Positioning Second-line Therapies for Pneumocystis Jirovecii Pneumonia (PCP Alternatives)

Inclusion Criteria: * Immunocompromised patients (including but not limited to HIV, solid organ transplant, solid tumors, hematological transplant and malignancies, systemic diseases, chemotherapy, long term corticosteroid use, and immunosuppressive therapies, as well as primary immunodeficiencies) in an emergency department, cliinic, or hospital * Age ≥18 years * Proven or probable Pneumocystis jirovecii pneumonia * Inability to receive trimethoprim-sulfamethoxazole due to contraindication, intolerance, toxicity, or treatment failure * Immunocompromised status * Ability to provide informed consent (or per local regulations) While participants may be enrolled in multiple domains of the SPIRIT-PCP Platform over time (if they are eligible and a domain is active), they may only be enrolled to single question once (e.g., they can be part PCP Alternatives and an eventual secondary prophylaxis domain; however, if they have a recurrence, they cannot be included in PCP Alternatives again). Exclusion Criteria: * The Platform will exclude: patients where we are unable to obtain informed consent, where patients or their proxy have declined to consent, where the treating team has declined participation, where follow up cannot be reliably obtained (e.g., lack of means of communication, patient non-resident of jurisdiction), where treatment with antibiotics is not in keeping with a patient's advanced care directives, and where death is deemed imminent (\<48h) as determined by the treating team and site investigator. Clinical: 1. Previous severe adverse reaction or hypersensitivity to clindamycin, primaquine, or atovaquone (mild-moderate PCP) or to clindamycin, primaquine, or pentamidine (severe PCP); 2. More than 7 calendar days of any therapy for PCP (no more than 4 can involve a study drug). 3. Known pregnancy or breastfeeding (pregnancy test will be offered) Drug specific exclusion criteria: 4. For clindamycin-primaquine: 1. Known G6PD deficiency OR family history of G6PD deficiency without excluding by testing\* 2. Known diagnosis of porphyria 3. Concomitant use of methotrexate or cyclophosphamide which cannot be held \*G6PD deficiency is an X-linked recessive genetic disease. Female patients without a family history are very unlikely to have this disease and so therapy can start while waiting for the test in the absence of a family history. Male patients should wait for test results prior to receiving primaquine even if they do not have a family history. For those without G6PD testing at diagnosis, it is a reasonable standard of care to order testing. 5. For pentamidine: 1. Absence of adequate intravenous access as determined by treating team and site investigator. In the event of loss of IV, up to 2 consecutive doses can be given intramuscularly if the patient is not systemically anticoagulated and does not have a coagulopathy. 2. Hypotension defined as systolic blood pressure below 90mmHg without pharmacologic support 3. Personal history of Torsade de Pointes or presence of a corrected QTc of greater than 490ms on ECG on date of enrollment 6. For atovaquone: 1. Receipt of PCP Prophylaxis (≥3 doses per week) for ≥ 4 weeks with atovaquone 2. inability to tolerate atovaquone with a meal or enteral feeding (e.g., prolonged NPO status is an exclusion as atovaquone must be taken with food for proper absorption) 3. Concurrent use of rifampin, rifabutin, or tetracycline (that cannot be stopped) 4. Reduced gastric absorption (patient must not have a medical condition which the treating team and/or site investigator believes will interfere with atovaquone absorption, e.g., total gastrectomy) Administrative: 1\. Trial site not participating in PCP Alternatives branch of the initial therapy domain