Infections in Hematopoietic Cell Transplant Recipients: Results From the Organ Transplant Infection Project, a Multicenter, Prospective, Cohort Study

Mindy G Schuster, Angela A Cleveland, Erik R Dubberke, Carol A Kauffman, Robin K Avery, Shahid Husain, David L Paterson, Fernanda P Silveira, Tom M Chiller, Kaitlin Benedict, Kathleen Murphy, Peter G Pappas, Mindy G Schuster, Angela A Cleveland, Erik R Dubberke, Carol A Kauffman, Robin K Avery, Shahid Husain, David L Paterson, Fernanda P Silveira, Tom M Chiller, Kaitlin Benedict, Kathleen Murphy, Peter G Pappas

Abstract

Background: Infection is a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Our object was to better define the epidemiology and outcomes of infections after HCT.

Methods: This was a prospective, multicenter cohort study of HCT recipients and conducted from 2006 to 2011. The study included 4 US transplant centers and 444 HCT recipients. Data were prospectively collected for up to 30 months after HCT using a standardized data collection tool.

Results: The median age was 53 years, and median follow up was 413 (range, 5-980) days. The most common reason for HCT was hematologic malignancy (87%). The overall crude mortality was 52%. Death was due to underlying disease in 44% cases and infection in 21%. Bacteremia occurred in 231 (52%) cases and occurred early posttransplant (median day 48). Gram-negative bloodstream infections were less frequent than Gram-positive, but it was associated with higher mortality (45% vs 13%, P = .02). Clostridium difficile infection developed in 148 patients (33%) at a median of 27 days post-HCT. There were 53 invasive fungal infections (IFIs) among 48 patients (11%). The median time to IFI was 142 days. Of 155 patients with cytomegalovirus (CMV) infection, 4% had CMV organ involvement. Varicella zoster infection (VZV) occurred in 13 (4%) cases and was disseminated in 2. Infection with respiratory viruses was seen in 49 patients. Pneumocystis jirovecii pneumonia was rare (1%), and there were no documented cases of nocardiosis, toxoplasmosis, endemic mycoses, or mycobacterial infection. This study lacked standardized antifungal and antiviral prophylactic strategies.

Conclusions: Infection remains a significant cause of morbidity and mortality after HCT. Bacteremias and C difficile infection are frequent, particularly in the early posttransplant period. The rate of IFI is approximately 10%. Organ involvement with CMV is infrequent, as are serious infections with VZV and herpes simplex virus, likely reflecting improved prevention strategies.

Keywords: infections; prospective; stem cell; transplant..

