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Pneumocystis pneumonia (PCP)

Etiology: - infection with Pneumocystis carinii (Pneumocystis jirovecii) in immunosuppressed patients - HIV1 infection - organ transplantation (1-6 months after transplantation) - immunosuppression in association with immunosuppressant drugs [4] - long-term treatment with glucocorticoids Epidemiology: 1) 20% of patients with HIV develop PCP 2) incidence increases with degree of immunosuppression 3) most common AIDS-defining condition 4) most common opportunistic infection in patients with AIDS [4] 5) most common cause of death in patients with AIDS Pathology: 1) within the lung Pneumocystis attaches to alveolar type I pneumocytes 2) slow propagation 3) increased alveolar capillary permeability 4) alterations in surfactants 5) injury to alveolar type I pneumocytes Clinical manifestations: 1) presentation is generally insidious 2) progressive dyspnea 3) fever, chills, night sweats 4) non-productive (dry) cough 5) tachypnea 6) tachycardia 7) weight loss 8) lung auscultation unremarkable or may be crackles 9) pneumothorax (see Complications:) 10) generally more severe with organ transplantation than HIV1 infection [4] 11) other signs of HIV1 infection - Kaposi sarcoma (pigmented skin lesions, red-purple to dark brown-black) - oropharyngeal candidiasis (white, non-adherent, mucosal plaques) Laboratory: 1) CD4 count < 200 cells/uL 2) histopathological staining a) specimens 1] sputum (induced by 3% saline) 2] bronchial brushings from bronchoalveolar lavage (BAL) 3] endotracheal aspirates b) reagents which stain the walls of cysts 1] methenamine silver 2] toluidine blue 3] cresyl echt violet c) Wright-Giemsa, which stains the nuclei of all developmental stages d) immunologic methods 1] monoclonal antibodies 2] immunoperoxidase 3] immunofluorescence e) claofluor (non-specific fluorochrome stain) f) Papanicolaou stain 3) reverse transciptase polymerase chain reaction (RT-PCR) for Pneumocystis jirovecii DNA 4) serology not available 5) no culture methods available 6) complete blood count (CBC): leukocyte count is variable 7) arterial blood gas (ABG): a) hypoxia b) wide A-a gradient 1] < 35 mm Hg & PaO2 > 70 mm Hg = mild 2] 35-45 mm Hg & PaO2 > 70 mm Hg = moderate 3] > 45 mm Hg & PaO2 < 70 mm Hg = severe c) respiratory alkalosis 8) increased serum lactate dehydrogenase (LDH) - reflects pulmonary inflammation 9) see ARUP consult [6] Special laboratory: 1) bronchoalveolar lavage for bronchial brushings if induced sputum does not yield diagnosis - endobronchial lesions are rare 2) pulmonary function tests (PFT) Radiology: 1) may be normal early in the course of the disease 2) bilateral diffuse interstitial infiltrates, beginning in perihilar area 3) nodular opacities & cavitary lesions may be seen 4) increased incidence of upper lobe infiltrates & pneumothorax in patient receiving aerosolized pentamidine 5) pleural effusions & lymphadenopathy are uncommmon & suggest another pathogen Complications: - pneumothorax (most common cause of pneumothorax in patient with AIDS) - prognosis more favorable with HIV1 infection than organ transplantation & is worst with long-term glucocorticoids [11] Differential diagnosis: 1) pneumonia due to a) bacteria or mycobacteria b) fungus c) virus 2) Kaposi's sarcoma - endobronchial violaceous macules or papules in the proximal airways - confluent hyperemic patches in the distal airways Management: 1) antimicrobial therapy: (21 days of therapy) a) trimethoprim/sulfamethoxazole (Bactrim, Septra) - Bactrim DS 2 tabs PO TID for 21 days - 5 mg/kg IV every 6 hours (based on trimethoprim) - step down to low-dose TMP-SMX (TMP 4-6 mg/kg/day) after 5 days of treatment lowers risk of adverse effects [9] b) alternatives in mild disease - atovaquone 750 mg (5 mL) PO BID with meals - dapsone 100 mg PO QD plus trimethoprim 15 mg/kg divided TID - clindamycin 600-900 mg IV every 8 hours plus primaquine 15-30 mg PO QD c) alternatives in moderate to severe disease - pentamidine 4 mg/kg IV/IM QD - trimetrexate 45 mg/m2 over 60 minutes QD plus tetrahydrofolate (Leucovorin) 20 mg/m2 IV/PO QID d) toxicity or intolerance often develops during the course of therapy & alternative agents may be necessary 2) adjunctive glucocorticoids a) indications: A-a gradient > 35 mm Hg or PaO2 < 70 mm Hg b) prednisone (within 72 hours) - 40 mg PO BID for 5 days; then - 40 mg PO QD for 5 days; then - 20 mg QD for duration of anti-PCP therapy c) benefits - minimize inflammatory response provoked by dying organisms - diminish deterioration of oxygenation - diminish likelihood of death, NNT = 9-22 [8] d) risks - increased risk of other infections, NNH = 5 [8] - increased frequency of oral candidiasis & mucocutaneous Herpes simplex - exacerbation of undiagnosed fungal infection or mycobacterial infection 3) prophylactic therapy: a) indications - recovery from PCP infection - HIV patients with CD4 counts < 200/mm3 - HIV patients with < 14% CD4/total lymphocytes - HIV patients with unexplained fevers lasting < 2 weeks - HIV patients with oral candidiasis - any AIDS-defining infection or Kaposi's sarcoma b) antimicrobial prophylaxis - TMP/SMZ (Bactrim DS or Septra DS: 1 tab PO QD) (3 times/week may suffice [3]) - dapsone 50-100 mg PO QD or 200 mg weekly - dapsone plus pyrimethamine 75 mg QD - aerosolized pentamidine 300 mg monthly - not as effective as Bactrim or dapsone - Fansidar (525 mg sulfadoxine & 25 mg pyrimethamine) - clindamycin (Cleocin) 450-600 mg BID-TID + primaquine 15 mg QD - atovaquone (Mepron) 750 mg QD-BID with or without pyrimethamine - sulfasalazine may lower risk in patients with rheumatoid arthritis [10] c) supplement with tetrahydrofolate (folinic acid) to prevent bone marrow suppression d) discontinue prophylaxis for PCP when CD4 count > 200/mm3 for 3 months [4,5]

