudomonas Gram negative rods Respirators/ventilators Most common source of infection Severe underlying disease Antibiotic therapy ICU Immunosuppression Pathogens Gram-negative bacteria Pseudomonas aeruginosa (respirators), Enterobacter, Acinetobacter, Escherichia coli Gram-positive bacteria (ie-Staphylococcus aureus) “necrotizing” or cavitary pneumonia, consider MRSA 38 Gram positive cocci in clusters Aspiration pneumonia Aspiration of gastric contents Occurs in debilitated patients while unconscious (ie-after a stroke) during repeated vomiting patients may have abnormal gag and swallowing reflexes that predispose to aspiration Note spray of aspirated material Pneumonia is partly chemical due to the irritating effects of gastric acid and partly bacterial (from the oral flora) Often more than one organism on culture Clinical: can be acute pneumonia often necrotizing fulminant clinical course frequent cause of death can cause acute lung injury lung abscess is common complication Klatt. Robbins Atlas of Pathology. Fourth edition. 39 “other” causative agents of pulmonary (respiratory) infections Moraxella catarrhalis can cause bacterial pneumonia, especially in elderly patients second most common bacterial cause of acute exacerbation of COPD otitis media in children along with S. pneumoniae and H. influenzae Staphylococcus aureus secondary bacterial pneumonia in children and healthy adults following viral respiratory illnesses ie-measles in children, influenza in both children and adults associated with a high incidence of complications lung abscess and empyema intravenous drug users at high risk for development of staphylococcal pneumonia in association with endocarditis healthcare-associated pneumonia 40 Causative agents of pulmonary infections Klebsiella pneumoniae Gram-negative bacterium More common in debilitated and malnourished people particularly chronic alcoholics Associated with thick, mucoid (often blood-tinged) sputum Produces an abundant viscid capsular polysaccharide, difficult to cough up Can be: patchy (bronchopneumonia, as shown upper) lobar (as shown, lower) Can destroy alveolar walls and form abscesses Can heal with scar formation 41 Farver, C. Pathology of Infectious Diseases. 2015. Figure 12-14. Desouches, et al. Mullers Imaging of the Chest. 2019. Figure 9.9 Causative agents of pulmonary infections Pseudomonas aeruginosa Healthcare-associated infections Pseudomonas Gram negative rods Superinfection in an influenza patient (as shown below) Cystic fibrosis immunocompromised and neutropenic patients propensity to invade blood vessels with extrapulmonary spread Pseudomonas septicemia is severe Requires antipseudomonal coverage ceftazidime ciprofloxacin (Cipro) or levofloxacin gentamicin cefepime aztreonam carbapenems ticarcillin Su, et al. Hournal of Microbiology and infection. 2019. Volume 52, Issue 2. Figure 1. 42 Causative agents of pulmonary infections Legionella pneumophila considered an “atypical” bacterial pneumonia also causes Pontiac fever, a related selflimited upper respiratory tract infection organism flourishes in artificial aquatic environments water-cooling towers and the tubing systems of domestic water supplies transmitted by: either inhalation of aerosolized organisms aspiration of contaminated drinking water 43 Causative agents of pulmonary infections Legionella pneumophila more common in patients with cardiac, renal, immunologic, or hematologic disease especially organ transplant recipients Pneumonia can be severe Frequently requires hospitalization High mortality in immunosuppressed patients Diagnosis can be made rapidly: detecting Legionella DNA in sputum using a polymerase chain reaction (PCR)– based test identification of Legionella antigens in the urine Culture still diagnostic gold standard, but takes 3-5 days 44 Chronic pneumonia Immunocompetent patients most often a localized lesion with or without regional lymph node involvement inflammatory reaction is often granulomatous caused by: Particular (peculiar) bacteria namely Mycobacterium tuberculosis (shown) Fungi Histoplasma capsulatum Immunocompromised