Infection prevention and control between legal requirements and German Society for Hygiene and Microbiology expert assessments: a cross-sectional study in September-November 2022.

BACKGROUND: In contrast to the beginning of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), pandemic, more and more hospital issues are now regulated by policy. AIM: To identify differences between expert recommendations and legal requirements regarding infection prevention and control (IPC) strategies. METHODS: A cross-sectional study was conducted between 29th September 2022 and 3rd November 2022 addressing 1319 members of the German Society for Hygiene and Microbiology. The response rate was 12%. This paper reports the expert recommendations on different IPC strategies. FINDINGS: The majority (66%) of experts recommended universal mask usage, with 34% recommending it seasonally, even after the SARS-CoV-2 pandemic. Medical microbiology (MM) experts were more likely to recommend continuing to wear the masks indefinitely compared with IPC experts. Concerning the mask type, medical masks were recommended more frequently by IPC experts (47.3%), while FFP2 masks were preferred by MM experts (31.8%). The majority (54.7%) of experts recommended universal screening of employees, mainly in settings with extremely vulnerable patients and if regional incidence rates were high, at a frequency of twice per week. The dominant advice (recommended by at least 50% of experts) for employees exposed to SARS-CoV-2 was daily testing and wearing a mask, regardless of the length of exposure. CONCLUSIONS: Expert recommendations deviate from the legal requirements and appear to be more differentiated and proportional. The influence of specific experience and expertise on mask recommendations should be investigated in more detail. For relevant policy decisions, a quick, focused and broad-based consultation of expertise could be of added value.

COVID-19 vaccination strategy for hospital staff in Germany: a cross-sectional study in March-April 2021.

BACKGROUND: SARS-CoV-2 vaccination for healthcare workers (HCWs) started in Germany in December 2020. Hospitals had little time to prepare a vaccination strategy. AIM: To gather information on the initial vaccination strategy for HCWs from the infection control practitioners in Germany. METHODS: A cross-sectional, ethically approved questionnaire was developed, formatted as an online survey and pre-tested. Infection control practitioners responsible for hygiene/infection prevention in 987 randomly selected German hospitals were invited to participate in the survey in March and April 2021. For statistical analysis, the hospitals were categorized into two groups based on bed capacity (<500 beds: small; ≥500 beds: large). FINDINGS: One hundred out of 987 (10%) infection control practitioners completed the survey. In 80% of the participating hospitals, HCW vaccination prioritization was based on recommendations of the German standing committee on vaccination (STIKO). Even so, only 54% prioritized the vaccination of HCWs with contact to vulnerable patients, thus deviating from STIKO recommendations. HCWs with a high personal health risk were prioritized for vaccination in 24% of the hospitals. Transferring unvaccinated HCWs to an area with less infection risk was considered by 2% of large and 12% of small hospitals. CONCLUSION: Vaccination prioritization differed across hospitals and deviated from STIKO recommendations. A pandemic preparedness concept should address the potential impact of divergent strategies compared to a common approach. In addition, further studies analysing the reasons why HCWs remain unvaccinated are needed to adopt effective strategies. This is especially important against the background of facility-based compulsory vaccination.

Infection control strategies for patients and accompanying persons during the COVID-19 pandemic in German hospitals: a cross-sectional study in March-April 2021.

BACKGROUND: Patients are at risk of nosocomial COVID-19 infection. The role of accompanying persons/visitors as potential infection donors is not yet well researched, but the risk will be influenced by prevention measures recommended by infection control practitioners. AIM: To collect information about COVID-19 infection control strategies for patients and accompanying persons from infection control practitioners in German hospitals. METHODS: A cross-sectional questionnaire was developed, ethically approved, pre-tested and formatted as an online tool. Infection control practitioners in 987 randomly selected German hospitals were invited to participate in March and April 2021. For statistical analysis, the hospitals were categorized as small (0-499 beds) or large (≥500 beds). FINDINGS: One hundred surveys were completed (response rate: 10%). A higher proportion of large (71%) than small (49%) hospitals let patients decide freely whether to wear medical or FFP2 masks. Most hospitals reported spatial separation for COVID-19 patients and non-COVID-19 cases (38%) or additionally for suspected COVID-19 cases (53%). A separation of healthcare teams for these areas existed in 54% of the hospitals. Accompaniment bans were more prevalent in large (52%) than in small hospitals (29%), but large hospitals granted more exemptions. CONCLUSION: The decision as to whether to separate areas and teams seemed to depend on the hospital's structural conditions, therefore impairing the implementation of recommendations. Accompaniment regulations differ between hospital sizes and may depend on patient numbers, case type/severity and patients' requirements. In the dynamic situation of a pandemic, it can be difficult to stay up to date with findings and recommendations on infection control.

