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Presenter: Lisa, Sharkey, Cambridge, United Kingdom
Authors: Sze Yeap, Effrossyni Gkrania-Klotsas, Lisa Sharkey, Stephen Middleton, Jeremy Woodward, Andrew Butler, Neil Russell, Paul Gibbs, Diane Bond, Samantha Duncan, Dunecan Massey
Sze Yeap1, Effrossyni Gkrania-Klotsas2, Lisa M. Sharkey1, Stephen J. Middleton1, Jeremy M. Woodward1, Andrew J. Butler3, Neil K. Russell3, Paul Gibbs3, Diane Bond3, Samantha Duncan3, Dunecan C.O. Massey1.
1Gastroenterology, Cambridge University Hospital, Cambridge, United Kingdom; 2Infectious Disease, Cambridge University Hospital, Cambridge, United Kingdom; 3Transplant Surgery, Cambridge University Hospital, Cambridge, United Kingdom
Introduction: Pneumocystis jiroveci pneumonia (PJP) is a life-threatening infection, thought to occur commonly in the first 6 months following solid organ transplant.[1]Therefore anti-PJP prophylaxis is generally recommended for 6–12 months post-transplant. However, a recent study has reported that most PJP occurred several years after transplant and affected patients who were no longer taking prophylaxis.[2] This raises the question of whether anti-PJP prophylaxis needs to be considered for longer periods. Accordingly, we have conducted a retrospective review of the incidence of PJP in our intestinal transplant cohort.
Methods: 61 patients patients underwent intestinal, modified multivisceral and full multivisceral transplantations at our transplant unit between February 2006 and February 2016. As per protocol, patients were started on oral Co-trimoxazole 480mg 3 times per week on day 14 post-transplant and this was discontinued after 6 months. Alternative such as nebulised Pentamidine or Atovaquone was given if patients were allergic to Co-trimoxazole or developed side effects such as leukopenia. Cases of PJP were identified through a review of case-records and microbiological samples. Demographic data and known risk factors for PJP (immunosuppression therapies, graft rejection, concurrent cytomegalovirus (CMV) infection, neutrophil and lymphocyte counts) were also collected.
Results: 5 out of 61 (8.2%) patients developed PJP, diagnosed from PCR bronchial washings obtained via bronchoscopy and alveolar lavage. All cases occurred beyond 6 months (median 22; range 14-58 months) post-transplant when they were no longer taking prophylaxis. All affected patients had had intestinal rejection prior to PJP diagnosis. The median time to diagnosis was 6 months (range 2-50 months) after treatment for rejection (pulsed methylprednisolone, anti-thymocyte globulin, alemtuzumab). None of the patients were taking prophylaxis at the time of diagnosis, except for one for a short period of time. This patient was started on Atovaquone prophylaxis following intensive anti-rejection treatment and developed PJP less than a month later. Other identifiable risk factors included extra-immunosuppression (prednisolone, rituximab, concomitant tacrolimus and sirolimus), recent or recurrent CMV infection (3/5), profound lymphopenia (median 0.06; 5/5), neutropenia (1/5) and >60 years old (4/5). 2 deaths occurred following diagnosis of PJP with subsequent multi-organ failure.
Conclusion: All PJP cases in our cohort occurred beyond 6 months post-transplant and seem to follow treatment for rejection. The affected patients were relatively over-immunosuppressed, lymphopenic and were not taking anti-PJP prophylaxis at the time of diagnosis. This suggests that duration of prophylaxis should be personalised based on their risk factors. Rather than stopping and restarting prophylaxis, we have elected to continue anti-PJP prophylaxis life-long in all of our cohort.
[1] S. I. Martin, J. A. Fishman and the AST. Infectious Diseases Community of Practice. Pneumocystis Pneumonia in Solid Organ Transplantation. American Journal of Transplantation 2013; 13: 272–279
[2] 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. Transpl Infect Dis 2012; 14: 510–518.
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