RAT Material - PJP/PCP

P. Jirovecii

What organism causes PJP/PCP in humans?

During early childhood; ⅔ of children 2-4 years of age have antibodies

The PJP initial infection usually occurs _____ and________

• Spreads via airborne route 

• Used to occur in 70-80% of people with advanced HIV (before prophylaxis)

• 20-40% mortality rate 

• 90% of cases patients have CD4 <200

Other PCP/PJP Epidemiology Points 1

• Incidence has gone down due to PCP prophylaxis and ART 

• Current incidence: <1 case per 100  person-years

• Most cases are now ppl who are unaware of HIV status or not receiving care or advanced immunosuppression (CD4 <100)

Other PJP/PCP Epidemiology Points 2

1. Dyspnea

2. Fever (main symptom)

3. Non-productive cough

4. Chest discomfort that worsens within days to weeks

Main clinical manifestations of PJP/PCP

Hypoxemia

• Mild: PaO2 >70 or A-a gradient <35

• Moderate: A-a gradient >35 to <45

• Severe: A-a gradient >45

What is the main lab abnormality of PCP/PJP?

• Lactate dehydrogenase >500 is common

• People with HIV may also have other pulmonary dysfunction (TB, kaposi sarcoma, toxoplasmosis)

• Sometimes ppl with infection can  have normal chest x ray, can use CT 

Other clinical manifestations / lab abnormalities of PJP/PCP

• CD4 100-200, if plasma HIV RNA level above detection limits OR

• CD4 <100, regardless of plasma HIV RNA levels

SO

start PPX with Bactrim 160/800 or 80/400 IF CD4 100-200 (HIV RNA level above limit) OR if CD4 < 100

Indication for Primary PPX

Bactrim (TMP/SMX) 1 DS (160/800mg) tablet po daily OR 1 SS (80/400mg) tab po daily

Preferred (1st line) PPX treatment of PJP/PCP

1. Bactrim DS

2. Dapsone w pyrimethamine + leucovorin

3. Atovaquone

B // DPL // A

Alternative primary PPX therapy for patients who are positive OR negative for toxoplasma

1. Dapsone

2. Pentamidine (nebulizer or IV)

D // P

Alternative primary PPX therapy for patients who are negative for toxoplasma

• CD4 increased from <200 to 200 cells or more for >3 months in response to ART

• Can consider if CD4 100-200 and HIV RNA remains below detection limit for >3-6 months

When would you discontinue PJP/PCP PRIMARY PPX?

• Bactrim (TMP-SMX): 15-20mg/kg/day (TMP) and 75-100mg/kg/day (SMX) IV q6-8 hours 

• Can switch to oral once clinical improvement

Treatment (not PPX) of Moderate to severe PJP/PCP - PREFERRED THERAPY

• Primaquine + clindamycin

• Pentamidine

Treatment (not PPX) of Moderate to severe PJP/PCP - ALTERNATIVE THERAPY

• Corticosteroids IF: 

  • PaO2 <70 at room air OR

  • A-a gradient > or equal to 35

• Prednisone taper

  • Days 1-5—-> 40mg po bid 

  • Days 6-10 —> 40mg po daily

  • Days 11-21—> 20mg po daily

Treatment (not PPX) of Moderate to severe PJP/PCP - ADJUNCTIVE THERAPY

• Bactrim (TMP-SMX): 15-20mg/kg/day (TMP) and 75-100mg/kg/day (SMX) IV q6-8 hours 

OR

• Bactrim (TMP/SMX) two DS tabs PO TID

Treatment (not PPX) of Mild to Moderate PJP/PCP - PREFERRED THERAPY

• Dapsone 

• Primaquine + clindamycin 

• Atovaquione

D // PC // A

Treatment (not PPX) of Mild to Moderate PJP/PCP - Alternative THERAPY

21 days for all regimens

• initiate secondary pox after tx is complete

Treatment duration of PCP/PJP Treatment (not PPX)

• ART should be initiated within 2 weeks of PCP diagnosis 

• People with HIV should be closely followed for recurrence symptoms after initiation of ART

ART considerations PJP/PCP

• immediately upon successful completion of PCP therapy and maintained until immune reconstitution occurs as a result of ART

• Can use

  • dapsone

  • dapsone + pyrimethamine +leucovorin,

  • atovaquone, or

  • pentamidine if HIV patient is intolerant to TMP-SMX

• TMP-SMX IS PREFERRED TX

When should secondary PCP/PJP PPX be STARTED?

• Adults w/ CD4 increased to >200 or more for >3 months as a result of ART

• Can potentially d/c in patients with HIV with CD4 100-200 AND HIV levels are below detection for 3-6 months

When should secondary PCP/PJP PPX be STOPPED?

• If CD4 decreases to <100 regardless of HIV viral load

• Ppl with CD4 100-200 w/ HIV viral load above detection limits

If PCP episode occurs for pt. w/ CD4 >200 while the pt. Is on ART, continue prophylaxis for life regardless of CD4 cell count rising

When should secondary PCP/PJP PPX be RESTARTED?