1. Fungal pneumonia Fungal pneumonia is an infection of the lungs by fungi It can be caused by either endemic or opportunistic fungi or a combination of both Case mortality in fungal pneumonias can be as high as 90% in immunocompromised patients – though immunocompetent patients generally respond well to anti-fungal therapy

2. Causes Specific instances of fungal infections that can manifest with pulmonary involvement include – Histoplasmosis – Coccidioidomycosis – Pulmonary blastomycosis – Pneumocystis pneumonia which typically occurs in immunocompromised people, especially AIDS

3. – Sporotrichosis primarily a lymphocutaneous disease, but can involve the lungs as well – Cryptococcosis contracted through inhalation of soil contaminated with the yeast, it can manifest as a pulmonary infection and as a disseminated one – Aspergillosis resulting in invasive pulmonary aspergillosis – Candidiasis rarely has pulmonary manifestations in immunocompromised patients

4. Pathophysiology Fungi typically enter the lung with inhalation of their spores – though they can reach the lung through the bloodstream if other parts of the body are infected Fungal pneumonia can be caused by reactivation of a latent infection Once inside the alveoli – fungi travel into the spaces between the cells and also between adjacent alveoli through connecting pores

5. This invasion triggers the immune system to respond by sending white blood cells responsible for attacking microorganisms (neutrophils) to the lungs The neutrophils engulf and kill the offending organisms but also release cytokines – result in a general activation of the immune system This results in the fever, chills, and fatigue common in bacterial and fungal pneumonia The neutrophils and fluid leaked from surrounding blood vessels fill the alveoli and result in impaired oxygen transportation

6. Diagnosis Fungal pneumonia can be diagnosed in a number of ways – The simplest and cheapest method is to culture the fungus from a patient's respiratory fluids Such tests are not only insensitive but take time to develop – studies have shown that slow diagnosis of fungal pneumonia is linked to high mortality Microscopy is another method but is also slow and imprecise Detection of antigens – significantly faster – less sensitive and specific Quantitative PCR – this is the most sensitive and specific test available – still presently limited

7. Treatment Fungal pneumonia can be treated with antifungal drugs – sometimes by surgical debridement

8. Parasitic pneumonia Parasitic pneumonia is an infection of the lungs by parasites It is a rare cause of pneumonia – occurring almost exclusively in immunocompromised persons There are a variety of parasites which can affect the lungs – generally, these parasites enter the body through the skin or by being swallowed – these parasites travel to the lungs, once inside the body, most often through the blood

9. Combination of cellular destruction and immune response causes disruption of oxygen transportation Depending on the type of parasite, antibiotics can be prescribed The most common parasites involved – Ascariasis – Schistosoma – Toxoplasma gondii

10. Pathophysiology Pneumonia frequently starts as an upper respiratory tract infection – that moves into the lower respiratory tract

11. Community acquired pneumonia (CAP) Estimates of the incidence of CAP range from 4 million to 5 million cases per year – with about 25% requiring hospitalization

12. Streptococcus pneumoniae remains the most commonly identified pathogen in community-acquired pneumonia Other pathogens have been reported to cause pneumonia in the community – Haemophilus influenzae, Mycoplasma pneumoniae, influenza A, Legionella species, and Chlamydophilia pneumoniae Other common causes in the immunocompetent patient include – Moraxella catarrhalis, Mycobacterium tuberculosis, and aspiration pneumonia The causative agent of community-acquired pneumonia remains unidentified in 30% to 50% of cases

13. PathogenCases (%) Streptococcus pneumoniae20-60 Haemophilus influenzae3-10 Staphylococcus aureus3-5 Gram-negative bacilli3-10 Legionella species2-8 Mycoplasma pneumoniae1-6 Chlamydia pneumoniae4-6 Viruses2-15 Aspiration6-10 Others3-5 Identified Pathogens in Community-Acquired Pneumonia

14. Mycoplasma pneumoniae No cell wall Mortality rate 1.4% Common Crowded places like – schools – homeless shelters – prisons No cell wall Mortality rate 1.4% Common Crowded places like – schools – homeless shelters – prisons Usually mild and responds well to antibiotics May be associated with – skin rash – hemolysis – myocarditis – pancreatitis Usually mild and responds well to antibiotics May be associated with – skin rash – hemolysis – myocarditis – pancreatitis

15. Mycoplasma pneumoniae

16. Chlamydia pneumoniae (Chlamydophila pneumoniae) Obligate intracellular organism 50% of adults are sero-positive Mild disease Sub-clinical infections are common 5-10% of community acquired pneumonia

