Frauke Mattner

Two case reports: Fatal Absidia corymbifera pulmonary tract infection in the first postoperative phase of a lung transplant patient receiving voriconazole prophylaxis, and transient bronchial Absidia corymbifera colonization in a lung transplant patient

Absidia corymbifera is a rare cause of pulmonary tract infection. There exist only 5 case reports predominantly diagnosed in bone marrow transplant patients. Lung transplant patients are at high risk for invasive fungal infections. Due to A. corymbifera as pathogen, known to be voriconazole resistant, a fatal invasive pulmonary mycosis occurred. In the present case voriconazole prophylaxis failed. A second patient showed a transient colonization of the bronchi. To prevent airborne transmitted invasive pulmonary mycosis in the first postoperative period of lung transplantation the patient should be situated in a room ventilated by HEPA-filtered air. The specific treatment should start very early when first suspicion arises. A review of the literature on pulmonary tract infections induced by Absidia corymbifera is provided.

Impact of Bacterial and Fungal Donor Organ Contamination in Lung, Heart–Lung, Heart and Liver Transplantation

We investigated to which extent bacterial and fungal donor organ contamination (DOC) caused posttransplant nosocomial infections (NI) in solid organ transplant (Tx) recipients. Between January 2002 to December 2003 (lung and heart Tx) and October 2003 to September 2004 (liver Tx), NIs were determined according to modified CDC criteria for NIs for all transplantations performed at Hannover Medical School. Organisms of the same species cultured from donor organs and infected transplantees were genotyped if available. Out of 282 solid organ recipients (140 lung-Tx, 16 heart-lung-Tx, 51 heart-Tx, 75 liver-Tx), 150 recipients (53.2%) received contaminated donor organs. Incidences of NIs were 33.7% in lung, 68.8% in heart-lung, 21.6% in heart, and 28% in liver recipients. In 11 out of 282 transplantees (3.9%, CI 95% 2.0–6.9%) organisms of NIs and of contamination of the donor organ were of the same species. Even if assuming five missing pairs of organisms as genetically identical, incidences of DOC-related posttransplant infections were only between 1.3% (CI95% 0.0; 7.2) in liver-Tx and 18.8% (CI95% 4; 45.6) in heart-lung Tx, and DOC related mortality was 0.4% (CI95% 0.0;1.9). Despite high DOC rates, posttransplant infections due to DOC were rare under the condition of adequate preoperative antibiotic prophylaxis and aseptic organ retrievement.

Detection of Epstein–Barr virus DNA in peripheral blood is associated with the development of bronchiolitis obliterans syndrome after lung transplantation

BACKGROUND The long-term success of lung transplantation is limited by the development of bronchiolitis obliterans syndrome (BOS). Virus infections may be involved in the development of BOS. OBJECTIVES The study intended to investigate whether there is an association of Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human adenovirus (HAdV) with the development of BOS and to identify risk factors for EBV detection in blood. STUDY DESIGN A prospective cohort study was conducted in lung and heart-lung transplant recipients (LTR) who are followed in our outpatient clinic. 385 LTR were monitored for CMV pp65 antigen, EBV and HAdV DNA in blood at follow-up visits for 6 months. The development of BOS was recorded for a median of 21 months. RESULTS EBV DNA, HAdV DNA and CMV pp65 antigen were detected at least once in, respectively, 202/385 LTR (52.5%), 10/382 LTR (2.6%) and 19/385 LTR (4.9%). Repeated EBV DNA detection and acute rejection were associated with the development of BOS. Variables associated with EBV DNA detection in blood were the diagnosis of BOS before study entry, retransplantation and immunosuppressive therapy with sirolimus or everolimus. CONCLUSIONS EBV reactivation is frequent in LTR. The variables found associated with EBV reactivation probably reflect increased immunosuppression. Repeated EBV DNA detection in blood, possibly reflecting chronic EBV replication, is associated with the development of BOS. The elucidation of whether and how EBV DNAemia triggers the development of BOS could improve long-term survival of LTR.

Evaluation of the Impact of the Source (Patient Versus Staff) on Nosocomial Norovirus Outbreak Severity

OBJECTIVE To study the dependence of infection risk and outbreak size on the type of index case (i.e., patient or staff). METHODS Nosocomial outbreaks were reviewed and categorized into those started by patients and those started by staff. Infection risks and outbreak sizes were evaluated taking into account the index case category. RESULTS Of the 30 nosocomial outbreaks of norovirus with person-to-person transmission, 20 (67%) involved patients as the index cases. Patient-indexed outbreaks affected significantly more patients than did staff-indexed outbreaks (difference in means, 16.25; 95% confidence interval [CI95], 5.1 to 27.0). For the numbers of affected staff, no dependence on the index case category was detectable (difference in means, -1.05; CI95, -9.0 to 6.9). For patients exposed during patient-indexed outbreaks, the risk of acquiring a norovirus infection was approximately 4.8 times as high as the corresponding risk for patients exposed during staff-indexed outbreaks (odds ratio [OR], 4.79; CI95, 1.82 to 8.28). The infection risk for exposed staff during patient-indexed outbreaks was approximately 1.5 times as high as the corresponding risk during staff-indexed outbreaks (OR, 1.51; CI95, 0.92 to 2.49). CONCLUSIONS Patient-indexed norovirus outbreaks generally affect more patients than do staff-indexed outbreaks. Staff appear to be similarly affected by both outbreak index category groups. This study demonstrates the importance of obtaining complete outbreak data, including the index case classification as staff or patient, during norovirus outbreak investigations. Such information may be useful for further targeting prevention measures

Utility of two novel multiplexing assays for the detection of gastrointestinal pathogens - a first experience.

