Neumonia Adquirida en la Comunidad e IAA

Pneumonia adquirida ennla comunidad, diapositivas upao 2024-II

1. Neumonia adquirida en la comunidad

2. DEFINICION Neumonía : Infección pulmonar aguda ocasionada por la invasión de microorganismos patógenos ( bacterias , virus, hongos y parásitos ). - Compromete el parénquima pulmonar : alveolos , intersticio , pleura visceral, vías respiratorias y estructuras vasculares . Neumonía Adquirida en la Comunidad Es una enfermedad respiratoria aguda , de origen infeccioso , ocasionada por la invasión parenquimal de microorganismos patógenos que fueron adquiridos fuera del ambiente hospitalario .

3. Otras definiciones

4. Prevalence and Risk Factors for Drug Resistance Health care-associated pneumonia: - Hospitalization for 2 days or more in the preceding 90 d - Residence in a nursing home or extended care facility - Receipt of home infusion therapy - C hronic dialysis within 30 days - Home wound care - A family member with a multidrug-resistant pathogen - Immunosuppressive disease or therapy In patients with community onset pneumonia, the presence of health care exposure is associated with more severe pneumonia Chronic corticosteroid, hematological malignancy, chemotherapy, AIDS, and neutropenia . Severe pneumonia was 45% in patients with health care exposure risk factors and 29% without the risk factors . The prevalence of drug-resistant pathogens ranged from 23 to 42 % Overtreated Failure to initiate effective antimicrobials in patients with drug-resistant pathogens is associated with worse outcomes A higher number of risk factors was associated with a higher probability of drug-resistant pathogens: No risk factor 3.5 % / Six risk factors 83.3 %

5. Aspectos epidemiologicos OMS: - Causa más común de muerte de origen infeccioso en el mundo - Cuarta causa de muerte en general - 3.5 millones de muertes anuales a nivel mundial USA : - 2019: 489 millones de NAC / 1.5 millones de defunciones Perú : - Segunda causa de muerte de origen infeccioso - 13.8% de todas las causas de muerte registradas el 2014 - C ausa de mayor tasa de hospitalización en MINSA y EsSalud Se asocia a carga económica y clínica significativa

6. Aspectos epidemiologicos Patógenos : - Variable en América Latina - Streptococcus pneumonia: 35% de casos - S. Pneumoniae resistente a penicilina : 39% Mortalidad - América Latina: 6% - Países desarrollados : 4%

7. Epidemiology 76 and 145 adults per 100,000 in the United States / year C hronic obstructive pulmonary disease (COPD ) Heart failure Prior stroke Diabetes mellitus Current smokers People living in impoverished areas 20% of patients hospitalized with CAP require ICU admission , with 75% of these admissions occurring on the first day of hospitalization . The mean age of patients with severe CAP in two different studies ranged from 60 to 67 years old Risk Factors for Mortality: Older age , male sex, comorbidities, alcohol use disorder, rapid radiographic spread , and bacteremia E arly admission to the ICU had higher severity of illness; late admission to the ICU had 2.6 higher 30-day mortality after adjustment for cofounders

8. Fisiopatologia

9. Mecanismos de defensa respiratorios Nasofaringe : Cornetes y vellos nasales , aparato mucociliar y secreción mucociliar Tráquea y Bronquios Tos , reflejo epiglótico , aparato mucociliar , secreción de inmunoglobulinas (IgG, IgM, IgA) Vías aéreas terminales y alvéolos : Macrófgos alveolares , linfáticos pulmonares , Surfactante , Complemento , Inmunoglobulinas , fibronectina , Citokinas (IL1 – FNT), leucocitos , polimorfonucleares , inmunidad mediada por células

10. Condiciones del huesped

11. Factores de virulencia Microorganismo Mecanismo Chlamydiophila pneumoniae Factor ciliostatico Mycoplasma pneumoniae Desprendimiento de cilios Virus Influenza Reduce la velocidad de producción del moco traqueal S. Pneumoniae N. meningitidis Proteasas que degradan la IgA secretoria Neumolisinas Mycobacterium spp Nocardia spp Legionella spp Resistencia a la actividad microbicida de la fagocitosis

