Lara Danziger-Isakov

The 2016 International Society for Heart Lung Transplantation listing criteria for heart transplantation: A 10-year update

Mandeep R. Mehra, MD (Chair), Charles E. Canter, MD, Margaret M. Hannan, MD, Marc J. Semigran, MD, Patricia A. Uber, PharmD, David A. Baran, MD, Lara Danziger-Isakov, MD, MPH, James K. Kirklin, MD, Richard Kirk, MD, Sudhir S. Kushwaha, MD, Lars H. Lund, MD, PhD, Luciano Potena, MD, PhD, Heather J. Ross, MD, David O. Taylor, MD, Erik A.M. Verschuuren, MD, PhD, Andreas Zuckermann, MD and on behalf of the International Society for Heart Lung Transplantation (ISHLT) Infectious Diseases, Pediatric and Heart Failure and Transplantation Councils

Outcomes from pandemic influenza A H1N1 infection in recipients of solid-organ transplants: a multicentre cohort study

BACKGROUND There are few data on the epidemiology and outcomes of influenza infection in recipients of solid-organ transplants. We aimed to establish the outcomes of pandemic influenza A H1N1 and factors leading to severe disease in a cohort of patients who had received transplants. METHODS We did a multicentre cohort study of adults and children who had received organ transplants with microbiological confirmation of influenza A infection from April to December, 2009. Centres were identified through the American Society of Transplantation Influenza Collaborative Study Group. Demographics, clinical presentation, treatment, and outcomes were assessed. Severity of disease was measured by admission to hospital and intensive care units (ICUs). The data were analysed with descriptive statistics. Proportions were compared by use of chi(2) tests. We used univariate analysis to identify factors leading to pneumonia, admission to hospital, and admission to an ICU. Multivariate analysis was done by use of a stepwise logistic regression model. We analysed deaths with Kaplan-Meier survival analysis. FINDINGS We assessed 237 cases of medically attended influenza A H1N1 reported from 26 transplant centres during the study period. Transplant types included kidney, liver, heart, lung, and others. Both adults (154 patients; median age 47 years) and children (83; 9 years) were assessed. Median time from transplant was 3.6 years. 167 (71%) of 237 patients were admitted to hospital. Data on complications were available for 230 patients; 73 (32%) had pneumonia, 37 (16%) were admitted to ICUs, and ten (4%) died. Antiviral treatment was used in 223 (94%) patients (primarily oseltamivir monotherapy). Seven (8%) patients given antiviral drugs within 48 h of symptom onset were admitted to an ICU compared with 28 (22.4%) given antivirals later (p=0.007). Children who received transplants were less likely to present with pneumonia than adults, but rates of admission to hospital and ICU were similar. INTERPRETATION Influenza A H1N1 caused substantial morbidity in recipients of solid-organ transplants during the 2009-10 pandemic. Starting antiviral therapy early is associated with clinical benefit as measured by need for ICU admission and mechanical ventilation. FUNDING None.

Working formulation for the standardization of definitions of infections in patients using ventricular assist devices

In 2009, the International Society for Heart and Lung Transplantation (ISHLT) recognized the importance of infectionrelated morbidity and mortality in patients using ventricular assist devices (VADs) and the growing need for a consensusbased expert opinion to provide standard definitions of infections in these patients. The aim of these standard definitions is to improve clinical-investigator communication, allowing meaningful comparison in practice and outcomes between different centers and different VAD devices. In 2010, a core group of experts, including infectious diseases specialists, cardiologists, pathologists, radiologists, and cardiothoracic surgeons, formed an ISHLT Infectious Diseases Working Group to develop agreed criteria for definitions of infections in VAD patients. These definitions have been created by adapting and expanding on existing standardized definitions, which are based on the pathophysiology of equivalent infectious processes in prosthetic devices, such as cardiac prosthetic valve infections, intravascular catheter-related infections, and prosthetic joint infections. These definitions have been divided into 3 sections: VAD-specific infections, VAD-related infections, and non-VAD infections. Owing to the constant shortage of donor organs, new allocation systems, and improved medical therapies for congestive cardiac failure, the overwhelming trend in cardiac transplantation has been toward listing principally the most critically ill patients, that is, those requiring inpatient inotropic therapy for mechanical circulatory support (MCS). The ventricular assist device (VAD) has an expanding role in the management of these patients, both as a bridge to transplantation and as a destination therapy (ie, alternative to transplantation). According to United Network of Organ Sharing (UNOS) registry data, 9,000 transplant candidates have undergone MCS since 1999, comprising 33% of all listed patients and 75% of all listed inpatients. 1

Vaccination in solid organ transplantation.

Transplant candidates and recipients are at increased risk of infectious complications of vaccine-preventable diseases. Every effort should be made to ensure that transplant candidates, their household members and healthcare workers have completed the full complement of recommended vaccinations prior to transplantation. Since the response to many vaccines is diminished in organ failure, transplant candidates should be immunized early in the course of their disease.

