INTRODUCTION — Pneumocystis pneumonia (PCP) is a potentially life-threatening infection that occurs in immunocompromised individuals. The nomenclature for the species of Pneumocystis that infects humans has been changed from Pneumocystis carinii to Pneumocystis jirovecii; this was done to distinguish it from the species that infects rats.
Patients with human immunodeficiency virus (HIV) and a low CD4 count are at the highest risk of PCP. Others at substantial risk include immunocompromised patients, such as hematopoietic stem cell and solid organ transplant recipients receiving immunosuppressant agents, those with cancer (particularly hematologic malignancies), and those receiving glucocorticoids, chemotherapeutic agents, and other immunosuppressive medications.
The treatment and prophylaxis of PCP in patients without HIV infection will be reviewed here. PCP in patients with HIV and the epidemiology, clinical manifestations, and diagnosis of PCP in patients without HIV are discussed separately. (See "Treatment and prevention of Pneumocystis infection in patients with HIV" and "Epidemiology, clinical manifestations, and diagnosis of Pneumocystis pneumonia in patients without HIV".)
TREATMENT
Trimethoprim-sulfamethoxazole — We recommend trimethoprim-sulfamethoxazole (TMP-SMX) as the treatment of choice for PCP of any severity in patients without HIV (table 1) [1]. The dose of TMP-SMX for patients with normal renal function is 15 to 20 mg/kg (dosing is based upon the TMP component and expressed as mg/kg per day of TMP) intravenously or orally daily in three or four divided doses. Dose may need to be adjusted if creatinine clearance changes during therapy. Patients should receive intravenous therapy until they are clinically stable (eg, PaO2 ≥60 mmHg, respiratory rate <25) and have a functioning gastrointestinal tract. For renal dose adjustment recommendations, refer to TMP-SMX drug information.
For patients with allergy to TMP-SMX, desensitization should ideally be performed since TMP-SMX is the most effective regimen. However, if the patient has a history of a severe allergy (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis), TMP-SMX should be avoided and desensitization should not be performed. (See "Treatment and prevention of Pneumocystis infection in patients with HIV", section on 'Desensitization for patients with a sulfa allergy' and "Sulfonamide allergy in HIV-uninfected patients".)
Large randomized trials have proven the efficacy of TMP-SMX in patients with HIV infection, whereas efficacy in patients without HIV infection has only been shown in a few small observational studies [2-4] and one comparative randomized trial [5]. (See "Treatment and prevention of Pneumocystis infection in patients with HIV".)
Some patients receiving TMP-SMX experience hyperkalemia, particularly those with renal insufficiency, older patients, those concurrently receiving other drugs that promote hyperkalemia, those receiving high doses of TMP-SMX, and those with disorders of potassium metabolism. Accordingly, we recommend monitoring potassium levels before and periodically after the institution of TMP-SMX therapy. Other adverse effects are discussed in greater detail separately. (See "Trimethoprim-sulfamethoxazole: An overview", section on 'Adverse effects and precautions'.)
Alternative agents by severity of disease — Alternative drugs for the treatment of PCP have been studied primarily in patients with HIV. Regimens that may be used for PCP when TMP-SMX cannot be used include clindamycin plus primaquine, trimethoprim plus dapsone, atovaquone, and intravenous (IV) pentamidine; dosing of these agents is summarized in the table (table 1). The choice of regimen in patients who cannot take TMP-SMX depends in part upon the severity of disease.
●For mild disease, options include:
•Clindamycin plus primaquine
•TMP plus dapsone
All of these agents can be given orally. Although there are limited data, we prefer oral atovaquone in patients with mild disease.
●For moderate disease, options include:
•Clindamycin plus primaquine
•TMP plus dapsone
Although there are limited data, we prefer clindamycin plus primaquine for patients with moderate disease.
●For severe disease, options include:
•Clindamycin plus primaquine
•Intravenous pentamidine
Clindamycin can be given intravenously, but primaquine is available only as an oral formulation. Pentamidine should be given intravenously.
