Citations

Abstract For cardiac transplantation in infants, T cells are depleted and the thymus is removed. These manipulations should cause profound defects in the T cell compartment. To test this concept, 20 subjects who underwent cardiac transplantation in infancy and healthy age-matched subjects were studied. The number of T cells in the blood was nearly normal in all subjects 1–10 years after surgery. However, newly generated T cells were undetectable in 10 recipients and 10-fold less than controls in 10, suggesting absence of thymic function. TCRβ chain diversity, measured by a novel technique, was ∼100-fold lower than controls. T cell function, deduced from levels of human herpesvirus 7 and response to hepatitis B immunization, were notably impaired. Yet cardiac transplant recipients were generally free of opportunistic infections. Our findings demonstrate a novel approach to measuring lymphocyte diversity and suggest that understanding how these subjects resist infection could yield important insights into immune fitness.

ABSTRACT Piperacillin-tazobactam (PTZ) is known to cause false-positive results in the Platelia Aspergillus enzyme-linked immunoassay (EIA), due to contamination with galactomannan (GM). We tested 32 lots of PTZ and 27 serum specimens from patients receiving PTZ. GM was not detected in the lots of PTZ; one serum specimen (3.7%) was positive. PTZ formulations commonly used in the United States today appear to be a rare cause for false-positive GM results.

AbstractObjectivesUrinary tract infection (UTI) is the most common infectious complication after kidney transplantation. We aim to determine its impact on allograft function as indicated by several measures such as iothalamate glomerular filtration rate (iGFR), estimated glomerular filtration rate (eGFR), and creatinine value.MethodsWe performed a single‐center retrospective cohort study to determine the impact ofUTIon kidney allograft outcome.ResultsThe study population consisted of 301 kidney transplant recipients; 84% were living donor transplants. One hundred and one patients (34%) developed at least one episode ofUTIand the incidence ofUTIduring the first year after transplantation was 25%. At the end of the follow‐up, theiGFRwas lower among patients who had developed at least oneUTI(p = 0.044). However,eGFRand creatinine values were not significantly different betweenUTIand non‐UTIgroups.ConclusionWhen kidney function was measured byeGFRand creatinine, there was no significant difference in allograft function between kidney recipients with or withoutUTI. However, when kidney function was measured by nuclear studies, there was a tendency toward impairment in allograft function among patients who developed atleast oneUTIafter transplantation.

AbstractBackgroundRespiratory syncytial virus (RSV) infections may be fatal in immunocompromised patients. Aerosolized ribavirin is used for treatment, but it is very costly, teratogenic, and inconvenient. We aimed to assess the outcome of oral ribavirin treatment, with or without intravenous immunoglobulin (IVIG), for RSV infections in moderately to severely immunocompromised patients.MethodsMedical records of RSV polymerase chain reaction (PCR)‐positive patients during 2011–2013 were reviewed retrospectively. Eligible patients were moderately to severely immunocompromised and received oral ribavirin (600–800 mg twice daily) with or without IVIG (500 mg/kg q 48 h) as per protocol.ResultsOf 96 adults with PCR‐proven RSV infection, 34 were moderately to severely immunocompromised and received oral ribavirin treatment. The mean age was 56.2 years (range: 18–90); 21 were male. Underlying conditions were hematologic malignancy with or without hematopoietic stem cell transplant (n = 25), lung transplant (n = 3), or receipt of cytotoxic chemotherapy (n = 11). The presenting symptoms were cough (94%), fever (62%), and dyspnea (59%). The most common radiographic findings were patchy and nodular infiltrates and opacities. Of 34 patients, 31 were hospitalized, with 13 admitted to the intensive care unit and 6 required mechanical ventilation. The median absolute lymphocyte count on presentation was 480 cells/mm3. RSV pneumonia developed in 24 patients. The median initial duration of oral ribavirin treatment was 10 days (range: 4–11); 4 patients were re‐treated. Of 34 patients, 19 received a mean of 2.7 doses of IVIG. Two patients had adverse reactions to ribavirin (hemolytic anemia and lactic acidosis in 1 patient, and altered mental status in another). No patient died from RSV infection. Three patients died from complications of their underlying illness; all others recovered clinically.ConclusionsOral ribavirin with or without IVIG is a well‐tolerated treatment for RSV infection in moderately to severely immunocompromised hosts. Comparative prospective studies should ideally be performed to determine if oral ribavirin is the optimal therapy for RSV infection in this patient population.

