Shiwei\u00a0Zhou,\u00a0Samuel L.\u00a0Aitken<\/h3>\n\n\n\nJAMA.\u00a0<\/em>Published online June 26, 2023. doi:10.1001\/jama.2023.9844<\/h3>\n\n\n\nPneumocystis jirovecii<\/em> is an opportunistic fungal pathogen that causes life-threatening pneumonia in immunocompromised patients. Patients with Pneumocystis<\/em> pneumonia (PCP) typically present with fever, nonproductive cough, dyspnea, and hypoxemia with diffuse bilateral ground-glass opacities on chest imaging.1<\/a><\/sup> PCP can be prevented by reducing immunosuppression and with chemoprophylaxis. Effective prophylaxis significantly decreases the incidence of infection.2<\/a><\/sup> This article summarizes current recommendations regarding prevention of PCP in patients who are immunocompromised.3<\/a><\/sup>-5<\/a><\/sup><\/a><\/p>\n\n\n\nIndications for Prophylaxis<\/h2>\n\n\n\n
Primary prophylaxis is intended to prevent a first episode of PCP and should be administered in patients at risk for PCP due to specific medical conditions or treatments (Table<\/a>). Primary prophylaxis for PCP is recommended for all patients with HIV\/AIDS who have CD4 T-lymphocyte count less than 200\/\u03bcL.3<\/a><\/sup> These patients should also receive antiretroviral therapy (ART). Prophylaxis for PCP is also recommended for those with CD4 cell percentage less than 14% or in patients with CD4 lymphocyte count between 200\/\u03bcL and 250\/\u03bcL whose ART is delayed or who cannot receive CD4 monitoring at least every 3 months.3<\/a><\/sup><\/a><\/p>\n\n\n\nTable. \u00a0Medical Conditions and Pharmaceutical Therapies Requiring Prophylaxis for\u00a0Pneumocystis\u00a0<\/em>Pneumonia in Adults<\/p>\n\n\n\n![\"\"\/](\"https:\/\/cdn.jamanetwork.com\/ama\/content_public\/journal\/jama\/0\/jit230012t1_1687548352.35904.png?Expires=1690927371&Signature=IzJrF~b2GPGWiLRjrwccuHLngCGmvBKht7jF9Z3zwg~ylXv6BLPtBNlPYh7ZCCBwqH6keJdOabCSAq63gSZK~tb~jlHxGeF34kLzlGAQoVjPDAi6K~MCGSSJI4cmTUXmfh43gmGGTVgZt9K5aZ9qmlKtrteYOZSznVIBFVHpPZGefbJUAG491fodnxbSRLm7jzt5pvGLbvYvknieNLmEzpsXvd25sJf46MkFAC24-9-un3laVyX5XpNyacWhdfyFjAxbfTb4N4N3XhV-PbWskIXPyVd0ixjmljMINNyfar2d~A6FOcL2WZ4nK~a6cpcNBl91mCr7MGm4QMGbkC~UCw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA\")
<\/figure>\n\n\n\nAmong patients without HIV who are immunocompromised, primary PCP prophylaxis is recommended for those with acute lymphoblastic leukemia receiving antileukemic therapy, recipients of allogeneic hematopoietic cell transplant (HCT) and solid organ transplant, and patients treated with the anti-CD52 antibody alemtuzumab, phosphatidylinositol 3-kinase inhibitors (eg, idelalisib, duvelisib), or temozolomide with concurrent radiotherapy.5<\/a><\/sup>-7<\/a><\/sup> Prophylaxis is also recommended for patients treated with purine analogue chemotherapeutic agents (eg, fludarabine, cladribine), patients with malignancy receiving autologous HCT, and recipients of chimeric antigen receptor T-cell therapy.1<\/a><\/sup>,5<\/a><\/sup><\/a><\/p>\n\n\n\nPatients receiving high-dose corticosteroid treatment (equivalent to \u226520 mg of prednisone daily for \u22651 month) who have an additional cause of immunodeficiency (eg, underlying malignancy, additional immunosuppressive medication) should receive PCP prophylaxis.5<\/a><\/sup>,7<\/a><\/sup> Patients with antineutrophil cytoplasmic antibody\u2013associated vasculitis, such as granulomatosis with polyangiitis, undergoing induction therapy should also receive PCP prophylaxis.8<\/a><\/sup> There is no consensus regarding PCP prophylaxis for patients with autoimmune or autoinflammatory conditions, although patients with rheumatoid arthritis, systemic sclerosis, and giant cell arteritis treated with high-dose corticosteroids have a lower risk for developing PCP compared with those with granulomatosis with polyangiitis.8<\/a><\/sup><\/a><\/p>\n\n\n\nAn increasing number of patients are treated with immune-modulating medications that are associated with PCP but lack consensus guidelines regarding prophylaxis.9<\/a><\/sup>,10<\/a><\/sup> These medications include checkpoint inhibitors (eg, ipilimumab, nivolumab), tumor necrosis factor inhibitors (eg, infliximab), anti-CD20 antibodies (eg, rituximab), bruton-tyrosine kinase inhibitors (eg, ibrutinib), and Janus kinase inhibitors (eg, ruxolitinib) (eTable in the Supplement<\/a>). Although these treatments alone do not require PCP prophylaxis, the coexistence of an additional risk factor (eg, high-dose corticosteroids, presence of absolute lymphopenia, other immunosuppressive drugs) may be an indication to initiate prophylaxis. Other factors that may indicate a need for PCP prophylaxis include immunosuppression from the patient\u2019s underlying disease process, history of previous opportunistic infections, older age, and comorbidities.<\/a><\/p>\n\n\n\nSecondary prophylaxis to prevent recurrence of PCP should be started in all patients after successful treatment of PCP if the immunosuppressed state persists.<\/a><\/p>\n\n\n\nProphylactic Therapy<\/h2>\n\n\n\n
