Respiratory infections 2 Flashcards
M2 inhibitors amantadine and rimantadine are no longer used for influenza.
They block formation of influenza-derived ion channels, which are important in virus uncoating.
Why is this?
Only reduced length of disease by 1 day
Do not work on influenza B
Rapidly increasing resistance since 2009
1 year old child presents with SOB/ fever
Diagnosed bronchiolitis.
What are most likely causes?
RSV -70% of cases. Causes most severe disease if <6 months of age. Usually Dec-Feb. 160k deaths occur annually due RSV.
Approx 2/3 of infants are infection during first year of life. All infants infected by age 2
Starts as URTI. Can progress to LRTI in 50% cases
Influenza Parainfluenza Coronavirusees Rhinoviruses Metapneumovirus Mycoplasma Bordetella pertussis
Where does RSV get its name from?
Virus attaches to cell membrane using viral G protein
viral F protein along with cellular receptor mediates viral entry
fusion protein causes neighbouroing cells to coalesce, resulting in multinucleated cells - termed syncytia
End result is damage to airway epithelium, and loss of ciliated epithelial cells
Cytokines cause oedema and immune response which can lead to narrowing of bronchioles - causing stridors
What treatment is there for RSV infection in children/ immunocompromised?
Ribavirin - aerosolised
IVIG - give with ribavirin, if patient immunocompromised for another reason
Palivizumab - humanised mouse monoclonal antibody given in summer as prophylaxis for winter. Not used as treatment
Reduces hospitalisation by 50%, and wheezing by 60%
Child with RSV.
What are infection control issues?
Droplet precautions in side room
Can have healthcare spread
Which patient groups should receive palivizumab RSV prophylaxis?
Palivizumab is a monoclonal antibody licensed for preventing serious lower respiratory-tract disease caused by respiratory syncytial virus in children at high risk of the disease; it should be prescribed under specialist supervision and on the basis of the likelihood of hospitalisation. Palivizumab is recommended for:
- children under 9 months of age with chronic lung disease (defined as requiring oxygen for at least 28 days from birth) and who were born preterm
- children under 6 months of age with haemodynamically significant, acyanotic congenital heart disease who were born preterm.
Palivizumab should be considered for:
- children under 2 years of age with severe combined immunodeficiency syndrome
- children under 1 year of age who require long-term ventilation
- children 1–2 years of age who require long-term ventilation and have an additional co-morbidity (including cardiac disease or pulmonary hypertension).
Daptomycin has good efficacy against gram positives which can cause pneumonia.
Why is daptomycin not used in pulmonary infections?
Can cause daptomycin- induced acute eosinophilic pneumonia
The precise mechanism for daptomycin-induced lung injury is unknown, but is believed to be related to daptomycin binding to pulmonary surfactant culminating in epithelial injury
35 year old feels unwell with malaise, headache, fever, chills, vomiting. Then develops cough and SOB.
CXR shows diffuse bilateral pulmonary infiltrates
Mycoplasma serology pending
Legionella urinary Ag neg
Sputum culture pending
Blood culture pending
What is most likely cause?
Legionella
Legionella Ag is part of cell wall that is excreted in urine
Only detects L. pneumophila serogroup 1 - which causes approx 80% of infections.
LegAg can be secreted in urine for weeks/ months after initial infection
Legionella urinary antigen is only positive in 80% patients.
What plates can be used to attempt to culture it?
How does it appear under microscopy?
buffered charcoal-yeast extract (BCYE) - although not routinely used. BAL fluid is best for this
will not grow on 5% blood agar
Microscopy - appears as long thin gram neg rod
How is legionella adapted for the environment?
What is its pathogenesis of infection?
Live in free water
Lives inside amoeba, and utilises their resources
Inhaled, enters pulmonary macrophages.
Releases proteins which block phagolysosome fusion, preventing death of bacteria
Why are beta-lactams not used against legionella infection?
