Treatment and prevention of Pneumocystis pneumonia in HIV-uninfected patients
- Charles F Thomas, Jr, MD
Charles F Thomas, Jr, MD
- Associate Professor of Medicine
- Mayo Clinic College of Medicine
- Andrew H Limper, MD
Andrew H Limper, MD
- Professor of Pulmonary Medicine
- Mayo Clinic College of Medicine
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.
HIV-infected patients with a low CD4 count are at the highest risk of PCP. Others at substantial risk include hematopoietic stem cell and solid organ transplant recipients, 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 HIV-infected patients and the epidemiology, clinical manifestations, and diagnosis of PCP in HIV-uninfected patients are discussed separately. (See "Treatment and prevention of Pneumocystis infection in HIV-infected patients" and "Epidemiology, clinical manifestations, and diagnosis of Pneumocystis pneumonia in HIV-uninfected patients".)
Trimethoprim-sulfamethoxazole — We recommend trimethoprim-sulfamethoxazole (TMP-SMX) as the treatment of choice for Pneumocystis pneumonia (PCP) of any severity in HIV-uninfected patients (table 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. For renal dose adjustment recommendations, see trimethoprim-sulfamethoxazole drug information. Because TMP-SMX has excellent bioavailability, oral administration is appropriate for all patients who have a functioning gastrointestinal tract.
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 HIV-infected patients", section on 'Desensitization for patients with a sulfa allergy' and "Sulfonamide allergy in HIV-uninfected patients".)
- Limper AH, Knox KS, Sarosi GA, et al. An official American Thoracic Society statement: Treatment of fungal infections in adult pulmonary and critical care patients. Am J Respir Crit Care Med 2011; 183:96.
- Hughes WT, Feldman S, Sanyal SK. Treatment of Pneumocystis carinii pneumonitis with trimethoprim-sulfamethoxazole. Can Med Assoc J 1975; 112:47.
- Lau WK, Young LS. Trimethoprim-sulfamethoxazole treatment of Pneumocystis carinii pneumonia in adults. N Engl J Med 1976; 295:716.
- Winston DJ, Lau WK, Gale RP, Young LS. Trimethoprim-sulfamethoxazole for the treatment of Pneumocystis carinii pneumonia. Ann Intern Med 1980; 92:762.
- Hughes WT, Feldman S, Chaudhary SC, et al. Comparison of pentamidine isethionate and trimethoprim-sulfamethoxazole in the treatment of Pneumocystis carinii pneumonia. J Pediatr 1978; 92:285.
- Smego RA Jr, Nagar S, Maloba B, Popara M. A meta-analysis of salvage therapy for Pneumocystis carinii pneumonia. Arch Intern Med 2001; 161:1529.
- Wazir JF, Ansari NA. Pneumocystis carinii infection. Update and review. Arch Pathol Lab Med 2004; 128:1023.
- Kamboj M, Weinstock D, Sepkowitz KA. Progression of Pneumocystis jiroveci pneumonia in patients receiving echinocandin therapy. Clin Infect Dis 2006; 43:e92.
- Limper AH, Offord KP, Smith TF, Martin WJ 2nd. Pneumocystis carinii pneumonia. Differences in lung parasite number and inflammation in patients with and without AIDS. Am Rev Respir Dis 1989; 140:1204.
- Kovacs JA, Hiemenz JW, Macher AM, et al. Pneumocystis carinii pneumonia: a comparison between patients with the acquired immunodeficiency syndrome and patients with other immunodeficiencies. Ann Intern Med 1984; 100:663.
- Pareja JG, Garland R, Koziel H. Use of adjunctive corticosteroids in severe adult non-HIV Pneumocystis carinii pneumonia. Chest 1998; 113:1215.
- Delclaux C, Zahar JR, Amraoui G, et al. Corticosteroids as adjunctive therapy for severe Pneumocystis carinii pneumonia in non-human immunodeficiency virus-infected patients: retrospective study of 31 patients. Clin Infect Dis 1999; 29:670.
- Yale SH, Limper AH. Pneumocystis carinii pneumonia in patients without acquired immunodeficiency syndrome: associated illness and prior corticosteroid therapy. Mayo Clin Proc 1996; 71:5.
- Mansharamani NG, Garland R, Delaney D, Koziel H. Management and outcome patterns for adult Pneumocystis carinii pneumonia, 1985 to 1995: comparison of HIV-associated cases to other immunocompromised states. Chest 2000; 118:704.
- Sepkowitz KA. Opportunistic infections in patients with and patients without Acquired Immunodeficiency Syndrome. Clin Infect Dis 2002; 34:1098.
- Ward MM, Donald F. Pneumocystis carinii pneumonia in patients with connective tissue diseases: the role of hospital experience in diagnosis and mortality. Arthritis Rheum 1999; 42:780.
- Sepkowitz KA, Brown AE, Telzak EE, et al. Pneumocystis carinii pneumonia among patients without AIDS at a cancer hospital. JAMA 1992; 267:832.
- Festic E, Gajic O, Limper AH, Aksamit TR. Acute respiratory failure due to pneumocystis pneumonia in patients without human immunodeficiency virus infection: outcome and associated features. Chest 2005; 128:573.
- Siegel JD, Rhinehart E, Jackson M, et al. 2007 Guideline for isolation precautions: Preventing transmission of infectious agents in healthcare settings, June 2007. http://www.cdc.gov/ncidod/dhqp/pdf/isolation2007.pdf (Accessed on July 02, 2008).
- National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology. Prevention and treatment of cancer-related infections. Version 2.2014. http://www.nccn.org (Accessed on November 06, 2014).