patients Infections can be widespread and systemic typically, worse infection and outcomes opportunistic infections those that would not necessarily cause disease in immunocompetent patients Robbins and Cotran. Pathologic Basis of Disease. Tenth Edition. Figure 8-25 45 Chronic pneumonia Mycobacterium tuberculosis Acquired from inhalation of aerosolized bacilli Infection proceeds in steps 46 Robbins and Cotran. Pathologic Basis of Disease. Tenth Edition. Figure 8-24; Robbins Atlas of Pathology. Fourth Edition. Figure 5.80 Chronic pneumonia Mycobacterium tuberculosis initial infection of macrophages Th1 lymphocyte response Granuloma contains the bacteria Granulomatous response involves epithelioid macrophages, lymphocytes and fibroblasts Cytokine and T cell response can cause tissue damage 47 Robbins Atlas of Pathology. Fourth Edition. Figure 5.87-88 Mycobacterium tuberculosis Clinical presentation: Fever Night sweats Cough Weight loss Hemoptysis Imaging: Primary lung: upper lobe, apex Progressive disease: can show cavitation, miliary pattern or bronchopneumonia Diagnosis: requires identification of the presence of bacilli interferon gamma release assay (QuantiFERON) cannot differentiate between past, latent or current infection Case courtesy of Assoc Prof Frank Gaillard, Radiopaedia.org, rID: 8632 48 Mycobacterium tuberculosis Primary tuberculosis Initial exposure Ghon focus Granulomatous inflammation focus Often subpleural Caseous necrosis Ghon focus Ghon complex with lymph nodes Ghon complex Includes hilar lymph nodes with granulomas 49 Robbins and Cotran. Pathologic Basis of Disease. Tenth Edition. Figure 8-25 Mycobacterium tuberculosis Primary tuberculosis central granular caseation epithelioid and multinucleate giant cells use of special stain for acid-fast organisms is indicated when granulomas (C) are present D. macrophages with large numbers of mycobacteria (acid-fast stain) 50 Robbins and Cotran. Pathologic Basis of Disease. Tenth Edition. Figure 8-26 Mycobacterium tuberculosis Secondary tuberculosis Also known as reactivation Can be reactivation of quiescent infection or reinfection Often a friable nodule most commonly at the apex Disseminated infection Miliary pattern in lungs and other viscera Vertebral bodies Cervical lymph nodes Epidydimus Meninges 51 Robbins and Cotran. Pathologic Basis of Disease. Tenth Edition. Figure 8-27 Robbins Atlas of Pathology. Fourth Edition. Figure 5.89 Chronic pneumonia Histoplasmosis Histoplasma capsulatum infection acquired by inhalation of dust particles soil contaminated with bird or bat droppings Endemic associations: along Ohio and Mississippi rivers Caribbean seen many places: Mexico, Central and South America, parts of eastern and southern Europe, Africa, eastern Asia, and Australia 52 Chronic pneumonia Histoplasmosis An intracellular pathogen (inside phagocytes, like M. tuberculosis) Can show similar clinical presentation to tuberculosis (1) self-limited and often latent primary pulmonary involvement may result in small coin lesions on chest radiography (2) chronic, progressive, secondary lung disease Often localized to lung apices causes cough, fever, and night sweats (3) spread to extrapulmonary sites mediastinum, adrenal glands, liver, or meninges (4) widely disseminated disease in immunocompromised patients Histoplasmosis can occur in immunocompetent individuals but more severe in those with depressed cell mediated immunity 53 Chronic pneumonia Histoplasmosis pathogenesis incompletely understood always infects via the lung macrophages ingest but cannot kill organism without T-cell help allows organisms to multiply within phagolysosomes fungi disseminate prior to the development of T-cell immunity takes 1 to 2 weeks 54 Robbins and Cotran. Pathologic Basis of Disease. Tenth Edition. Figure 15-37 B Chronic pneumonia Histoplasmosis Th1 helper T cells recognize fungal antigens and secrete IFN- artifactual clear zone around central blue nucleus gives cell membrane the appearance of a capsule activates macrophages and enables them to kill intracellular yeasts Histoplasma induces macrophages