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Pneumocystis is a fungus that can cause a dangerous pneumonia in people whose immune system is weakened by some cancer treatments, steroids or a stem cell transplant. An inexpensive antibiotic, co-trimoxazole, taken a few times a week or daily, prevents it very well. People who cannot take it have other options: atovaquone, dapsone or an inhaled medicine once a month.
AGIHO (2020) strongly recommends chemoprophylaxis for the groups its Table 7 lists at significant risk: acute lymphoblastic leukaemia, allogeneic stem cell transplant, long-term steroids above 20 mg prednisone equivalent daily for more than 4 weeks, and fludarabine with cyclophosphamide and rituximab (prevent PJP A-I, reduce mortality A-IIr), and for idelalisib, alemtuzumab and temozolomide with radiotherapy (A-IIu,t). Intermediate risk (R-CHOP14, escalated BEACOPP, nucleoside analogues, brain irradiation with high-dose steroids, CD4 below 200/µl) may or may not receive it (C-III). ASCO/IDSA (2018) set the threshold at regimens with more than 3.5% risk, for example 20 mg or more prednisone equivalent daily for a month or more, or purine analogues. ECIL-5 (2016) lists ALL, allogeneic HSCT, alemtuzumab, fludarabine with cyclophosphamide and rituximab, more than 4 weeks of corticosteroids and primary immune deficiencies in children, for the entire period at risk.
Co-trimoxazole (trimethoprim-sulfamethoxazole) is first choice (AGIHO A-IIt,r; ECIL-5 A-II adults, A-I children), at one single-strength tablet daily or one double-strength tablet daily or thrice weekly (B-IIt); ECIL-5 gives it 2 to 3 times weekly and notes children may do equally well once weekly (B-II). Second line: atovaquone 1500 mg daily with a fatty meal (A-IIt), dapsone 100 mg daily after G6PD testing (A-IIt), or aerosolised pentamidine 300 mg monthly (B-IIt), which is probably less effective and needs staff protection. For idelalisib the label asks for prophylaxis from the start and for 2 to 6 months after stopping.
Why: In these groups the pneumonia is common enough, and deadly enough, that prevention clearly pays.
“Oncologic patients at significant risk for PcP are those treated for acute lymphoblastic leukemia, those treated with a combination of fludarabine, cyclophosphamide, and rituximab [129], and patients undergoing allogeneic HSCT [128, 130].”
Why: It prevents the pneumonia and reduces deaths from it.
“The administration of chemoprophylaxis in patients with one of these three risk factors is thus strongly recommended to prevent PcP (A-I) and reduce mortality (A-IIr).”
AGIHO/DGHO, Annals of Hematology 2021 · A-I (prevent PcP); A-IIr (reduce mortality)
Why: These treatments carry a documented high risk, and for idelalisib the drug label requires it.
“Based on the documented high-risk situation, we strongly recommend chemoprophylaxis against PcP for patients receiving temozolomide (in combination with radiotherapy), idelalisib, or alemtuzumab (A-IIu,t) (Tables 7 and 8).”
AGIHO/DGHO, Annals of Hematology 2021 · A-IIu,t
Why: These patients occasionally get the infection, but no study shows prophylaxis helps them and many more would need treating to prevent one case.
“Such patients at moderate risk may or may not receive chemoprophylaxis to prevent PcP (C-III) and to reduce mortality (C-III).”
Why: It is the most effective option, and also protects against toxoplasmosis, nocardiosis and actinomycosis.
“For these reasons, TMP-SMX is the first-choice agent for PcP prophylaxis (A-IIt,r).”
AGIHO/DGHO, Annals of Hematology 2021 · A-IIt,r
Why: The schedules work equally well; three times a week caused fewer stoppings for side effects in a study in people with HIV.
“We recommend using any of these dosing regimens (B-IIt).”
Why: The risk lasts as long as the immune suppression, not just the days of chemotherapy.
“Trimethoprim/sulfamethoxazole given 2-3 times weekly is the drug of choice for the primary prophylaxis of PCP in adults ( A-II: ) and children ( A-I: ) and should be given during the entire period at risk.”
European Conference on Infections in Leukaemia (ECIL-5), Journal of Antimicrobial Chemotherapy 2016 · A-II (adults); A-I (children)
Why: It worked well and does not lower blood counts; lower doses were less effective, and fat helps it absorb.