For severe disease, we prefer intravenous clindamycin plus oral primaquine because this regimen is less toxic than IV pentamidine. Patients should receive clindamycin intravenously until they are clinically stable (eg, PaO2 ≥60 mmHg, respiratory rate <25) and have a functioning gastrointestinal tract, at which point they can be switched to oral clindamycin. The efficacy of clindamycin plus primaquine was illustrated in a meta-analysis of salvage treatment of 456 patients with HIV and 41 patients without HIV who had confirmed PCP but did not improve with conventional antipneumocystis therapy (most commonly TMP-SMX or IV pentamidine) [6]. The combination of clindamycin plus primaquine was the most effective alternative treatment in such patients. (See "Treatment and prevention of Pneumocystis infection in patients with HIV".)
IV pentamidine is not often used because it is associated with substantial toxicity (eg, hypotension, hypoglycemia, nephrotoxicity, and pancreatitis) and must be administered parenterally. In a randomized trial of 50 patients with PCP, IV pentamidine (4 mg/kg once daily) was as effective as TMP-SMX [5].
Patients should be tested for glucose-6-phosphate dehydrogenase deficiency before taking dapsone or primaquine. (See "Treatment and prevention of Pneumocystis infection in patients with HIV".)
The cyst wall of P. jirovecii contains beta-D-glucan, the synthesis of which is inhibited by echinocandins (eg, caspofungin) [7]. The role for echinocandins in treating or preventing PCP in humans is not established. Case reports of progression of disease in patients receiving echinocandins have been published [8].
Duration of therapy — The duration of therapy for PCP in patients without HIV infection has not been adequately studied. Given the fulminant presentation and poor outcomes in patients without HIV [9], we suggest treating for 21 days. These recommendations have been extrapolated from the recommended duration of therapy for patients with HIV infection, who have a greater risk of relapse with 14 than 21 days of therapy, and who have a greater organism burden and slower clinical response than patients without HIV [9,10]. (See 'Outcomes' below and "Epidemiology, clinical manifestations, and diagnosis of Pneumocystis pneumonia in patients without HIV", section on 'Clinical manifestations'.)
Patients without HIV who have PCP should start to show clinical improvement by the seventh day of therapy. Patients who are not improving after seven days of therapy may require re-evaluation to look for other coinfections. If no other explanation is found, these patients should be considered to have treatment failure and are treated in the same way as patients with HIV who fail initial therapy. (See "Treatment and prevention of Pneumocystis infection in patients with HIV", section on 'Treatment failure'.)
Patients are usually symptomatically better after 21 days of therapy for PCP. A clinician with expertise in the management of PCP (eg, an infectious diseases specialist) should be consulted to assist with the management of patients with severe or protracted illness despite appropriate therapy.
After completing the course of treatment, patients should be considered for antimicrobial therapy at a reduced dose to prevent recurrent infection (ie, secondary prophylaxis). The antimicrobial regimens used for secondary prophylaxis are the same as those used to prevent initial infection and are described below. (See 'Regimens' below.)
Adjunctive glucocorticoids — Adjunctive glucocorticoids are recommended in patients with HIV and moderate or severe PCP because their use improves clinical outcomes and mortality without increasing the risk of other opportunistic infections. (See "Treatment and prevention of Pneumocystis infection in patients with HIV", section on 'Use of corticosteroids'.)
Given the fulminant course and high mortality with moderate to severe PCP in patients without HIV, we suggest the use of glucocorticoid therapy in patients with PCP who, while breathing room air, have an arterial blood gas measurement that shows a partial pressure of oxygen <70 mmHg or an alveolar-arterial (A-a) oxygen gradient ≥35 mmHg, or hypoxemia on pulse oximetry (eg, room air oxygen saturation <92 percent). Patients who worsen clinically and meet criteria for glucocorticoids while receiving anti-Pneumocystis therapy are also candidates for adjunctive glucocorticoids. The glucocorticoid regimen is shown in the table (table 1). (See "Treatment and prevention of Pneumocystis infection in patients with HIV", section on 'Corticosteroid regimen'.)
Patients who do not meet the above criteria for glucocorticoid therapy but are receiving glucocorticoids for some other reason (eg, graft-versus-host disease) should continue their current regimen.