References

    1. Mendes ET, Dulley F, Basso M, et al. Healthcare-associated infection in hematopoietic stem cell transplantation patients: risk factors and impact on outcome. Int J Infect Dis 2012; 16:e424–8.
    1. Ninin E, Milpied N, Moreau P, et al. Longitudinal study of bacterial, viral, and fungal infections in adult recipients of bone marrow transplants. Clin Infect Dis 2001; 33:41–7.
    1. Piñana JL, Montesinos P, Martino R, et al. Incidence, risk factors, and outcome of bacteremia following autologous hematopoietic stem cell transplantation in 720 adult patients. Ann Hematol 2014; 93:299–307.
    1. Kontoyiannis DP, Marr KA, Park BJ, et al. Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001–2006: overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) database. Clin Infect Dis 2010; 5:1091–100.
    1. Neofytos D, Horn D, Anaissie E, et al. Epidemiology and outcome of invasive fungal infection in adult hematopoietic stem cell transplant recipients: analysis of Multicenter Prospective Antifungal Therapy (PATH) Alliance registry. Clin Infect Dis 2009; 48:265–73.
    1. Martín-Peña A, Aguilar-Guisado M, Espigado I, et al. Prospective study of infectious complications in allogeneic hematopoietic stem cell transplant recipients. Clin Transplant 2011; 25:468–74.
    1. Gil L, Styczynski J, Komarnicki M. Infectious complication in 314 patients after high-dose therapy and autologous hematopoietic stem cell transplantation: risk factors analysis and outcome. Infection 2007; 35:421–7.
    1. Krüger W, Rüssmann B, Kröger N, et al. Early infections in patients undergoing bone marrow or blood stem cell transplantation–a 7 year single centre investigation of 409 cases. Bone Marrow Transplant 1999; 23:589–97.
    1. Ljungman P, Ward KN, Crooks BN, et al. Respiratory virus infections after stem cell transplantation: a prospective study from the infectious diseases working party of the European group for blood and marrow transplantation. Bone Marrow Transplant 2001; 28:479–84.
    1. Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control 2008; 36:309–32.
    1. De Pauw B, Walsh TJ, Donnelly JP, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) consensus group. Clin Infect Dis 2008; 46:1813–21.
    1. Erard V, Guthrie KA, Seo S, et al. Reduced mortality of cytomegalovirus pneumonia after hematopoietic cell transplantation due to antiviral therapy and changes in transplantation practices. Clin Infect Dis 2015; 61:31–9.
    1. Mulanovich VE, Ahmed SI, Öztürk T, et al. Toxoplasmosis in allo-SCT patients: risk factors and outcomes at a transplantation center with a low incidence. Bone Marrow Transplant 2011; 46:273–7.
    1. de Medeiros BC, de Medeiros CR, Werner B, et al. Disseminated toxoplasmosis after bone marrow transplantation: report of 9 cases. Transpl Infect Dis 2001; 3:24–8.
    1. Al-Anazi KA, Al-Jasser AM, Al-Anazi WK. Infections caused by non-tuberculous mycobacteria in recipients of hematopoietic stem cell transplantation. Front Oncol 2014; 4:311.
    1. Doucette K, Fishman JA. Nontuberculous mycobacterial infection in hematopoietic stem cell and solid organ transplant recipients. Clin Infect Dis 2004; 38:1428–39.
    1. Wang HL, Seo YH, LaSala PR, et al. Nocardiosis in 132 patients with cancer: microbiological and clinical analyses. Am J Clin Pathol 2014; 142:513–23.
    1. Chaaban S, Wheat LJ, Assi M. Cryptococcal meningitis post autologous stem cell transplantation. Transpl Infect Dis 2014; 16:473–6.
    1. Glenn TJ, Blair JE, Adams RH. Coccidioidomycosis in hematopoietic stem cell transplant recipients. Med Mycol 2005; 43:705–10.
    1. Haydoura S, Wallentine J, Lopansri B, et al. Disseminated histoplasmosis in allogeneic bone marrow transplant: a diagnosis not to be missed. Transpl Infect Dis 2014; 16:822–6.
    1. Almyroudis NG, Fuller A, Jakubowski A, et al. Pre- and post-engraftment bloodstream infection rates and associated mortality in allogeneic hematopoietic stem cell transplant recipients. Transpl Infect Dis 2005; 7:11–7.
    1. Poutsiaka DD, Price LL, Ucuzian A, et al. Blood stream infection after hematopoietic stem cell transplantation is associated with increased mortality. Bone Marrow Transplant 2007; 40:63–70.
    1. Mikulska M, Del Bono V, Raiola AM, et al. Blood stream infections in allogeneic hematopoietic stem cell transplant recipients: reemergence of Gram-negative rods and increasing antibiotic resistance. Biol Blood Marrow Transplant 2009; 15:47–53.
    1. Oliveira AL, de Souza M, Carvalho-Dias VM, et al. Epidemiology of bacteremia and factors associated with multi-drug-resistant Gram-negative bacteremia in hematopoietic stem cell transplant recipients. Bone Marrow Transplant 2007; 39:775–81.
    1. Collin BA, Leather HL, Wingard JR, Ramphal R. Evolution, incidence, and susceptibility of bacterial bloodstream isolates from 519 bone marrow transplant patients. Clin Infect Dis 2001; 33:947–53.
    1. Mikulska M, Del Bono V, Bruzzi P, et al. Mortality after bloodstream infections in allogeneic haematopoietic stem cell transplant (HSCT) recipients. Infection 2012; 40:271–8.
    1. Blennow O, Ljungman P, Sparrelid E, et al. Incidence, risk factors, and outcome of bloodstream infections during the pre-engraftment phase in 521 allogeneic hematopoietic stem cell transplantations. Transpl Infect Dis 2014; 16:106–14.
    1. Hakki M, Limaye AP, Kim HW, et al. Invasive Pseudomonas aeruginosa infections: high rate of recurrence and mortality after hematopoietic cell transplantation. Bone Marrow Transplant 2007; 39:687–93.
    1. Lucado J, Gould C, Elixhauser A. Clostridium difficile infections (CDI) in hospital stays, 2009 HCUP statistical brief no. 124. Rockville, MD: US Department of Health and Human Services, Agency for Healthcare Research and Quality; Available at .
