1. PCP in adults: Presentation , Treatment and Prophylaxis
Prof. David W. Denning
Professor of Infectious Diseases in Global Health
The University of Manchester, UK

2. Presentation in adults

3. Clinical presentation of PCP in adults
When do you suspect PCP in an adult?
Atypical presentation of pneumonia with the following risk factors:-
HIV-infection
ART-naïve, CD4<200
Non-compliant with ART
Previous PCP episode
Not on PCP prophylaxis
Unknown HIV status
Bone marrow transplant
Solid-organ transplant
Lymphoma and haematological malignancy
Chronic corticosteroid use / immunosuppressive therapy
Katz et al. Arch Intern Med 1991;151:

4. Clinical presentation of PCP in adults
HIV-infected adults
INSIDIOUS progression of symptoms over SEVERAL Weeks
Non-productive cough
Exertional dyspnoea
Fatigue
Fevers
Chills
Sweats
Other associated events
Weight loss
Recurrent bacterial pneumonias
Oral candidiasis
Extra-pulmonary pneumocystosis
In ART-naïve patients with advanced AIDS
CNS, GIT or disseminated infections

5. Clinical presentation of PCP in adults
HIV-negative adults
More RAPID progression and SEVERE disease
Non-productive cough
Exertional dyspnoea
Fatigue
Fevers
Chills
Sweats
Onset of symptoms often during the time of discontinuation or dose reduction of immunosuppressive therapy

6. Clinical presentation of PCP in adults
Physical examination
Non-specific signs
Fevers
Tachypnoea
Tachycardia
Cyanosis; uncommon in adults
Physical examination
Pulmonary exam
Often normal
Mild crackles
Diminished breath sounds
Sign of pneumothorax

7. Differential diagnoses
The commonest differential diagnoses are:
Bacterial pneumonia (especially non-HIV)
CMV or other viral pneumonitis
Invasive aspergillosis (especially non-HIV)
Pulmonary embolism

8. Differential diagnoses
Pulmonary FUNGAL infections
Histoplasmosis
Cryptococcosis
Invasive aspergillosis
Cocidioidomycosis
Blastomycosis (rare)
Pulmonary mucormycosis
Pulmonary and systemic symptoms of pulmonary fungal infections are quite similar
Except for mucormycosis, cutaneous skin manifestations are common in many of these fungal infections
Unlike PCP, pulmonary mucormycosis is common in diabetics

9. Differential diagnoses
Pulmonary (MYCO)BACTERIAL infections
Pulmonary TB
Bacterial pneumonia
Mycoplasma pneumonia
Legionella pneumonia
Non-tuberculous mycobacterial infections
Similar pulmonary manifestations
Bacterial pneumonias tend to be more rapid and acute
Focal lung findings, chest pain and productive sputum are frequent in bacterial pneumonia
PTB presents with systemic symptoms similar to PCP
Atypical bacterial infections present with dry cough similar to that of PCP

10. Differential diagnoses
Pulmonary VIRAL infections
Cytomegalovirus pneumonitis
Influenza
Other viral pneumonias
CMV pneumonitis is usually associated with a non-productive cough and minimal findings on lung examination and is more common in HIV-negative patients
Influenza has signs and symptoms similar to PCP and does not respond to empirical antibiotic therapy

11. Differential diagnoses
Pulmonary OTHER conditions
Pulmonary Kaposi's sarcoma
Acute respiratory distress syndrome
Pulmonary embolus
Sarcoidosis
Non-infectious interstitial lung diseases
Lymphoid interstitial pneumonitis
Pulmonary symptoms similar to those of PCP are common in this conditions
Unlike PCP, these conditions are often associated with pleural effusion

12. PCP versus other conditions
In PCP: Hypoxia or exercise-induced hypoxia (reduced O2 saturation) is worse than the chest X-ray would suggest.

13. Treatment

14. Treatment considerations
Severity of the disease
Based on blood gas analysis or
Room air partial pressure of oxygen (pO2)
Toxicities of the agents
Adjunctive therapy
Moderate-severe PCP

15. Grading of severity of PCP
In adults and children, the severity of PCP may be graded as:
Mild-to-moderate PCP:
Arterial blood gas room air pO2 ≥70 mmHg or
Alveolar-arterial (A-a) gradient ≤35 mmHg.
Moderate-to-severe PCP:
Arterial blood gas room air pO2 <70 mmHg or
Alveolar-arterial (A-a) gradient >35 mmHg

16. Mild to moderate Pneumocystis pneumonia
Drug of choice
Co-trimoxazole in high dosage
Alternative agents (in patients intolerant of cotrimoxazole)
Clindamycin + primaquine
Atovaquone (mild only)
Dapsone + trimethoprim (mild only)
1. Atovaquone is licensed for the treatment of mild to moderate pneumocystis infection in patients who cannot tolerate co-trimoxazole.
2. A combination of dapsone with trimethoprim is given by mouth for the treatment of mild to moderate disease [unlicensed indication].
3. A combination of clindamycin and primaquine by mouth is used in the treatment of mild to moderate disease [unlicensed indication]; this combination is associated with considerable toxicity

