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Biomedical subjects

Nina Singh

Publications and source records attributed to Nina Singh.

At least 19 recordsLinked to original sources
PubMed2006

Systemic and cerebrospinal fluid T-helper cytokine responses in organ transplant recipients with Cryptococcus neoformans infection.

BACKGROUND: The role of Th1 and Th2 mediated cytokine responses in the pathogenesis of Cryptococcus neoformans infection in organ transplant recipients has not been defined. METHODS: We assessed cytokine levels in the sera and CSF collected prospectively at the time of diagnosis of infection in 25 transplant recipients with cryptococcosis. Serum levels were compared with those in healthy individuals and transplant recipients without cryptococcosis. IFN-gamma or IL-12 (Th1)/IL-10 (Th2) ratio < 1.0 was considered a dominant Th2 response. RESULTS: Cases had lower ratios of IFN-gamma/IL-10 (p = 0.03) and IL-12/IL-10 (p = 0.03) compared to healthy individuals. Cytokine responses, however, did not differ significantly for cases vs. transplant controls. Cases with fungemia compared to those without fungemia tended to have higher serum IL-10 levels (p = 0.07) and lower IL-12/IL-10 ratios (p = 0.06). CSF ratios of IFN-gamma/IL-10 (p = 0.04) and IL-12/IL-10 (p = 0.04) were lower in cases with cryptococcal meningitis compared to those without meningitis; 80% (8/10) of the cases with cryptococcal meningitis vs. 0% (4/4) of those without meningitis had CSF IFN-gamma/IL-10 ratio of < 1.0 (p = 0.015). The levels of IL-10 (p = 0.04) and IFN-gamma (p = 0.04) in the CSF in cases with cryptococcal meningitis were significantly higher than those in their serum, respectively. CONCLUSIONS: High expression of Th2 phenotype in cryptococcal meningitis and in fungemia suggests that Th dysregulation may contribute to the pathogenesis of cryptococcosis in organ transplant recipients.

Cryptococcus neoformans↗
PubMed2006

Combination of voriconazole and caspofungin as primary therapy for invasive aspergillosis in solid organ transplant recipients: a prospective, multicenter, observational study.

BACKGROUND: : The efficacy of the combination of voriconazole and caspofungin when used as primary therapy for invasive aspergillosis in organ transplant recipients has not been defined. METHODS: : Transplant recipients who received voriconazole and caspofungin (n=40) as primary therapy for invasive aspergillosis (proven or probable) in a prospective multicenter study between 2003 and 2005 were compared to a control group comprising a cohort of consecutive transplant recipients between 1999 and 2002 who had received a lipid formulation of AmB as primary therapy (n=47). In vitro antifungal testing of Aspergillus isolates to combination therapy was correlated with clinical outcome. RESULTS: : Survival at 90 days was 67.5% (27/40) in the cases, and 51% (24/47) in the control group (HR 0.58, 95% CI, 0.30-1.14, P=0.117). However, in transplant recipients with renal failure (adjusted HR 0.32, 95% CI: 0.12-0.85, P=0.022), and in those with A. fumigatus infection (adjusted HR 0.37, 95% CI: 0.16-0.84, P=0.019), combination therapy was independently associated with an improved 90-day survival in multivariate analysis. No correlation was found between in vitro antifungal interactions of the Aspergillus isolates to the combination of voriconazole and caspofungin and clinical outcome. CONCLUSIONS: : Combination of voriconazole and caspofungin might be considered preferable therapy for subsets of organ transplant recipients with invasive aspergillosis, such as those with renal failure or A. fumigatus infection.

Adult↗
PubMed2006

Impact of an aggressive infection control strategy on endemic Staphylococcus aureus infection in liver transplant recipients.

