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Biomedical subjects

Nina Singh

Publications and source records attributed to Nina Singh.

At least 19 recordsLinked to original sources

Impact of evolving trends in recipient and donor characteristics on cytomegalovirus infection in liver transplant recipients.

BACKGROUND: This study determines whether the recipient and donor characteristics that influence the cytomegalovirus (CMV) infection rate after liver transplantation have changed. METHODS: The recipient and donor characteristics that may affect the rate of CMV infection were assessed in 232 liver transplant recipients at our institution during a 14-year period (1989-2003). RESULTS: Since 1989, the age of recipients (P=0.0001) and donors (P=0.0001) has increased significantly. Pretransplant CMV seropositivity in recipients has decreased significantly (P=0.0001, 86.4% [1989-1992] to 53.7% [2000-2003]), whereas donor CMV seropositivity has remained unchanged (P>0.20). As a result, there has been a significant increase in the proportion of high-risk (CMV recipient-/donor+) patients (P=0.012); 10.6% of recipients from 1989 to 1992 versus 24.1% of recipients from 2000 to 2003 were CMV recipient-/donor+. The Child-Pugh scores of recipients have remained unchanged over time. However, the proportion of patients undergoing transplantation while being cared for in the intensive care unit has decreased significantly over time (P=0.0002). Despite an increase in the rate of CMV infection (P=0.09), the incidence of CMV disease has decreased significantly (P=0.0004). CONCLUSIONS: The proportion of high-risk patients (CMV recipient-/donor+) has increased significantly over time, attributable largely to a declining rate of CMV seropositivity in recipients before transplantation. These data have implications for guiding prophylactic practices and resource use after liver transplantation.

Adult↗

Efficacy of galactomannan antigen in the Platelia Aspergillus enzyme immunoassay for diagnosis of invasive aspergillosis in liver transplant recipients.

The utility of galactomannan antigen for diagnosing invasive aspergillosis was evaluated in 154 liver transplant recipients. Sample agreement was 98.5%, and patient specificity was 87%. Galactomannan positivity correlated with mortality, even when controlled for the number of tests performed. Whether galactomannan positivity identifies a subgroup at risk for poor outcome warrants further evaluation.

Adult↗

Opportunistic mycelial fungal infections in organ transplant recipients: emerging importance of non-Aspergillus mycelial fungi.

To determine the spectrum and impact of mycelial fungal infections, particularly those due to non-Aspergillus molds, 53 liver and heart transplant recipients with invasive mycelial infections were prospectively identified in a multicenter study. Invasive mycelial infections were due to Aspergillus species in 69.8% of patients, to non-Aspergillus hyalohyphomycetes in 9.4%, to phaeohyphomycetes in 9.4%, to zygomycetes in 5.7%, and to other causes in 5.7%. Infections due to mycelial fungi other than Aspergillus species were significantly more likely to be associated with disseminated (P=.005) and central nervous system (P=.07) infection than were those due to Aspergillus species. Overall mortality at 90 days was 54.7%. The associated mortality rate was 100% for zygomycosis, 80% for non-Aspergillus hyalohyphomycosis, 54% for aspergillosis, and 20% for phaeohyphomycosis. Thus, non-Aspergillus molds have emerged as significant pathogens in organ transplant recipients. These molds are more likely to be associated with disseminated infections and to be associated with poorer outcomes than is aspergillosis.

Adolescent↗

Changes in the spectrum and risk factors for invasive candidiasis in liver transplant recipients: prospective, multicenter, case-controlled study.