In contrast to patients with HIV, there are limited data on the efficacy of adjunctive glucocorticoids for the treatment of PCP in patients without HIV. The available limited data do not provide support for the routine use of adjunctive glucocorticoids in patients without HIV but with PCP who have mild to moderate disease. In a retrospective cohort study evaluating the outcomes of 323 hospitalized patients without HIV who had P. jirovecii pneumonia, there were no differences in mortality, length of stay, admission to the intensive care unit, or need for mechanical ventilation in the 258 patients who received adjunctive corticosteroids versus the 65 who did not [11]. A second retrospective study of 31 patients without HIV but with PCP also found no difference in the need for mechanical ventilation or mortality between the glucocorticoid-treated and -untreated groups [12].
However, in severe disease, data suggest adjunctive glucocorticoids may be beneficial. In a meta-analysis of 16 retrospective observational studies that includes over 2500 cases of PCP in patients without HIV, corticosteroids were associated with lower mortality in those with respiratory failure (odds ratio 0.63, 95% CI 0.41-0.95) [13]. In one of the retrospective studies included in the meta-analysis that looked at 30 patients without HIV but with severe PCP, 16 patients who received the equivalent of ≥60 mg of prednisone per day had a significantly shorter duration of mechanical ventilation, intensive care unit admission, and supplemental oxygenation than the 14 patients who received the equivalent of ≤30 mg of prednisone per day or were on a glucocorticoid taper [14]. However, similar rates of mechanical ventilation and in-hospital mortality were observed. It remains unclear whether corticosteroids are beneficial, however, the greater degree of inflammation in the lungs of patients without HIV provides some rationale for glucocorticoid therapy [9].
OUTCOMES — In the absence of appropriate antibiotic therapy, the mortality from PCP in patients without HIV is 90 to 100 percent [2]. In treated patients, the outcomes in those without HIV are generally worse than in patients with HIV; mortality from PCP in patients with HIV infection is approximately 10 to 20 percent compared with 35 to 50 percent in those without HIV [10,15-18]. Patients with cancer have the highest mortality [10,19]. Patients without HIV who have PCP also have higher rates of hospitalization and intensive care unit admission [16].
Severe PCP is associated with higher mortality [16,20]. As an example, in a retrospective review of 30 patients without HIV but with PCP and respiratory failure, the mortality was 67 percent [20]. Mortality was associated with an elevated APACHE III score on the day of intensive care unit admission, delay in intubation, duration of mechanical ventilation, and the development of pneumothorax [20]. (See "Predictive scoring systems in the intensive care unit", section on 'Acute Physiologic and Chronic Health Evaluation (APACHE)'.)
INFECTION CONTROL — Hospitalized patients with PCP should be cared for with standard precautions, although they should not be placed in the same room with other immunocompromised individuals due to the potential for person-to-person transmission [21].
PROPHYLAXIS
Indications — The risk for PCP is determined by the degree of cell-mediated immune deficiency and can occur due to immunocompromising conditions or receipt of immunosuppressive agents. The number of drugs associated with increased risk for PCP is constantly expanding; the more commonly used ones are listed below. In general, PCP prophylaxis should be considered in patients receiving drugs associated with lymphodepletion that are likely to cause significant defects in cell-mediated immune deficiency.
We recommend PCP prophylaxis for:
●Patients with certain primary immunodeficiencies (eg, severe combined immunodeficiency, idiopathic CD4 T-lymphocytopenia, hyper-immunoglobulin [Ig]M syndrome) [22,23].
●Patients with acute lymphocytic leukemia [24].
●Solid organ transplant recipients, often for at least six months to one year following transplantation and during periods of high doses of immunosuppressive medications (eg, during treatment for acute rejection) [25]; lung transplant recipients typically receive lifelong prophylaxis. (See "Prophylaxis of infections in solid organ transplantation", section on 'Pneumocystis pneumonia' and "Fungal infections following lung transplantation", section on 'Pneumocystis jirovecii'.)
●Allogeneic hematopoietic cell transplant (HCT) recipients beginning after engraftment and continuing for as long as immunosuppressive therapy is given; the typical duration of PCP prophylaxis is six months in allogeneic HCT recipients but is longer in those requiring treatment for graft-versus-host disease [24,26]. This is discussed in detail elsewhere. (See "Prevention of infections in hematopoietic cell transplant recipients", section on 'Pneumocystis prophylaxis'.)
●Selected autologous HCT recipients, including those who have an underlying hematologic malignancy, such as lymphoma, myeloma, or leukemia, especially when intensive treatment or conditioning regimens have included a purine analog (eg, fludarabine, cladribine) or high-dose glucocorticoids [24,26]. This is discussed in detail elsewhere. (See "Prevention of infections in hematopoietic cell transplant recipients", section on 'Pneumocystis prophylaxis'.)