Reduction of nosocomial bloodstream infections and nosocomial vancomycin-resistant Enterococcus faecium on an intensive care unit after introduction of antiseptic octenidine-based bathing.

BACKGROUND: Vancomycin-resistant Enterococcus faecium (VRE) is emerging in German intensive care units (ICUs). On a 32-bed surgical ICU at a university hospital, increasing numbers of nosocomial cases occurred despite enforcement of hand hygiene and environmental disinfection. AIM: To introduce universal octenidine-based bathing in order to reduce the burden of VRE. METHODS: Between January 2012 and March 2014, patients were screened for VRE on admission and twice weekly. Active surveillance was undertaken for VRE infections and colonizations, and for bloodstream infections (BSI) with any pathogen. Intervention in this before-after study comprised of standardized octenidine-based bathing. Distinct subgroups of VRE colonizations or infections were defined and used for statistical analysis of frequency, prevalence and incidence density. FINDINGS: In the pre-intervention period (January 2012 to April 2013), the admission prevalence of VRE was 4/100 patients and the mean incidence density of nosocomial cases was 7.55/1000 patient-days (PD). Pulsed-field gel electrophoresis analysis revealed prevalence of three vanA and two vanB clusters. In the post-intervention period (August 2013 to March 2014), the admission prevalence of VRE was 2.41/100 patients and the mean incidence density of nosocomial cases was 2.61/1000 PD [P = 0.001 (pre- vs post-intervention)]. Thirteen nosocomial VRE infections were identified in the pre-intervention period, compared with one nosocomial VRE infection in the post-intervention period. Incidence densities of BSI pre- and post-intervention were 2.98 and 2.06/1000 PD (P = 0.15), respectively. CONCLUSION: The epidemiology of emerging VRE appeared as a complex mix of admitted cases and transmissions in small clusters, challenging infection control measures. The implementation of universal octenidine-based bathing combined with a standardized washing regime led to a significant reduction in nosocomial VRE.

[CF Lung Disease - a German S3 Guideline: Module 2: Diagnostics and Treatment in Chronic Infection with Pseudomonas aeruginosa]. / S3-Leitlinie: Lungenerkrankung bei Mukoviszidose ­ Modul 2: Diagnostik und Therapie bei der chronischen Infektion mit Pseudomonas aeruginosa.

Cystic Fibrosis (CF) is the most common autosomal-recessive genetic disease affecting approximately 8000 people in Germany. The disease is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene leading to dysfunction of CFTR, a transmembrane chloride channel. This defect causes insufficient hydration of the epithelial lining fluid which leads to chronic inflammation of the airways. Recurrent infections of the airways as well as pulmonary exacerbations aggravate chronic inflammation, lead to pulmonary fibrosis and tissue destruction up to global respiratory insufficiency, which is responsible for the mortality in over 90 % of patients. The main aim of pulmonary treatment in CF is to reduce pulmonary inflammation and chronic infection. Pseudomonas aeruginosa (Pa) is the most relevant pathogen in the course of CF lung disease. Colonization and chronic infection are leading to additional loss of pulmonary function. There are many possibilities to treat Pa-infection. This is a S3-clinical guideline which implements a definition for chronic Pa-infection and demonstrates evidence-based diagnostic methods and medical treatment for Pa-infection in order to give guidance for individual treatment options.

Preclinical in vivo and in vitro comparison of the translocator protein PET ligands [18F]PBR102 and [18F]PBR111.

