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

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

– 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

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

• 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

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

Treatment

• Fungal pneumonia can be treated with antifungal drugs– sometimes by surgical debridement

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

• 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

Pathophysiology

• Pneumonia frequently starts as an upper respiratory tract infection– that moves into the lower respiratory tract

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

• 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

Pathogen Cases (%)

Streptococcus pneumoniae 20-60

Haemophilus influenzae 3-10

Staphylococcus aureus 3-5

Gram-negative bacilli 3-10

Legionella species 2-8

Mycoplasma pneumoniae 1-6

Chlamydia pneumoniae 4-6

Viruses 2-15

Aspiration 6-10

Others 3-5

Identified Pathogens in Community-Acquired Pneumonia

Mycoplasma pneumoniae

• 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

Mycoplasmapneumoniae

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

Psittacosis

• Chlamydophila psittaci

• Exposure to birds• Bird owners, pet

shop employees, vets

• Parrots, pigeons and poultry

• Birds often asymptomatic

• 1st: Tetracycline• Alt: Macrolide

• Coxiella burnetii

• Exposure to farm animals• mainly sheep

• 1st: Tetracycline• 2nd: Macrolide

Q fever

Legionella pneumophila

• Hyponatremia– common

– (<130mmol/L)

• Bradycardia

• WBC < 15,000

• Acute Renal failure

• Legionnaire's disease

• ICU admissions

TEM image of L. pneumophila

Legionnaires on ICU

Symptoms

• Insidious onset

• Mild URTI to severe pneumonia

• Headache

• Malaise

• Fever

• dry cough

• Arthralgia / myalgia

Signs

• Minimal

• Few crackles

• Rhonchi

• Low grade fever

History and physical examination

• Clinical syndromes characterizing pneumonic infections caused by various agents

– the diagnosis of pneumonia can be challenging– often overlap one another

Microbiologic Differential Diagnosis of Pneumonia (Historical Features)

History Associated Organisms

Alcoholism Streptococcus 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 birds Chlamydia psittaci

Exposure to rabbits Francisella tularensis

HIV infection “Typical” bacterial pathogens, M. tuberculosis, Pneumocystis jiroveci, cytomegalovirus, Cryptococcus spp., Histoplasma spp., Coccidioides spp.

Travel to desert Coccidioides spp., Hantavirus (Sin Nombre virus)

Farm exposure Coxiella burnetii (animals), Aspergillus spp. (barns, hay)

History Associated Organisms

Post-influenza S. pneumoniae, S. aureus, Streptococcus pyogenes, H. influenzae

Aspiration Mixed aerobic, anaerobic

Marijuana smoking Aspergillus spp.

Anatomic abnormality of lung parenchyma, e.g., bronchiectasis, cystic fibrosis

Pseudomonas aeruginosa, Burkholderia cepacia, S. aureus

Injection drug use S. aureus, anaerobes, M. tuberculosis, and S. pneumoniae

Obstruction of large airway Anaerobes, S. pneumoniae, H. influenzae, S. aureus

Incarceration M. tuberculosis

Neutropenia Aspergillus spp., Zygomycetes

Asplenia S. pneumoniae, H. influenzae

Hospital-acquired pneumonia (HAP)

Introduction

• Nosocomial pneumonia is the 2nd 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

Introduction

• The incidence of nosocomial pneumonia in ventilated patients is 10x higher than non-ventilated patients

• The reported crudemortality for HAPis 30% to greaterthan 70%

Pathogenesis

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

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

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

Causative Agents

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

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

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

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

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

• Methicillin-resistant S. aureus (MRSA)

• MDR Pseudomonas aeruginosa

• Enterobacter, E. coli, and K. pneumoniae

• Acinetobacter species, Stenotrophomonas, maltophilia, and Burkholderia cepacia

• All of which have increasing resistance to commonly used antimicrobials

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

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

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

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

Treatment• Most initial therapy is empiric because no

pathogen is identified or results are not available when antimicrobial decisions are made in most patients

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

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

Treatment

• The mortality can be reduced with early appropriate empiric therapy

(Form 30 % with appropriate therapy to more than 90 % with inappropriate

therapy) .

----

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

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

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

Treatment• Combination of antipseudomonal drugs is

controversial

1. Traditionalantipseudomonal beta-lactam with an AminoglycosideSynergy but potential nephrotoxicity

2. Another approachantipseudomonal beta-lactam with a Fluoroquinolone

No benefit of synergy but reduce concern of nephrotoxicity, and quinolone gets into the lungs at higher concentrations.

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