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1.
Am J Transplant ; 18(1): 113-124, 2018 01.
Article in English | MEDLINE | ID: mdl-28898527

ABSTRACT

This study evaluated the independent contribution of voriconazole to the development of squamous cell carcinoma (SCC) in lung transplant recipients, by attempting to account for important confounding factors, particularly immunosuppression. This international, multicenter, retrospective, cohort study included adult patients who underwent lung transplantation during 2005-2008. Cox regression analysis was used to assess the effects of voriconazole and other azoles, analyzed as time-dependent variables, on the risk of developing biopsy-confirmed SCC. Nine hundred lung transplant recipients were included. Median follow-up time from transplantation to end of follow-up was 3.51 years. In a Cox regression model, exposure to voriconazole alone (adjusted hazard ratio 2.39, 95% confidence interval 1.31-4.37) and exposure to voriconazole and other azole(s) (adjusted hazard ratio 3.45, 95% confidence interval 1.07-11.06) were associated with SCC compared with those unexposed after controlling for important confounders including immunosuppressants. Exposure to voriconazole was associated with increased risk of SCC of the skin in lung transplant recipients. Residual confounding could not be ruled out because of the use of proxy variables to control for some confounders. Benefits of voriconazole use when prescribed to lung transplant recipients should be carefully weighed versus the potential risk of SCC. EU PAS registration number: EUPAS5269.


Subject(s)
Antifungal Agents/adverse effects , Carcinoma, Squamous Cell/etiology , Lung Diseases/surgery , Lung Transplantation/adverse effects , Skin Neoplasms/etiology , Voriconazole/adverse effects , Adolescent , Adult , Aged , Carcinoma, Squamous Cell/pathology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Skin Neoplasms/pathology , Transplant Recipients , Young Adult
2.
Am J Transplant ; 15(5): 1369-75, 2015 May.
Article in English | MEDLINE | ID: mdl-25703251

ABSTRACT

Infection with Strongyloides stercoralis is typically asymptomatic in immunocompetent hosts, despite chronic infection. In contrast, immunocompromised hosts such as solid organ transplant recipients are at risk for hyperinfection syndrome and/or disseminated disease, frequently resulting in fatal outcomes. Infection in these recipients may result from reactivation of latent infection or infection through transmission from an infected donor. We describe the Centers for Disease Control and Prevention's experience with seven clusters of donor-derived infection from 2009 to 2013. Six of the seven (86%) donors were born in Latin America; donor screening was not performed prior to organ transplantation in any of these investigations. Eleven of the 20 (55%) organ recipients were symptomatic, two of whom died from complications of strongyloidiasis. We also describe the New York Organ Donor Network (NYODN) experience with targeted donor screening from 2010 to 2013. Of the 233 consented potential donors tested, 10 tested positive for Strongyloides antibody; and 18 organs were transplanted. The majority (86%) of the donors were born in Central or South America. Fourteen recipients received prophylaxis after transplantation; no recipients developed strongyloidiasis. The NYODN experience provides evidence that when targeted donor screening is performed prior to transplantation, donor-derived infection can be averted in recipients.


Subject(s)
Donor Selection/methods , Strongyloides stercoralis , Strongyloidiasis/complications , Transplantation , Adult , Aged , Animals , Centers for Disease Control and Prevention, U.S. , Female , Humans , Immunocompromised Host , Kidney Transplantation/adverse effects , Latin America , Liver Transplantation/adverse effects , Male , Middle Aged , Postoperative Complications , Strongyloidiasis/epidemiology , Tissue Donors , Transplant Recipients , United States
3.
Transpl Infect Dis ; 17(1): 14-20, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25620387

