Transportation capacity for patients with highly infectious diseases in Europe: a survey in 16 nations.

Highly infectious diseases (HIDs) are defined as being transmissible from person to person, causing life-threatening illnesses and presenting a serious public health hazard. In most European Union member states specialized isolation facilities are responsible for the management of such cases. Ground ambulances are often affiliated with those facilities because rapid relocation of patients is most desirable. To date, no pooled data on the accessibility, technical specifications and operational procedures for such transport capacities are available. During 2009, the 'European Network for HIDs' conducted a cross-sectional analysis of hospitals responsible for HID patients in Europe including an assessment of (a) legal aspects; (b) technical and infrastructure aspects; and (c) operational procedures for ground ambulances used for HID transport. Overall, 48 isolation facilities in 16 European countries were evaluated and feedback rates ranged from 78% to 100% (n = 37 to n = 48 centres). Only 46.8% (22/47) of all centres have both national and local guidelines regulating HID patient transport. If recommended, specific equipment is found in 90% of centres (9/10), but standard ambulances in only 6/13 centres (46%). Exclusive entrances (32/45; 71%) and pathways (30/44; 68.2%) for patient admission, as well as protocols for disinfection of ambulances (34/47; 72.3%) and equipment (30/43; 69.8%) exist in most centres. In conclusion, the availability and technical specifications of ambulances broadly differ, reflecting different preparedness levels within the European Union. Hence, regulations for technical specifications and operational procedures should be harmonized to promote patient and healthcare worker safety.

Strategies to enhance rational use of antibiotics in hospital: a guideline by the German Society for Infectious Diseases.

INTRODUCTION: In the time of increasing resistance and paucity of new drug development there is a growing need for strategies to enhance rational use of antibiotics in German and Austrian hospitals. An evidence-based guideline on recommendations for implementation of antibiotic stewardship (ABS) programmes was developed by the German Society for Infectious Diseases in association with the following societies, associations and institutions: German Society of Hospital Pharmacists, German Society for Hygiene and Microbiology, Paul Ehrlich Society for Chemotherapy, The Austrian Association of Hospital Pharmacists, Austrian Society for Infectious Diseases and Tropical Medicine, Austrian Society for Antimicrobial Chemotherapy, Robert Koch Institute. MATERIALS AND METHODS: A structured literature research was performed in the databases EMBASE, BIOSIS, MEDLINE and The Cochrane Library from January 2006 to November 2010 with an update to April 2012 (MEDLINE and The Cochrane Library). The grading of recommendations in relation to their evidence is according to the AWMF Guidance Manual and Rules for Guideline Development. CONCLUSION: The guideline provides the grounds for rational use of antibiotics in hospital to counteract antimicrobial resistance and to improve the quality of care of patients with infections by maximising clinical outcomes while minimising toxicity. Requirements for a successful implementation of ABS programmes as well as core and supplemental ABS strategies are outlined. The German version of the guideline was published by the German Association of the Scientific Medical Societies (AWMF) in December 2013.

[Specialized clinical facilities for the treatment of highly contagious, life-threatening infectious diseases : a comparison between Germany and 15 European nations]. / Behandlungseinrichtungen für hochkontagiöse, lebensbedrohliche Erkrankungen : Deutschland im Vergleich zu 15 europäischen Staaten.

BACKGROUND: Patients suffering from highly contagious, life-threatening infections should be treated in specialized clinical facilities that follow the highest infection control standards. Consensus statements defining technical equipment and operational procedures have been published in recent years, but the level of adherence to these has not been evaluated. METHODS: Data summarized here comparing German and European isolation facilities are the partial results of a cross-sectional analysis conducted by the "European Network for Highly Infectious Diseases" that included 48 clinical care facilities in 16 European nations. Data collection was conducted using questionnaires and on-site visits, focussing on aspects of infrastructure, technical equipment, and the availability of trained personnel. RESULTS: Although all centres enrolled were listed as "isolation units", all aspects evaluated differed broadly. Eighteen facilities fulfilled the definition of a 'High Level Isolation Unit', as 6/8 enrolled German facilities did. In contrast, 24 facilities could not operate independently from their co-located hospital. DISCUSSION: Within and between nations contributing data disparities regarding the fulfilment of guidelines published were seen. German isolation facilities mostly fulfilled all criteria evaluated and performed on a high technical level. However, data presented do not reflect the current situation in Germany due to the time that has elapsed since the study was conducted. Hence, longitudinal data collection and harmonisation of terminology at least on national level needs to be implemented.

