Bio

Bio


Clinical Focus: Immunocompromised Host Infectious Diseases

This includes the prevention, diagnosis and treatment of Infections:

1) following Solid Organ Transplantation (Kidney, Pancreas, Liver, Heart, Lung, Small Bowel)
2) following Bone Marrow (Stem Cell) Transplants
3) in patients with Hematologic Malignancies
4) in patients receiving Chemotherapy for Solid Tumors
5) in patients with HIV who receive Solid Organ or Bone Marrow Transplants
6) in patients who are on Immunomodulators for Auto-Immune Diseases

Academic Appointments


Administrative Appointments


  • Immunocompromised Host ID Service, Stanford University, Division of Infectious Diseases (2013 - Present)
  • Co-Director, Transplant and Oncology ID Service, Johns Hopkins University School of Medicine (2003 - 2010)
  • Co-PI, AIDS Clinical Trials Unit, Johns Hopkins University School of Medicine (2001 - 2003)

Honors & Awards


  • Sidney Finegold Outstanding Reviewer Award, Clinical Infectious Diseases Journal (2009)
  • Associate Editor, Transplant Infectious Diseases Journal (2004-present)
  • Award for Outstanding Research, Case Western Reserve University (UHC) (1997)
  • William Dodd Robinson Award for Excellence in Internal Medicine, University of Michigan (1994)

Professional Education


  • Fellowship, Johns Hopkins University School of Medicine, Infectious Diseases (2001)
  • Residency, University Hospitals of Cleveland (Case Western Reserve), Internal Medicine (1997)
  • Medical School, University of Michigan, Medicine (1994)

Research & Scholarship

Current Research and Scholarly Interests


My research and scholarly interests have focused on tailoring antimicrobial prophylaxis in specific highly immunocompromised hosts depending on their specific infectious disease risks. I am interested in developing diagnostic algorithms and treatment protocols that will improve the quality of care in transplant and oncology patients.

I also have an interest in training ID fellows in this very specialized area of patient care. To that end, we have started a new ICHS ID fellowship with a specialized curriculum and are developing supplemental educational materials to enhance this training, which can be implemented at other academic training centers.

Publications

Journal Articles


  • Epidemiology, risk factors, and outcomes of Clostridium difficile infection in kidney transplant recipients TRANSPLANT INFECTIOUS DISEASE Neofytos, D., Kobayashi, K., Alonso, C. D., Cady-Reh, J., Lepley, D., Harris, M., Desai, N., Kraus, E., Subramanian, A., TREADWAY, S., OSTRANDER, D., Thompson, C., Marr, K. 2013; 15 (2): 134-141

    Abstract

    We sought to describe the epidemiology and risk factors for Clostridium difficile infection (CDI) among kidney transplant recipients (KTR) between 1 January 2008 and 31 December 2010.A single-institution retrospective study was conducted among all adult KTR with CDI, defined as a positive test for C. difficile by a cell cytotoxic assay for C. difficile toxin A or B or polymerase chain reaction test for toxigenic C. difficile.Among 603 kidney transplants performed between 1 January 2008 and 31 December 2010, 37 (6.1%) patients developed CDI: 12 (of 128; 9.4%) high-risk (blood group incompatible and/or anti-human leukocyte antigen donor-specific antibodies) vs. 25 (of 475; 5.3%, P = 0.08) standard-risk patients. The overall rate of CDI increased from 3.7% in 2008 to 9.4% in 2010 (P = 0.05). The median time to CDI diagnosis was 9 days, with 27 (73.0%) patients developing CDI within the first 30 days after their transplant, and 14 (51.8%) developing CDI within 7 days. A case-control analysis of 37 CDI cases and 74 matched controls demonstrated the following predictors for CDI among KTR: vancomycin-resistant Enterococcus colonization before transplant (odds ratio [OR]: 3.6, P = 0.03), receipt of an organ from Centers for Disease Control high-risk donor (OR: 5.9, P = 0.006), and administration of high-risk antibiotics within 30 days post transplant (OR: 6.6, P = 0.001).CDI remains a common early complication in KTR, with rates steadily increasing during the study period. Host and transplant-related factors and exposure to antibiotics appeared to significantly impact the risk for CDI among KTR.