12. fisiopatologia Exposición frecuente al aire contaminado : 100 um : Se depositan en la vía aérea superior 10 um : Secreciones nasales < 5 um : Llega a los alveolos (100 microorganismos ): ASPIRACION < 1 um : Mycoplasma, Chlamydophila y Coxiella : AEROSOLES Aspiración traqueal frecuente de la flora nasofaríngea Macroaspiración Diseminación hematógena / Traslocación bacteriana Diseminación desde un foco contiguo Posterior a una infección viral del tracto respiratorio superior

13. Systemic Inflammatory Response Cytokine levels are generally very high and tend to decrease over the next 5 days Peripheral blood neutrophils are the primary cells that drive the release of both inflammatory and anti-inflammatory cytokines Excessive production of inflammatory cytokines, or Imbalance between inflammatory and anti-inflammatory cytokines Pathogen virulence and load, and intrinsic host predisposition (comorbidities and genetics) Single-gene polymorphisms of CD86 L . pneumophila , S . pneumoniae , or Enterobacteriaceae

14. Systemic Inflammatory Response L ocal and systemic responses may show different degrees of inflammation Patients with severe CAP had a higher plasma cytokine response when compared with patients with non severe CAP S evere CAP had two times higher levels of proinflammatory cytokines IL-6, TNF-α , and CXCL8, and four to five times higher levels of adaptive immunity-related cytokines interferon-γ and IL-17 Plasma high serum levels of IL-6, IL-8, and C-reactive protein on the first day of admission were independent predictors of treatment failure A dmission to the ICU had higher serum levels of IL-6, procalcitonin , and C-reactive protein D eath had significantly higher serum levels of procalcitonin , C-reactive protein, TNF-α, IL-6, and IL-8

15. Etiologia Es importante conocer los agentes responsables de la NAC para poder instaurar tratamientos empíricos adecuados 40 – 60%: No se identifica agente etiológico / Limitación de las pruebas diagnósticas Diversos factores pueden modificar la etiología : huésped , ambiente , laboral > 100 microorganismos reportados como agentes causales Los patógenos “ atípicos ” no son identificados rutinariamente en la práctica clínica Influenza: agente viral predominante de NAC en adultos

16. NEUMONIA ADQUIRIDA EN LA COMUNIDAD: ETIOLOGIA MICROBIANA SEGUN PAIS EEUU ESPAÑA SUECIA ISRAEL ASIA TOTAL EVALUADOS 730 3524 184 126 995 PATOGENO IDENTIFICADO 177 (24.2) 1463 (41.5) 124 (67.4) 84 (66.7) 428 (44.8) PATOGENO NO IDENTIFICADO 553 (75.8) 2060 (58.5) 60 (32.6) 42 (33.3) 527 (55.2)

17. Virus: 22% Bacterias: 19% 4%

18. Aetiology Vary based on geography, season, population demographics, and the presence of pandemics and epidemics. Viruses are the most commonly identified causes of both SCAP and non-SCAP in the United States, and globally. 18 to 30% of cases are due to a virus . National surveillance study in China (2009 – 2020) - Influenza (10 %) - Respiratory syncytial virus (9%) - Rhinovirus (7 %) - Parainfluenza virus (5 %) - Adenovirus (3.6 %) - Human metapneumovirus (1.8 %)

19. HOSPITALIZACION (%) UCI (%) Streptococcus pneumonia 20-30 15-25 Haemophilus influenza 3-7 4-8 Legionella spp 3-10 7-12 Mycoplasma pneumoniae 3-8 1-2 Chlamydia pneumoniae 3-8 < 1 Virus 6-12 3-6 Staphylococcus aureus 1-3 5-10 Enterobacterias 1-5 3-8 Pseudomona aeruginosa 1-3 3-8 Sin etiologia identificada 40-60 50-60 Chest 2008; 133:610-617 Microorganismos causantes

20. ESTUDIOS NACIONALES SOBRE ETIOLOGIAS DE NEUMONIA ADQUIRIDA EN LA COMUNIDAD AUTOR AÑO n CULTIVO POSITIVO ETIOLOGIA n % TOTAL % AISLAMIENTOS VARELA, C. 1984 37 ND NEUMOCOCO ND ND ND AGUILAR 1999 130 31 NEUMOCOCO MICOPLASMA CLAMIDIA 10 7 3 7.69 5.38 2.3 32.26 22.58 9.68 RIVEROS, A. 2000 2000 ND NEUMOCOCO ND ND 66 ND: DATO NO CONSIGNADO