Influenza Vaccination in the Organ Transplant Recipient: Review and Summary Recommendations

Influenza virus causes a spectrum of illness in transplant recipients with a high rate of lower respiratory disease. Seasonal influenza vaccination is an important public health measure recommended for transplant recipients and their close contacts. Vaccine has been shown to be safe and generally well tolerated in both adult and pediatric transplant recipients. However, responses to vaccine are variable and are dependent on various factors including time from transplantation and specific immunosuppressive medication. Seasonal influenza vaccine has demonstrated safety and no conclusive evidence exists for a link between vaccination and allograft dysfunction. Annually updated trivalent inactivated influenza vaccines have been available and routinely used for several decades, although newer influenza vaccination formulations including high‐dose vaccine, adjuvanted vaccine, quadrivalent inactivated vaccine and vaccine by intradermal delivery system are now available or will be available in the near future. Safety and immunogenicity data of these new formulations in transplant recipients requires investigation. In this document, we review the current state of knowledge on influenza vaccines in transplant recipients and make recommendations on the use of vaccine in both adult and pediatric organ transplant recipients.

A 2010 working formulation for the standardization of definitions of infections in cardiothoracic transplant recipients

Shahid Husain, MD, MS, Martha L. Mooney, MD, MS, FACP, Lara Danziger-Isakov, MD, MPH, Frauke Mattner, MD, PhD, Nina Singh, MD, Robin Avery, MD, FIDSA, Michael Ison, MD, MS, Atul Humar, MD, MSc, Robert F. Padera, MD, PhD, Leo P. Lawler, MD, FRCR, Andy Fisher, PhD, FRCP, Richard J. Drew, MD, Kate F. Gould, MBBS, MRCP, FRCP, Amparo Sole, MD, PhD, Sean Studer, MD, MSc, Patricia Munoz, MD, Lianne G. Singer, MD, FRCPC, and Margaret Hannan, MD, FRCP, FRCPath, for the ISHLT Infectious Diseases Council Working Group on Definitions From the Division of Infectious Diseases, Transplant Infectious Diseases, University Health Network, University of Toronto, Toronto, Ontario, Canada; Eastern Virginia Medical School, Sentara Norfolk Transplant Center, Norfolk, Virginia; Center for Pediatric Infectious Diseases, Department of Infectious Disease, Medicine Institute, The Cleveland Clinic, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio; Infection Control and Hospital Epidemiology, Institute for Medical Microbiology, Hannover Medical School, Hannover, Germany; Division of Infectious Diseases, Veteran Affairs Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania; Divisions of Infectious Diseases and Organ Transplantation, Northwestern University, Feinberg School of Medicine, Chicago, Illinois; Department of Medicine, Division of Infectious Diseases, University of Alberta, Edmonton, Alberta, Canada; Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts; Respiratory Transplant Medicine, Newcastle University, Institute of Transplantation, Freeman Hospital, Newcastle Upon Tyne, UK; Mater Misericordiae University Hospital, Dublin, Ireland; Health Protection Agency Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK; Hospital Universitario La Fe, Valencia, Spain; Division of Pulmonary & Critical Care, Newark Beth Israel Medical Center, Newark, New Jersey; and Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Maranon, Universidad Complutense, Madrid, Spain.

Results from a Prospective, International, Epidemiologic Study of Invasive Candidiasis in Children and Neonates

Background: Candida species are the third most common cause of pediatric health care–associated bloodstream infection in the United States and Europe. To our knowledge, this report from the International Pediatric Fungal Network is the largest prospective, multicenter observational study dedicated to pediatric and neonatal invasive candidiasis. Methods: From 2007 to 2011, we enrolled 196 pediatric and 25 neonatal patients with invasive candidiasis. Results: Non-albicans Candida species predominated in pediatric (56%) and neonatal (52%) age groups, yet Candida albicans was the most common species in both groups. Successful treatment responses were observed in pediatric (76%) and neonatal patients (92%). Infection with Candida parapsilosis led to successful responses in pediatric (92%) and neonatal (100%) patients, whereas infection with Candida glabrata was associated with a lower successful outcome in pediatric patients (55%). The most commonly used primary antifungal therapies for pediatric invasive candidiasis were fluconazole (21%), liposomal amphotericin B (20%) and micafungin (18%). Outcome of pediatric invasive candidiasis was similar in response to polyenes (73%), triazoles (67%) and echinocandins (73%). The most commonly used primary antifungal therapies for neonatal invasive candidiasis were fluconazole (32%), caspofungin (24%) and liposomal amphotericin B (16%) and micafungin (8%). Outcomes of neonatal candidiasis by antifungal class again revealed similar response rates among the classes. Conclusions: We found a predominance of non-albicans Candida infection in children and similar outcomes based on antifungal class used. This international collaborative study sets the foundation for large epidemiologic studies focusing on the unique features of neonatal and pediatric candidiasis and comparative studies of therapeutic interventions in these populations.