    View details for DOI 10.1111/tid.12030

    View details for Web of Science ID 000317287900011

    View details for PubMedID 23173772

  • Mycobacterium tuberculosis Infections in Solid Organ Transplantation AMERICAN JOURNAL OF TRANSPLANTATION Subramanian, A. K., Morris, M. I. 2013; 13: 68-76

    View details for DOI 10.1111/ajt.12100

    View details for Web of Science ID 000315907900009

    View details for PubMedID 23465000

  • Outcomes of Kidney Transplantation in HIV-Infected Recipients NEW ENGLAND JOURNAL OF MEDICINE Stock, P. G., Barin, B., Murphy, B., Hanto, D., Diego, J. M., Light, J., Davis, C., Blumberg, E., Simon, D., Subramanian, A., Millis, J. M., Lyon, G. M., Brayman, K., Slakey, D., Shapiro, R., Melancon, J., Jacobson, J. M., Stosor, V., Olson, J. L., Stablein, D. M., Roland, M. E. 2010; 363 (21): 2004-2014

    Abstract

    The outcomes of kidney transplantation and immunosuppression in people infected with human immunodeficiency virus (HIV) are incompletely understood.We undertook a prospective, nonrandomized trial of kidney transplantation in HIV-infected candidates who had CD4+ T-cell counts of at least 200 per cubic millimeter and undetectable plasma HIV type 1 (HIV-1) RNA levels while being treated with a stable antiretroviral regimen. Post-transplantation management was provided in accordance with study protocols that defined prophylaxis against opportunistic infection, indications for biopsy, and acceptable approaches to immunosuppression, management of rejection, and antiretroviral therapy.Between November 2003 and June 2009, a total of 150 patients underwent kidney transplantation; survivors were followed for a median period of 1.7 years. Patient survival rates (±SD) at 1 year and 3 years were 94.6±2.0% and 88.2±3.8%, respectively, and the corresponding mean graft-survival rates were 90.4% and 73.7%. In general, these rates fall somewhere between those reported in the national database for older kidney-transplant recipients (≥65 years) and those reported for all kidney-transplant recipients. A multivariate proportional-hazards analysis showed that the risk of graft loss was increased among patients treated for rejection (hazard ratio, 2.8; 95% confidence interval [CI], 1.2 to 6.6; P=0.02) and those receiving antithymocyte globulin induction therapy (hazard ratio, 2.5; 95% CI, 1.1 to 5.6; P=0.03); living-donor transplants were protective (hazard ratio, 0.2; 95% CI, 0.04 to 0.8; P=0.02). A higher-than-expected rejection rate was observed, with 1-year and 3-year estimates of 31% (95% CI, 24 to 40) and 41% (95% CI, 32 to 52), respectively. HIV infection remained well controlled, with stable CD4+ T-cell counts and few HIV-associated complications.In this cohort of carefully selected HIV-infected patients, both patient- and graft-survival rates were high at 1 and 3 years, with no increases in complications associated with HIV infection. The unexpectedly high rejection rates are of serious concern and indicate the need for better immunotherapy. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00074386.).

    View details for Web of Science ID 000284310000005

    View details for PubMedID 21083386

  • Recommended curriculum for subspecialty training in transplant infectious disease on behalf of the American Society of Transplantation Infectious Diseases Community of Practice Educational Initiatives Working Group TRANSPLANT INFECTIOUS DISEASE Avery, R., CLAUSS, H., Danziger-Isakov, L., Davis, J., Doucette, K., van Duin, D., FISHMAN, J., Gunseren, F., Humar, A., Husain, S., Isada, C., Julian, K., Kaul, D., Kumar, D., Martin, S., Michaels, M., Morris, M., SILVEIRA, F., Subramanian, A. 2010; 12 (3): 190-194