to secrete TNF recruits and stimulates other macrophages to kill Histoplasma Robbins Atlas of Pathology. Fourth Edition. Figure 5.90 55 Chronic pneumonia Histoplasmosis Clinical presentation: fever, cough, malaise, headache, myalgia, polyarthralgia and abdominal pain clinical, imaging and pathologic(granulomas) similar to sarcoidosis Laboratory: antigen detection in urine, blood or lavage fluid; antibodies (less reliable in immunocompromised patients) Imaging: often normal acute infection can show airspace consolidation involving multiple lung segments with small nodules (upper right) chronic or healed can show well-defined nodules with central calcifications representing old granulomas Granulomas can become necrotic and may coalesce to produce areas of consolidation Undergo fibrosis and concentric calcification (tree-bark appearance, shown lower right) 56 Robbins and Cotran. Pathologic Basis of Disease. Tenth Edition. Figure 15-37 A. Radiopaedia.org Chronic pneumonia Blastomyces dermatitidis Lives in soil dimorphic fungus Central and Southeastern United States Three clinical forms: pulmonary blastomycosis disseminated blastomycosis rare primary cutaneous pneumonia most often resolves spontaneously Results in suppurative granulomas note neutrophils Macrophages have difficulty ingesting and killing yeast Broad-based yeast budding, as shown Double-contoured wall 57 Robbins and Cotran. Pathologic Basis of Disease. Tenth Edition. Figure 15-38 Chronic pneumonia Blastomyces dermatitidis 58 Robbins Atlas of Pathology. Fourth Edition. Figure 5.91 Chronic pneumonia Coccidioides immitus Fungus endemic in Southwest US and Mexico Thick-walled, non-budding spherules (release endospores) Most people have been exposed Nearly everyone who inhales spores becomes infected Pathology: infective arthroconidia ingested by alveolar macrophages block fusion of phagosome and lysosome Limits intracellular killing Develops a delayed-type hypersensitivity reaction to the fungus most are asymptomatic can involve lung (common) and skin (less common) 59 Robbins and Cotran. Pathologic Basis of Disease. Tenth Edition. Figure 15-39 Chronic pneumonia Coccidioides immitus Spherules burst to release endospores Infection can be disseminated Liver, as shown, right 60 Robbins Atlas of Pathology. Fourth Edition. Figure 5.92 Immunocompromised patient Pneumocystis jiroveci pneumonia Diagnosis by bronchoalveolar lavage Fever, non-productive cough and dyspnea T lymphocyte CD4 < 200/mm3 crushed pinspons Balls 61 Robbins Atlas of Pathology. Fourth Edition. Figure 5.95 Immunocompromised patient Nontuberculosis mycobacteria Mycobacterium avium intracellulare Can be disseminated disease in immunocompromised T lymphocyte CD4 < 200/mm3 Other at-risk populations: older, Caucasian thin females peculiar suppression of cough reflex middle-aged or elderly male smokers (often with COPD) or chronic ethanol use Imaging: bronchiectasis and bronchial wall thickening-most common Clinical presentation: insidious, with chronic cough usually productive of purulent sputum no hemoptysis or constitutional symptoms (differentiate from tuberculosis) https://radiopaedia.org/articles/pulmonary-mycobacterium-avium-complexinfection?lang=us 62 Immunocompromised patient Cytomegalovirus herpesvirus double-stranded DNA virus ubiquitous human pathogen Particularly at risk of developing CMV pneumonia Cmv-note intranuclear inclusion advanced HIV disease recipients of hematopoietic stem cell and lung transplants 63 Zander. Pulmonary Pathology. Second Edition. Figure 13.5. 