ABSTRACT

BACKGROUND: Fungal infections remain a substantial cause of mortality in lung transplant (LTx) recipients, yet no comprehensive consensus guidelines have been established for antifungal prophylaxis and treatment of Aspergillus infection in these patients. METHODS: A cross-sectional study surveyed the directors from 27 of 64 (45.5%) active LTx centers in the United States to examine clinical practice variations in Aspergillus prophylaxis and treatment of colonization and invasive aspergillosis (IA) in LTx recipients. RESULTS: Antifungal prophylaxis increased from 52.3% in 2011 to 77.8% in 2013, with the most common agent being inhaled amphotericin B (61.9%), followed by oral voriconazole (51.9%). A total of 74.1% of centers treat Aspergillus airway colonization, with 80.0% of centers using oral voriconazole. All centers treat IA, with 92.6% using oral voriconazole. The duration of Aspergillus prophylaxis and treatment of colonization or IA varied widely across centers from 3 months to >1 year. A total of 51.9% of centers reported internal practice variations in the treatment of IA. Factors guiding treatment decisions included microbiologic culture and sensitivity (74.1%), ease of administration (59.3%), interaction with other medications (55.5%), side effect profile (51.8%), and center guidelines (48.1%). Although 85.2% of LTx centers recommended routine skin cancer screening for LTx recipients, only 44.4% of LTx centers reported having a dedicated transplant dermatologist. CONCLUSION: Most active US LTx centers currently employ antifungal prophylaxis and treat Aspergillus colonization and IA, although choice of agent, route of administration, and duration of therapy across and within centers continue to differ substantially. The number of transplant dermatologists available among US LTx centers is limited. Overall, a strong need exists for more comprehensive consensus guidelines to direct antifungal prophylaxis and treatment of Aspergillus infection in LTx recipients.


Subject(s)
Amphotericin B/therapeutic use , Antifungal Agents/therapeutic use , Aspergillosis/prevention & control , Aspergillus/drug effects , Lung Transplantation/adverse effects , Voriconazole/therapeutic use , Cross-Sectional Studies , Humans , Pre-Exposure Prophylaxis , Surveys and Questionnaires , United States
5.
Transpl Infect Dis ; 14(3): 248-58, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22385394

ABSTRACT

BACKGROUND: The optimal method of both predicting and preventing cytomegalovirus (CMV) disease in lung transplant recipients remains unclear. In particular, the most appropriate duration of CMV prophylaxis post transplant is unresolved. We report herein our experience with a planned indefinite regimen of valganciclovir prophylaxis and monitoring of quantitative CMV load in bronchoalveolar lavage (BAL) fluid. METHODS: We performed a single-center observational study with both prospective and retrospective components. The included patients (n = 128) received a planned regimen of indefinite valganciclovir prophylaxis post transplant, regardless of donor (D)/recipient (R) CMV serostatus. Real-time polymerase chain reaction assay for detection of CMV in BAL was prospectively performed over a 1-year period. Clinical data were reviewed retrospectively; median follow-up was 24.8 months (range 1-93 months). RESULTS: Sixty-five patients (50.6%) discontinued valganciclovir prophylaxis, either temporarily or permanently, with a primary cause of mild leukopenia. Six cases of CMV disease were identified (4.7%), with no significant difference between those who were on continuous prophylaxis or not (4.6% vs. 4.9%; P = non-significant [ns]). However, those who discontinued prophylaxis showed an increased incidence of laboratory-detected CMV infection (40.7% vs. 12.7%; P = 0.001). High-risk D+/R- patients did not demonstrate a significantly increased incidence of CMV disease (8.1% vs. 3.3% other serotypes; P = ns). Three patients (2.3%) developed valganciclovir-resistant CMV disease. Molecular detection of CMV in BAL fluid was significantly more sensitive than shell vial culture. However, BAL CMV viral load was not predictive of subsequent disease development. CONCLUSIONS: Extended valganciclovir prophylaxis for all lung transplant recipients led to a low incidence of CMV disease and resistance. In such low-incidence populations, routine quantitation of CMV in BAL did not confer significant clinical benefit over non-quantitative methods in prediction of CMV disease onset.


