American Journal of Transplantation 2014; 14: 984 Wiley Periodicals Inc.

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Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons doi: 10.1111/ajt.12654

Letter to the Editor

Muted, But Not Mute To the Editor: Thank you to Dr. McKinnell et al for their interest in the updated guidelines on Pneumocystis pneumonia (PCP) in solid organ transplantation (SOT) published by the American Society of Transplantation (AST) Infectious Diseases Community of Practice in the American Journal of Transplantation this past year (1). I particularly appreciate their thoughtful comments about use of adjunctive glucocorticoid therapy in the treatment of PCP (2). In 1990, Bozzette et al (3) published the results of glucocorticoid use in HIV-infected patients with PCP in a randomized, multicenter controlled trial. With more than 300 patients enrolled, the results were clear. Hypoxic patients who received glucocorticoids in combination with anti-Pneumocystis therapy had a lower cumulative risk of respiratory failure and death compared to patients who received anti-Pneumocystis therapy alone. Since that time, adjunctive glucocorticoids have been a cornerstone of treatment for PCP in HIV-infected patients. The question on Dr. McKinnell and colleagues’ minds (and indeed, on the minds of all transplant physicians) is whether or not these same outcomes could translate to the SOT population. Since no prospective trial of a similar nature has been conducted in SOT patients (and likely never will), we are forced to rely on small-scale retrospective analyses which, as rightly pointed out, have been inconclusive. The most recent analysis consisted of only 19 cases from a single institution over 12 years (4). In that study, all SOT recipients who were hypoxic received adjunctive glucocorticoids and their outcomes were no different compared to hypoxic HIV-infected PCP patients who also received glucocorticoids. Since this is an improvement compared to historical outcomes of PCP treatment over 20 years ago where adjunctive therapies were traditionally not used, it can be theorized that glucocorticoids played a role. Given what we know about the degree of lung injury that occurs with PCP, this seems perfectly plausible. However, a lot of diagnostic and clinical management strategies in SOT recipients have improved over the last 10 years—much less the past 20 years—which could account for such improved outcomes. These are issues that always confound drawing strong conclusions from historical control comparisons. Complicating the picture further is our knowledge that PCP tends to be different in SOT compared to HIV with SOT

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recipients historically already likely on glucocorticoids, presenting with a more rapid onset, a different organismal burden and a greater likelihood of experiencing a delay in diagnosis. Perhaps today’s better outcomes are even due to a greater role of infectious diseases specialists with a background and training in transplantation! What we do know is that better use of prophylaxis has the biggest implications for affecting the incidence of disease over time, and thus overall outcomes. It is hoped that the multitude of recent outbreak investigations of PCP in SOT recipients not taking prophylaxis lend credence to the ongoing need of chemoprophylactic preventative measures (5). As for adjunctive glucocorticoids, the AST PCP guidelines should continue to list their use as an ongoing treatment measure, but until more definitive data can be presented, the recommendation and discussion on adjunctive glucocorticoids must remain unfortunately muted. S. I. Martin The Division of Infectious Diseases and The Comprehensive Transplant Center, The Ohio State University Wexner Medical Center, Columbus, OH  Corresponding author: Stanley I. Martin, [email protected]

References 1. Martin SI, Fishman JA; AST Infectious Diseases Community of Practice. Pneumocystis pneumonia in solid organ transplantation. Am J Transplant 2013; 13 (Suppl 4): 272–279. 2. McKinnell JA, Cannella AP, Injean P, Gregson A. Adjunctive glucocorticoid therapy for non-HIV-related Pneumocystis carinii pneumonia (NH-PCP). Am J Transplant 2014; 14: 982–983. 3. Bozzette SA, Sattler FR, Chiu J, et al. A controlled trial of early adjunctive treatment with glucocorticoids for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. California Collaborative Treatment Group. N Engl J Med 1990; 323: 1451–1457. 4. McKinnell JA, Cannella AP, Kunz DF, et al. Pneumocystis pneumonia in hospitalized patients: A detailed examination of symptoms management, and outcomes in human immunodeficiency virus (HIV)-infected and HIV-uninfected persons. Transplant Infect Dis 2012; 14: 510–518. 5. Sassi M, Ripamonti C, Mueller NJ, et al. Outbreaks of Pneumocystis pneumonia in 2 renal transplant centers linked to a single strain of Pneumocystis: Implications for transmission and virulence. Clin Infect Dis 2012; 54: 1437–1444.

Muted, but not mute.

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