BACKGROUND: This study determines whether the spectrum, risk factors, and outcome of invasive candidiasis in liver transplant recipients have changed. METHODS: Thirty-five consecutive liver transplant recipients with invasive candidiasis were prospectively studied in a case-controlled, multicenter study. One control was matched with the case for duration of hospitalization and the other for antibiotic use so that risk factors unique in liver transplantation could be elicited. RESULTS: In matched-pair analysis, antibiotic prophylaxis for spontaneous bacterial peritonitis (odds ratio [OR] 8.3, P=0.002), posttransplant dialysis (OR 7.6, P=0.0009), and retransplantation (OR 16.4, P=0.0018) were independently significant predictors of invasive candidiasis. Candida spp. included C. albicans in 65% of patients, C. glabrata in 21%, C. tropicalis in 9%, C. parapsilosis in 3%, and C. guilliermondii in 3%. Patients with C. albicans infections were less likely to have received antifungal prophylaxis than those with non-albicans Candida infections (13.6% vs. 50%, P=0.04). The mortality rate was 36.1% for the cases and 2.8% for the controls (OR 25.0, 95% confidence interval, 6.2-100.5, P=0.0002). Non-albicans Candida infections (P=0.04) and prior antifungal prophylaxis (P=0.05) correlated with poorer outcome in the cases. CONCLUSIONS: Our study has identified predictors for Candida infections in the current era that have implications relevant for targeting the prophylaxis toward the high-risk patients. Routine use of antifungal prophylaxis warrants concern given the emergence of non-albicans Candida spp. as significant pathogens after liver transplantation and higher mortality in patients with these infections.

Anti-Bacterial Agents↗

Lack of efficacy of mupirocin in the prevention of infections with Staphylococcus aureus in liver transplant recipients and candidates.

BACKGROUND: Infections with Staphylococcus aureus are a significant problem in patients in liver transplant units. An association between prior nasal carriage with and subsequent infections has been documented previously in liver transplant recipients and patients with cirrhosis. However, the role of decolonization with mupirocin applied intranasally for the prevention of S. aureus infections in these patients has not been determined. METHODS: S. aureus nasal carriage was prospectively sought in 70 consecutive liver transplant candidates. Mupirocin two times per day for 5 days was administered to the carriers. Follow-up nasal cultures to document decolonization were performed 5 days after the final application of mupirocin. The primary endpoint was the development of S. aureus infections. RESULTS: Thirty-one of 70 patients (44%) were found to be nasal carriers and 27 of 31 nasal carriers (87%) were successfully decolonized. However, 12 of 27 patients (37%) successfully decolonized became recolonized with S. aureus, and an additional nine patients who were initially noncarriers became newly colonized with S. aureus during the study period. Despite the use of mupirocin, 16 of 70 patients (23%) developed an infection with S. aureus. No isolate was found to be mupirocin resistant. CONCLUSION: Elimination of S. aureus nasal carriage by mupirocin did not prevent S. aureus infections in patients in our liver transplant unit.

Adult↗

Fungal infections in the recipients of solid organ transplantation.

The advent of effective antibacterial and antiviral prophylatic and therapeutic strategies has led to the emergence of opportunistic mycoses as a principal cause of infection-related mortality in organ transplant recipients. Candida and Aspergillus species have accounted for most invasive fungal infections in organ transplant recipients. Epidemiologic trends within the last decade, however, are notable for the emergence of mycelial fungi other than Aspergillus as increasingly important pathogens in these patients. This article reviews the epidemiology, clinical manifestations, pathogenetic basis, diagnosis, and management of invasive fungal infections after organ transplantation in context of emerging trends and new developments in these areas.

Antibiotic Prophylaxis↗

Aspergillus infections after lung transplantation: clinical differences in type of transplant and implications for management.

