F. Mattner

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

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.

Impact of graft colonization with gram-negative bacteria after lung transplantation on the development of bronchiolitis obliterans syndrome in recipients with cystic fibrosis

Bronchiolitis obliterans syndrome (BOS) represents the leading cause of late mortality after lung transplantation (LTx). Cystic fibrosis (CF) patients frequently show airway colonization with gram-negative bacteria (GNB) both before and after LTx. Graft colonization with GNB and its relevance towards BOS development were investigated in a CF population after LTx. Adult CF patients receiving LTx and surviving at least 6 months were included in this prospective observational study between 1/1/2002 and 30/6/2006 in a single center and followed until 31/3/2007. Pre- and post-LTx respiratory culture samples were compared for the presence of identical GNB. BOS-free survival was compared in colonized and non-colonized patients. Fifty-nine adult CF patients with a median age at LTx of 25.5 (18-49) years were included and had a median follow-up of 966 (128-1889) days. Seven patients (15%) demonstrated immediate eradication of GNB in lower respiratory tract samples. A further 18 patients (34%) demonstrated transient colonization. Thirty-four recipients had further positive samples after LTx. Eighteen patients (31%) developed BOS >or=stage 1, 508 (114-1167) days after LTx. Freedom of graft colonization with pseudomonads was independently associated with less frequent development of BOS (p=0.006). Persistent graft colonization with pseudomonads increases the prevalence of BOS after LTx in CF patients. A significant proportion of post-LTx CF patients demonstrates subsequent GNB eradication during later follow-up and this may have a protective role against development of BOS. Strategies to eradicate airway colonization or reduce bacterial load may prevent BOS in CF patients after LTx.

Long-term persistence of MRSA in re-admitted patients

BackgroundA better knowledge of methicillin-resistant Staphylococcus aureus (MRSA) persistence in hospitalised patients may impact on specific prevention strategies. We have investigated the persistence of MRSA-carriage in patients admitted and re-admitted to a university hospital.Patients and methodsBetween January 2002 and October 2005 all MRSA-positive patients admitted to the university hospital of Hannover Medical School were assessed at first admission and all subsequent re-admissions. Patients re-admitted at least once were analysed for the persistence or loss of MRSA. The association of possible factors influencing the persistence of MRSA colonisation or infection (age group, gender, decolonisation therapy during first hospital stay due to MRSA positivity and colonisation of different anatomical sites) was analysed using univariate, multivariate and time-dependent analyses.ResultsA total of 1,032 patients who had tested positive at least once for MRSA were admitted to our hospital during the study period, accounting for 2,038 admissions. Of these patients, 403 (39.1%) were admitted more than once (from two times to 21 times), and 238 (59.1%) of the re-admitted patients remained MRSA positive during all subsequent admissions. Fifty-five (13.6%) patients tested MRSA negative at their last admission, and 61 (15.1%) tested MRSA negative at at least two consecutive admissions. In 27 (6.7%) patients, the MRSA status differed more than once between subsequent admissions. Overall, the half-life time (HLT) of MRSA persistence was 549xa0days, with the duration of persistence dependent on the colonisation of different anatomical sites (HLT only wounds 117xa0days; HLT mouth, throat, bronchial secretions 627xa0days; HLT nose, wounds and other body sites 801xa0days; pxa0<xa00.01) and was prolonged if more than one body site was MRSA-positive (HR 2.18, 95% confidence interval 1.52–3.15).ConclusionA detailed knowledge of the dynamics of the loss of MRSA infection could result in a reduction of the incidence of MRSA in the future. Multiple anatomical site carriage of MRSA appeared to predict a prolonged persistence in our cohort of patients re-admitted to a university hospital.

Surveillance with successful reduction of central line-associated bloodstream infections among neutropenic patients with hematologic or oncologic malignancies

To determine nosocomial catheter-associated bloodstream infections (CA-BSIs) and to improve the prevention measures, we performed a prospective surveillance in our hematopoietic stem cell transplantation unit at our university hospital. During the 36-month study period all patients with at least two consecutive neutropenic days (NDs) were included. After the first 18xa0months the recorded data were analyzed and compared with reference data and were then presented to the clinical staff. An intensive training to improve the handling of central venous lines was performed afterwards. At the end of the last 18-month study period the data were evaluated and a multivariate analysis was conducted. Altogether 268 patients were treated for a period of 10,013 patient days including 4,286 NDs. A total of 202/268 (75.4%) patients underwent transplantation (157/76.6% allogeneic, 48/23.4% autologous). Eighty-seven CA-BSIs were identified. The incidence density was 24.3 CA-BSI episodes per 1,000 NDs in the first period and 16.2 in the second. A significant reduction in the CA-BSI rate of adults was achieved (OR 0.58; 95% CI 0.339–0.987; pu2009<u20090.05). Significant risk factors for nosocomial CA-BSIs during the neutropenic phase were AML as underlying disease as well as transplantations.

Risk factors associated with surgical site infections following vascular surgery at a German university hospital.

