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Perth Haematology :: Dr Steven Ward

PCP

 

Pneumocystis carinii pneumonia (PCP)

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Increasing incidence as more immunosuppressive therapy

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Actually a fungal eucaryote. New name Pneumocytis jirovecii

 

PCP in the cancer patient

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Compared to HIV related PCP:
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Shorter, rapidly progressive illness (2 weeks); sicker

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Less sweating or weight loss

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Radiology: diffuse bilateral interstitial pneumonia. Wide range from normal film to focal consolidation. Pleural effusion is very rare.

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 With cancer and chemotherapy the immunosuppression is mild and longer lasting than neutropenia, with slower recovery of CD4+ cells than CD8+ cells.

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 Steroids: Glucocorticoid therapy is the most commonly linked risk-factor. PCP can occur early in therapy (within a month) and seems related to current dose rather than cumulative exposure. PCP may become symptomatic on reduction of steroid doses. Propose considering PCP prophylaxis is prednisolone 20mg/day over a month [total dose 560mg] [or 90mg dexamethasone]. Continue prophylaxis over the tapering period.

 

 

PCP Prophylaxis

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PCP has high mortality in cancer patients, and is relatively easy to prevent. Related to immune effects of tumour or treatment

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 ALL: very high-risk

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 Hodgkin Disease: high-risk (25%); recent reports lower (1%)

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NHL: heterogeneous group. Variable risk. Indolent NHL and gentle therapy lower risk

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CLL: If fludarabine used, or high-dose steroids. [6 months prophylaxis for purine analogue, or until CD4 > 300]

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HTLV-1 Leukaemia/lymphoma: very-high risk.

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CNS lymphoma: high-risk

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Steroid therapy: When expected dose over 1 month is 20mg/day [560mg] for prednisolone or 4mg/day for dexamethasone [90mg].

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Fludarabine and Cladribine: Commence with therapy and continue 6 months after, or until CD4 > 300/uL.

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 Methotrexate: For high-dose therapy. CNS NHL, and >3g/m2 or with steroids. [NB: added toxicity with Seprtin and Dapsone with MTX].

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Combination chemotherapy: all ALL protocols

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 Previous PCP and ongoing immunosuppression

 

 

Prophylaxis Drugs and Doses

Sulfamethoxazole / Trimethoprim (Septrin, Resprim)

One Double strength (DS) tablet [800/160mg] bd on two days a week (ie 4 tablets per week). This is first choice. Superior efficacy, activity against other pathogens, cost and ease of use.

Dapsone 200mg daily

Effective, inferior to Septrin

NB: G6PD deficiency and Heinz body Haemolytic Anaemia; methaemoglobuinaemia Dapsone levels are increased by azole antifungals; increases CyA levels

Pentamidine 300mg nebuilised monthly

Effective, inferior to Septrin; more expensive; poorer drug penetration to upper lobes; exposure to staff; bronchospasm (up to 40%)

Atovaquone 1500mg daily

Daily dosing required.

Azithromycin 1200mg weekly

May be beneficial, less effective than all above.

 

 

Diagnosis of PCP

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 Induced sputum or bronchoscopy specimens if possible

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Often treated on presumptive or suspected diagnosis in the appropriate clinical setting

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Sulphonamide desensitisation protocols are often successful

 

Treatment of PCP

Mild to moderate disease: Pa02 > 70mmHg on room air; A-a gradient <35 mmHg; Sa02 > 94% on room air

         Sulfamethoxazole / Trimethoprim 25+5mg/kg  to 35+7mg/kg orally q8h for 21 days (eg 70kg = 2 DS tablets tid) OR if allergy:

         Dapsone 100mg daily for 21 days plus Trimethoprim 300mg q8h for 21 days OR

         Atovaquone 750mg bd for 21 days

 

Severe disease: Pa02 <70mmHg on room air; A-a gradient >35mmHg; Sa02 <94% on room air

         Steroids: prednisolone 40mg bd for 5 days; then 40mg daily for 5 days then 20mg daily for 11 days PLUS

         Sulfamethoxazole / Trimethoprim 25+5 mg/kg orally or IV q6h for 21 days (70kg = 2 DS tablets qid) OR

         Pentamidine 4mg/kg up to 300mg IV daily for 21 days. IV pentamidine risks are renal, haematological, pancreatic (glucose), cardiac arrhythmia.