●Patients receiving a glucocorticoid dose equivalent to ≥20 mg of prednisone daily for one month or longer who also have another cause of immunocompromise (eg, certain hematologic malignancies or a second immunosuppressive drug) [1,17,24,27-34].
●Patients receiving phosphatidylinositol 3-kinase inhibitors (eg, idelalisib and ibrutinib) [35-38]. (See "Prevention of infections in patients with chronic lymphocytic leukemia", section on 'Bruton tyrosine kinase and phosphatidylinositol 3-kinase inhibitors'.)
●Patients receiving alkylating agents, such as a purine analog (eg, cladribine, fludarabine) alone, or triazenes (eg, temozolomide) if used concurrently with steroids or radiotherapy [24,39]. (See "Prevention of infections in patients with chronic lymphocytic leukemia", section on 'Purine analog-cyclophosphamide combination therapy'.)
●Patients receiving certain monoclonal antibodies that cause lymphodepletion (eg, anti-CD52, anti-CCR4, anti-SLAMF [signaling lymphocyte activation molecule family], polatuzumab vedotin).
•Patients receiving an anti-CD52 monoclonal antibody (eg, alemtuzumab) should receive PCP prophylaxis for a minimum of two months after completion of therapy or until the CD4 count is >200 cells/microL, whichever occurs later [24,40].
•Patients receiving an anti-CD20 monoclonal antibody (eg, rituximab) or a checkpoint inhibitor (eg, pembrolizumab, nivolumab, durvalumab) with or without concurrent glucocorticoid should also receive PCP prophylaxis [41].
Data are limited to support a broad recommendation for PCP prophylaxis in patients receiving many other immunomodulatory agents, including:
●Janus-associated kinase inhibitors (eg, tofacitinib, baricitinib, upadacitinib).
●Mammalian target of rapamycin inhibitors (eg, temsirolimus, everolimus) [42].
When deciding whether to administer PCP prophylaxis in patients receiving these agents, clinicians should consider the underlying condition, presence of other concomitant immunosuppressive drugs (eg, glucocorticoids), duration of therapy, and the patient’s comorbidities (eg, lung function). Presence of underlying lung disease (eg, pulmonary fibrosis) may increase risk of PCP [43].
Guidelines have been published for the use of PCP prophylaxis in patients with cancer, including HCT recipients [44-48], as well as in solid organ transplant recipients [49]. There are no published guidelines for PCP prophylaxis among patients with rheumatologic or dermatologic diseases receiving immunosuppressive drugs, but some advocate its use in such patients when they are receiving high-dose immunosuppressive therapy [50-53].
In a meta-analysis of randomized trials of PCP prophylaxis in immunocompromised patients without HIV infection, the authors concluded that prophylaxis is warranted when the risk of PCP is higher than 6 percent [54].
PCP prophylaxis should be considered in patients with other conditions that cause immunocompromise based upon their risk of PCP. (See "Epidemiology, clinical manifestations, and diagnosis of Pneumocystis pneumonia in patients without HIV", section on 'Risk factors'.)
Regimens — Trimethoprim-sulfamethoxazole (TMP-SMX) is the recommended first-line agent for PCP prophylaxis based upon its proven efficacy (table 2) [1,24,26,27,29,54]. For patients with normal renal function, it may be given as one double-strength tablet daily or three times per week or as one single-strength tablet daily. For renal dose adjustment recommendations, see TMP-SMX drug information. For those who are intolerant of TMP-SMX, desensitization should be attempted when possible. Although leukopenia and agranulocytosis are reported side effects of TMP-SMX, from our experience, patients who initiate TMP-SMX after neutrophil recover tend to do well. TMP-SMX also prevents Toxoplasma gondii infections as well as some bacterial infections, such as pneumococcal, nocardial, and listerial infections. Some clinicians have been hesitant to use TMP-SMX for PCP prophylaxis in patients receiving methotrexate due to concern for myelosuppression. However, prophylactic doses of TMP-SMX appear to be safe in patients with granulomatosis with polyangiitis (GPA) receiving methotrexate [34,55]. (See "Treatment and prevention of Pneumocystis infection in patients with HIV", section on 'Desensitization for patients with a sulfa allergy' and "Sulfonamide allergy in HIV-uninfected patients".)