BACKGROUND: Invasive aspergillosis is a serious opportunistic infection in lung transplant recipients. It has not been fully discerned whether there are differences in the characteristics, risk factors and outcome of Aspergillus infection in single as compared with bilateral lung transplant recipients. METHODS: English-language articles identified by a MEDLINE search through December 2000 and bibliographies were used as data sources to identify cases of Aspergillus infections in lung transplant recipients. The studies selected had to have provided a definition of invasive aspergillosis to distinguish colonization from infection. RESULTS: The median incidence of Aspergillus infections in lung transplant recipients was 6.2%. In total, 58% (45 of 78) of the Aspergillus infections were tracheobronchitis or bronchial anastomotic infections, 32% (25 of 78) were invasive pulmonary, and 22% (25 of 78) were disseminated infections. Single lung transplant recipients with Aspergillus infections were significantly older (p = 0.006), more likely to have had chronic obstructive pulmonary disease as an underlying illness (p = 0.05), more likely to have developed Aspergillus infections later after transplantation (p = 0.019), and tended to have a higher incidence of invasive aspergillosis (p = 0.11) than all other lung transplant recipients. Overall mortality in lung transplant recipients with Aspergillus infections was 52%. Single lung transplant recipients (p = 0.03), and patients with late-onset infections (occurring at least 3 months after transplantation ([p = 0.045]) infections had significantly higher mortality. CONCLUSIONS: Single lung transplant recipients with Aspergillus infections had an overall greater morbidity and poorer outcome than other types of lung transplant recipients. Recognition of the unique characteristics of Aspergillus infections in single lung (vs bilateral or heart-lung) transplant recipients has implications relevant for the management of lung transplant recipients with aspergillosis.

Aspergillosis↗

Impact of current transplantation practices on the changing epidemiology of infections in transplant recipients.

The spectrum of infections in transplant recipients has been substantially affected by novel immunosuppressive regimens and the use of antimicrobial agents. Epidemiology and presentation of traditional opportunistic pathogens has changed. Invasive aspergillosis and cytomegalovirus occur later in the post-transplant period. The incidence of infections that were previously encountered rarely--eg, BK virus nephropathy--has increased, the clinical course of hepatitis C virus recurrence has become more aggressive, the risk factors for invasive aspergillosis have changed, and non-aspergillus moulds are occurring more commonly in transplant recipients. Recognition of these trends as they unfold has significant implications for the clinical care of the transplant recipients, for providing insights into the pathogenesis, and for continually improving the approaches to the management of infections.

Communicable Diseases↗

Treatment of opportunistic mycoses: how long is long enough?

For most opportunistic mycoses no optimum duration of antifungal therapy has been defined. Although a long course of therapy is prudent, especially for mycelial fungal infections, excessively and unnecessarily extended courses of treatment incur a risk of toxicity and the expense of the therapeutic regimen. On the basis of existing reports on the pathogenesis and the effect of duration of therapy and other variables on outcome and response rate in fungal infections, this review proposes guidelines that may facilitate a rational approach to decision-making about the duration of antifungal therapy.

Animals↗

Trends in risk profiles for and mortality associated with invasive aspergillosis among liver transplant recipients.

To discern whether the characteristics and outcome of invasive aspergillosis in liver transplant recipients have evolved during the past decade, 26 patients who underwent transplantation during 1990-1995 (known as "the earlier cohort") were compared with 20 patients who underwent transplantation during 1998-2001 (known as "the later cohort"). Twenty-three percent of the Aspergillus infections in the earlier cohort occurred > or =90 days after transplantation, compared with 55% of such infections in the later cohort (P=.026). The earlier cohort was significantly more likely to have disseminated infection (P=.034) and central nervous system (CNS) involvement (P=.0004) than was the later cohort. The mortality rate was significantly higher for the earlier cohort (92%) than for the later cohort (60%; P=.012). Only disseminated infection (not the year of transplantation) approached statistical significance as an independent predictor of outcome. In the current era, invasive aspergillosis occurs later in the posttransplantation period, is less likely to be associated with CNS infection, and is associated with a lower mortality rate, compared with invasive aspergillosis in the early 1990s.

Adolescent↗

Safety and efficacy of isoniazid chemoprophylaxis administered during liver transplant candidacy for the prevention of posttransplant tuberculosis.