    Abstract

    The American Society of Transplantation Infectious Diseases (ID) Community of Practice has established an education workgroup to identify core components of a curriculum for training specialists in transplant ID. Clinical, laboratory, and research training form the triad of components on which an additional year of ID training, dedicated to the care of solid organ and hematopoietic stem cell transplant recipients, should be based. The recommended training environment would have access to adequate numbers of transplant patients, along with qualified faculty committed to teaching specialized fellows in this area. The learning objectives for both inpatient and outpatient clinical training are presented. The laboratory component requires trainees to attain expertize in utilizing and interpreting cutting-edge diagnostics used in transplant medicine. The research component may involve basic science, and translational or clinical research individualized to the trainee. Finally, suggestions for evaluation of both the fellows and the training program are provided.

    View details for DOI 10.1111/j.1399-3062.2010.00510.x

    View details for Web of Science ID 000278315600002

    View details for PubMedID 20624259

  • MELD Score Is an Important Predictor of Pretransplantation Mortality in HIV-Infected Liver Transplant Candidates GASTROENTEROLOGY Subramanian, A., Sulkowski, M., Barin, B., Stablein, D., Curry, M., Nissen, N., Dove, L., Roland, M., Florman, S., Blumberg, E., Stosor, V., Jayaweera, D. T., Huprikar, S., Fung, J., Pruett, T., Stock, P., Ragni, M. 2010; 138 (1): 159-164

    Abstract

    Human immunodeficiency virus (HIV) infection accelerates liver disease progression in patients with hepatitis C virus (HCV) and could shorten survival of those awaiting liver transplants. The Model for End-Stage Liver Disease (MELD) score predicts mortality in HIV-negative transplant candidates, but its reliability has not been established in HIV-positive candidates.We evaluated predictors of pretransplantation mortality in HIV-positive liver transplant candidates enrolled in the Solid Organ Transplantation in HIV: Multi-Site Study (HIVTR) matched 1:5 by age, sex, race, and HCV infection with HIV-negative controls from the United Network for Organ Sharing.Of 167 HIVTR candidates, 24 died (14.4%); this mortality rate was similar to that of controls (88/792, 11.1%, P = .30) with no significant difference in causes of mortality. A significantly lower proportion of HIVTR candidates (34.7%) underwent liver transplantation, compared with controls (47.6%, P = .003). In the combined cohort, baseline MELD score predicted pretransplantation mortality (hazard ratio [HR], 1.27; P < .0001), whereas HIV infection did not (HR, 1.69; P = .20). After controlling for pretransplantation CD4(+) cell count and HIV RNA levels, the only significant predictor of mortality in the HIV-infected subjects was pretransplantation MELD score (HR, 1.2; P < .0001).Pretransplantation mortality characteristics are similar between HIV-positive and HIV-negative candidates. Although lower CD4(+) cell counts and detectable levels of HIV RNA might be associated with a higher rate of pretransplantation mortality, baseline MELD score was the only significant independent predictor of pretransplantation mortality in HIV-infected liver transplant candidates.

    View details for DOI 10.1053/j.gastro.2009.09.053

    View details for Web of Science ID 000273427700026

    View details for PubMedID 19800334

  • Outcomes of liver transplant recipients with hepatitis C and human immunodeficiency virus coinfection LIVER TRANSPLANTATION Terrault, N. A., Roland, M. E., Schiano, T., Dove, L., Wong, M. T., Poordad, F., Ragni, M. V., Barin, B., Simon, D., Olthoff, K. M., Johnson, L., Stosor, V., Jayaweera, D., Fung, J., Sherman, K. E., Subramanian, A., Millis, J. M., Slakey, D., Berg, C. L., Carlson, L., Ferrell, L., Stablein, D. M., Odim, J., Fox, L., Stock, P. G. 2012; 18 (6): 716-726