Related

outpatient management of HIV related pneumonia pneumocystis chorioretinitis Pneumocystis jirovecii; Pneumocystis carinii (PCP)

General

pneumocystosis fungal pneumonia

References

  1. Manual of Medical Therapeutics, 28th edition, Ewald & McKenzie (eds) Little, Brown & Co, 1995, pg 332
  2. Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 908-910
  3. Journal Watch vol 19 #22, pg 175, Nov 15, 1999
  4. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2012, 2015, 2018, 2021. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  5. Journal Watch 22(20):150, 2002 Yeni PG et al Antiretroviral treatment for adult HIV infection in 2002: updated recommendations of the International AIDS Society- USA Panel. JAMA 288:222, 2002 PMID: 12095387 - Dybul M et al Guidelines for using antiretroviral agents among HIV- infected adults and adolescents. Ann Intern Med 137:381, 2002 PMID: 12617573 - Dybul M et al Guidelines for Using Antiretroviral Agents Among HIV-Infected Adults and Adolescents Recommendations of the Panel on Clinical Practices for Treatment of HIV* MMWR Recomm Rep. 2002 May 17;51(RR-7):1-55 PMID: 12027060 http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5107a1.htm - Masur H et al Guidelines for preventing opportunistic infections among HIV-infected persons--2002. Recommendations of the U.S. Public Health Service and the Infectious Diseases Society of America. Ann Intern Med 137:435, 2002 PMID: 12617574 http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5108a1.htm
  6. ARUP Consult: Pneumocystis jirovecii The Physician's Guide to Laboratory Test Selection & Interpretation https://arupconsult.com/content/pneumocystis-jirovecii
  7. Carmona EM, Limper AH. Update on the diagnosis and treatment of Pneumocystis pneumonia. Ther Adv Respir Dis. 2011 Feb;5(1):41-59. PMID: 20736243
  8. The NNT: Systemic Steroids for Pneumocystis Pneumonia (PCP,PJ) http://www.thennt.com/nnt/steroids-for-pcppj-pneumonia/ - Briel M, Bucher HC, Boscacci R, Furrer H. Adjunctive corticosteroids for Pneumocystis jiroveci pneumonia in patients with HIV-infection. Cochrane Database Syst Rev. 2006 Jul 19;(3):CD006150. PMID: 16856118
  9. Creemers-Schild D, Kroon FP, Kuijper EJ, de Boer MG. Treatment of Pneumocystis pneumonia with intermediate-dose and step-down to low-dose trimethoprim-sulfamethoxazole: lessons from an observational cohort study. Infection. 2015 Oct 15. [Epub ahead of print] PMID: 26471512
  10. Nunokawa T et al. Prophylactic effect of sulfasalazine against Pneumocystis pneumonia in patients with rheumatoid arthritis: A nested case-control study. Semin Arthritis Rheum 2019 Feb; 48:573 PMID: 30057321 https://www.sciencedirect.com/science/article/pii/S0049017218300441
  11. Lecuyer R et al. Characteristics and prognosis factors of Pneumocystis jirovecii pneumonia according to underlying disease: A retrospective multicentre study. Chest 2024 Jan 11; [e-pub]. PMID: 38215935 https://journal.chestnet.org/article/S0012-3692(24)00022-9/fulltext