The Pneumonia formerly known as PCP

Pneumocysitis jirovecii pneumonia was previosuly named Pneumocystis carinii pneumonia. Some of the debate regarding the name change can be found here and in the associated references. Previously classified as a protozoa, but molecular studies have shown it to likely be a FUNGUS.

Generally occurs in HIV+ patients with a CD4 count below 200 cells/mm3. Can also occur in other immunosuppressed hosts.

PRESENTATION
Subacute onset of (exertional) dyspnea, dry cough +/- "low-grade" fever.
Physical Exam shows tachypnea, tachycardia and normal lung auscultation in 50% (the remainder having crackles etc.).
CXR - classically bilateral, perihilar interstitial infiltrates, but can show almost anything (or nothing). However, pleural effusions and/or lymphadenopathy is very rare.

DIAGNOSIS
In addition to the clinical presentation, microscopic examination of (induced) sputum, BAL fluid or tissue can be performed. PJP cannot be readily cultured (be sure to specify you want sputum tested for PJP if it is in your Ddx), it can be seen with methenamine silver or immunofluorescence stains.

Laboratory data is generally not very informative. LDH is elevated in 90%, but this is very non-specific.

TREATMENT
TMP-SMX - high dose (see reference) x 21 days. Alternatives included inhaled pentamidine and atovaquone. Remember to start prophylaxis after finishing treatment!

Patients with PCP may worsen after two to three days of therapy, possibly from inflammation in response to dying organisms.

Corticosteroids are of benefit in patients who are hypoxic at presentation (PaO2 on room air less than 70mmhg or oxygen saturation <90%)

The benefit of steroids in PCP was shown in a study conducted in Toronto in 1987.

A NEJM review article can be found here

Thanks to prior CMRs for some of the above.



As discussed at noon rounds: Nystatin was isolated from Streptomyces noursei by Elizabeth Lee Hazen and Rachel Fuller Brown. The soil sample where they discovered nystatin was from the garden of Hazen's friends, Walter B. Nourses, therefore the strain was called noursei. It contained a substance that they first named fungicidin, a name that had already been used for another substance. They then renamed the substance nystatin in honor of the New York State Public Health Department, where they worked.

What's the diff?

CLOSTRIDIUM DIFFICILE

Gram positive anaerobic bacillus - cytotoxin producing. Disease caused when toxin(s) bind to the surface of intestinal epithelial cells, where they are internalized and catalyze the glucosylation of cytoplasmic rho proteins, leading to cell death.

Typical occurs in elderly/instiutionalized especially after receiving antibioitics. Historically Clindamycin has been associated with high risk of C diff, in the Quebec outbreak in 2003, fluoroquinolone use was also associated with the development of infection. Direct person-to person spread occurs and previously healthy/younger/non institutionalized patients have also been infected.

PREVENTION

need responsible antibiotic use
infection-control measures (contact precautions, hand hygiene, environmental decontamination)

DIAGNOSIS
Microbiology

• C. diff toxin assay (EIA) detects toxins A and B and has ~70% sensitivity, with ~90-95% sensitivity on three tests. The specificity is> 95%.
• The most sensitive assay is the test for cytopathic effect, which is not available here
• You can also culture Clostridium difficile from the stool, but this is not routinely done, as there are nonpathogenic strains
  
• A positive toxin assay in a patient with minimal or no symptomsshould not prompt treatment. (i.e. only send for toxin testing if there is sufficient pre-test probability)

Radiology

• Consider AXR to assess for toxic megacolon -a maximum colonic diameter greater than 6 cm is consistent with megacolon, may also see bowel wall changes
  
• CT scan helpful for further assessment and to R/O other causes of colonic distension etc.. May show thickening of the bowel wall, colitis, ileus
  

Sigmoid/Colonoscopy
Generally avoided with typical presentation and positive toxin EIA

Concern regarding endoscopy/insuflation of air causing perforation, especially if toxic megacolon present

May see pseudomembranes diagnostic of pseudomembranous colitis
Consider endoscopy if:

• Atypical presentation (ileus etc.)
• Other diagnoses suspected/need to be ruled out
• Failure of C. difficile infection to respond to therapy
  

TREATMENT

See table from NEJM review here.

First Episode
***If possible stop offending antibiotics***

• Mild/Moderate Disease
  
  • Metronidazole OR Vancomycin (PO) duration 10-14d
    
• Severe Disease
  
  • Defined as:
    
    • Two of (Age above 60, Febrile, WBC above 15, Albumin below 25)
      
    • OR hypotension/shock or Cr greater than 1.5x normal, or toxic megacolon, peritoneal signs, perforated bowel
      
  • Infectious Disease +/- General Surgery Consultation
  • ICU Consult for patients with hemodynamic comprimise
    
  • Vancomycin (PO) unless severe illeus/toxic megacolon, then Metronidazole (IV) duration 10-14d (Vanco has more rapid symptom resolution and a lower risk of treatment failure).

Relapse

• First relapse --> can repeat last treatment depending on severity
• Second relapse --> vancomycin taper. ID consult.

NEJM Review article (2008) can be found here.
A paper discussing Vanco as first line treatment can be found here.
Thanks to Dr. T.C Lee for some of the above post.