Outbreak of methicillin-resistant Staphylococcus aureus colonization and infection in a neonatal intensive care unit epidemiologically linked to a healthcare worker with chronic otitis.

OBJECTIVE To describe the investigation and interventions necessary to contain an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) colonization and infection in a neonatal intensive care unit (NICU). DESIGN Retrospective case finding that involved prospective performance of surveillance cultures for detection of MRSA and molecular typing of MRSA by repetitive-sequence polymerase chain reaction (rep-PCR). SETTING Level III NICU in a tertiary care center. PARTICIPANTS Three neonates in a NICU were identified with MRSA bloodstream infection on April 16, 2004. A point prevalence survey identified 6 additional colonized neonates (attack rate, 75% [9 of 12 neonates]). The outbreak strain was phenotypically unusual. INTERVENTIONS Cohorting and mupirocin therapy were initiated for neonates who had acquired MRSA during the outbreak. Contact precautions were introduced in the NICU, and healthcare workers (HCWs) were retrained in cleaning and disinfection procedures and hand hygiene. Noncolonized neonates and newly admitted patients had surveillance cultures performed 3 times per week. RESULTS Two new colonized neonates were identified 1 month later. HCW X, who had worked in the NICU since June 2003, was identified as having chronic otitis. MRSA was isolated from cultures of swab specimens from HCW Xs ear canal and nares. HCW X was epidemiologically linked to the outbreak. Molecular typing (by rep-PCR) confirmed that the isolates from HCW X and from the neonates were more than 90% similar. Retrospective review of NICU isolates revealed that the outbreak strain was initially cultured from a neonate 2 months after HCW X began working on the unit. The epidemic strain was eradicated after removing HCW X from patient care in the NICU. CONCLUSION An outbreak of MRSA colonization and infection in a NICU was epidemiologically linked to a HCW with chronic otitis externa and nasal colonization with MRSA. Eradication was not achieved until removal of HCW X from the NICU. Routine surveillance for MRSA may have allowed earlier recognition of the outbreak and is now standard practice in our NICU.

Effects of influenza immunization on humoral and cellular alloreactivity in humans

Background. Alloreactive T cells and anti-human leukocyte antigen antibodies mediate transplant injury. Environmental exposures, including vaccinations, may activate the alloimmune repertoire leading to accelerated allograft injury. To test whether vaccination impacts human alloimmunity, we analyzed humoral and cellular immune reactivity in subjects undergoing influenza vaccination. Methods. We serially obtained blood samples from 30 healthy subjects and 8 kidney and 9 lung transplant recipients who received influenza vaccination, and from 20 healthy unvaccinated controls. We measured cellular and humoral anti-influenza responses, anti-human leukocyte antigen antibodies, and alloreactive T-cell immunity (interferon-&ggr; ELISPOT) at 0, 2, 4, and 12 weeks after vaccination. Results. Vaccination induced influenza-reactive humoral and cellular responses in control subjects and in transplant recipients. Only two of 30 vaccinated volunteers developed new alloantibodies, but none of the transplant patients. Vaccination also specifically and significantly augmented cellular alloimmunity based on reactivity to a panel of stimulators in both healthy subjects and in transplant recipients within 4 weeks of vaccination. The enhanced cellular alloresponse waned toward prevaccine levels by week 12. Conclusion. Our findings newly demonstrate that influenza vaccination can have a significant impact on the potency of the alloimmune repertoire. Because the strength of the alloresponse influences long-term graft function, our results suggest that further investigation of alloimmune monitoring after vaccination is needed.

Solid Organ Transplantation From Hepatitis B Virus–Positive Donors: Consensus Guidelines for Recipient Management

Use of organs from donors testing positive for hepatitis B virus (HBV) may safely expand the donor pool. The American Society of Transplantation convened a multidisciplinary expert panel that reviewed the existing literature and developed consensus recommendations for recipient management following the use of organs from HBV positive donors. Transmission risk is highest with liver donors and significantly lower with non‐liver (kidney and thoracic) donors. Antiviral prophylaxis significantly reduces the rate of transmission to liver recipients from isolated HBV core antibody positive (anti‐HBc+) donors. Organs from anti‐HBc+ donors should be considered for all adult transplant candidates after an individualized assessment of the risks and benefits and appropriate patient consent. Indefinite antiviral prophylaxis is recommended in liver recipients with no immunity or vaccine immunity but not in liver recipients with natural immunity. Antiviral prophylaxis may be considered for up to 1 year in susceptible non‐liver recipients but is not recommended in immune non‐liver recipients. Although no longer the treatment of choice in patients with chronic HBV, lamivudine remains the most cost‐effective choice for prophylaxis in this setting. Hepatitis B immunoglobulin is not recommended.