“Low-dose atovaquone has been described to be less effective in PcP prophylaxis [164]; thus, 1500 mg atovaquone should be administered once daily (off-label use) (A-IIt).”
Why: Dapsone works as well as co-trimoxazole but can break down red cells in G6PD deficiency and cause methaemoglobinaemia.
“Testing for glucose-6-phosphat dehydrogenase deficiency is recommended prior to administration of dapsone.”
Why: It has no blood or drug interactions but probably works less well, gives no protection against toxoplasmosis, and exposes staff to the drug.
“Our recommendation to use aerosolized pentamidine (300 mg once/month) is moderate (B-IIt) (Table 9).”
How care is usually carried out, read from the guidelines and standards cited. Your own team's protocol and their judgement come first; this page is for understanding it, not for doing it yourself.
Co-trimoxazole for the whole period of risk is the agreed first choice (AGIHO 2020 A-IIt,r; ECIL-5 2016 A-II adults, A-I children). The guidelines agree on the core indications (ALL, allogeneic transplant, fludarabine-based chemoimmunotherapy, alemtuzumab, prolonged steroids) but draw the line differently: AGIHO names significant, intermediate and special-indication groups and leaves intermediate risk to judgement (C-III); ASCO/IDSA (2018) use a numerical threshold of more than 3.5% risk, with 20 mg or more prednisone equivalent daily for a month or longer as the example; ECIL-5 adds primary immune deficiencies in children and other regimens case by case. On the schedule, AGIHO accepts daily or thrice-weekly dosing (B-IIt), ECIL-5 recommends 2 to 3 times weekly and allows once weekly in children (B-II). For children with solid tumours, a 2017 guideline suggests offering prophylaxis to all children having immunosuppressive therapy unless contraindicated.
AGIHO/DGHO, Annals of Hematology 2021 · European Conference on Infections in Leukaemia (ECIL-5), Journal of Antimicrobial Chemotherapy 2016 · ASCO and IDSA, Journal of Clinical Oncology 2018 · Journal of Pediatric Hematology/Oncology 2017
Where it differs: Recommends prophylaxis for chemotherapy regimens associated with more than 3.5% risk of Pneumocystis pneumonia, for example 20 mg or more prednisone equivalents daily for a month or more, or purine analogues.
Evidence: Read as an abstract only, so the grade is not given here.
Where it differs: Uses a single weekly dose instead of 2 to 3 times weekly in children.
Evidence: ECIL-5 says recent data indicate children may benefit equally, graded B-II.
European Conference on Infections in Leukaemia (ECIL-5), Journal of Antimicrobial Chemotherapy 2016
Where it differs: Offers co-trimoxazole to all children with malignancies on immunosuppressive therapy unless there are clear contraindications, rather than only those in named high-risk groups.
Evidence: A paediatric guideline read as an abstract only; it argues from the high mortality of the pneumonia and the safety and low cost of co-trimoxazole.
| Recommendation | Grade, as printed | Source |
|---|---|---|
| Prophylaxis for significant-risk groups, to prevent PJP | A-I | AGIHO/DGHO, Annals of Hematology 2021 |
| Prophylaxis for significant-risk groups, to reduce mortality | A-IIr | AGIHO/DGHO, Annals of Hematology 2021 |
| Prophylaxis with idelalisib, alemtuzumab or temozolomide with radiotherapy | A-IIu,t | AGIHO/DGHO, Annals of Hematology 2021 |
| Intermediate-risk groups may or may not receive prophylaxis | C-III | AGIHO/DGHO, Annals of Hematology 2021 |
| Co-trimoxazole as first choice | A-IIt,r | AGIHO/DGHO, Annals of Hematology 2021 |
| Co-trimoxazole 2 to 3 times weekly for the entire period at risk | A-II (adults); A-I (children) | European Conference on Infections in Leukaemia (ECIL-5), Journal of Antimicrobial Chemotherapy 2016 |
| Once-weekly co-trimoxazole in children “Recent data indicate that children may benefit equally from a once-weekly regimen ( B-II: ).” | B-II | European Conference on Infections in Leukaemia (ECIL-5), Journal of Antimicrobial Chemotherapy 2016 |
| Aerosolised pentamidine 300 mg monthly as second choice | B-IIt | AGIHO/DGHO, Annals of Hematology 2021 |
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