17. Mild-to-moderate PCP: Drug dosing
Co-trimoxazole
15-20 mg/ kg/day, PO or IV given in divided doses every 6-8 hours
Dapsone
100mg, PO, once daily
Trimethoprim
15 mg/kg/day, PO, given in divided doses every 8 hours
Clindamycin
mg, PO, every 6-8 hours
Primaquin
15-30mg, PO, once daily
Atovaquone
750 mg , PO, twice daily
1. Atovaquone is licensed for the treatment of mild to moderate pneumocystis infection in patients who cannot tolerate co-trimoxazole.
2. A combination of dapsone with trimethoprim is given by mouth for the treatment of mild to moderate disease [unlicensed indication].
3. A combination of clindamycin and primaquine by mouth is used in the treatment of mild to moderate disease [unlicensed indication]; this combination is associated with considerable toxicity

18. Severe Pneumocystis pneumonia
Drug of choice
Co-trimoxazole, high dosage, by mouth or intravenously
i.e  mg/kg daily in 2–4 divided doses for 14–21 days.
Alternative agents
Indications: Intolerance or lack of response to co-trimoxazole
Clindamycin IV + primaquine PO
Pentamidine, by intravenous infusion
Potentially toxic drug causing hypotension during or immediately after infusion
Co-trimoxazole dose for treatment is 120 mg/kg daily in 2–4 divided doses for 14–21 days.

19. Severe PCP: Drug dosing
Co-trimoxazole:
15-20 mg/kg/day , IV, in divided doses every 6-8 hours
Clindamycin:
mg, IV , every 6-8 hours; OR
mg , PO, every 6-8 hours
-and-
Primaquine:
15-30 mg, PO, once daily
Pentamidine: 4 mg/kg , IV, once daily
Prednisolone:
40 mg, PO, BD, for 5 days, then
40 mg, PO, OD, for 5 days, then
20 mg , PO, OD, for 11 days OR
Methylprednisolone
30mg, IV, BD for 5 days, then
30mg, IV, OD for 5 days, then
15mg once daily until patient can be given oral prednisone
Co-trimoxazole dose for treatment is 120 mg/kg daily in 2–4 divided doses for 14–21 days.

20. Adjunctive therapy Prednisolone (or IV hydrocortisone) for 21 days
Life-saving addition in moderate-severe PCP
Standard dose for 5 days , then reduced to complete the 21 days
Should be commenced at the same time as anti-PCP therapy
Most effective if initiated within hours
Corticosteroids should be withdrawn before anti-PCP therapy is completed

21. PCP prophylaxis

22. Primary prophylaxis
Indicated for patients with severe immunodeficiency
Prophylaxis continues until immune recovery
This should be in addition to ART
PCP prophylaxis should NOT be discontinued in the following scenarios:-
On going immunosuppressive therapy
Oral candidiasis or any other opportunistic infections
Continued weight loss

23. Secondary prophylaxis
All patients with previous PCP infection
Prophylaxis continues until immune reconstitution
CD4>200 cells/µL for 3 consecutive months
Secondary prophylaxis should be started concurrently with the end of PCP treatment and continued for life, unless immune reconstitution occurs with antiretroviral therapy

24. *Inhaled pentamidine is better tolerated compared to IV
Anti-PCP prophylaxis
Drug of choice
Co-trimoxazole
By mouth
Daily or alternative days
Reduce dose to improve tolerance
Alternative agent
Petamidine
Inhaled (preferred) or IV route*
Patients on inhaled pentamidine have a small risk of extrapulmonary pneumocystosis
Dapsone or atovaquone can also be used
*Inhaled pentamidine is better tolerated compared to IV
1. Both dapsone and atovaquone have been used for PCP prophylaxis but none of the two has been licensed for this indication
2. Cotrimoxazole dosing regimens for PCP prophylaxis are as follows:
Daily dosing: 960 mg once daily, reduced if not tolerated to 480 mg once daily.
Alternatively day dosing: 960 mg once daily on alternate days (3 times weekly) or alternatively 960 mg twice a day on alternate days (3 times weekly).

25. Summary
Pneumocystis jirovecii pneumonia (PCP) is the most common AIDS-defining opportunistic infection associated with significant morbidity and mortality
The clinical manifestation tend to be insidious in HIV-infected patients but rapidly progressive and severe in HIV-negative patients
Cotrimoxazole is the drug of choice for primary and secondary prophylaxis, and treatment of PCP
Alternative agents are used in case of lack of response to co-trimoxazole or intolerance to it

26. END