PURPOSE: To determine the metabolic profiles of the translocator protein ligands PBR102 and PBR111 in rat and human microsomes and compare their in vivo binding and metabolite uptake in the brain of non-human primates (Papio hamadryas) using PET-CT. METHODS: In vitro metabolic profiles of PBR102 and PBR111 in rat and human liver microsomes were assessed by liquid chromatography-tandem mass spectrometry. [18F]PBR102 and [18F]PBR111 were prepared by nucleophilic substitution of their corresponding p-toluenesulfonyl precursors with [18F]fluoride. List mode PET-CT brain imaging with arterial blood sampling was performed in non-human primates. Blood plasma measurements and metabolite analysis, using solid-phase extraction, provided the metabolite profile and metabolite-corrected input functions for kinetic model fitting. Blocking and displacement PET-CT scans, using PK11195, were performed. RESULTS: Microsomal analyses identified the O-de-alkylated, hydroxylated and N-de-ethyl derivatives of PBR102 and PBR111 as the main metabolites. The O-de-alkylated compounds were the major metabolites in both species; human liver microsomes were less active than those from rat. Metabolic profiles in vivo in non-human primates and previously published rat experiments were consistent with the microsomal results. PET-CT studies showed that K1 was similar for baseline and blocking studies for both radiotracers; VT was reduced during the blocking study, suggesting low non-specific binding and lack of appreciable metabolite uptake in the brain. CONCLUSIONS: [18F]PBR102 and [18F]PBR111 have distinct metabolic profiles in rat and non-human primates. Radiometabolites contributed to non-specific binding and confounded in vivo brain analysis of [18F]PBR102 in rodents; the impact in primates was less pronounced. Both [18F]PBR102 and [18F]PBR111 are suitable for PET imaging of TSPO in vivo. In vitro metabolite studies can be used to predict in vivo radioligand metabolism and can assist in the design and development of better radioligands.

Analysis of norovirus outbreaks reveals the need for timely and extended microbiological testing.

BACKGROUND: Norovirus outbreaks in hospitals remain a substantial threat despite many recommendations for prevention published recently. AIM: To analyse the factors contributing to onset of a norovirus outbreak in hospitals in order to identify new prevention options. METHODS: Data from 71 norovirus outbreaks occurring in five German hospitals between 2002 and 2012 were analysed focusing on the start conditions: the weekday of outbreak, the time span between the first symptomatic cases and the outbreak onset date, the timing of a positive norovirus test result in an outbreak, and presence of concomitant Clostridium difficile infections. FINDINGS: In 68 (96%) outbreaks index cases were identifiable. In 30 of 44 (68%) outbreaks the index case patient acquired norovirus infection in hospital. In 20% of all outbreaks, the index case was a staff member. Nine outbreaks were caused by not isolating contact patients during the incubation time after their exposure to a symptomatic case. Case numbers in norovirus outbreaks were lower when the norovirus test results were available before the outbreak onset (P = 0.028). In 30 of 46 (64%) norovirus outbreaks, C. difficile toxin tests were positive in up to ten patients. Co-infection or subsequent infection with norovirus and C. difficile in single patients occurred in nine (20%) outbreaks. CONCLUSION: Future prevention strategies should focus not only on patients but also on staff. Constant surveillance for new cases of diarrhoea and vomiting and timely adherence to contact precautions for all exposed persons is crucial in outbreak control, as is the need for extended microbiological testing.

Radiosynthesis, In Vivo Biological Evaluation, and Imaging of Brain Lesions with [123I]-CLINME, a New SPECT Tracer for the Translocator Protein.

The high affinity translocator protein (TSPO) ligand 6-chloro-2-(4'-iodophenyl)-3-(N,N-methylethyl)imidazo[1,2-a]pyridine-3-acetamide (CLINME) was radiolabelled with iodine-123 and assessed for its sensitivity for the TSPO in rodents. Moreover neuroinflammatory changes on a unilateral excitotoxic lesion rat model were detected using SPECT imaging. [(123)I]-CLINME was prepared in 70-80% radiochemical yield. The uptake of [(123)I]-CLINME was evaluated in rats by biodistribution, competition, and metabolite studies. The unilateral excitotoxic lesion was performed by injection of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid unilaterally into the striatum. The striatum lesion was confirmed and correlated with TSPO expression in astrocytes and activated microglia by immunohistochemistry and autoradiography. In vivo studies with [(123)I]-CLINME indicated a biodistribution pattern consistent with TPSO distribution and the competition studies with PK11195 and Ro 5-4864 showed that [(123)I]-CLINME is selective for this site. The metabolite study showed that the extractable radioactivity was unchanged [(123)I]-CLINME in organs which expresses TSPO. SPECT/CT imaging on the unilateral excitotoxic lesion indicated that the mean ratio uptake in striatum (lesion:nonlesion) was 2.2. Moreover, TSPO changes observed by SPECT imaging were confirmed by immunofluorescence, immunochemistry, and autoradiography. These results indicated that [(123)I]-CLINME is a promising candidate for the quantification and visualization of TPSO expression in activated astroglia using SPECT.