2018 Immunocompromised patient Candida albicans budding cells and pseudohyphae more frequently in immunocompromised hosts may form micro abscess within lung parenchyma contains few inflammatory cells but numerous budding cells and organisms appearing in cytologic specimens such as sputum collection or bronchoscopy are oropharyngeal contaminants and unlikely to represent lower respiratory tract infection Robbins Atlas of Pathology. Fourth Edition. eFigure 5.16 balloon andyeast annals conida 64 Immunocompromised patient Nocardia (braziliensis and asteroides) may form abscesses within lung parenchyma can spread to brain disease ranges from cutaneous infection to severe pulmonary or central nervous system disease disseminated disease has poor prognosis ubiquitous-present in soil may appear filamentous; beaded, and branching bacilli Gram positive rod bacteria; weakly acid fast (with Fite stain-a modified AFB stain; negative on Ziehl-Nielson stain) immunocompromised patients at higher risk can occur in transplant patients 65 Robbins Atlas of Pathology. Fourth Edition. eFigure 5.17 Pneumonia workup General approach involves combination of: Clinical features (fever, dyspnea, cough, and sputum production) Imaging demonstration of infiltrate lobar consolidations (shown above-LLL), interstitial infiltrates (shown below), and/or cavitations Additional workup generally reserved for Hospitalized and immunocompromised Failed initial empiric therapy Outbreak, season or suspected organism (COVID, influenza, Legionella) 66 Image courtesy of Thomas J Marrie. 2023 UpToDate Pneumonia-role of imaging In addition to a constellation of suggestive clinical features (shown below), a demonstrable infiltrate by chest radiograph or other imaging technique (CT, ultrasound), with or without supporting microbiological data, is essentially required for the diagnosis of pneumonia Fever, chills (rigors) Cough, sputum production Dyspnea, chest pain (Leukocytosis) Tachypnea Confusion in elderly Chest imaging: Infiltrates may be subtle, they “blossom” with hydration 67 Diagnostic testing-options available Blood and possibly cultures No additional testing indicated if decision is to treat outpatient (begin empiric therapy) Respiratory tract sputum and cultures Influenza and COVID-19 rapid tests Methicillin-resistant staph aureus nasal swab (PCR or culture) When planning to deescalate empiric MRSA coverage in hospital-acquired pneumonia If negative, has a high negative predictive value for MRSA pneumonia vancomycin or linezolid can be discontinued or switched to a MSSA appropriate coverage if staph is suspected by gram stain Urinary pneumococcal antigen Urinary Legionella antigen, possibly PCR (if available) Pleural fluid culture in setting of effusion (usually if > 5cm on imaging) Respiratory pathogen panel (viral nucleic acid) HIV 68 Diagnostic Testing Blood cultures and microbial sensitivity Indicated in hospitalized certain other patients May be less certainly of antibiotic coverage and can make changes as appropriate Respiratory tract cultures On hospitalized patients Sputum YES!, you get a rapid Gram stain Viruses/viral culture supplanted by molecular panels in many places COVID-19 rapid and PCR tests Influenza rapid test In season, rapid, quick, readily available Urinary pneumococcal antigen Excellent specificity Can be tested after antibiotics started Urinary Legionella antigen or PCR Pleural fluid culture in setting of effusion (usually if > 5cm on CXR) Usually on sicker, hospitalized patients with an effusion 69 Management decisions Site of care (where to treat?) Home, inpatient Level of care ICU, general medical floor Suspected pathogens (what to treat?) Streptococcus pneumoniae, Mycoplasma, Chlamydophila, Legionella Concept of empiric Antibiotic selection therapy addresses these latter two questions 70 Site of care decision Almost all major decisions regarding management of community acquired pneumonia (including diagnostis and treatment) revolve around the initial assessment of severity Site-of-care decisions (hospital vs. outpatient, intensive care unit [ICU] vs. general medical floor) are important areas for quality and outcome improvement in management of community acquired pneumonia Examples: Minimize hospitalization related issues venous thromboemboli use (overuse) of intravenous antibiotics additional hospital acquired infections 71 Site of care decision Objective criteria or scores should always be supplemented with physician determination of subjective factors Examples: ability to safely and reliably take oral medication availability of outpatient support resources Pneumonia Severity Index Prognostic model