Razonable, Raymund R.

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.

AbstractBackgroundToll‐like receptor 3 (TLR3) is implicated in the pathogenesis of viral diseases owing to its ability to recognize viral double‐stranded RNA. We hypothesized that single nucleotide polymorphism (SNP) in TLR3 gene that impairs the function of the protein‐receptor influences the outcome of hepatitis C virus (HCV) infection after liver transplantation.MethodsThe clinical characteristics of 611 liver recipients (HCV‐infected: n = 153, non‐HCV‐infected: n = 458) were assessed to investigate the impact of TLR3 L412F SNP on transplant outcomes.ResultsTLR3 L412F is common, and it was significantly more prevalent among the HCV‐infected cohort (57.5% vs. 45.2%, P = 0.008). In a multivariate analysis, TLR3 L412F was significantly associated with chronic hepatitis C (odds ratio: 1.73, 95% confidence interval [CI]: 1.13–2.65, P = 0.01). In an analysis that compared HCV‐infected patients with wild‐type versus TLR3 L412F, a marginally higher rate of allograft failure and mortality was observed in the TLR3 L412F group (44.3% vs. 30.8%, P = 0.09). However, in a multivariate analysis, only donor age was significantly associated with allograft failure and mortality (relative risk: 1.04, 95% CI: 1.007–1.06, P = 0.02).ConclusionTLR3 L412F is significantly common in HCV‐infected liver recipients, and may be associated with worse outcomes. However, larger studies are needed to determine its significant association with allograft failure and mortality after liver transplantation for chronic hepatitis C.

Abstract Transmission of pathogens from donor to recipient is a potential complication of organ transplantation. Herein, we describe the clinical course and outcomes of 4 transplant recipients who received tissues from a donor with multi‐organ infection with Klebsiella pneumoniae carbapenemase ( KPC )‐producing K. pneumoniae . Recipient 1 underwent simultaneous liver and kidney transplantation for alpha‐1 antitrypsin deficiency and alcohol‐related cirrhosis, and acute tubular necrosis, respectively. Soon after transplantation, he developed an infected hematoma and peritonitis due to KPC ‐producing K. pneumoniae despite receiving tigecycline prophylaxis. He was treated with a prolonged course of tigecycline, amikacin, and meropenem, in conjunction with surgical evacuation and percutaneous drainage of the infected fluid collections. Recipient 2 underwent living‐donor liver transplantation for cholangiocarcinoma and primary sclerosing cholangitis using vein graft from the donor infected with KPC ‐producing K. pneumoniae . Culture of the preservation fluid containing the vein graft was positive for KPC ‐producing K. pneumoniae . The patient received preemptive amikacin and tigecycline, and he did not develop any infection (as evidenced by negative surveillance blood cultures). The isolates from the donor and Recipients 1 and 2 were indistinguishable by pulsed‐field gel electrophoresis. Recipients 3 and 4 underwent kidney and heart transplantation, respectively; both patients received perioperative tigecycline prophylaxis and did not develop infections due to KPC ‐producing K. pneumoniae . All transplant recipients had good short‐term outcomes. These cases highlight the importance of inter‐institutional communication and collaboration to ensure the successful management of recipients of organs from donors infected with multidrug‐resistant organisms.

AbstractHuman herpesvirus‐6 (HHV‐6) is unique among human herpesviruses because of its ability to integrate into chromosomes. This entity, termed chromosomally integrated HHV‐6 (CIHHV‐6), is often mistaken for active infection and treated unnecessarily. The clinical significance of CIHHV‐6 in transplant recipients is not defined. Herein, the clinical characteristics of 7 liver transplant patients with CIHHV‐6 from our recent study, together with 14 other published cases of CIHHV‐6 were reviewed. Of the 21 cases, CIHHV‐6B was reported most commonly among solid organ transplant recipients, while CIHHV‐6A was mostly seen in allogeneic hematopoietic stem cell recipients. None of the 21 patients developed clinical symptoms related to HHV‐6 after transplantation. However, antiviral therapy was administered to 5 asymptomatic patients mistaken to have HHV‐6 infection because of their very high HHV‐6 DNA levels, 3 who developed symptomatic cytomegalovirus disease, and 1 with graft‐versus‐host disease that was mistaken for HHV‐6 infection. In patients who received antiviral therapy, there was no apparent decline in HHV‐6 DNA load, although change in viral kinetics is difficult to discern in the setting of high baseline HHV‐6 DNA load. Clinicians should be aware of this entity of CIHHV‐6 so that antiviral therapy can be considered in the proper clinical context.