17. Psittacosis Chlamydophila psittaci Exposure to birds Bird owners, pet shop employees, vets Parrots, pigeons and poultry Birds often asymptomatic 1st: Tetracycline Alt: Macrolide Chlamydophila psittaci Exposure to birds Bird owners, pet shop employees, vets Parrots, pigeons and poultry Birds often asymptomatic 1st: Tetracycline Alt: Macrolide

18. Coxiella burnetii Exposure to farm animals mainly sheep 1st: Tetracycline 2nd: Macrolide Coxiella burnetii Exposure to farm animals mainly sheep 1st: Tetracycline 2nd: Macrolide Q fever

19. Legionella pneumophila Hyponatremia – common – (<130mmol/L) Bradycardia WBC < 15,000 Acute Renal failure Hyponatremia – common – (<130mmol/L) Bradycardia WBC < 15,000 Acute Renal failure Legionnaire's disease ICU admissions Legionnaire's disease ICU admissions TEM image of L. pneumophila

20. Legionnaires on ICU

21. Symptoms Insidious onset Mild URTI to severe pneumonia Headache Malaise Fever dry cough Arthralgia / myalgia Insidious onset Mild URTI to severe pneumonia Headache Malaise Fever dry cough Arthralgia / myalgia Signs Minimal Few crackles Rhonchi Low grade fever Minimal Few crackles Rhonchi Low grade fever

22. History and physical examination Clinical syndromes characterizing pneumonic infections caused by various agents – the diagnosis of pneumonia can be challenging – often overlap one another

23. Microbiologic Differential Diagnosis of Pneumonia (Historical Features) HistoryAssociated Organisms AlcoholismStreptococcus pneumoniae, oral anaerobes, Mycobacterium tuberculosis Chronic obstructive lung disease (COPD)S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Legionellaspp. Exposure to bat or bird droppings, construction sites, caves Histoplasma capsulatum Exposure to birdsChlamydia psittaci Exposure to rabbitsFrancisella tularensis HIV infection“Typical” bacterial pathogens, M. tuberculosis, Pneumocystis jiroveci, cytomegalovirus, Cryptococcus spp., Histo plasma spp., Coccidioides spp. Travel to desertCoccidioides spp., Hantavirus (Sin Nombre virus) Farm exposureCoxiella burnetii (animals), Aspergillus spp. (barns, hay)

24. HistoryAssociated Organisms Post-influenzaS. pneumoniae, S. aureus, Streptococcus pyogenes, H. influenzae AspirationMixed aerobic, anaerobic Marijuana smokingAspergillus spp. Anatomic abnormality of lung parenchyma, e.g., bronchiectasis, cystic fibrosis Pseudomonas aeruginosa, Burkholderia cepacia, S. aureus Injection drug useS. aureus, anaerobes, M. tuberculosis, and S. pneumoniae Obstruction of large airwayAnaerobes, S. pneumoniae, H. influenzae, S. aureus IncarcerationM. tuberculosis NeutropeniaAspergillus spp., Zygomycetes AspleniaS. pneumoniae, H. influenzae

25. Hospital-acquired pneumonia (HAP)

26. Introduction Nosocomial pneumonia is the 2 nd most common hospital-acquired infections after UTI – Accounting for 31 % of all nosocomial infections Nosocomial pneumonia is the leading cause of death from hospital-acquired infections The incidence of nosocomial pneumonia is the highest at the ICU

27. Introduction The incidence of nosocomial pneumonia in ventilated patients is 10x higher than non-ventilated patients The reported crude mortality for HAP is 30% to greater than 70%

28. Pathogenesis --- The Prevention of Ventilator-Associated Pneumonia Vol.340 Feb 25, 1999 NEJM

29. Classification Early-onset nosocomial pneumonia – Occurs during the first 4 days of admission Usually is due to – S. pneumoniae, MSSA (Methicillin Sensitive Staph. aureus), H. Influenza, or anaerobes Late-onset nosocomial pneumonia – Occurs at more than 4 days of admission – More commonly by Gram negative organisms especially – P. aeruginosa, Acinetobacter, Enterobacteriaceae (Klebsiella, Enterobacter, Serratia) or MRSA

30. Causative Agent Enteric Gram negative bacilli – are isolated most frequently particularly in patients with late-onset disease patients with serious underlying disease often already on broad-spectrum antibiotics Prior use of broad-spectrum antibiotics and an immunocompromised state make resistant Gram- negative organisms more likely

31. Causative Agents P. aeruginosa and Acinetobacter are common causes of late-onset pneumonia, particularly in the ventilated patients

32. Causative Agents S. aureus is isolated in about 20~40% of cases and is particularly common in – Ventilated patients after head trauma, neurosurgery, and wound infection – In patients who had received prior antibiotics or Prolonged care in ICU MRSA ( methicillin resistant S. aureus ) is seen more commonly in patients who – Received corticosteroids – Undergone mechanical ventilation >5 days – Presented with chronic lung disease – Had prior antibiotics therapy