Considers the following and assigns risk: age < 50 years absence (or presence) of coexisting conditions: Neoplastic disease Heart failure Cerebrovascular disease Renal disease Liver disease absence of physical examination findings: Altered mental status Systolic blood pressure 30 (tachypnea) Systolic blood pressure < 90 age > 65 One point each Score points validates admission to hospital Score points supports inpatient or closely supervised outpatient 73 additional laboratory testing Patients should be investigated for specific pathogens that would significantly alter standard (empirical) management decisions, when the presence of such pathogens is suspected on the basis of clinical and epidemiologic clues Routine use of common tests, such as blood and sputum cultures is somewhat controversial Important for epidemiologic reasons including the antibiotic susceptibility patterns used to develop treatment guidelines Example situations in which additional testing is used: Severity of individual patient Specifically defined and established “special” situations (Table 3 on subsequent slide) When the test is likely to have the highest yield (quality performance measures for collection, transport, and processing of samples can be met) 74 additional testing indications Strongest indication for extensive diagnostic testing is in the critically ill/severe community acquired pneumonia (CAP) patient Take home summary: admitted patients will receive sputum Gram stain and culture +/- urine antigen testing severe patients may receive additional testing, namely blood cultures in setting of septic symptoms 75 76 additional testing considerations Procalcitonin Associated with bacterial infection as the source of inflammation Used to know when to discontinue antibiotics Prognosis in critically ill false positive can occur with surgery, trauma, shock or severe liver failure false negatives can happen if level is checked very early in the disease course Plasma lactate patient with septic symptoms good prognostic marker monitor treatment effectiveness (esp trauma and sepsis) Viral respiratory pathogen panel 77 Blomkalns. Lactate-a Marker for Sepsis and Trauma. EMCREG. 2007 78 © 2007 by the Infectious Diseases Society of America Lionel A. Mandell et al. Clin Infect Dis. 2007;44:S27-S72 Osteopathic considerations Somatic dysfunction as a representation of respiratory difficulty or dysfunction T2-T7 C2-C3 Identity tissue texture changes and resistance to springing or articulation May represent viscerosomatic reflexes Primary lymphatic drainage from the lung and its associated tissues: pretracheal nodes intercostal vessels axillary nodes to lymphatic ducts Goal is to optimize and move to normalize balance 79 Osteopathic considerations 1918 influenza epidemic Pre-antibiotic era Lower mortality in pneumonia patients treated with osteopathic manual medicine (Kuchera and Kuchera, Osteopathic Considerations in Systemic Dysfunctions) Goals of treatment: improve venous and lymphatic flow improve arterial circulation to carry immune system products to the lungs ease removal of accumulated bronchial secretions decrease the workload of breathing All aim to assist the body’s immunologic front against the infection 80 Osteopathic considerations Treatment options: lymphatic or thoracic pump (shown) improve venous and lymphatic flow favorably affect arterial circulation rib-raising free bronchial secretions more easily expectorated normalize sympathetic innervation to the lung thoracic chain ganglia lie directly anterior to corresponding rib heads pneumonia results in hypersympathetic activity rib raising initially stimulates sympathetic outflow, but eventually will result in inhibition decrease workload of breathing by improving the compliance of the thorax restore the intrinsic elastic forces in the thorax re-dome diaphragm 81 Roland H, Brown A, Rousselot A, Freeman N, Wieting JM, Bergman S, Mondal D. Osteopathic Manipulative Treatment Decreases Hospital Stay and Healthcare Cost in the Neonatal Intensive Care Unit. Medicines. 2022; 9(10):49. https://doi.org/10.3390/medicines9100049