Subject(s)
Antiviral Agents/therapeutic use , Cytomegalovirus Infections/prevention & control , Cytomegalovirus/isolation & purification , Ganciclovir/analogs & derivatives , Lung Transplantation , Adult , Aged , Bronchoalveolar Lavage Fluid/virology , Cytomegalovirus/genetics , Cytomegalovirus Infections/epidemiology , Cytomegalovirus Infections/virology , DNA, Viral/analysis , Female , Ganciclovir/therapeutic use , Humans , Male , Middle Aged , Prospective Studies , Real-Time Polymerase Chain Reaction , Retrospective Studies , Valganciclovir , Viral Load
6.
Transpl Infect Dis ; 13(5): 536-9, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21504526

ABSTRACT

Pantoea agglomerans is a gram-negative rod that is frequently found on the exterior of many plants, fruits, vegetables, and in soil, and it is used as a biopesticide in the agriculture industry. Recent reports have implicated P. agglomerans in systemic infections of immunocompromised hosts and neonates, as well as more localized infections in healthy hosts. P. agglomerans as a cause of hospital-acquired pneumonia has not been well characterized. We report a case of P. agglomerans pneumonia in a heart-lung transplant recipient following transplantation. The organism was susceptible to multiple antimicrobial agents and treated successfully with ertapenem. We review the patient's course and the relevant literature, and discuss implications for the future.


Subject(s)
Enterobacteriaceae Infections/microbiology , Heart-Lung Transplantation/adverse effects , Immunocompromised Host , Pantoea , Pneumonia, Bacterial/microbiology , Communicable Diseases, Emerging , Enterobacteriaceae Infections/etiology , Humans , Pneumonia, Bacterial/etiology
7.
Am J Transplant ; 11(4): 672-80, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21401868

ABSTRACT

Donor-derived transmission of Trypanosoma cruzi, the etiologic agent of Chagas disease, has emerged as an issue in the United States over the past 10 years. Acute T. cruzi infection causes substantial morbidity and mortality in the posttransplant setting if not recognized and treated early. We assembled a working group of transplant infectious disease specialists, laboratory medicine specialists, organ procurement organization representatives and epidemiologists with expertise in Chagas disease. Based on review of published and unpublished data, the working group prepared evidence-based recommendations for donor screening, and follow-up testing and treatment of recipients of organs from infected donors. We advise targeted T. cruzi screening of potential donors born in Mexico, Central America and South America. Programs can consider transplantation of kidneys and livers from T. cruzi-infected donors with informed consent from recipients. However, we recommend against heart transplantation from infected donors. For other organs, we recommend caution based on the anticipated degree of immunosuppression. Our recommendations stress the need for systematic monitoring of recipients by polymerase chain reaction, and microscopy of buffy coat and advance planning for immediate antitrypanosomal treatment if recipient infection is detected. Data on management and outcomes of all cases should be collected to inform future guidelines and to assist in coordination with public health authorities.


Subject(s)
Chagas Disease/diagnosis , Chagas Disease/therapy , Organ Transplantation/adverse effects , Practice Guidelines as Topic , Trypanocidal Agents/therapeutic use , Trypanosoma cruzi/isolation & purification , Chagas Disease/transmission , Humans , Tissue Donors
8.
Am J Transplant ; 11(4): 848-51, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21426487

ABSTRACT

Donor-derived Trypanosoma cruzi infection in solid organ transplant recipients is associated with significant morbidity and mortality. Little is known about T. cruzi screening practices among U.S. organ procurement organizations (OPOs). We distributed a questionnaire to all U.S. OPO directors, requesting data on T. cruzi screening strategies, laboratory methods, number of donors screened, disposition of organs from positive donors and attitudes toward screening. Fifty-eight (100%) U.S. OPOs responded to the survey. Donor screening began in 2002 and is presently performed by 11 (19%) OPOs. Among screening OPOs, four screen all donors and seven use a risk-based strategy. Three different T. cruzi serology tests are used for donor screening. During 2008, 9/993 (0.9%) donors screened positive by a T. cruzi screening test, 6/9 (66%) had confirmatory tests performed and 4/6 (66%) had positive confirmatory tests. These results led to the nonuse of five donors and 17 organs. Five organs from three seropositive donors were transplanted in 2008 without recognized disease transmission. Variability of T. cruzi donor screening strategies, laboratory methods and disposition of organs from positive donors currently exists. Further research is needed to identify the risk of donor-derived T. cruzi infections to help inform the best screening strategy.