33. Causative Agents Anaerobes are common in patients predisposed to aspiration Ventilator associated pneumonia (VAP) with anaerobes occurred more often with oropharyngeal intubation than nasopharyngeal intubation

34. Ventilator-associated Pneumonia (VAP) Definition – Nosocomial pneumonia that has developed in patient who are receiving mechanical ventilation Classification – Early-onset within 48-72 hours after tracheal intubation – which complicates the intubation process – Late-onset after 72 hours

35. HAP Causes HAP is caused by a spectrum of bacterial pathogens – may be polymicrobial – rarely due to viral and fungal pathogens unless immunocompromised patients; e.g., bone marrow transplants Common pathogens include – aerobic gram-negative bacilli Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli – gram-positive organisms Staphylococcus aureus

36. Methicillin-resistant S. aureus (MRSA) MDR Pseudomonas aeruginosa Enterobacter, E. coli, and K. pneumoniae Acinetobacter species, Stenotrophomonas, malto philia, and Burkholderia cepacia All of which have increasing resistance to commonly used antimicrobials

37. Pathogenesis Requires 2 important processes 1. Bacterial colonization of the aerodigestive tract 2. Aspiration of contaminated secretion into the Lower airway Prevents mechanical clearance by cough and the mucociliary escalator

38. for Prevention for VAP The oral regimen (topical gentamicin, Colistin, Vancomycin cream q6h for 3 weeks) treating oropharyngeal colonization could prevent VAP --- Prevention of VAP by oral decontamination American journal of respiratory critical care medicine2001 164:382-8

39. Preventions for VAP Non-pharmacologic strategies Effective hand washing and use of protective gowns and gloves Semirecumbent positioning Avoidance of large gastric volume Oral (non-nasal) intubation Continuous subglottic suctioning Humidification with heat and moisture exchanger Posture change --- The Prevention of Ventilator-Associated Pneumonia Vol.340 Feb 25, 1999 NEJM

40. Preventions for VAP Pharmacologic strategies Stress-ulcer prophylaxis Combination antibiotic therapy Prophylactic antibiotic therapy Chlorhexidine oral rinse Prophylactic treatment of neutropenic patients Vaccines --- The Prevention of Ventilator-Associated Pneumonia Vol.340 Feb 25, 1999 NEJM

41. Treatment Most initial therapy is empiric because no pathogen is identified or results are not available when antimicrobial decisions are made in most patients

42. Treatment Initially be treated with a broad-spectrum antibiotic regimen aimed at covering all likely bacterial pathogen This regimen should subsequently be narrowed, according to the result of culture

43. Treatment The pathogen may be influenced by coexisting illnesses, prior treatment, and length of hospitalization The frequency of ICU-acquired P. aeruginosa carriage or colonization/infection was 23.4% at 7 days and 57.8% at 14 days ---- Current opinion in infectious disease 2002, 15:387-94, copyright LWW

44. Treatment The mortality can be reduced with early appropriate empiric therapy (Form 30 % with appropriate therapy to more than 90 % with inappropriate therapy). ----

45. Treatment Guidelines by American Thoracic Society has separated patients into three groups, each with a set of probable pathogens. Group 1: mild to moderate HAP with no risk factor Group 2: mild to moderate HAP with risk factor Group 3a: severe HAP, early-onset with no risk factor Group 3b: severe HAP, late-onset or with risk factor

46. Treatment For mild-to-moderate HAP, monotherapy has been shown to be effective For severe HAP in which infection with resistant organisms is likely, combination therapy probably should be instituted until culture result are available

47. Treatment Patients for S. aureus infection, agents against this organism are necessary, including Vancomycin if MRSA is suspected Linezolid is comparable with Vancomycin. The advantage of Linezolid is less possible nephrotoxicity ---- current opinion in infectious disease 2002, 15:387-94, copyright LWW

48. Treatment Combination of antipseudomonal drugs is controversial 1.Traditional antipseudomonal beta-lactam with an Aminoglycoside Synergy but potential nephrotoxicity 2. Another approach antipseudomonal beta-lactam with a Fluoroquinolone No benefit of synergy but reduce concern of nephrotoxicity, and quinolone gets into the lungs at higher concentrations.

49. Response to Therapy If no clinical response is noted or deterioration occurs, we need to consider 1. Infectious causes Resistant pathogen Superinfection Unusual pathogens Lung abscess Extrapulmonary infection 2. Noninfectious events Heart: congestive heart failure (CHF) Lung: fibroproliferative acute respiratory distress syndrome (ARDS), pulmonary emboli, Atelectesis