21. The Rationale for Determining the Etiology of Severe Community-Acquired Pneumonia The importance of identifying the specific etiology of SCAP is debatable Clinical outcomes were not impacted by microbiological studies compared with empirical treatment Blood and respiratory tract specimen cultures have higher yield in SCAP B ecause antibiotic regimens for SCAP may include anti-MRSA and/or antipseudomonal therapy for patients with risk factors, the opportunity for antibiotic de-escalation is greater The clinical instability of patients with SCAP justifies a more comprehensive approach to pathogen detection to ensure appropriate therapy is administered in a timely fashion . Antibiotics can be avoided or discontinued

22. Condiciones epidemiologicas y/o factores de riesgo relacionados a patogenos especificos en neumonia adquirida en la comunidad

23. microbiologia

24. Streptococcus pneumoniae Alcoholism , COPD, and nursing home residency Transmitted through droplets or contact with contaminated surfaces Colonization is thought to be a prerequisite for invasive disease . Predominant carriers of S . Pneumoniae : children Approximately 10% of adults are also asymptomatic carriers. Pneumococcal vaccine - 23-valent polysaccharide vaccine (1983) - 7-valent pneumococcal conjugate (2000) - 13-valent pneumococcal conjugate vaccine (PCV13 ) (2010) Continues to be one of the most commonly identified bacterial etiologies of SCAP.

25. Streptococcus pneumoniae Gram-positive α- hemolytic bacteria Colonizes the upper respiratory tract in healthy individuals. 90 serotypes / Degrees of virulence Serotypes 1 and 19A: bacteremic pneumonia, meningitis, and hemolytic uremic syndrome Virulence of S. pneumoniae is primarily related to the structure of the capsular polysaccharide, which aids in establishing contact with the epithelium and also acts as a barrier to phagocytosis .

26. Streptococcus pneumoniae Surface protein CbpA interacts with the immunoglobulin receptor of respiratory epithelial cells, leading to bacterial entry into the cell. Pneumolysin , a pore-forming exotoxin produced by all serotypes of S. pneumoniae , exhibits lytic activity against cholesterol-containing cell membranes leading to cellular toxicity , DNA damage, cell cycle arrest, and inflammation

27. Staphylococcus aureus Gram-positive cocci-shaped bacteria , often identified in clusters Less than 2 % of hospitalized CAP cases in adults . During the coronavirus disease, was the most common bacterial pathogen present at the time of intubation R esults in significantly more ARDS , septic shock, and in-hospital mortality Clinical features of methicillin-sensitive S . aureus SCAP = community-acquired methicillin-resistant S. aureus (MRSA) SCAP : both include multifocal infiltrates, hemoptysis, and pleural effusion Many S. aureus virulence factors are encoded on mobile genetic elements that can be efficiently transferred between strains.

28. Staphylococcus aureus Exotoxins Alpha- hemolysin toxin - Leads to pore formation and cell death Panton Valentine leucocidin (PVL) toxin - Associated with SCAP - Necrosis , hemorrhage and severe hypoxemic respiratory failure.

29. Legionella pneumophila Aerobic gram-negative bacillus CAP: only 1% - An important cause of SCAP Transmission through water system 15 serogroups , Serogroup 1 in 70 to 90% of severe respiratory disease T hree atypical CAP pathogens: Mycoplasma and Chlamydophila species Atypical organisms: 8.1 % of cases

30. Enterobacteriaceae Large taxonomic family of gram Negative bacteria 6% of cases - Increased risk of death Klebsiella species and Escherichia coli Risk factors: previous hospitalization , prior antibiotic therapy, alcoholism, aspiration, and chronic lung disease. More frequently identified in patients with SCAP compared with patients with non-SCAP - Severe disease was an independent risk factor for Enterobacteriaceae pneumonia - Potential for drug resistance to standard CAP treatment regimens

31. Pseudomonas aeruginosa Colonizes the respiratory tract: structural lung disease, such as COPD , bronchiectasis , and cystic fibrosis, and those with chronic tracheostomy Never occurs in patients who have not been exposed to prior antibiotics. Intrinsically resistant to several common CAP antibiotics 2 to 8% of cases More commonly associated with SCAP than other pathogens - Only 11.3 % of culture-positive cases require ICU admission - Case fatality rate: 50 % of cases - Independent risk factor for death in CAP patients