The Frankfurt Ebola patient.

UNLABELLED: Since the Ebola virus was discovered in 1976, the largest outbreak to date is the ongoing epidemic in West Africa based on the number of cases. The number of infected people is high among aid workers, some of whom have been treated at intensive care units in specialized centers in Europe and the USA. A 38-year-old patient who got infected with the Ebola virus was treated in a special isolation ward at the Frankfurt University Hospital from 10/3/14 to 11/19/14. During intensive care of the patient, X-rays were essential for control of the cardiopulmonary system and for follow-up. Special guidelines had to be considered for performing X-rays due to the risk of transmitting the virus. These are presented and discussed in the following. KEY POINTS: Chest radiographs are essential in the intensive care monitoring of Ebola patients. Chest radiographs help to assess the extent of pulmonary edema and capillary leak syndrome. With careful observance of hygiene guidelines, he risk of transmission can be virtually eliminated.

Improved virological and immunological efficacy of resistance-guided switch in antiretroviral therapy: a Frankfurt HIV cohort analysis.

To evaluate the treatment outcome of antiretroviral therapy, depending on the use and utility of a concept of resistance-guided switch, patients from the Frankfurt HIV cohort have been followed for 24 weeks. If available, prior resistance data have been evaluated and patients were grouped into their expected viral response. The data of 354 patients were thus analysed, taking into account the genotypic sensitivity score of the administered medication (> or ≤2). When looking at the proportion of patients who achieved a viral load of <50/ml, the response rates differed significantly better for patients with a favourable resistance scoring as compared to an unfavourable one (71.9 % as compared to 56.0 %, p = 0.008). Interestingly, patients with a favourable resistance score also showed a better immunological response, as measured by median CD4 cell count of 391/µl [interquartal range (IQR) 250-530/µl] against 287/µl (IQR 174-449/µl) and a larger total increase of 141/µl against 38/µl. A significant virological and immunological benefit could be demonstrated for patients of a cohort with resistance-guided antiretroviral therapy adjustments.

[Changing spectrum of renal disease in HIV infection]. / Veränderungen im Spektrum der Nierenerkrankungen bei HIV-Infektion.

BACKGROUND AND OBJECTIVE: Renal disease is a common complication in HIV-infected patients. The causes and spectrum of kidney disease among these patients is extensive, including HIV-related and HIV unrelated causes. Our objective was to assess the changes in distribution of renal disease under antiretroviral therapy (ART). PATIENTS AND METHODS: Retrospective analysis of all patients from the Frankfurt HIV Cohort (FHC) who underwent renal biopsy because of chronic, progressive renal disease between 1989 and 2012. Two time periods were defined: 1989-2001 (early period) and 2000-2012 (late period). RESULTS: 69 HIV-infected patients, mostly Caucasian and male, underwent renal biopsy (early period: 22 patients, late period: 47 patients). During the total observation time immuncomplex-mediated glomerulonephritis (26.1 %), hypertensive (20.3 %) and diabetic nephropathy (20.3 %) were the most frequent causes of chronic renal disease. HIV-associated renal diseases were predominant in the first period, whereas hypertensive and diabetic kidney disease accounted for almost 50 % of cases diagnosed in the late period. Other types of renal disease frequently encountered during the late period include renal AA-amyloidosis and tenofovir-related kidney disease. CONCLUSION: The underlying pathology of renal disease in HIV-infected patients is highly variable and evolving. Since the introduction of HAART, renal disease not directly related to HIV has become the predominant cause, reflecting the growing burden of co-morbidities in this aging population.

Acute kidney injury caused by tenofovir disoproxil fumarate and diclofenac co-administration.