Subject(s)
Antibodies, Protozoan/immunology , Chagas Disease/transmission , Donor Selection , Organ Transplantation , Tissue Donors , Tissue and Organ Procurement/standards , Trypanosoma cruzi/immunology , Antibodies, Protozoan/blood , Chagas Disease/diagnosis , Chagas Disease/prevention & control , Health Surveys , Humans , Prospective Studies , Surveys and Questionnaires , United States
9.
J Clin Microbiol ; 39(2): 804-7, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11158158

ABSTRACT

We report the first described case of Arthrographis kalrae pansinusitis and meningitis in a patient with AIDS. The patient was initially diagnosed with Arthrographis kalrae pansinusitis by endoscopic biopsy and culture. The patient was treated with itraconazole for approximately 5 months and then died secondary to Pneumocytis carinii pneumonia. Postmortem examination revealed invasive fungal sinusitis that involved the sphenoid sinus and that extended through the cribiform plate into the inferior surfaces of the bilateral frontal lobes. There was also an associated fungal meningitis and vasculitis with fungal thrombosis and multiple recent infarcts that involved the frontal lobes, right caudate nucleus, and putamen. Post mortem cultures were positive for A. kalrae.


Subject(s)
AIDS-Related Opportunistic Infections/microbiology , Meningitis, Fungal/microbiology , Mitosporic Fungi , Mycoses/complications , Sphenoid Sinusitis/microbiology , AIDS-Related Opportunistic Infections/complications , Adult , Fatal Outcome , Humans , Male , Meningitis, Fungal/pathology , Mitosporic Fungi/classification , Mitosporic Fungi/isolation & purification , Mycoses/pathology , Pneumonia, Pneumocystis/complications , Pneumonia, Pneumocystis/pathology , Sphenoid Sinusitis/pathology
11.
Psychosom Med ; 58(2): 131-7, 1996.
Article in English | MEDLINE | ID: mdl-8849629

ABSTRACT

OBJECTIVE: The effects of lifestyle incongruity on blood pressure were tested in a cross-sectional study of 711 modernizing adult men and women, ages 25 to 64 years, residing in nine villages throughout Western Samoa. METHODS: Lifestyle incongruity (LI) was conceptualized as the mismatch between a 21-item material possessions and lifestyle scale and an eight-part occupational rank score. LI was measured by the arithmetic difference between the standardized distributions of lifestyle and occupation. Blood pressure (BP) was measured three times in the seated position, averaged and adjusted for body mass. Sex-stratified analyses were performed and adjusted BP was regressed on LI, age, and socioeconomic rank. RESULTS: In men systolic BP was associated (p < .01) with incongruity between material way of life and occupation. Men with higher occupation scores than lifestyle scores had significantly higher systolic BP. This association was stronger and significant for both systolic and diastolic BP among young (<40 years) men and all men from the more economically developed island. On the other hand, among older women diastolic BP was significantly (p < .01) higher among those whose material lifestyles exceeded their occupational class. CONCLUSIONS: The results in men, especially the young group, suggest two explanations: 1) financial demands from the extended family on young men with better paying jobs may reduce material consumption and produce psychosocial stress; 2) upward socioeconomic mobility marked by good jobs but a lag in material lifestyle may represent work stress. The results in older women support the suggestion of earlier studies that excess material consumption for enhancement of social prestige (living beyond ones' means) leads to stress and elevations in BP.


Subject(s)
Blood Pressure , Life Style , Adult , Age Factors , Cross-Sectional Studies , Culture , Female , Humans , Independent State of Samoa , Male , Middle Aged , Rural Population , Sex Factors , Socioeconomic Factors , Urban Population
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