Methodological Aspects of the Phase II Study AFF006 Evaluating Amyloid-beta -Targeting Vaccine AFFITOPE® AD02 in Early Alzheimer's Disease - Prospective Use of Novel Composite Scales.

BACKGROUND: Optimized scales and composite outcomes have been proposed as a way to more accurately measure Alzheimer's disease related decline. AFFITOPE® AD02, is an amyloid-beta (Aß)-targeting vaccine to elicit anti-Aß antibodies. IMM-AD04, commonly known as Alum, originally designated as a control agent, appeared to have disease-modifying activity in a multicenter, parallel group phase II study in early AD patients. OBJECTIVES: To develop adapted outcomes for cognition, function and a composite scale with improved sensitivity to decline and treatment effects in early AD (mild plus prodromal AD) based on historical data and to assess these adapted outcomes in this phase II study. DESIGN: Data from public datasets was analyzed using a partial least squares model in order to identify an optimally weighted cognitive outcome, Adapted ADAS-cog, and an optimally weighted ADL outcome, Adapted ADCS-ADL which were prospectively defined as co-primary endpoints for the study and were also combined into a composite scale. Data from 162 patients in the placebo groups of ADCS studies and 156 mild patients in the ADNI I study were pooled for this analysis. The Adapted ADAS-cog scale considered 13 ADAS-cog items as well as several Neuropsychological test items and CogState items, the Adapted ADCS-ADL considered all ADCS-ADL items. After the pre-specified analyses were complete, additional adapted and composite scales were investigated in a post-hoc manner. Evaluation of the adapted and composite scales was performed on Phase II trial data for AFFITOPE® AD02 (AFF006, Clinical Trial Identifier: NCT01117818) and historic data in early AD. Least square means, standard deviations, and least squares mean to standard deviation ratios were compared among adapted and composite scales and traditional scales for the 5 treatment groups in the phase II study and overall for the historic data. Treatment effect sizes and p-values were also compared for the phase II study. RESULTS: Cognitive items that were selected for the adapted cognitive scale (aADAS-cog) and had the highest weights were Word Recall, Word Recognition, and Orientation. Delayed Word Recall and Digit Cancellation were among the items excluded due to lack of improved sensitivity to decline. Highly weighted ADL items included in the adapted functional scale (aADCS-ADL) were using the telephone, traveling, preparing a meal/snack, selecting clothing, shopping and using appliances. Excluded items were primarily basic ADLs such as eating, walking, toileting and bathing. Comparisons between traditional scales and primary outcome adapted scales show improved sensitivity to group differences with the adapted scales in the phase II trial. Most of the improvement in the sensitivity of the aADAS-cog and the aADCS-ADL is due to a larger treatment difference observed rather than the improved sensitivity to decline in the comparison groups. CONCLUSION: To our knowledge, this is the first study to prospectively use optimized scales as primary endpoints and to demonstrate the superior power of optimized scales and composites in early disease. Although it is possible that the treatment difference between randomized groups is due to a factor other than the treatment itself, for instance baseline imbalance, the improved power to detect these differences still argues in favor of the adapted scales. The issue of oversensitivity to detect treatment effects is controlled by selection of the alpha level for significance, and in our case will happen less than 5% of the time. Clinical relevance of the treatment difference should be assessed separately from statistical significance, and in this phase II study, is supported by significant or similar sizes of effect on function, behaviour and quality of life outcomes, which are important to patients and caregivers.

Results from a Phase II Study to Assess the Clinical and Immunological Activity of AFFITOPE® AD02 in Patients with Early Alzheimer's Disease.