BACKGROUND: Methicillin-resistant Staphylococcus aureus has emerged as a leading pathogen in transplant recipients and has become endemic in many institutions where transplantation is performed. The role of active surveillance programs based on the detection of colonization in the prevention of S. aureus infection in liver transplant recipients has not been defined. METHODS: A total of 47 consecutive patients who underwent liver transplantation during 1996-1999 were compared with 97 patients who received a liver transplant during 2000-2004 after implementation of an intensive intervention program that included use of surveillance cultures to detect nasal and rectal colonization, use of cohorting and contact isolation precautions, and decolonization with intranasal mupirocin therapy. RESULTS: The rate of new acquisition of S. aureus colonization of nares after transplantation decreased from 45.6% (21 of 46 patients) during the preintervention period to 9.9% (9 of 91 patients) during the postintervention period (P<.001). An increased length of hospital stay (odds ratio, 1.03; 95% confidence interval, 1.01-1.05; P<.002) was associated with new carriage acquisition, and transplantation during the postintervention period (odds ratio, 0.21; 95% confidence interval, 0.08-0.51; P<.001) was independently protective against new carriage. The rate of infection due to S. aureus decreased from 40.4% (19 of 47 patients) during the preintervention period to 4.1% (4 of 97 patients) during the postintervention period (P<.001), and the rate of bacteremia decreased from 25.5% (12 of 47 patients) to 4.1% (4 of 97 patients), respectively (P<.001). Overall, S. aureus infections occurred more frequently among patients with new carriage than among patients who were carriers at the time of transplantation (P<.001) or patients who were noncarriers (P<.001). CONCLUSIONS: Use of active surveillance cultures to detect colonization and implementation of targeted infection control interventions proved to be effective in curtailing new acquisition of S. aureus colonization and in decreasing the rate of S. aureus infection that was endemic in our population of liver transplant recipients.

Cohort Studies↗
PubMed2006

Cytomegalovirus infection in solid organ transplant recipients: new challenges and their implications for preventive strategies.

BACKGROUND: Late-onset CMV disease is being increasingly recognized as a significant post-transplantation complication. OBJECTIVES: To discern the impact of antiviral prophylactic strategies on the emerging syndrome of late-onset CMV disease in organ transplant recipients. STUDY DESIGN: Review of existing reports and published data relevant to antiviral prophylaxis in organ transplant recipients. RESULTS: Prevention of CMV using prophylaxis has proven effective and is widely employed in organ transplant recipients. However, late-onset CMV disease is increasingly being recognized as a significant complication in these patients. The more potent the activity of the antiviral drug and the longer duration of prophylaxis, the greater likelihood of late-onset CMV disease. CMV seronegative recipients of seropositive donor allografts appear to be at a uniquely high risk. A higher proportion of patients with late-onset CMV have tissue invasive disease. Late-onset CMV disease in liver transplant recipients conferred an independently higher risk of mortality in the first post-transplant year. Prolonged antiviral therapy may impair the recovery of CMV-specific T-cell responses. Preemptive therapy appears to be less likely to be associated with CMV disease. CONCLUSIONS: Discernment of the pathophysiologic basis of late-onset CMV warrants investigation. Preemptive therapy may be the preferable approach to CMV prophylaxis.

Antiviral Agents↗
PubMed2006

Invasive aspergillosis in the recipients of liver retransplantation.

Retransplantation is a major risk factor for invasive aspergillosis in liver transplant recipients. However, the risk for invasive aspergillosis with time elapsed since retransplantation, clinical characteristics, and outcome of patients who develop this infection after retransplantation of the liver has not been defined. Patients comprised 17 liver retransplant recipients with invasive aspergillosis between 1990 and 2004. Retransplantation was considered early if it was performed within 30 days and late if performed after 30 days of the first or primary transplant. Retransplant recipients comprised 25% of all cases of invasive aspergillosis after liver transplantation. Fifty-three percent of the Aspergillus infections occurred within 30 days, and 76% within 90 days of retransplantation. In all, 53% (9/17) of the patients were late retransplant recipients. Late compared to early retransplant recipients with invasive aspergillosis were more likely to have central nervous system involvement with invasive aspergillosis (56% vs. 0%, P = 0.03). Mortality rate was 100% for late and 63% for early retransplant recipients with Aspergillus infections. In conclusion, time-varying risk for invasive aspergillosis after retransplantation has implications relevant for guiding antifungal prophylaxis. Given a greater risk for disseminated infection and poor outcome in late retransplant recipients with aspergillosis, potent and aggressive antifungal therapy should be considered upfront in these patients.

Adolescent↗
PubMed2006

Late-onset invasive aspergillosis in organ transplant recipients in the current era.

We assessed predictive factors and characteristics of patients with late-onset invasive aspergillosis in the current era of novel immunosuppressive agents. Forty transplant recipients with invasive aspergillosis were included in this prospective, observational study initiated in 2003 at our institutions. In 50% (20/40) of these patients, the infections were late-occurring. Receipt of sirolimus in conjunction with tacrolimus for refractory rejection or cardiac allograft vasculopathy (P=0.047) was significantly associated with late-onset infection. The use of depleting or non-depleting T or B-cell antibodies, either as induction or as antirejection therapy did not correlate with time to onset of invasive aspergillosis. Mortality at 90 days was 20% (4/20) for the patients with early-onset infection and 45% (9/20) for those with late-onset infection (P=0.17). Thus, nearly one-half of the Aspergillus infections in transplant recipients in the current era are late-occurring. These data have implications relevant for prophylactic strategies and guiding clinical management of transplant recipients presenting with pulmonary infiltrates.