32. Less Common Etiologies Histoplasma capsulatum Blastomyces Coccidiodes Pneumocystis jirovecii Nontuberculous mycobacterium

33. Neumonia atipica Signos y sintomas pulmonares Subagudo / Asintomatico Hallazgos sutiles : - Infiltrados no lobares - Manifestaciones extrapulmonares Signos y sintomas extrapulmonares Confusion Mental Cefalea Mialgias Dolor de oidos Dolor abdominal Diarrea Rash Faringitis No exudativa Hemoptisis Esplenomegalia Bradicardia relativa

34. Patogenos atipicos

35. Cuadro Clinico Síntomas Fiebre Malestar Escalofríos – Sudoración Dolor Torácico ( pleurítico ) Tos Expectoración purulenta Disnea *** Ancianos : Síntomas inespecíficos Signos Confusión Taquipnea Taquicardia Matidez Crepitantes Broncofonía Soplo Bronquial Murmullo vesicular disminuído Vibraciones vocales disminuídas o abolidas

36. Criterios diagnósticos

37. Neumonia : Criterios de fang Infiltrado radiografico 1 Criterio mayor: Fiebre mayor a 37.8C Tos Espectoración 2 Criterios menores : Dolor pleurítico Disnea Leucocitosis Estado mental alterado Síndrome de Consolidación O

38. imagenes Radiografía : - Hospitalización - Evolución desfavorable - Complicación - Malignidad - 20% inicialmente normal

39. imagenes Ecografía : - Sensibilidad 95 % - Especificidad 93 %

40. imagenes Tomografía - Duda diagnóstica - Complicación - Diagnóstico alternativo

41. Examenes auxiliares generales Hemograma Glucosa Urea – Creatinina Proteína C Reactiva cuantitativa Velocidad de Sedimentación Globular Procalcitonina Perfil hepático Gases Arteriales

42. Traditional Diagnostic Testing for Community-Acquired Pneumonia Pretreatment Gram stain and culture of respiratory secretions (SCAP or non-SCAP ) Advantages - Direct sampling from the site of infection - Can be obtained noninvasively (patient who is alert) <10 squamous epithelial cells, and >25 leukocytes Gram stain yield: Sensitivity 45% Specificity 87 to 97% Endotracheal aspirate (ETA ) bronchoalveolar lavage ( BAL) Bronchoscopy with culture (50 % yield in patients without diagnosis by traditional methods) Culture-based testing is more likely to be available in resource-limited settings Low cost. Limitations - Antibiotic receipt prior to sample collection - Transport time - Temperature - Handling in the microbiology laboratory

43. Blood Cultures Low yield over all in adults with CAP Bacteremia in 14.7% (SCAP) - 7.8 % (non-SCAP) 13.9 % of patients had blood culture positivity with yield increased with higher Pneumonia Severity Index scores Urinary Antigen Testing S. pneumoniae and L. pneumophila Detect the immunologically active C polysaccharide of the bacterial cell wall SCAP patients are more likely to have a positive UAT for S . Pneumoniae than non severe cases and that appositive test can improved antibiotic stewardship . Legionella Particularly helpful - 15minutes Sensitivity: 80 - 93 % Specificity: 99 - 100 % 25 to 57% reduced odds of mortality in patients receiving UAT compared with patients who did not receive these tests

44. others Matrix-Assisted Laser Desorption / Ionized Time of Flight Rapid Molecular Techniques - Nucleic Acid Amplification Tests - Microarray-Based Assays - Next-Generation Sequencing

45. Examenes auxiliares especializados Muestras de secreción nasofaríngea BK en esputo / Aspirado gástrico – PPD Prueba rápida HIV Análisis citoquímico y cultivo de líquido pleural Broncoscopía

46. Criterios de hospitalizacion : clinico

47. Criterios de hospitalizacion : clinico

48. Criterios de admision a uci

49. tratamiento Régimen empírico : NO EVIDENCIA SOLIDA Exposición previa a antibiótico en los últimos 3 meses Patógeno mas probable Tasas de Resistencia Comorbilidad Medidas generales : Oxigenoterapia / Soporte nutricional / Tromboprofilaxis / Corticoides