OBJECTIVES: The primary objective of this clinical trial was to assess the clinical activity of various doses and formulations of AFFITOPE® AD02 following its repeated s.c. administration to patients with early Alzheimer´s disease (AD), based on the evaluation of cognitive and functional domains. DESIGN: It was designed as a randomized, placebo-controlled, parallel group, double blind, multicenter phase II trial with 10 regular outpatient visits and 6 telephone interviews. SETTING: The trial was performed at 32 sites in six countries. PARTICIPANTS: A total of 332 patients were enrolled and 265 patients completed the trial in 3 treatment groups with AD02 and 2 control groups with aluminum oxihydroxide, here named IMM-AD04. Patients were randomly assigned to 5 groups: two doses of IMM-AD04, 25µg AD02 (in two different formulations) and 75µg AD02. INTERVENTION: At months 0, 1, 2, 3, 9 and 15, each patient received a single s.c. injection of the corresponding preparations of AFFITOPE® AD02 or the control, IMM-AD04. MEASUREMENTS: Co-primary efficacy outcomes included a measure of cognition (adapted AD Assessment Scale cognitive [aADAS cog]), and a measure of function (adapted AD Cooperative Trial Activities of Daily Living [aADCS-ADL]). A primary composite score was the sum of these two scores. RESULTS: Treatments were generally well tolerated and adverse events (AEs) were seen at similar rates across all treatment groups, with the exception that more injection site reactions were seen in the groups with a higher level of adjuvant. None of the AD02 groups showed a benefit over the IMM-AD04 controls for primary or exploratory efficacy outcomes. The control groups differed on aADCS-ADL and therefore couldn't be pooled (p=0.039). Unexpectedly, the 2mg IMM-AD04 showed statistically significant effects over the other groups on several clinical outcomes including: aADAS-cog, aADL, Composite, ADAS-cog, CDR-sb, and QOL-AD Caregiver as well as two biomarker outcomes: right and total hippocampal volume (all p<0.05). 48% of patients in the IMM-AD04 2mg group had no decline in the composite outcome over 18 months compared to 17%-31% in the other groups, which is consistent with historical placebo groups. CONCLUSION: No significant treatment effects were seen for the investigational compound AD02. However, the IMM-AD04 2mg group showed statistically significant effects over all other groups on several clinical outcomes as well as a slowing of decline on right hippocampal volume. The data support further development of IMM-AD04 as a disease modifying agent in line with EMA/FDA definitions.

Comparison of in vivo binding properties of the 18-kDa translocator protein (TSPO) ligands [(18)F]PBR102 and [ (18)F]PBR111 in a model of excitotoxin-induced neuroinflammation.

PURPOSE: The in vivo binding parameters of the novel imidazopyridine TSPO ligand [(18)F]PBR102 were assessed and compared with those of [(18)F]PBR111 in a rodent model of neuroinflammation. The validity of the key assumptions of the simplified reference tissue model (SRTM) for estimation of binding potential (BP) was determined, with validation against a two-tissue compartment model (2TC). METHODS: Acute neuroinflammation was assessed 7 days after unilateral stereotaxic administration of (R,S)-α-amino-3-hydroxy-5-methyl-4-isoxazolopropionique (AMPA) in anaesthetized adult Wistar rats. Anaesthetized rats were implanted with a femoral arterial cannula then injected with a low mass of [(18)F]PBR102 or [(18)F]PBR111 and dynamic images were acquired over 60 min using an INVEON PET/CT camera. Another population of rats underwent the same PET protocol after pretreatment with a presaturating mass of the same unlabelled tracer (1 mg/kg) to assess the validity of the reference region for SRTM analysis. Arterial blood was sampled during imaging, allowing pharmacokinetic determination of radiotracer concentrations. Plasma activity concentration-time curves were corrected for unchanged tracer based on metabolic characterization experiments in a separate cohort of Wistar rats. The stability of neuroinflammation in both imaging cohorts was assessed by [(125)I] CLINDE TSPO quantitative autoradiography, OX42/GFAP immunohistochemistry, Fluoro-Jade C histology, and elemental mapping using microparticle-induced x-ray emission spectroscopy. The BP of each ligand were assessed in the two cohorts of lesioned animals using both SRTM and a 2TC with arterial parent compound concentration, coupled with the results from the presaturation cohort for comparison and validation of the SRTM. RESULTS: The BPs of [(18)F]PBR102 [(18)F]PBR111 were equivalent, with improved signal-to-noise ratio and sensitivity compared with [(11)C]PK11195. The presaturation study showed differences in the volume of distribution between the ipsilateral striatum and the striatum contralateral to the injury (0.7) indicating that an assumption of the SRTM was not met. The modelling indicated that the BPs were consistent for both ligands. Between the SRTM and 2TC model, the BPs were highly correlated, but there was a bias in BP. CONCLUSION: [(18)F]PBR102 and [(18)F]PBR111 have equivalent binding properties in vivo, displaying significantly greater BPs with lower signal-to-noise ratio than [(11)C]PK11195. While an assumption of the SRTM was not met, this modelling approach was validated against 2TC modelling for both ligands, facilitating future use in longitudinal PET imaging of neuroinflammation.