For patients who cannot take TMP-SMX, we suggest either dapsone (with pyrimethamine if Toxoplasma prophylaxis is indicated) or atovaquone. For patients in whom hematologic toxicity is a concern (eg, HCT recipients), we favor atovaquone because dapsone can cause agranulocytosis and hemolytic anemia. For patients in whom hematologic toxicity is not a concern, we prefer dapsone because it is less expensive than atovaquone. Patients should be tested for glucose-6-phosphate dehydrogenase deficiency before taking dapsone.
Another alternative for PCP prophylaxis is aerosolized pentamidine. However, we rarely use aerosolized pentamidine because it is less effective than the other regimens, requires special equipment, and has been associated with transmission of Mycobacterium tuberculosis. In addition, it is only effective locally; if dispersal of the aerosol does not reach all portions of the lungs, untreated areas remain at risk for PCP. (See "Treatment and prevention of Pneumocystis infection in patients with HIV", section on 'Patients with a sulfa allergy'.)
PCP prophylaxis should be continued until the risk factor for the disease is no longer present [24,26,27]. (See 'Indications' above.)
Caution should be exercised in discontinuation of PCP prophylaxis in patients who have received high-dose glucocorticoids and/or cyclophosphamide, since prolonged immunosuppression may persist after discontinuation of such agents. Although the CD4 count has not been shown to correlate with risk of PCP in patients without HIV, some experts have suggested discontinuing prophylaxis only in patients who have had a CD4 count >200 cells/microL for at least six months [31].
Some data suggest that sulfonamide-containing antibiotics, including TMP-SMX, can cause exacerbations of systemic lupus erythematosus (SLE), particularly in patients with adverse reactions to these agents. As a result, many rheumatologists avoid TMP-SMX prophylaxis in patients with SLE. We suggest atovaquone as an alternative agent in such patients who require PCP prophylaxis (table 2). (See "Overview of the management and prognosis of systemic lupus erythematosus in adults", section on 'Issues with specific therapies'.)
PCP prophylaxis in hematopoietic cell transplant recipients and lung transplant recipients is discussed in detail separately. (See "Prevention of infections in hematopoietic cell transplant recipients", section on 'Pneumocystis prophylaxis' and "Fungal infections following lung transplantation", section on 'Pneumocystis pneumonia'.)
Efficacy — PCP prophylaxis with TMP-SMX is highly effective, and it is therefore considered the first-line agent. This approach has been recommended in several guidelines by major organizations [1,24,26,27]. In a retrospective study from Denmark that identified 50 cases of PCP in patients without HIV infection during 2002 to 2004, the majority of patients (82 percent) never received PCP prophylaxis, whereas 16 percent had PCP prophylaxis discontinued months prior to diagnosis [56].
Trimethoprim-sulfamethoxazole — The effectiveness of TMP-SMX prophylaxis was illustrated in a meta-analysis of 13 randomized controlled trials that included 1412 immunocompromised patients without HIV infection who had undergone autologous hematopoietic cell or solid organ transplantation or had a hematologic malignancy [54]. TMP-SMX prophylaxis was associated with an 85 percent reduction in the occurrence of PCP compared with no prophylaxis or fluoroquinolone prophylaxis, which is inactive against Pneumocystis (relative risk [RR] 0.15, 95% CI 0.04-0.62). The number needed to treat to prevent one infection was 19. Mortality due to PCP was also significantly reduced (RR 0.17, 95% CI 0.03-0.94), although all-cause mortality was not. Using data from two trials, no differences in efficacy were found between once-daily and thrice-weekly administration schedules for TMP-SMX.
A cost-effectiveness analysis in patients with GPA receiving immunosuppressive drugs suggested that PCP prophylaxis with TMP-SMX increased quality-adjusted life expectancy and reduced costs [57].
TMP-SMX is generally well tolerated in patients without HIV infection, as the meta-analysis described above found that adverse events necessitating cessation of therapy (leukopenia, thrombocytopenia, severe dermatologic reactions) occurred in only 3.1 percent of adults [54]. In contrast, TMP-SMX has a high rate of adverse effects in patients with HIV. (See "Treatment and prevention of Pneumocystis infection in patients with HIV", section on 'Patients without a sulfa allergy'.)