- Tomblyn M, Chiller T, Einsele H, et al. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant 2009; 15:1143.
- Cooley L, Dendle C, Wolf J, et al. Consensus guidelines for diagnosis, prophylaxis and management of Pneumocystis jirovecii pneumonia in patients with haematological and solid malignancies, 2014. Intern Med J 2014; 44:1350.
- Martin SI, Fishman JA, AST Infectious Diseases Community of Practice. Pneumocystis pneumonia in solid organ transplantation. Am J Transplant 2013; 13 Suppl 4:272.
- Ognibene FP, Shelhamer JH, Hoffman GS, et al. Pneumocystis carinii pneumonia: a major complication of immunosuppressive therapy in patients with Wegener's granulomatosis. Am J Respir Crit Care Med 1995; 151:795.
- Suryaprasad A, Stone JH. When is it safe to stop Pneumocystis jiroveci pneumonia prophylaxis? Insights from three cases complicating autoimmune diseases. Arthritis Rheum 2008; 59:1034.
- Stern A, Green H, Paul M, et al. Prophylaxis for Pneumocystis pneumonia (PCP) in non-HIV immunocompromised patients. Cochrane Database Syst Rev 2014; :CD005590.
- Huang L, Morris A, Limper AH, et al. An Official ATS Workshop Summary: Recent advances and future directions in pneumocystis pneumonia (PCP). Proc Am Thorac Soc 2006; 3:655.
- Sepkowitz KA, Brown AE, Armstrong D. Pneumocystis carinii pneumonia without acquired immunodeficiency syndrome. More patients, same risk. Arch Intern Med 1995; 155:1125.
- Thomas CF Jr, Limper AH. Pneumocystis pneumonia. N Engl J Med 2004; 350:2487.
- http://www.fda.gov/cder/foi/label/2007/103948s5070lbl.pdf (Accessed on July 02, 2008).
- Temodar (temozolomide) prescribing information. http://www.merck.com/product/usa/pi_circulars/t/temodar_capsules/temodar_pi.pdf (Accessed on February 11, 2013).
- Stiehm ER, Ochs HD, Winkelstein JA. Immunodeficiency disorders: General considerations. In: Immunological Disorders in Infants and Children, 5th ed, Stiehm ER, Ochs HD, Winkelstein JA (Eds), Elsevier Saunders, Philadephia 2004. p.289.
- Ochs HD, Stiehm ER, Winkelstein JA. Antibody deficiencies. In: Immunological Disorders in Infants and Children, 5th ed, Stiehm ER, Ochs HD, Winkelstein JA (Eds), Elsevier Saunders, Philadephia 2004. p.357.
- TORISEL Kit (temsirolimus) injection, for intr avenous infusion only. Highlights of prescribing information. http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022088s016lbl.pdf (Accessed on October 13, 2014).
- Li J, Huang XM, Fang WG, Zeng XJ. Pneumocystis carinii pneumonia in patients with connective tissue disease. J Clin Rheumatol 2006; 12:114.
- Meuli K, Chapman P, O'Donnell J, et al. Audit of pneumocystis pneumonia in patients seen by the Christchurch Hospital rheumatology service over a 5-year period. Intern Med J 2007; 37:687.
- White ES, Lynch JP. Pharmacological therapy for Wegener's granulomatosis. Drugs 2006; 66:1209.
- Kadoya A, Okada J, Iikuni Y, Kondo H. Risk factors for Pneumocystis carinii pneumonia in patients with polymyositis/dermatomyositis or systemic lupus erythematosus. J Rheumatol 1996; 23:1186.
- Langford CA, Talar-Williams C, Barron KS, Sneller MC. A staged approach to the treatment of Wegener's granulomatosis: induction of remission with glucocorticoids and daily cyclophosphamide switching to methotrexate for remission maintenance. Arthritis Rheum 1999; 42:2666.
- Ahn IE, Jerussi T, Farooqui M, et al. Atypical Pneumocystis jirovecii pneumonia in previously untreated patients with CLL on single-agent ibrutinib. Blood 2016; 128:1940.
- Important drug warning (Gilead). Decreased overall survival and increased risk of serious infections in patients receiving ZYDELIG (idelalisib). http://zydelig.com/Content/pdf/Zydelig-Safety-Info-FINAL.pdf (Accessed on March 29, 2016).
- Overgaard UM, Helweg-Larsen J. Pneumocystis jiroveci pneumonia (PCP) in HIV-1-negative patients: a retrospective study 2002-2004. Scand J Infect Dis 2007; 39:589.
- Chung JB, Armstrong K, Schwartz JS, Albert D. Cost-effectiveness of prophylaxis against Pneumocystis carinii pneumonia in patients with Wegner's granulomatosis undergoing immunosuppressive therapy. Arthritis Rheum 2000; 43:1841.
- Colby C, McAfee S, Sackstein R, et al. A prospective randomized trial comparing the toxicity and safety of atovaquone with trimethoprim/sulfamethoxazole as Pneumocystis carinii pneumonia prophylaxis following autologous peripheral blood stem cell transplantation. Bone Marrow Transplant 1999; 24:897.
- Torre-Cisneros J, De la Mata M, Pozo JC, et al. Randomized trial of weekly sulfadoxine/pyrimethamine vs. daily low-dose trimethoprim-sulfamethoxazole for the prophylaxis of Pneumocystis carinii pneumonia after liver transplantation. Clin Infect Dis 1999; 29:771.
- Alternative agents
- Duration of therapy
- Adjunctive glucocorticoids
- INFECTION CONTROL
- - Trimethoprim-sulfamethoxazole
- - Other drugs
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS
- PCP treatment
- Infection control
- PCP prophylaxis