Trimethoprim-sulfamethoxazole is the drug of choice for PCP prophylaxis for patients with and without HIV (Table<\/a>). Prophylactic dosing of trimethoprim-sulfamethoxazole for patients with normal kidney function is typically 1 double-strength oral tablet (800\/160 mg) daily or 3 times per week or 1 single-strength tablet (400\/80 mg) daily, and is usually well-tolerated. Exanthem and nausea are common adverse effects.2<\/a><\/sup> If trimethoprim-sulfamethoxazole is discontinued for a mild adverse effect, reinstitution of medication should be considered after resolution of the adverse reaction. Those with allergic reactions may require desensitization with allergy consultation.3<\/a><\/sup><\/a><\/p>\n\n\n\nAlternatives for PCP prophylaxis include atovaquone, dapsone, and monthly administration of aerosolized pentamidine. All patients should have glucose-6 phosphate dehydrogenase levels measured by blood test prior to initiating dapsone. According to the National Comprehensive Cancer Network, monthly intravenous pentamidine is an acceptable alternative for PCP prophylaxis among HCT recipients,5<\/a><\/sup> but it is not recommended by the National Institutes of Health for patients with HIV due to insufficient evidence.3<\/a><\/sup> In clinical practice, the adverse effect profile, tolerability, and the health care insurance coverage of the patient often influence selection of alternative prophylaxis regimens. Due to increased risk of myelosuppression in patients with hematologic malignancy or HCT, and due to increased rates of nephrotoxicity in kidney transplant recipients, alternatives to trimethoprim-sulfamethoxazole should be considered in these patients.6<\/a><\/sup><\/a><\/p>\n\n\n\nDuration of Prophylaxis<\/h2>\n\n\n\n
Prophylaxis for PCP should continue as long as the immunosuppressive state persists. Among patients with HIV, PCP prophylaxis can be discontinued when CD4 lymphocyte counts increase to greater than 200\/\u03bcL for more than 3 months in response to ART.3<\/a><\/sup> Prophylaxis may also be discontinued if CD4 counts are 100\/\u03bcL to 200\/\u03bcL in patients whose HIV plasma RNA levels remain below the limits of detection for at least 3 months.3<\/a><\/sup> Prophylaxis may be discontinued in patients treated with alemtuzumab and purine analogue agents whose CD4 count improves to greater than 200\/\u03bcL.5<\/a><\/sup><\/a><\/p>\n\n\n\nPatients with acute lymphoblastic leukemia should continue PCP prophylaxis through the end of maintenance therapy.5<\/a><\/sup> Allogeneic HCT recipients begin prophylaxis at engraftment and should continue prophylaxis through at least 6 months after transplant or longer if immunosuppression is ongoing. Because the effect of immunosuppressive medications (eg, rituximab, temozolomide, idelalisib) may persist after drug discontinuation, duration of PCP prophylaxis should be individualized based on the medication received.<\/a><\/p>\n\n\n\nAll solid organ transplant recipients should receive prophylaxis for at least 6 to 12 months after the transplant, after which prophylaxis should be prescribed during periods of intensive immunosuppression for allograft rejection, infection with Cytomegalovirus<\/em>, or prolonged neutropenia.6<\/a><\/sup> Lifetime prophylaxis is recommended for recipients of lung and small bowel transplant as well as solid organ transplant recipients with previous PCP infection.6<\/a><\/sup><\/a><\/p>\n\n\n\nPatients requiring PCP prophylaxis usually have multiple comorbid health conditions and are often cared for by multiple subspecialists, including hematology, oncology, infectious diseases, rheumatology, pulmonology, and transplant. Discussion and coordination of initiation and discontinuation of PCP prophylaxis across these clinicians can be beneficial.<\/a><\/p>\n\n\n\nPatients at risk for PCP should receive safe and effective prophylaxis while they are immunosuppressed; trimethoprim-sulfamethoxazole is the agent of choice.<\/p>\n","protected":false},"excerpt":{"rendered":"
JAMA Insights June 26, 2023 Prophylaxis […]<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[25,23],"tags":[],"_links":{"self":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/24300"}],"collection":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=24300"}],"version-history":[{"count":2,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/24300\/revisions"}],"predecessor-version":[{"id":24507,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/24300\/revisions\/24507"}],"wp:attachment":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=24300"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=24300"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=24300"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}