50. Tratamiento antibiotico Ambulatorio sin factor de riesgo Amoxicilina 500mg TID, o Doxicilina 100mg BID, o Azitromicina 500mg QD, o Claritromicina 500mg QD Ambulatorio con factor de riesgo Levofloxacino 750mg QD, o Amoxicilina 1gr TID, Amoxicilina Clavulánico 1gr/125 BID, Cefuroxima 500mg BID + Azitromicina o Claritromicina , o Doxicilina

51. tratamiento Hospitalizado Ceftriaxona 2gr EV QD o Ampicilina Sublactam 3gr EV QID o Cefuroxima 750mg EV TID + Azitromicina 500mg QD, o Levofloxacino 750mg QD Hospitalizado en uci Ceftriaxona 2gr EV QD o Cefotaxima 1g EV TID o Cefuroxima 1.5g EV TID + Azitromicina 500mg QD, o Levofloxacino 750mg QD

52. tratamiento Pseudomona aeruginosa Cefalosporina de 3ra – 4ta Generación , o Carbapenem + Aminoglucósido o Azitromicina o Fluoroquinolona S. Aureus Vancomicina , o Linezolid Hemoptisis – Influenza reciente – Neutropenia – Hemodialysis – Insuficiencia cardiaca congestiva Enfermedad pulmonar estructural – EPOC – Bronquiectasias – ATB previo - Corticoides

53. Complicaciones Absceso pulmonar Necrosis pulmonar Enfermedad Multilobar Fistula Broncopleural Derrame pleural Empiema Neumotorax Sepsis ARDS

54. Diagnostico diferencial Diagnóstico Diferencial Neumonía viral Tuberculosis pulmonar Insuficiencia Cardíaca Congestiva Neumonía por agentes atípicos Tromboembolismo pulmonar Atelectasia Neumonia por bacterias típicas Neumonitis por hipersensibilidad Daño pulmonar por fármacos Daño pulmonar por radioterapia Cancer pulmonar primario o metastásico Linfangiosis carcinomatosa Lupus eritematoso sistémico Granulomatosis de Wegener Síndrome de Churg -Strauss Sarcoidosis Neumonía Eosinofílica Cuerpo extraño Malformaciones congenitas broncopulmonares Edema pulmonar Neumotórax espontáneo

55. Falla al Tratamiento Posibles Causas Diagnóstico incorrecto TEP / IMA / Edema pulmonar Cáncer broncogénico Bronquiectasias Neumonía eosinofílica Neumonía Organizada Criptogénica Hemorragia alveolar Cuerpo extraño Malformaciones congénitas ( secuestro lobar) Patógeno Atípicos Resistencia Gérmen no cubierto Antibiótico Inadecuada dosificación Hipersensibilidad No adherencia al tratamiento Mecanismos de defensa alterados Locales ( bronquiectasias , obstruccion bronquial , aspiración ) Sistémicas (HIV, hipogammaglobulinemia ) Complicaciones Derrame pleural Empiema Absceso pulmonar ARDS Flebitis Sepsis / Metástasis infecciosa Insuficiencia renal

56. Incident Cardiovascular Diseases 5.8 % of the patients developed an acute myocardial infarction. ST-segment elevation was present in 24% of the cases of acute myocardial infarction: Patients with higher Pneumonia Severity Index scores New or worsening arrhythmias, or myocardial infarction , occurred in 26.7% of inpatients and 2.1% of outpatients Inpatients - New or worsening heart failure (66.8 %) - New or worsening arrhythmias (22.1%), and - Myocardial infarction (3.6 %) Patients with cardiac complications had more severe pneumonia: Pneumonia Severity Index score Higher risk of death Increased inflammation generated by pneumonia causes plaque instability in the coronary arteries, conduction abnormalities, and thrombophilia myocardial hypoxia and direct invasion of the coronary plaques by the pathogen

57. Outcomes CAP: in-hospital, 30-day , and 1-year mortality were 6.5, 13, and 30.6%, respectively Severe CAP: in-hospital , 30-day, and 1-year mortality were 17, 27, and 47 %, respectively Severe CAP was associated with 2.5 higher odds of in-hospital death compared with nonsevere CAP CAP discharged from the hospital have twice the risk of death compared with the general population