AbstractElizabethkingia species are environmental bacteria that rarely cause infection in neonates and immunocompromised adults, usually as part of nosocomial outbreaks. We report an isolated fatal case of disseminated Elizabethkingia species infection in a lung transplant recipient and review the literature of this bacterial infection in transplant recipients.

SUMMARY The negative impact of cytomegalovirus (CMV) infection on transplant outcomes warrants efforts toward improving its prevention, diagnosis, and treatment. During the last 2 decades, significant breakthroughs in diagnostic virology have facilitated remarkable improvements in CMV disease management. During this period, CMV nucleic acid amplification testing (NAT) evolved to become one of the most commonly performed tests in clinical virology laboratories. NAT provides a means for rapid and sensitive diagnosis of CMV infection in transplant recipients. Viral quantification also introduced several principles of CMV disease management. Specifically, viral load has been utilized (i) for prognostication of CMV disease, (ii) to guide preemptive therapy, (iii) to assess the efficacy of antiviral treatment, (iv) to guide the duration of treatment, and (v) to indicate the risk of clinical relapse or antiviral drug resistance. However, there remain important limitations that require further optimization, including the interassay variability in viral load reporting, which has limited the generation of standardized viral load thresholds for various clinical indications. The recent introduction of an international reference standard should advance the major goal of uniform viral load reporting and interpretation. However, it has also become apparent that other aspects of NAT should be standardized, including sample selection, nucleic acid extraction, amplification, detection, and calibration, among others. This review article synthesizes the vast amount of information on CMV NAT and provides a timely review of the clinical utility of viral load testing in the management of CMV in solid organ transplant recipients. Current limitations are highlighted, and avenues for further research are suggested to optimize the clinical application of NAT in the management of CMV after transplantation.

AbstractBackgroundHematopoietic stem cell transplant (HSCT) recipients have increased morbidity from respiratory viral infections. Pandemic influenza A – A(H1N1)/pdm09 – in 2009–2010 was associated with increased severity of illness in patients with underlying co‐morbidities including HSCT, but the factors that contribute to severe disease in HSCT patients are not well characterized.MethodsWe conducted a multicenter review of microbiologically proven influenza A(H1N1)pdm09 in the HSCT population between April 2009 and April 2010 to determine factors that are associated with severe disease.ResultsWe identified 37 adult patients (26 allogeneic and 11 autologous HSCT recipients). Median time from transplant to diagnosis was 411 days (range 4 days–14.9 years). Three cases were hospital acquired. Twenty‐eight of 37 (75.7%) had confirmed A(H1N1)pdm09. Presumed viral lower respiratory tract infection was present in 12/37 (32.4%) patients. Antiviral therapy was given to 33/37 (89%) patients, primarily oseltamivir (n = 24) and oseltamivir before or after another antiviral (n = 8). Excluding those with nosocomial A(H1N1)pdm09, 18/34 (52.9%) were hospitalized and 6 (33%) required admission to an intensive care unit. Mortality within 30 and 60 days of symptom onset was 7/37 (18.9%) and 11/37 (29.7%), respectively. Factors associated with mortality included nosocomial acquisition (P = 0.023), receipt of mycophenolate mofetil (P = 0.001), or antilymphocyte antibody (P = 0.005) within the past 6 months, reduced‐intensity conditioning (P = 0.027), and bacteremia (P = 0.021).ConclusionsA(H1N1)pdm09 infection was particularly severe in HSCT recipients, specifically among those receiving augmented immunosuppression for graft‐versus‐host disease. The high mortality of the nosocomial cases highlights the need for strict infection‐control measures in hospitals during influenza outbreaks.