- do not penetrate infected macrophages well
- legionella produces beta-lactamase
- macrolides/ quinolones are used
Patient diagnosed with legionella pneumonia on ITU.
What are infection control measures?
Not spread person-person, so no personal protection needed
Need to ensure outbreak is not hospital related - check water/ air conditioning
PCP normally diagnosed by BAL PCR
What would microscopy findings be?
Silver stain will show dark cyst like structures 5microns diameter
AML patient with SOB.
CXR bilateral patchy changes
BAL shows septate hyphae with acute-angle branching
What is the organism?
Aspergillus - septate hyphae with acute-angle branching
Fusarium can have similar appearance
Candida/ Trichosporon are yeasts
PCP is yeast-like
Often BAL is negative in invasive aspergillus. Fungi invades the pneumocytes, so biopsy is required
What are most common species of aspergillus which cause invasive infection?
A. fumigatus
A. flavus
A. niger
What tests can be used for diagnosis of invasive aspergillosis?
Sputum/ BAL
Lung biopsy
Serum/BAL B-D-glucan and galactomannan
Both serum carbohydrates found in aspergillus cell walls
B-D-glucan goes up in candida infection as well. Galactomannan is more specific to aspergillus
Where is Aspergillus found in nature?
grain, hay, decaying vegetable, soil , plants
Aflatoxin is produced by A flavus on improperly stored grain and nuts. It has been linked to HCC
What spectrum of disease can Aspergillus cause?
ABPA - hypersensitivity reaction to hyphal antigens found in the bronchi. Stimulates mucus production, inflammation, and eosinophils in the bronchi. Usually patients have asthma or CF.
Aspergilloma - usually have cavity from pre-existing lung disease. Can be asymptomatic. But can invade locally and cause massive pulmonary haemorrhage
Invasive Aspergillosis
Severely immunosuppressed patients e.g transplant patients can routinely be given prophylactic anti-fungals. Usually an azole or echinocandin
What is coverage like for each of these drugs for aspergillus/ candida
fluconazole
itraconazole
voriconazole
anidulafungin
caspofungin
fluconazole - has no activity against aspergillus, but does have activity against candida
itraconazole - aspergillus + candida
voriconazole - aspergillus + candida (plus also fusarium)
anidulafungin - aspergillus + candida
caspofungin - aspergillus + candida
All drugs ineffective against Fusarium (except vori), Trichophyton, and the zygomycetes (Mucor/ Rhisops)
What is utility of blood cultures in invasive aspergillosis?
It invades pneumocytes, and rarely enters bloodstream.
Blood cultures are almost never positive
Patient presents unwell with sinusitis.
Fluid from ethmoid sinus is analysed by microscopy.
This shows broad, aseptate hyphae with right angle branching. Has ribbon like appearance
What is the organism?
Mucormycetes cause disease mucomycosis. In this case rhinocererebral mucormycosis. Fungus is angioinvasive
Aspergillus has thin, septate hyphae, with acute angle branching
Which species are included in Mucormycetes?
Mucor
Rhizopus - causes 70% of infections
Rhizomucor
Lichtheimia
May look the same by microscopy. But important to differentiate, as may have different response to anti-fungals
Where are Mucormycetes found naturally?
Environemnt -
- fruit/ bread or any other decaying food
- soil
Our patient with sinusitis likely inhaled the conidia of the fungus
What diagnostic tests are used for Mucormycosis?
Biopsy/ wash from normally sterile site e.g sinus
If grown from sinus drainage or aspirate of sinus, then can still be likely cause. However, some patents are colonised, and fungus is not causing disease
Mucormycosis has higher prevalence in patients with diabetes. Why is this?
Hyperglycaemia impairs phagocytic cell function, allowing evasion of immune clearance
Hyperglycaemia can lead to DKA. Acidic environment helps growth of mucormycoses
Bone marrow transplant patients are other most common group infected
What is treatment for mucormycosis?
Surgical debridement is mainstay
Resistant to azoles/ echinocandins
Liposomal amphotericin B is treatment of choice. Some evidence this plus echinocandin can be more effective
Patient has symptoms of pneumonia over months. CXR shows constant right hilar mass.