BackgroundCause for gastroenteritis range from viral, bacterial to parasitic pathogens. Rapid Multiplexing techniques like ProGastro_SSCS and xTAG_GPP can detect broad panels of pathogens simultaneously.We performed a field test with a total number of 347 stool samples from adult hospitalized patients that were tested with the Luminex xTAG GPP assay; of the 157 samples positively tested for at least one pathogen by xTAG GPP a total number of 30 samples was retested with the ProGastro SSCS assay. Assays were compared to standard routine diagnostics.FindingsMultiplexing significantly reduced the time to the initial identification of a pathogen. Moreover, multiplexing detected pathogens for which a diagnostic assays was not requested by the physician and thus may be an important tool for avoiding nosocomial outbreaks.ConclusionThis first frontline approach with these assays approves their utility compared to conventional microbiological methods.

Surveillance invasiver Fadenpilzmykosen in lungentransplantierten Patienten: Effekt antimykotischer Prophylaxe mit Itraconazol und Voriconazol

Von Jan 2002 bis Dez 2003 wurden alle Lungentransplantierten der Medizinischen Hochschule Hannover prospektiv während des postoperativen Krankenhausaufenthalts hinsichtlich der Entwicklung von invasiven Fadenpilzmykosen beobachtet. Patienten wurden als positiv eingestuft, wenn die EORTC‐Kriterien ‘probable or proven’ erfüllt waren. Retrospektiv wurde ermittelt, welche antimykotische Prophylaxe die Patienten erhielten. Von 157 lungentransplantierten Patienten entwickelten 8 eine invasive Mykose (Inzidenz 5.1% nach 17 ± 10 Tagen postoperativ). Sie führten zu einer 14‐fach erhöhten Mortalität (OR 13.8, CI95% 2.5–82, P = 0.001). Präoperative Kolonisierung der Atemwege mit Aspergillus stellte einen signifikanten Risikofaktor dar (P < 0.001, OR 21.9, CI95% 4.9–97). 101 Patienten erhielten vom ersten postoperativen Tag an Itraconazol als antimykotische Prophylaxe. 6 von ihnen entwickelten eine invasive Aspergillose (4.7%). 38 Patienten erhielten eine erst nach >14 Tagen einsetzende antimykotische Prophylaxe mit Itraconazol. Von diesen entwickelten 2 Patienten (3%) eine invasive Aspergillose. Bei 18 Patienten, von denen 10 präoperativ mit Aspergillus besiedelt waren, wurde seit Ende 2002 eine Prophylaxe mit Voriconazol in den ersten 30 postoperativen Tagen durchgeführt. Darunter kam es zu einer Zygomykose. Invasive Fadenpilzmykosen treten bei Lungentransplantierten trotz einer antimykotischen Prophylaxe mit einer hohen Inzidenz von 5% in der frühen postoperativen Phase auf und führen zu einer hohen Mortalität. Ein Management, bei definierten Hochrisikopatienten eine Voriconazol‐Prophylaxe durchzuführen, scheint einer Itraconazolprophylaxe überlegen zu sein. Zur definitiven Klärung sind jedoch noch kontrollierte Studien an größeren Patientenkollektiven erforderlich.

Clinical relevance of and risk factors for HSV-related tracheobronchitis or pneumonia: results of an outbreak investigation

IntroductionHerpes simplex virus (HSV) type 1 was identified in respiratory specimens from a cluster of eight patients on a surgical intensive care unit within 8 weeks. Six of these patients suffered from HSV-related tracheobronchitis and one from HSV-related pneumonia only. Our outbreak investigation aimed to determine the clinical relevance of and risk factors associated with HSV-related tracheobronchitis or pneumonia in critically ill patients, and to investigate whether the cluster was caused by nosocomial transmission.MethodsA retrospective cohort study was performed to identify risk factors for the outcomes of HSV-related tracheobronchitis or pneumonia and death using univariable analysis as well as logistic regression analysis. Viruses were typed by molecular analysis of a fragment of the HSV type 1 glycoprotein G.ResultsThe cohort of patients covering the outbreak period comprised 53 patients, including six patients with HSV-related tracheobronchitis and one patient with pneumonia only. HSV-related tracheobronchitis or pneumonia was associated with increased mortality (100% in patients with versus 17.8% in patients without HSV-related tracheobronchitis or pneumonia; P < 0.0001). The interaction of longer duration of ventilation and tracheotomy was associated with HSV-related tracheobronchitis or pneumonia in multivariable analysis.Identical HSV type 1 glycoprotein G sequences were found in three patients and in two patients. The group of three identical viral sequences belonged to a widely circulating strain. The two identical viral sequences were recovered from bronchoalveolar lavages of one patient with HSV-related tracheobronchitis and of one patient without clinical symptoms. These viral sequences showed unique polymorphisms, indicating probable nosocomial transmission.ConclusionHSV-related tracheobronchitis or pneumonia is associated with increased mortality in critically ill patients. Care should be taken to avoid nosocomial transmission and early diagnosis should be attempted.