Surgical site infection (SSI) after vascular surgery is a serious complication increasing morbidity, mortality, and costs for healthcare systems. A 4-year retrospective cohort study was performed in a university hospital with patients who had undergone arterial vascular surgery below the aortic arch. Investigated variables included demographics and clinical data. Forty-four of 756 patients experienced SSI, 29 of which were superficial, five were deep, and 10 had organ/space infections. Coagulase-negative staphylococci (22%), enterococci (20%), and Staphylococcus aureus (18%) were the most common pathogens. Independent risk factors for SSIs were femoral grafting [odds ratio (OR) 6·7], peripheral atherosclerotic disease, Fontaine stages III-IV (OR 4·1), postoperative drainage >5 days (OR 3·6), immunosuppression (OR 2·8), duration of operation >214 min (OR 2·8), and body mass index >29 (OR 2·6). The application of perioperative antibiotic prophylaxis was an independent protective factor (OR 0·2). Patients with certain risk factors for SSIs warrant special attention for infection prevention.

Five-years surveillance of invasive aspergillosis in a university hospital

BackgroundAs the most common invasive fungal infection, invasive aspergillosis (IA) remains a serious complication in immunocompromised patients, leading to increased mortality. Antifungal therapy is expensive and may result in severe adverse effects.The aim of this study was to determine the incidence of invasive aspergillosis (IA) cases in a tertiary care university hospital using a standardized surveillance method.MethodsAll inpatients at our facility were screened for presence of the following parameters: positive microbiological culture, pathologists diagnosis and antifungal treatment as reported by the hospital pharmacy. Patients fulfilling one or more of these indicators were further reviewed and, if appropriate, classified according to international consensus criteria (EORTC).Results704 patients were positive for at least one of the indicators mentioned above. Applying the EORTC criteria, 214 IA cases were detected, of which 56 were proven, 25 probable and 133 possible. 44 of the 81 (54%) proven and probable cases were considered health-care associated. 37 of the proven/probable IA cases had received solid organ transplantation, an additional 8 had undergone stem cell transplantation, and 10 patients were suffering from some type of malignancy. All the other patients in this group were also suffering from severe organic diseases, required long treatment and experienced several clinical complications. 7 of the 56 proven cases would have been missed without autopsy. After the antimycotic prophylaxis regimen was altered, we noticed a significant decrease (p = 0.0004) of IA during the investigation period (2003-2007).ConclusionSolid organ and stem cell transplantation remain important risk factors for IA, but several other types of immunosuppression should also be kept in mind. Clinical diagnosis of IA may be difficult (in this study 13% of all proven cases were diagnosed by autopsy only). Thus, we confirm the importance of IA surveillance in all high-risk patients.

Adverse Effects of Rabies Pre- and Postexposure Prophylaxis in 290 Health-Care-Workers Exposed to a Rabies Infected Organ Donor or Transplant Recipients

The recent unfortunate rabies transmissions through solid organ transplants of an infected donor in Germany required the initiation of a vaccination program to protect health care workers (HCWs) with close contact to rabies-infected patients. A systematic follow-up of adverse effects was initiated. Rabies postexposure prophylaxis (PEP) was started in 269 HCWs at four German hospitals. Pre-exposure prophylaxis (PreEP) was administered to 74 HCWs caring for an already diagnosed rabies patient. At each vaccination date, HCWs were interviewed for symptoms possibly representing adverse effects. Adverse effects of PEP and PrePEP were compared. Out of 269 HCWs, 216 were included for the investigation of adverse effects. Of these 216 HCWs, 114 (53%) individuals developed at least one systemic adverse effect. Incidences of tiredness (30.6%), malaise (26.4%), headache (26.9%), dizziness (14.8%), and chills (13.0%) declined in the course of PEP (p < 0.05), whereas incidences of fever (7.4%), paraesthesias (7.9%), arthralgias (1.9%), myalgias (4.2%), nausea (9.3%), diarrheas (2.8%) and vomiting (1.4%) did not. In 11 (5.1%) HCWs PEP was discontinued mostly due to adverse reactions (four suffered strong headaches, two HCWs meningeal irritations, two chills, one paraesthesia, one malaise, and one a rush). Systemic effects of PEP or PreEP did not differ significantly. Despite relatively high incidences of moderate severe adverse reactions rabies PEP is safe. Strong headache, tiredness, dizziness, and paraesthesias are the most important postvaccinal symptoms. Vaccinees suffering from adverse effects of PEP must be strongly encouraged to complete PEP, as it is to date the only protection against fatal rabies.

Viremia after lung transplant: a cohort study on risk factors and symptoms associated with detection of Epstein-Barr virus

Background The frequency and impact of detection of Epstein-Barr virus in the blood of lung and heart-lung transplant recipients in the postoperative period is poorly characterized. Objective To investigate the frequency of virus detection, associated clinical symptoms and risk factors, and influence of virus detection on outcome. Methods A cohort of 98 lung transplant recipients were monitored for Epstein-Barr virus in blood before transplant and during their posttransplant hospital stay (median 4 weeks, range 1–21 weeks). Patients were followed up for retransplant or death for a median of 17 months. Results Epstein-Barr virus DNA was detected in 15 recipients (18.1%) before and in 39 recipients (41.5%) after transplant. Median viral load after transplant was 2300 copies per milliliter of blood (range, 900–45 000 copies/mL). Detection of Epstein-Barr virus DNA before transplant and mechanical ventilation before transplant were associated with detection of Epstein-Barr virus DNA after transplant. Shortness of breath, fatigue, and hoarseness were associated with detection of viral DNA after transplant. The incidence of retransplant or death was not increased in recipients who had viral DNA detected in their blood. Conclusions Epstein-Barr virus DNA in the blood before transplant and mechanical ventilation before transplant were associated with detection of viral DNA after transplant. Detection of viral DNA after transplant was frequent and clinically relevant.