Pneumocystis jirovecii<\/em> is an opportunistic fungal pathogen that causes life-threatening pneumonia in immunocompromised patients. Patients with Pneumocystis<\/em> pneumonia (PCP) typically present with fever, nonproductive cough, dyspnea, and hypoxemia with diffuse bilateral ground-glass opacities on chest imaging.1<\/a><\/sup> PCP can be prevented by reducing immunosuppression and with chemoprophylaxis. Effective prophylaxis significantly decreases the incidence of infection.2<\/a><\/sup> This article summarizes current recommendations regarding prevention of PCP in patients who are immunocompromised.3<\/a><\/sup>-5<\/a><\/sup><\/a><\/p>\n\n\n\n Primary prophylaxis is intended to prevent a first episode of PCP and should be administered in patients at risk for PCP due to specific medical conditions or treatments (Table<\/a>). Primary prophylaxis for PCP is recommended for all patients with HIV\/AIDS who have CD4 T-lymphocyte count less than 200\/\u03bcL.3<\/a><\/sup> These patients should also receive antiretroviral therapy (ART). Prophylaxis for PCP is also recommended for those with CD4 cell percentage less than 14% or in patients with CD4 lymphocyte count between 200\/\u03bcL and 250\/\u03bcL whose ART is delayed or who cannot receive CD4 monitoring at least every 3 months.3<\/a><\/sup><\/a><\/p>\n\n\n\n Table. \u00a0Medical Conditions and Pharmaceutical Therapies Requiring Prophylaxis for\u00a0Pneumocystis\u00a0<\/em>Pneumonia in Adults<\/p>\n\n\n\n Among patients without HIV who are immunocompromised, primary PCP prophylaxis is recommended for those with acute lymphoblastic leukemia receiving antileukemic therapy, recipients of allogeneic hematopoietic cell transplant (HCT) and solid organ transplant, and patients treated with the anti-CD52 antibody alemtuzumab, phosphatidylinositol 3-kinase inhibitors (eg, idelalisib, duvelisib), or temozolomide with concurrent radiotherapy.5<\/a><\/sup>-7<\/a><\/sup> Prophylaxis is also recommended for patients treated with purine analogue chemotherapeutic agents (eg, fludarabine, cladribine), patients with malignancy receiving autologous HCT, and recipients of chimeric antigen receptor T-cell therapy.1<\/a><\/sup>,5<\/a><\/sup><\/a><\/p>\n\n\n\n Patients receiving high-dose corticosteroid treatment (equivalent to \u226520 mg of prednisone daily for \u22651 month) who have an additional cause of immunodeficiency (eg, underlying malignancy, additional immunosuppressive medication) should receive PCP prophylaxis.5<\/a><\/sup>,7<\/a><\/sup> Patients with antineutrophil cytoplasmic antibody\u2013associated vasculitis, such as granulomatosis with polyangiitis, undergoing induction therapy should also receive PCP prophylaxis.8<\/a><\/sup> There is no consensus regarding PCP prophylaxis for patients with autoimmune or autoinflammatory conditions, although patients with rheumatoid arthritis, systemic sclerosis, and giant cell arteritis treated with high-dose corticosteroids have a lower risk for developing PCP compared with those with granulomatosis with polyangiitis.8<\/a><\/sup><\/a><\/p>\n\n\n\n An increasing number of patients are treated with immune-modulating medications that are associated with PCP but lack consensus guidelines regarding prophylaxis.9<\/a><\/sup>,10<\/a><\/sup> These medications include checkpoint inhibitors (eg, ipilimumab, nivolumab), tumor necrosis factor inhibitors (eg, infliximab), anti-CD20 antibodies (eg, rituximab), bruton-tyrosine kinase inhibitors (eg, ibrutinib), and Janus kinase inhibitors (eg, ruxolitinib) (eTable in the Supplement<\/a>). Although these treatments alone do not require PCP prophylaxis, the coexistence of an additional risk factor (eg, high-dose corticosteroids, presence of absolute lymphopenia, other immunosuppressive drugs) may be an indication to initiate prophylaxis. Other factors that may indicate a need for PCP prophylaxis include immunosuppression from the patient\u2019s underlying disease process, history of previous opportunistic infections, older age, and comorbidities.<\/a><\/p>\n\n\n\n Secondary prophylaxis to prevent recurrence of PCP should be started in all patients after successful treatment of PCP if the immunosuppressed state persists.