[Surveillance of invasive mold infections in lung transplant recipients: effect of antimycotic prophylaxis with itraconazole and voriconazole].

Von Jan 2002 bis Dez 2003 wurden alle Lungentransplantierten der Medizinischen Hochschule Hannover prospektiv während des postoperativen Krankenhausaufenthalts hinsichtlich der Entwicklung von invasiven Fadenpilzmykosen beobachtet. Patienten wurden als positiv eingestuft, wenn die EORTC‐Kriterien ‘probable or proven’ erfüllt waren. Retrospektiv wurde ermittelt, welche antimykotische Prophylaxe die Patienten erhielten. Von 157 lungentransplantierten Patienten entwickelten 8 eine invasive Mykose (Inzidenz 5.1% nach 17 ± 10 Tagen postoperativ). Sie führten zu einer 14‐fach erhöhten Mortalität (OR 13.8, CI95% 2.5–82, P = 0.001). Präoperative Kolonisierung der Atemwege mit Aspergillus stellte einen signifikanten Risikofaktor dar (P < 0.001, OR 21.9, CI95% 4.9–97). 101 Patienten erhielten vom ersten postoperativen Tag an Itraconazol als antimykotische Prophylaxe. 6 von ihnen entwickelten eine invasive Aspergillose (4.7%). 38 Patienten erhielten eine erst nach >14 Tagen einsetzende antimykotische Prophylaxe mit Itraconazol. Von diesen entwickelten 2 Patienten (3%) eine invasive Aspergillose. Bei 18 Patienten, von denen 10 präoperativ mit Aspergillus besiedelt waren, wurde seit Ende 2002 eine Prophylaxe mit Voriconazol in den ersten 30 postoperativen Tagen durchgeführt. Darunter kam es zu einer Zygomykose. Invasive Fadenpilzmykosen treten bei Lungentransplantierten trotz einer antimykotischen Prophylaxe mit einer hohen Inzidenz von 5% in der frühen postoperativen Phase auf und führen zu einer hohen Mortalität. Ein Management, bei definierten Hochrisikopatienten eine Voriconazol‐Prophylaxe durchzuführen, scheint einer Itraconazolprophylaxe überlegen zu sein. Zur definitiven Klärung sind jedoch noch kontrollierte Studien an größeren Patientenkollektiven erforderlich.

An infection with linezolid-resistant S. aureus in a patient with left ventricular assist system

We report an infection with a linezolid-resistant S. aureus in a patient with a left ventricular assist system. Linezolid should be used with caution when invasive devices or foreign materials are in place or therapeutic courses last longer than 14 d. Previous cases of linezolid-resistant S. aureus are summarized.

Risk of rabies infection and adverse effects of postexposure prophylaxis in healthcare workers and other patient contacts exposed to a rabies virus-infected lung transplant recipient.

BACKGROUND Rabies virus was inadvertently transmitted to a lung transplant recipient through donor lungs. The patient was given ventilatory assistance and cared for postoperatively for 6 weeks before a diagnosis of rabies virus infection was made. Postexposure prophylaxis (PEP) was offered to potentially exposed healthcare workers (HCWs). METHODS Only HCWs classified as belonging to possible and/or proven contact groups (according to a standardized interview) received PEP. The risk of individual HCWs being exposed to rabies virus was reassessed on the basis of viral concentrations measured in the patients excretions and body fluids. HCWs who were vaccinated as part of PEP were followed up prospectively according to a standardized procedure. RESULTS Of 179 HCWs and other patient contacts, 132 met the eligibility criteria for PEP (118 [89.4%] with possible contact and 14 [10.6%] with proven contact with the patients excretions and/or body fluids). One hundred thirty-one individuals started PEP, and 126 met the inclusion criteria for analysis. Of these, 48 (38%) developed at least 1 adverse effect (8 [6.3%] had fever, 37 [29.4%] had headache, 3 [2.4%] had lymphadenopathy, 17 [13.5%] had dizziness, and 6 [4.8%] had paresthesia). No HCW or other patient contact developed rabies or serious PEP-related adverse effects. Reassessment of the individuals risk of infection as a function of the viral concentration in the patients excretions and/or body fluids (up to 5.12 x 10(7) copies/mL) revealed that 103 HCWs (78.0%) had contact with high-risk substances (89 [67.40%] had possible contact and 14 [10.7%] had proven contact). CONCLUSION HCWs can be exposed to significant viral concentrations in excretions and/or body fluids from rabies virus-infected lung transplant recipients. Because widespread use of PEP entails the possibility of significant health problems for HCWs considered to be at risk of contracting rabies, applying a rational indication for PEP is crucial.