BACKGROUND: Optimal timing of initiation of isoniazid chemoprophylaxis in liver transplant recipients who test positive on the tuberculin skin test has not been defined. We sought to determine whether isoniazid prophylaxis administered during liver transplant candidacy was safe and effective for the prevention of posttransplantation tuberculosis. METHODS: During a 9-year period, 18 liver transplant candidates with tuberculin skin test greater than 5 mm or recent conversion to positive tuberculin skin test were identified and received isoniazid chemoprophylaxis for 12 months. For each case, a control matched with the patient for underlying liver disease and age (within 5 years of the case) was included. Liver function tests were assessed monthly. The median follow-up was 55 months and ranged up to 107 months for the cases. RESULTS: At baseline, the cases had a total bilirubin of 2.2 mg/dL, alanine aminotransferase of 106 IU/L, prothrombin time of 14.2 sec, and serum albumin of 2.9 gm/dL (mean values). Hepatic function tests did not differ significantly for the cases at 3, 6, 9, and 12 months when compared with those at baseline or between the cases and controls at each of the above time points. Discontinuation of prophylaxis was not required in any of the patients. The outcome (proportion of patients who underwent transplantation or were dead or alive at the last follow-up) and survival time for the cases did not differ significantly from those of the controls (P >0.20). CONCLUSION: In liver transplant candidates at risk for infection after transplantation, isoniazid chemoprophylaxis used during candidacy was well tolerated and did not adversely effect hepatic function or outcome as compared with the control patients.

Adult↗

Bleeding complications precipitated by unrecognized Gingko biloba use after liver transplantation.

Because of its neurocognitive enhancing effects, Gingko biloba has emerged as amongst the most commonly used herbal products. We report a liver transplant recipient with potentially life-threatening toxicity resulting from Gingko biloba use. Seven days after a second liver transplantation for recurrent hepatitisB virus infection, subphrenic hematoma was documented in a 59-year-old Korean patient. Failure to control bleeding with CT-guided drainage necessitated exploratory laparotomy for the evacuation of a large subphrenic hematoma. Three weeks later, an episode of vitreous hemorrhage was documented. Unbeknownst to his care providers, the patient had been consuming Gingko biloba throughout the postoperative period. No further bleeding episodes occurred after the cessation of Gingko biloba use. Unrecognized use of herbal products may be associated with serious side effects and adverse clinical sequelae in transplant recipients. Given their increasing popularity, the use of herbal products should be routinely sought as part of the history in transplant recipients.

Ginkgo biloba↗

The impact of novel immunosuppressive agents on infections in organ transplant recipients and the interactions of these agents with antimicrobials.

Several of the new immunosuppressive agents that are used to treat transplant recipients possess in vitro activity against specific pathogens, enhance the activity of antimicrobial agents, or have unique drug interactions with antimicrobial agents. Mycophenolate mofetil may have a protective effect against Pneumocystis carinii; it also enhances the activity of ganciclovir and has strong antiviral activity against human immunodeficiency virus type 1. High doses of mycophenolate mofetil have been associated with a higher frequency of tissue-invasive cytomegalovirus disease but not with asymptomatic cytomegalovirus infection. Rapamycin exhibits potent in vitro fungicidal activity against Cryptococcus neoformans and several pathogenic fungi in transplant recipients; however, it is not known whether its immunosuppressive effect in organ transplant recipients outweighs its antifungal activity. Recognition of the unique characteristics of these agents and the evolving spectrum of opportunistic infections has implications for the differential diagnosis, management, and prophylaxis of infections in organ transplant recipients in the modern immunosuppressive era.

Anti-Infective Agents↗

Trends in invasive fungal infections in liver transplant recipients: correlation with evolution in transplantation practices.