    Abstract

    Hepatitis C virus (HCV) is a controversial indication for liver transplantation (LT) in human immunodeficiency virus (HIV)-infected patients because of reportedly poor outcomes. This prospective, multicenter US cohort study compared patient and graft survival for 89 HCV/HIV-coinfected patients and 2 control groups: 235 HCV-monoinfected LT controls and all US transplant recipients who were 65 years old or older. The 3-year patient and graft survival rates were 60% [95% confidence interval (CI) = 47%-71%] and 53% (95% CI = 40%-64%) for the HCV/HIV patients and 79% (95% CI = 72%-84%) and 74% (95% CI = 66%-79%) for the HCV-infected recipients (P < 0.001 for both), and HIV infection was the only factor significantly associated with reduced patient and graft survival. Among the HCV/HIV patients, older donor age [hazard ratio (HR) = 1.3 per decade], combined kidney-liver transplantation (HR = 3.8), an anti-HCV-positive donor (HR = 2.5), and a body mass index < 21 kg/m(2) (HR = 3.2) were independent predictors of graft loss. For the patients without the last 3 factors, the patient and graft survival rates were similar to those for US LT recipients. The 3-year incidence of treated acute rejection was 1.6-fold higher for the HCV/HIV patients versus the HCV patients (39% versus 24%, log rank P = 0.02), but the cumulative rates of severe HCV disease at 3 years were not significantly different (29% versus 23%, P = 0.21). In conclusion, patient and graft survival rates are lower for HCV/HIV-coinfected LT patients versus HCV-monoinfected LT patients. Importantly, the rates of treated acute rejection (but not the rates of HCV disease severity) are significantly higher for HCV/HIV-coinfected recipients versus HCV-infected recipients. Our results indicate that HCV per se is not a contraindication to LT in HIV patients, but recipient and donor selection and the management of acute rejection strongly influence outcomes.

    View details for DOI 10.1002/lt.23411

    View details for Web of Science ID 000304524000012

    View details for PubMedID 22328294

  • Donor-derived organ transplant transmission of coccidioidomycosis TRANSPLANT INFECTIOUS DISEASE Dierberg, K. L., Marr, K. A., Subramanian, A., Nace, H., Desai, N., Locke, J. E., Zhang, S., Diaz, J., Chamberlain, C., Neofytos, D. 2012; 14 (3): 300-304

    Abstract

    Coccidioidomycosis in solid organ transplant recipients most often occurs as a result of primary infection or reactivation of latent infection. Herein, we report a series of cases of transplant-related transmission of coccidioidomycosis from a single donor from a non-endemic region whose organs were transplanted to 5 different recipients. In all, 3 of the 5 recipients developed evidence of Coccidioides infection, 2 of whom had disseminated disease. The degree of T-cell immunosuppression and timing of antifungal therapy initiation likely contributed to development of disease and disease severity in these recipients. This case series highlights the importance of having a high index of suspicion for Coccidioides infection in solid organ transplant recipients, even if the donor does not have known exposure, given the difficulties of obtaining a detailed and accurate travel history from next-of-kin.

    View details for DOI 10.1111/j.1399-3062.2011.00696.x

    View details for Web of Science ID 000305076700012

    View details for PubMedID 22176496

  • Fungal infection presenting as giant cell tubulointerstitial nephritis in kidney allograft TRANSPLANT INFECTIOUS DISEASE Bagnasco, S. M., Subramanian, A. K., Desai, N. M. 2012; 14 (3): 288-291

    Abstract

    Giant cell tubulointerstitial nephritis in the kidney allograft caused by infection is rare, and donor-transmitted infection in transplanted kidneys is also rare. In this case report, we describe an unusual histological manifestation of Candida albicans in the graft biopsy of a 53-year-old male kidney transplant recipient with decreased renal function 12 days post transplant. Several giant cells were present in the tubulointerstitial inflammation, as well as yeasts, with no evidence of rejection, and the histological diagnosis was confirmed by urine culture. Donor urine culture was positive for C. albicans, suggestive of a possible donor-transmitted infection. Prompt antifungal treatment eradicated the infection, and averted systemic spread. To our knowledge, there are no previous reports of Candida infection with giant cell tubulointerstitial nephritis in human renal allograft.

    View details for DOI 10.1111/j.1399-3062.2011.00676.x

    View details for Web of Science ID 000305076700009

    View details for PubMedID 22093412

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