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.

[Outbreak of Burkholderia cepacia complex caused by contaminated alcohol-free mouthwash]. / Ausbruch mit Burkholderia-cepacia-Komplex durch kontaminierte Mundspüllösung.

BACKGROUND: A total of three intensive care units (ICU) at a German university hospital were involved in an outbreak of Burkholderia cepacia complex (Bcc). METHODS: Patients with microbiological detection of Bcc were evaluated. Products used for mouth hygiene were microbiologically tested. The clonal identity of Bcc was proven by pulse-field gel electrophoresis (PFGE). RESULTS: On 3 ICUs 12 cases were identified whereby the first detection of Bcc was in respiratory specimens of 11 patients and 1 in a wound swab from the oral cavity. Of these patients six developed ventilator-associated pneumonia (VAP). Investigations revealed that five different batches of an alcohol-free mouthwash containing hexetidine were highly contaminated. Isolates of Bcc from patients and mouthwashes were genetically indistinguishable. A recall of the product was initiated. After elimination of the product from the ICUs no more cases were identified. CONCLUSIONS: The source of the outbreak was an intrinsically contaminated alcohol-free mouthwash. Detection of Bcc in specimens from ICU patients should lead to further investigations. Antiseptic oral care products are recommended for reducing the risk of VAP but they may be microbiologically contaminated and, in consequence, increase the risk. The safety of patient care products should be increased by stricter regulations.

Vaccination for Parkinson's disease.

Idiopathic Parkinson's disease (PD) is, like other neurodegenerative diseases such as Alzheimer's disease (AD) considered a proteinopathy. Thus, a disease that is driven by the accumulation and aggregation of misfolded proteins, in case of PD α-synuclein (aSyn) is incriminated. Accordingly, removal of aSyn is assumed of having the potential to modify the course of the disease. Both active and passive aSyn targeting immunotherapy were found to modify disease in mice overexpressing human aSyn and recapitulating various aspects of synucleopathies. Translating immunotherapy to humans needs to consider the issue of potential autoimmunity. PD vaccines developed by AFFiRiS integrate the safety concept as applied for the company's AD vaccine candidates. This includes the use of short antigens, precluding activation of aSyn-specific T cells and, thus, cellular autoimmunity. Moreover, the selection of AFFITOPES® for clinical development is based on the principle of exclusive aSyn reactivity of vaccine-induced Abs excluding crossreactivity to ß-synuclein (bSyn), which is ensured by the AFFITOME® platform technology. PD01, the first in class aSyn vaccine developed by AFFiRiS is about to enter the clinical phase of development.

Increase of patients co-colonised or co-infected with methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium or extended-spectrum ß-lactamase-producing Enterobacteriaceae.