Adult↗
PubMed2006

Treatment of solid organ transplant patients with invasive fungal infections: should a combination of antifungal drugs be used?

PURPOSE OF REVIEW: Combined antifungal drug therapy is widely used in severe invasive mycoses in solid organ transplant (SOT) recipients. We have reviewed the available data in the literature. RECENT FINDINGS: No single randomized study on antifungal combination therapy in SOT patients has been performed. Existing information does not support the use of combination therapy in invasive candidiasis in SOT patients. Indeed, initial combination therapy with amphotericin B and 5-flucytosine is recommended for SOT patients with central nervous system cryptococcosis, mainly with increased white blood cell counts in the cerebrospinal fluid or with altered mental status. No impact on outcome was observed with combination therapy in Scedosporium infections in SOT patients. The combination of voriconazole and terbinafine may be an attractive option for S. prolificans infections. A prospective study of voriconazole plus caspofungin as initial therapy for invasive aspergillosis in SOT patients found that combination therapy was independently associated with reduced mortality in patients with renal failure and in those with Aspergillus fumigatus infection, even when adjusted for other factors predictive of mortality in the study population. SUMMARY: Combination therapy should be considered for severe forms of invasive fungal infections in SOT patients; however, multicenter studies of such patients are urgently needed.

Antifungal Agents↗
PubMed2006

Immunotherapy with tacrolimus (FK506) does not select for resistance to calcineurin inhibitors in Candida albicans isolates from liver transplant patients.

In Candida albicans, calcineurin mediates tolerance to azole antifungal drugs, survival in serum, and virulence. In this study, we examined 24 Candida isolates from liver transplant recipients receiving a calcineurin inhibitor as a component of their immunosuppressive therapy. We were unable to detect a difference in susceptibility to calcineurin inhibitors in combination with fluconazole, serum, or calcium in these isolates.

Calcineurin Inhibitors↗
PubMed2006

Antibody response to Cryptococcus neoformans capsular polysaccharide glucuronoxylomannan in patients after solid-organ transplantation.

Cryptococcosis is an important complication of solid-organ transplantation, but the risk factors for disease are poorly understood. The goal of this study was to investigate whether specific or nonspecific serum immunoglobulin levels determined in samples obtained before and after solid-organ transplantation differed in patients who did or did not develop cryptococcosis after transplantation. We analyzed pretransplantation sera from 25 subjects, 15 who subsequently developed cryptococcosis and 10 who did not, and posttransplantation sera from 24 subjects, 13 who developed cryptococcosis and 11 who did not. All subjects received a tacrolimus-based immunosuppressive regimen. Total immunoglobulin levels were measured by immunodiffusion, and Cryptococcus neoformans capsular polysaccharide glucuronoxylomannan (GXM)-specific serum antibody levels were determined by enzyme-linked immunosorbent assays. The results showed that solid-organ transplantation had a significant effect on total immunoglobulin and GXM-reactive antibody levels. GXM-reactive antibody levels differed in subjects who did and did not develop cryptococcosis. In pretransplant serum samples, the levels of GXM-reactive immunoglobulin M (IgM) were significantly lower in subjects who developed cryptococcosis after transplantation than in those who did not. For posttransplant serum samples, the levels of GXM-reactive IgM and IgG were significantly higher among the subjects who developed cryptococcosis than among those who did not. These findings suggest that perturbations in the preexisting antibody or B-cell repertoire and/or related to treatment of rejection, transplantation, or immunosuppressive therapy could translate into an increased risk for transplant-associated cryptococcosis.

Adult↗
PubMed2006

Alternative therapy use in liver transplant recipients.

BACKGROUND: The extent of use of alternative therapies and the psychosocial variables predictive of their use have not been well defined in liver transplant recipients. OBJECTIVE: To determine types of alternative therapies used by liver transplant recipients and to assess psychosocial, behavioral, and quality of life variables associated with the use of alternative therapies in these patients. METHODS: Assessment of types of alternative therapies used, demographic characteristics, satisfaction with social support, coping styles, sense of personal control (mastery), quality of life, and health beliefs in 32 liver transplant recipients. RESULTS: Overall, 34.4% of the liver transplant recipients used a form of alternative therapy. Herbal products were used by 45% of the alternative therapy users and included milk thistle (silymarin), eclipta, and green beet leaf-all considered "hepatic tonics". Alternative therapy users tended to have greater problem-focused coping skills than nonusers (P = .08). Nineteen percent of the patients incurred annual out-of-pocket expense of at least dollars 100 for alternative therapies. Patients incurring out-of-pocket expenses reported better overall health (P = .02), were more likely to be employed (P = .025), and had higher mastery scores (P = .01). CONCLUSIONS: Use of alternative therapies is common after liver transplantation. Herbal products used by liver transplant recipients are disease specific; that is, they claim to promote liver health.