Other drugs — Other drugs that can been used for PCP prophylaxis in patients without HIV include atovaquone, dapsone with or without pyrimethamine, and aerosolized pentamidine (table 2).
Randomized trials in patients without HIV are limited [58,59]. One such trial that compared atovaquone with TMP-SMX for PCP prophylaxis in 39 patients following autologous hematopoietic cell transplantation showed that atovaquone is well tolerated in this patient population [58]. No firm conclusions can be reached about the relative efficacy of atovaquone since the number of patients studied was small and no patient in either arm developed PCP.
The comparative efficacy of PCP prophylaxis regimens has been more extensively studied in patients with HIV. (See "Treatment and prevention of Pneumocystis infection in patients with HIV", section on 'Regimens for prophylaxis'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Pneumocystis pneumonia in patients without HIV".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Pneumocystis pneumonia (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Treatment
•Preferred regimen − We recommend trimethoprim-sulfamethoxazole (TMP-SMX) as the preferred medication for the treatment of Pneumocystis pneumonia (PCP) in patients without HIV (table 1) (Grade 1B). The dose of TMP-SMX for patients with normal renal function is 15 to 20 mg/kg (dosing is based upon the TMP component and expressed as mg/kg per day of TMP) intravenously or orally daily in three or four divided doses. The usual duration of therapy is 21 days. (See 'Trimethoprim-sulfamethoxazole' above and 'Duration of therapy' above.)
•Alternative regimens − For patients with allergy to TMP-SMX, desensitization should ideally be performed since TMP-SMX is the most effective regimen. Exceptions include patients with a history of a severe allergy (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis). In these cases, TMP-SMX should be avoided and desensitization should not be performed. Alternative regimens for treatment of PCP are discussed above. (See 'Trimethoprim-sulfamethoxazole' above and 'Alternative agents by severity of disease' above.)
•Adjunctive glucocorticoids − We suggest using adjunctive glucocorticoids in patients without HIV who, while breathing room air, have an arterial blood gas measurement that shows a partial pressure of oxygen <70 mmHg or an alveolar-arterial (A-a) oxygen gradient ≥35 mmHg or hypoxemia on pulse oximetry (eg, room air oxygen saturation <92 percent) (Grade 2B). (See 'Adjunctive glucocorticoids' above.)
●Outcomes − The outcomes for immunocompromised patients without HIV who are treated for PCP are generally worse than in those with HIV; mortality from PCP in patients with HIV is approximately 10 to 20 percent compared with 35 to 50 percent in those without HIV. (See 'Outcomes' above.)
●Infection control − Hospitalized patients with PCP should be cared for using standard precautions, although they should not be placed in the same room with other immunocompromised individuals due to the potential for person-to-person spread. (See 'Infection control' above.)
●Prophylaxis
•Risk factors for PCP − PCP is a potentially life-threatening infection that occurs in immunocompromised individuals, especially in those with HIV but also in hematopoietic cell and solid organ transplant recipients, those with cancer (particularly hematologic malignancies), and those receiving glucocorticoids, chemotherapeutic agents, and other immunosuppressive medications. (See 'Introduction' above.)
•Indications for PCP prophylaxis
-We recommend PCP prophylaxis for the following high-risk groups: patients receiving a glucocorticoid dose equivalent to ≥20 mg of prednisone daily for one month or longer who also have another cause of immunocompromise; allogeneic hematopoietic cell transplant and solid organ transplant recipients; patients with acute lymphocytic leukemia; patients receiving certain immunosuppressive drugs (eg, rituximab, alemtuzumab, temozolomide in conjunction with radiotherapy, idelalisib); and selected autologous hematopoietic cell transplant recipients (Grade 1A). (See 'Indications' above.)
-PCP prophylaxis may also be indicated in other situations; these scenarios are discussed above. (See 'Indications' above.)
•Prophylaxis regimens − For most patients who require PCP prophylaxis, we recommend TMP-SMX (table 2) (Grade 1A). For patients with normal renal function, TMP-SMX may be given as one double-strength tablet daily or three times per week or as one single-strength tablet daily. Alternative regimens are discussed above. (See 'Regimens' above.)
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