    1. Centers for Disease Control and Prevention (CDC). Vitals signs: preventing Clostridium difficile infections. MMWR Morb Mortal Wkly Rep 2012; 61:157–62.
    1. Magill SS, Edwards JR, Bamberg W, et al. Multistate point-prevalence survey of health care-associated infections. N Engl J Med 2014; 370:1198–208.
    1. Guddati AK, Kumar G, Ahmed S, et al. Incidence and outcomes of Clostridium difficile-associated disease in hematopoietic cell transplant recipients. Int J Hematol 2014; 99:758–65.
    1. Kamboj M, Son C, Cantu S, et al. Hospital-onset Clostridium difficile infection rates in persons with cancer or hematopoietic stem cell transplant: a C3IC network report. Infect Control Hosp Epidemiol 2012; 33:1162–5.
    1. Alonso CD, Treadway SB, Hanna DB, et al. Epidemiology and outcomes of Clostridium difficile infections in hematopoietic stem cell transplant recipients. Clin Infect Dis 2012; 54:1053–63.
    1. Trifilio SM, Pi J, Mehta J. Changing epidemiology of Clostridium difficile-associated disease during stem cell transplantation. Biol Blood Marrow Transplant 2013; 19:405–9.
    1. Willems L, Porcher R, Lafaurie M, et al. Clostridium difficile infection after allogeneic hematopoietic stem cell transplantation: incidence, risk factors, and outcome. Biol Blood Marrow Transplant 2012; 18:1295–301.
    1. Chakrabarti S, Lees A, Jones SG, Milligan DW. Clostridium difficile infection in allogeneic stem cell transplant recipients is associated with severe graft-versus-host disease and non-relapse mortality. Bone Marrow Transplant 2000; 26:871–6.
    1. Callejas-Díaz A, Gea-Banacloche JC. Clostridium difficile: deleterious impact on hematopoietic stem cell transplantation. Curr Hematol Malig Rep 2014; 9:85–90.
    1. Chemaly RF, Ghosh S, Bodey GP, et al. Respiratory viral infections in adults with hematologic malignancies and human stem cell transplantation recipients: a retrospective study at a major cancer center. Medicine (Baltimore) 2006; 85:278–87.
    1. Hassan IA, Chopra R, Swindell R, Mutton KJ. Respiratory viral infections after bone marrow/peripheral stem-cell transplantation: the Christie hospital experience. Bone Marrow Transplant 2003; 32:73–7.
    1. Corzo-León DE, Satlin MJ, Soave R, et al. Epidemiology and outcomes of invasive fungal infections in allogeneic haematopoietic stem cell transplant recipients in the era of antifungal prophylaxis: a single-centre study with focus on emerging pathogens. Mycoses 2015; 58:325–36.
    1. Li L, Wang J, Zhang W, et al. Risk factors for invasive mold infections following allogeneic hematopoietic stem cell transplantation: a single center study of 190 recipients. Scand J Infect Dis 2012; 44:100–7.
    1. Bow EJ. Invasive fungal infection in haematopoietic stem cell transplant recipients: epidemiology from the transplant physician’s viewpoint. Mycopathologia 2009; 168:283–97.
    1. Garcia-Vidal C, Upton A, Kirby KA, Marr KA. Epidemiology of invasive mold infections in allogeneic stem cell transplant recipients: biological risk factors for infection according to time after transplantation. Clin Infect Dis 2008; 47:1041–50.
    1. Post MJ, Lass-Floerl C, Gastl G, Nachbaur D. Invasive fungal infections in allogeneic and autologous stem cell transplant recipients: a single-center study of 166 transplanted patients. Transpl Infect Dis 2007; 9:189–95.
    1. Pagano L, Caira M, Nosari A, et al. Fungal infections in recipients of hematopoietic stem cell transplants: results of the SEIFEM B-2004 study–Sorveglianza epidemiologica infezioni fungine nelle emopatie maligne. Clin Infect Dis 2007; 45:1161–70.
    1. Liu YC, Chien SH, Fan NW, et al. Incidence and risk factors of probable and proven invasive fungal infection in adult patients receiving allogeneic hematopoietic stem cell transplantation. J Microbiol Immunol Infect 2016; 49:567–74.
    1. Kontoyiannis DP, Lionakis MS, Lewis RE, et al. Zygomycosis in a tertiary-care cancer center in the era of Aspergillus-active antifungal therapy: a case-control observational study of 27 recent cases. J Infect Dis 2005; 191:1350–60.
    1. Vazquez JA, Miceli MH, Alangaden G. Invasive fungal infections in transplant recipients. Ther Adv Infect Dis 2013; 1:85–105.
    1. Lanternier F, Sun HY, Ribaud P, et al. Mucormycosis in organ and stem cell transplant recipients. Clin Infect Dis 2012; 54:1629–36.
    1. Trifilio SM, Bennett CL, Yarnold PR, et al. Breakthrough zygomycosis after voriconazole administration among patients with hematologic malignancies who receive hematopoietic stem-cell transplants or intensive chemotherapy. Bone Marrow Transplant 2007; 39:425–9.
    1. Nucci M, Marr KA. Emerging fungal diseases. Clin Infect Dis 2005; 41:521–6.
    1. Xhaard A, Lanternier F, Porcher R, et al. Mucormycosis after allogeneic haematopoietic stem cell transplantation: a French Multicentre Cohort Study (2003-2008). Clin Microbiol Infect 2012; 18:E396–400.
    1. Hill QA, Kelly RJ, Patalappa C, et al. Survival of patients with hematological malignancy admitted to the intensive care unit: prognostic factors and outcome compared to unselected medical intensive care unit admissions, a parallel group study. Leuk Lymphoma 2012; 53:282–8.
    1. Hamalainen S, Kuittinen T, Matinlauri I, et al. Severe sepsis in autologous stem cell transplant recipients: microbiological aetiology, risk factors and outcome. Scand J Infect Dis 2009; 41:14–20.
    1. Agarwal S, O’Donoghue S, Gowardman J, et al. Intensive care unit experience of haemopoietic stem cell transplant patients. Intern Med J 2012; 42:748–54.
    1. Soubani AO, Kseibi E, Bander JJ, et al. Outcome and prognostic factors of hematopoietic stem cell transplantation recipients admitted to a medical ICU. Chest 2004; 126:1604–11.

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