OBJECTIVES: The renal elimination of tenofovir (TFV) may be subject to renal drug-drug interactions that may increase the risk of kidney injury. Case reports indicated that diclofenac might increase TFV-associated nephrotoxicity via a drug-drug interaction, leading to an increased intracellular TFV concentration in proximal tubular cells. METHODS: A retrospective analysis of data for all patients from the Frankfurt HIV Cohort (FHC) who had diclofenac prescriptions between January 2008 and June 2012 was carried out. RESULTS: Among 89 patients with diclofenac use, 61 patients (68.5%) were treated with tenofovir disoproxil fumarate (TDF) and 28 patients (31.5%) were treated with TDF-sparing combination antiretroviral therapy (cART). Thirteen patients (14.6%) developed acute kidney injury (AKI) shortly after initiating diclofenac treatment. AKI occurred exclusively in TDF-treated patients, although all had previously stable renal function. All cases were accompanied by new onset of at least two parameters indicating proximal tubular damage, such as normoglycaemic-glucosuria and hypophosphataemia. TFV-associated nephrotoxicity was demonstrated by renal biopsy in four cases. Additionally, 11.5% of patients on TDF treatment developed new-onset proximal tubular damage, while having a preserved glomerular filtration rate. In contrast, diclofenac did not affect renal function in patients with TDF-sparing cART, as only one case of isolated hypophataemia was observed in these patients. In univariate analysis, risk factors for AKI were TDF-containing cART (P = 0.0076) and pre-existing hypophosphataemia (P = 0.0086). CONCLUSIONS: Drug-drug interaction caused by diclofenac could exacerbate TFV-associated nephrotoxicity. Diclofenac should be used with caution in patients on TDF therapy, especially in those with hypophosphataemia. Our findings need to be confirmed in larger studies.

Delay in the administration of appropriate antimicrobial therapy in Staphylococcus aureus bloodstream infection: a prospective multicenter hospital-based cohort study.

OBJECTIVES: Early broad-spectrum antimicrobial treatment reduces mortality in patients with septic shock. In a multicenter, prospective observational study, we explored whether delayed appropriate antimicrobial therapy (AAT) influences outcome in Staphylococcus aureus bloodstream infection (SAB). METHODS: Two hundred and fifty-six patients with SAB from ten German study centers were enrolled and followed for 3 months. Predisposing factors, clinical features, diagnostic procedures, antimicrobial therapy, and outcome were recorded. The appropriateness of antimicrobial therapy was judged by a trained physician based on in vitro activity, dosage, and duration of therapy. Therapy was considered to be delayed when more than 24 h elapsed between the first positive blood culture and the start of appropriate therapy. The association of delayed therapy with overall mortality and SAB-related events (i.e., attributable mortality or late SAB-related complications) was assessed by crosstabulation and propensity score-based logistic regression. RESULTS: One hundred and sixty-eight patients received AAT during their hospital stay, of whom 42 (25%) received delayed AAT. The overall mortality and the occurrence of severe sepsis or septic shock were lower in patients with delayed AAT, pointing towards confounding by indication. Adjusted 90-day mortality (adjusted odds ratio [OR] 0.91, 95% confidence interval [CI] [0.39-2.13], p 0.82) and SAB-related events (adjusted OR 1.46, 95% CI [0.47-4.51], p 0.52) also failed to show a significant impact of delayed AAT on outcome. CONCLUSION: In patients with SAB, early AAT may not improve survival. However, confounding by indication is a major challenge when analyzing and interpreting observational studies on the impact of delayed AAT.

End-stage renal disease and dialysis in HIV-positive patients: observations from a long-term cohort study with a follow-up of 22 years.

OBJECTIVES: Renal disease is a common and serious complication in HIV-infected patients. METHODS: A retrospective cohort analysis for the period 1989-2010 was carried out to determine the prevalence, incidence and risk factors for end-stage renal disease (ESRD). ESRD was defined as initiation of renal replacement therapy. Three time periods were defined: 1989-1996 [pre-highly active antiretroviral therapy (HAART)], 1997-2003 (early HAART) and 2004-2010 (late HAART). RESULTS: Data for 9198 patients [78.2% male; 88.9% Caucasian; cumulative observation time 68 084 patient-years (PY)] were analysed. ESRD was newly diagnosed in 35 patients (0.38%). Risk factors for ESRD were Black ethnicity [relative risk (RR) 5.1; 95% confidence interval (CI) 2.3-10.3; P < 0.0001], injecting drug use (IDU) (RR 2.3; 95% CI 1.1-4.6; P = 0.02) and hepatitis C virus (HCV) coinfection (RR 2.2; 95% CI 1.1-4.2; P = 0.03). The incidence of ESRD decreased in Black patients over the three time periods [from 788.8 to 130.5 and 164.1 per 100 000 PY of follow-up (PYFU), respectively], but increased in Caucasian patients (from 29.9 to 41.0 and 43.4 per 100 000 PYFU, respectively). The prevalence of ESRD increased over time and reached 1.9 per 1000 patients in 2010. Mortality for patients with ESRD decreased nonsignificantly from period 1 to 2 (RR 0.72; P = 0.52), but significantly from period 1 to 3 (RR 0.24; P = 0.006), whereas for patients without ESRD mortality decreased significantly for all comparisons. ESRD was associated with a high overall mortality (RR 9.9; 95% CI 6.3-14.5; P < 0.0001). CONCLUSION: As a result of longer survival, the prevalence of ESRD is increasing but remains associated with a high mortality. The incidence of ESRD declined in Black but not in Caucasian patients. IDU and HCV were identified as additional risk factors for the development of ESRD.