<\/a><\/p>\n\n\n\n Trimethoprim-sulfamethoxazole is the drug of choice for PCP prophylaxis for patients with and without HIV (Table<\/a>). Prophylactic dosing of trimethoprim-sulfamethoxazole for patients with normal kidney function is typically 1 double-strength oral tablet (800\/160 mg) daily or 3 times per week or 1 single-strength tablet (400\/80 mg) daily, and is usually well-tolerated. Exanthem and nausea are common adverse effects.2<\/a><\/sup> If trimethoprim-sulfamethoxazole is discontinued for a mild adverse effect, reinstitution of medication should be considered after resolution of the adverse reaction. Those with allergic reactions may require desensitization with allergy consultation.3<\/a><\/sup><\/a><\/p>\n\n\n\n Alternatives for PCP prophylaxis include atovaquone, dapsone, and monthly administration of aerosolized pentamidine. All patients should have glucose-6 phosphate dehydrogenase levels measured by blood test prior to initiating dapsone. According to the National Comprehensive Cancer Network, monthly intravenous pentamidine is an acceptable alternative for PCP prophylaxis among HCT recipients,5<\/a><\/sup> but it is not recommended by the National Institutes of Health for patients with HIV due to insufficient evidence.3<\/a><\/sup> In clinical practice, the adverse effect profile, tolerability, and the health care insurance coverage of the patient often influence selection of alternative prophylaxis regimens. Due to increased risk of myelosuppression in patients with hematologic malignancy or HCT, and due to increased rates of nephrotoxicity in kidney transplant recipients, alternatives to trimethoprim-sulfamethoxazole should be considered in these patients.6<\/a><\/sup><\/a><\/p>\n\n\n\n Prophylaxis for PCP should continue as long as the immunosuppressive state persists. Among patients with HIV, PCP prophylaxis can be discontinued when CD4 lymphocyte counts increase to greater than 200\/\u03bcL for more than 3 months in response to ART.3<\/a><\/sup> Prophylaxis may also be discontinued if CD4 counts are 100\/\u03bcL to 200\/\u03bcL in patients whose HIV plasma RNA levels remain below the limits of detection for at least 3 months.3<\/a><\/sup> Prophylaxis may be discontinued in patients treated with alemtuzumab and purine analogue agents whose CD4 count improves to greater than 200\/\u03bcL.5<\/a><\/sup><\/a><\/p>\n\n\n\n Patients with acute lymphoblastic leukemia should continue PCP prophylaxis through the end of maintenance therapy.5<\/a><\/sup> Allogeneic HCT recipients begin prophylaxis at engraftment and should continue prophylaxis through at least 6 months after transplant or longer if immunosuppression is ongoing. Because the effect of immunosuppressive medications (eg, rituximab, temozolomide, idelalisib) may persist after drug discontinuation, duration of PCP prophylaxis should be individualized based on the medication received.<\/a><\/p>\n\n\n\n All solid organ transplant recipients should receive prophylaxis for at least 6 to 12 months after the transplant, after which prophylaxis should be prescribed during periods of intensive immunosuppression for allograft rejection, infection with Cytomegalovirus<\/em>, or prolonged neutropenia.6<\/a><\/sup> Lifetime prophylaxis is recommended for recipients of lung and small bowel transplant as well as solid organ transplant recipients with previous PCP infection.6<\/a><\/sup><\/a><\/p>\n\n\n\n Patients requiring PCP prophylaxis usually have multiple comorbid health conditions and are often cared for by multiple subspecialists, including hematology, oncology, infectious diseases, rheumatology, pulmonology, and transplant. Discussion and coordination of initiation and discontinuation of PCP prophylaxis across these clinicians can be beneficial.<\/a><\/p>\n\n\n\n Patients at risk for PCP should receive safe and effective prophylaxis while they are immunosuppressed; trimethoprim-sulfamethoxazole is the agent of choice.<\/p>\n","protected":false},"excerpt":{"rendered":" JAMA Insights June 26, 2023 Prophylaxis […]<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[25,23],"tags":[],"_links":{"self":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/24300"}],"collection":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=24300"}],"version-history":[{"count":2,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/24300\/revisions"}],"predecessor-version":[{"id":24507,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/24300\/revisions\/24507"}],"wp:attachment":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=24300"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=24300"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=24300"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}Indications for Prophylaxis<\/h2>\n\n\n\n
<\/figure>\n\n\n\nProphylactic Therapy<\/h2>\n\n\n\n
Duration of Prophylaxis<\/h2>\n\n\n\n