Non-infectious causes include malignancy
What are infectious causes?
Chronic infections which are slow growing
- blastomycosis
- coccidioides
- histoplasma
- mycobacteria
- nocardia
- Actinomyces
Patient with right sided pneumonia, and tender papule on right nose.
Silver stain shows large, round budding yeast. With broad connecting base connecting mother cell to daughter cell
What is the causative organism?
Blastomycosis
Normally lives in soil - so take history of exosure e.g chopping wood.
Found in North America
Blastomycosis commonly invades lungs and skin.
What are sites are often infected?
Once disseminated can affect any organ - bones, joints, genitourinary, prostate
Why is calcofluor-KOH examination of sputum useful to identify fungal disease?
Fungi are refractory to KOH, whereas human tissues and bacteria are dissolved
26 year old from Vietnam, recently moved to USA. Presents with right axillary mass, and CXR shows apical lesion.
What is in differential diagnosis?
Chronic infections which are slow growing
- Penicillium (Talaromyces) - Vietnam
- blastomycosis - Eastern USA
- coccidioides - Arizona
- histoplasma
- mycobacteria
- nocardia
- Actinomyces
- malignancy e.g lymphoma
Bacterial cultures can be reviewed on a bench. Fungal cultures must be reviewed in a safety cabinet.
Why is this?
Fungal spores are easily aerosolized, and can be inhaled by laboratory worker
Fungal spores could aerosolise and contaminate other plates
Coccidioides highest prevalence is soil in Arizona/ Southern California. Can be related to construction and disturbing soil
What are most common presentations?
Valley fever - flu like illness. Cough, fever, myalgia
Common in San Joaquin valley of California
<5% of infections cause dissemination - to bone, skin, meninges
Patients with transplant are at risk of CMV infection/ reactivation.
Ganciclovir, foscarnet, and cidofovir are all anti-virals used for treatment.
Ganciclovir/ cidofovir slow and stop CMV DNA chain elongation by competing with dGTP
Foscarnet is non-competitive inhibitor of CMV DNA polymerase
What are common mechanisms of CMV drug resistance which emerge?
CMV drug resistance mutations
Viral kinase - UL97 mutation - resistance to ganciclovir
DNA polymerase - UL54 mutation - resistance to ganciclovir, foscarnet, cidofovir
Which nematode larvae pass through lung during their life cycle? (3)
Ascaris
Hookwrom - Necator/ Ancylostoma
Strongyloides
Patient on high dose corticosteroids, who previously lived in Vietnam. You are concerned of hyperinfection.
How to diagnosis strongyloides infection?
Stool examination - however this is very insensitive
Serology - if positive, and clinical suspicion, then just treat with ivermectin
Eosinophilia - although if immunosuppressed, may not be raised
What complications are associated with strongyloides hyperinfection?
Invasion of blood/ CNS - postulated migrating larvae can transport gram neg bacteria with them from the bowel
If find more than one gram negative species on CSF, then consider than a larvae has transported the infection
Ventilated patients at risk of VAP.
Why is this?
No gag reflex, so can aspirate upper airway secretions
Biofilm forms on ET tube - can become colonised
Organisms from upper airway can “leak” around ET tube, and aspirated into lung
Why is the timing of VAP important from a microbiological perspective?
<5 days intubated - usual organisms which cause CAP
> 5 days intubated, then more likely gram-negs or staph aureus
Patient has VAP, >5 days since intubation
Gram stain - gram neg bacilli
Oxidase negative
Glucose non-fermenter
What is the cause?
Acinetobacter.
Resistant strains emerging, which are carbapenemase-producers
Pseudomonas is oxidase pos
Klebsiella/ Enterobacter is glucose fermenters
What is colistin mechanism of action?
What is colistin spectrum of action?
Disrupts cell membrane by binding to lipopolysaccharides and phospholipids on outer membrane
Gram negatives