Adaptation, Psychological↗
PubMed2005

Antifungal management practices and evolution of infection in organ transplant recipients with cryptococcus neoformans infection.

BACKGROUND: Therapeutic practices for Cryptococcus neoformans infection in transplant recipients vary, particularly with regards to antifungal agent employed, and duration of therapy. The risk of relapse and time to recurrence is not known. We assessed antifungal treatment practices for cryptococcosis in a cohort of prospectively followed organ transplant recipients. METHODS: The patients comprised 83 transplant recipients with cryptococcosis followed for a median of 2.1 and up to 5.2 years. RESULTS: Patients with central nervous system infection (69% vs. 16%, P = 0.00001), disseminated infection (82.7% vs. 20%, P = 0.00001), and fungemia (29% vs. 8%, P = 0.046) were more likely to receive regimens containing amphotericin B than fluconazole as primary therapy. The use of fluconazole, on the other hand, was more likely for infection limited to the lungs (64% vs. 14%, P = 0.00002). Survival at 6 months tended to be lower in patients whose CSF cultures at 2 weeks were positive compared to those whose CSF cultures were negative (50% vs. 91%, P = 0.06). Maintenance therapy was employed in 68% (54/79) of the patients who survived >3 weeks. The median duration of maintenance therapy was 183 days; 55% received maintenance for > or = 6 months and 25% for >1 year. Relapse was documented in 1.3% (1/79) of the patients. CONCLUSIONS: A majority of the organ transplant recipients with cryptococcosis receive maintenance antifungal therapy for 6 months with low risk of relapse. These data can assist in trials to assess the optimal therapeutic approach and duration of therapy for cryptococcosis in transplant recipients.

Adult↗
PubMed2005

Allograft loss in renal transplant recipients with cryptococcus neoformans associated immune reconstitution syndrome.

This study describes the association of allograft loss and immune reconstitution syndrome (IRS) in the course of Cryptococcosis neoformans infection in renal transplant recipients. Patients comprised 54 renal allograft recipients with cryptococcosis in a prospective, multicenter study. IRS developed in 5.5% (3/54) of the renal transplant recipient with C. neoformans infection. The renal allograft was lost to chronic rejection in 66% (2/3) of the patients with cryptococcosis who developed IRS compared to 5.9% (3/51) of those who did not (P=0.012). Kaplan-Meier survival analysis showed that subsequent to cryptococcal infection the probability of allograft survival was significantly lower in patients who developed IRS compared to those who did not develop IRS (P=0.0004). Temporal association of graft loss with IRS suggests a common pathophysiologic basis for these entities with implications relevant for the optimal management of renal transplant recipients with cryptococcosis.

Cryptococcosis↗
PubMed2005

Indirect outcomes associated with cytomegalovirus (opportunistic infections, hepatitis C virus sequelae, and mortality) in liver-transplant recipients with the use of preemptive therapy for 13 years.

BACKGROUND: The effect of preemptive therapy on indirect sequelae associated with cytomegalovirus (CMV) in liver-transplant recipients has not been clearly delineated. METHODS: Thirteen years of outcome with the use of preemptive therapy were assessed in a cohort of 216 consecutive liver-transplant recipients. RESULTS: The incidence of major infections (31% vs. 44.3%), bacterial infections (31% vs. 39.2%), bacteremia (19% vs. 29.1%), or fungal infections (3.4% vs. 7.6%) did not differ significantly for patients with CMV infection who received preemptive therapy compared with those who never developed CMV infection and did not receive antiviral prophylaxis for CMV (P>0.20 for all variables). The rate of opportunistic infections also did not differ when patients were stratified by primary CMV infection, reactivation infection, or no CMV infection. Recurrent hepatitis C virus (HCV) hepatitis occurred in 55.6% of the patients with CMV treated with preemptive therapy and 49.8% of those without CMV infection (P>0.20). The probability of survival at 6 months, 12 months, 2 years, and 3 years was also comparable for the two groups. CONCLUSIONS: Liver-transplant recipients with CMV infection, including high-risk R-/D+ patients, when followed using the preemptive therapy approach had no significant difference in meaningful outcomes such as opportunistic superinfections, HCV recurrence rates, rejection, and survival when compared with the patients in whom CMV infection never developed and who did not receive antiviral prophylaxis for CMV.

Acyclovir↗