PURPOSE: To determine the incidence of patients co-colonised or co-infected with methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium or extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae in four German tertiary care hospitals. METHODS: This study was conducted at four tertiary care hospitals (all with >1,000 beds) in different geographic regions in Germany (Berlin in the east, Luebeck in the north, Freiburg in the southwest and Nuernberg in the southeast). Routine surveillance data on MRSA, vancomycin-resistant enterococci (VRE) and ESBL-producing bacteria were analysed from 2007 to 2009. Co-colonisation or co-infection was defined as a patient having positive cultures for at least two of the following resistant pathogens: MRSA, VRE faecium or different species of ESBL-producing Enterobacteriaceae within one calendar year. RESULTS: A total of 896,822 patients were analysed, of which 10,066 patients harboured MRSA, VRE faecium and/or ESBL-producing Enterobacteriaceae, and 542 patients co-harboured at least two of those resistant pathogens. In 2009, 7.6% of the MRSA patients, 13.7% of the VRE faecium patients and even 16.1% of the ESBL-producing Enterobacteriaceae patients were co-colonised or co-infected. The incidence of patients with co-infection or co-colonisation increased steadily from 5 (2007) to 7 per 10,000 patients (2009). CONCLUSIONS: Patients harbouring ESBL-producing Enterobacteriaceae or VRE faecium had a higher risk of being co-colonised or co-infected compared to what was to be extrapolated from their overall incidence. This might be linked to their gastrointestinal reservoir and impracticality to decolonise the gut of resistant VRE and ESBL-producing Enterobacteriaceae.

Hospital-wide outbreak of Burkholderia contaminans caused by prefabricated moist washcloths.

We experienced a hospital outbreak of Burkholderia contaminans (Burkholderia cepacia Group K) in a German university hospital with two campuses. Cases were defined as the microbiological detection of B. cepacia complex (BCC) in any clinical specimen sent to the laboratory during 30 June to 21 October 2008. Species identification of BCC was performed by recA gene sequencing, followed by pulsed-field gel electrophoresis (PFGE; SpeI digest) for clonal identity. In total, 61 BCC-positive cases were diagnosed at the two campuses. At least nine patients contracted a ventilator-associated pneumonia with BCC. One patient suffered an infection of a pacing wire insertion site and four patients had septicaemia. Sixteen patients died in hospital, none thought to be due to the outbreak strain. BCC was eventually found in packages of moist prefabricated washcloths used for intensive care patients. German healthcare authorities were informed and a Europe-wide alarm (RAPEX) was initiated through the systems to prevent infections in other hospitals. PFGE proved clonal identity between isolates from clinical specimens and washcloths of both campuses. After elimination of the contaminated washcloths no further cases occurred. This example of a relatively newly introduced product raises the question of whether current regulations are adequate to protect consumers. For critically ill patients, care products should be carefully evaluated. In case of infections due to contaminated products, immediate communication to healthcare authorities is required, including RAPEX warning if products are sold across Europe.

Incidence and impact of herpes simplex and cytomegalovirus detection in the respiratory tract after lung transplantation.

Herpesvirus infections cause morbidity in lung transplant recipients. The study was conducted to investigate the incidence and impact of herpes simplex virus (HSV) and cytomegalovirus (CMV) detection in the respiratory tract (RT) of lung and heart-lung transplant recipients (LTR) during the postoperative phase. In a prospective cohort study, 91 LTR having at least 1 nasopharyngeal swab (NPS) sent for virus diagnostics were monitored for CMV and HSV detection in NPS during their post-transplant hospital stay on cardiothoracic surgery wards (median 4 weeks) by direct immunofluorescence testing for HSV, virus culture, and CMV and HSV polymerase chain reaction (PCR). Bronchoalveolar lavages (BALs) were analyzed with the same protocol except that HSV PCR was only performed on request. Risk factor analysis for the outcome '90-day mortality' was performed. Fifteen LTR had virus detection in NPS (16.5%): 9 had CMV, 5 had HSV, and 1 had both CMV and HSV. Four of 84 LTR had CMV detection in BAL (4.8%). Absence of CMV detection in NPS had a negative predictive value of 98.8% for absence of CMV detection in BAL. HSV DNA detection in NPS, especially if detected within 8 days after transplantation, was associated with 90-day mortality. In conclusion, detection of herpesviruses in the RT was clinically relevant and frequent, despite antiviral prophylaxis.

Long-term persistence of MRSA in re-admitted patients.

BACKGROUND: A 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 METHODS: Between 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. RESULTS: A 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 549 days, with the duration of persistence dependent on the colonisation of different anatomical sites (HLT only wounds 117 days; HLT mouth, throat, bronchial secretions 627 days; HLT nose, wounds and other body sites 801 days; p < 0.01) and was prolonged if more than one body site was MRSA-positive (HR 2.18, 95% confidence interval 1.52-3.15). CONCLUSION: A 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.