BACKGROUND: The incidence of invasive fungal infections, particularly invasive candidiasis, after liver transplantation is strongly influenced by surgical factors and technical complexity of the surgery. We assessed the temporal trends in invasive fungal infections in the context of evolution in liver transplantation practices, technical developments, and other risk factors. METHODS: Demographic and clinical characteristics of the patients, transplantation-related variables, and rates of infection were longitudinally analyzed over the last 10 years in 190 consecutive liver transplant recipients at our institution. Trends for categorical data were evaluated using the Cochran-Armitage trend test and for continuous variables using analysis of variance with linear contrast. RESULTS: A decrease in the length of operation (P=0.03), intraoperative transfusion requirements (P=0.0001), cold ischemic time (P<0.0001), use of roux-en-Y biliary anastomosis (P=0.0015), rate of biopsy proven rejection (P<0.0001), and retransplantation (P=0.056) was documented over the successive years. A significant decline in Child-Pugh score (P=0.02) and in the proportion of patients transplanted as UNOS 2a occurred (P=0.0001). Although the incidence of cytomegalovirus infection remained unchanged, a significant increase in the frequency of primary cytomegalovirus infection (P=0.045), and a decrease in cytomegalovirus disease (P=0.0006) was documented. Over the same time period, a significant decrease in the incidence of invasive candidiasis (P=0.015), and an insignificant increase in the rate of invasive aspergillosis (P=0.20) occurred. CONCLUSION: Notable technical developments in liver transplantation practices and risk profiles of patients have occurred over the decade. These variables may have a role in influencing the evolving trends in invasive fungal infections in liver transplant recipients.

Adult↗

Nocardia infection in lung transplant recipients.

BACKGROUND: Nocardia is responsible for infection in both normal and immunocompromised hosts. Organ transplant recipients are increasingly recognized as a sub-group of immunocompromised patients in whom nocardia is an important pathogen. The frequency of nocardia in organ transplant recipients varies between 0.7% and 3%. Nocardia infection has largely been reported in heart, kidney and liver transplant recipients. Presentations of nocardia in lung transplant recipients have been restricted primarily to case reports. The present study reviews the clinical and epidemiologic characteristics of nocardia infection in lung transplant recipients at our institution. METHODS: A retrospective cohort study of 473 lung transplant recipients from January 1991 to November 2000 was done at a university hospital. Patient demographics, immunosuppressive regimen at the time of isolation of nocardia species, use of trimethoprim-sulfamethoxazole for Pneumocystis carinii prophylaxis, rejection episodes in the preceding 6 months, concurrent pathogens, site of infection, radiologic findings and treatment and outcome were recorded. RESULTS: Nocardia infection was found in 2.1% (10 of 473) of our lung transplant recipients. Median time of onset was 34.1 months after transplantation. Nocardia species included N farcinica in 30% (3 of 10), N nova in 30% (3 of 10), N asteroides complex in 30% (3 of 10) and N brasiliensis in 10% (1 of 10) of patients. Post-transplant diabetes was present in 50% (5 of 10) of patients. The primary indication for lung transplantation was emphysema in 40% (4 of 10). Native lung involvement was noted in 75% (3 of 4) of patients with single lung transplant. Breakthrough nocardia infection were noted in 6 patients who were receiving trimethoprim-sulfamethoxazole prophylaxis for P carinii pneumonia; all breakthrough isolates remained susceptible to trimethoprim-sulfamethoxazole. Overall mortality was 40% (4 of 10). All patients (3 of 3) with infection due to N farcinica, except 1 (1 of 7) with infection due to other nocardia species, died. Seventy-five percent (3 of 4) of deaths were attributable to nocardia infection. CONCLUSIONS: Nocardia infection tended to involve the native lung in single lung transplant recipients. Trimethoprim-sulfamethoxazole for P carinii prophylaxis at the doses given was not protective against nocardiosis in these patients. Infection with N farcinica was associated with poor outcome. Thus, species identification and extended courses of antibiotics based on antimicrobial susceptibility testing are important in management of these patients.

Adult↗