Tuberculosis skin test, but not interferon-γ-releasing assays is affected by BCG vaccination in HIV patients.

OBJECTIVE: Of this study was to compare the results of tuberculin skin test (TST) with two interferon-γ releasing-assays (IGRA) in a cohort of HIV positive patients, to analyze impact of prior Bacille-Calmette-Guérin (BCG)-vaccination. METHODS: Prospective cross sectional study, enrolling only asymptomatic adult HIV infected outpatients from a large German University hospital clinic. All participants were simultaneously tested for latent tuberculosis infection (LTBI) by QuantiFERON-TB Gold, T-SPOT.TB and TST. Only individuals with available definite results (positive/negative, indeterminates excluded) from all three test systems and recalling BCG-vaccination status by interview questionnaire were evaluated. RESULTS: From 286 study participants, 133 were evaluable; BCG-vaccination history was positive for 18 individuals, and negative for 115. The proportion of individuals with a positive TST was significantly higher for vaccinated (n = 6, 33.3%) than for unvaccinated individuals (n = 13, 11.3%, p = 0.013). There were no significant differences in the proportion of patients with CDC stage C, origin from a TB endemic country or in the CD4 count between the two groups. CONCLUSION: TST but not IGRAs interfered significantly with prior BCG vaccination in a cohort of HIV infected individuals from a low prevalence TB country. Therefore IGRA should preferentially be used for LTBI-testing in BCG-vaccinated adult HIV-patients.

Infection control practices in facilities for highly infectious diseases across Europe.

BACKGROUND: The management of patients with highly infectious diseases (HIDs) is a challenge for healthcare provision requiring a high level of care without compromising the safety of other patients and healthcare workers. AIM: To study the infection control practice in isolation facilities participating in the European Network for Highly Infectious Diseases (EuroNHID) project. METHODS: A survey was conducted during 2009 of 48 isolation facilities caring for patients with HIDs in 16 European countries. Checklists and standard evaluation forms were used to collect and interpret data on hand hygiene, routine hygiene and disinfection, and waste management. FINDINGS: Forty percent of HIDs had no non-hand-operated sinks or alcohol-based antiseptic distributors, while 27% did not have procedures for routine hygiene, final disinfection, or safe discarding of non-disposable objects or equipment. There was considerable variation in the management of waste and in the training of housekeeping personnel. EuroNHID has developed recommendations for hand hygiene, disinfection, routine hygiene, and waste management. CONCLUSIONS: Most aspects of hand hygiene, routine hygiene and disinfection, and waste management were considered at least partially adequate in the majority of European isolation facilities dedicated for the care of patients with HIDs. But considerable variability was observed, with management of waste and training of housekeeping personnel being generally less satisfactory.

Trypanosoma brucei rhodesiense infection in a German traveller returning from the Masai Mara area, Kenya, January 2012.

In January 2012, a case of Human African Trypanosomiasis (HAT) has been identified in Germany in a traveller returning from the Masai Mara area in Kenya. The 62-year-old man had travelled to the Masai Mara game park from 18 to 19 January 2012 and developed fever on 28 January. The infection with Trypanosoma brucei rhodesiense was confirmed by laboratory testing three days hereafter.

Isolation rooms for highly infectious diseases: an inventory of capabilities in European countries.

Isolation of patients with highly infectious diseases (HIDs) in hospital rooms with adequate technical facilities is essential to reduce the risk of spreading disease. The European Network for Infectious Diseases (EUNID), a project co-funded by European Commission and involving 16 European Union member states, performed an inventory of high level isolation rooms (HIRs, hospital rooms with negative pressure and anteroom). In participating countries, HIRs are available in at least 211 hospitals, with at least 1789 hospital beds. The adequacy of this number is not known and will depend on prevailing circumstances. Sporadic HID cases can be managed in the available HIRs. HIRs could also have a role in the initial phases of an influenza pandemic. However, large outbreaks due to natural or to bioterrorist events will need management strategies involving healthcare facilities other than HIRs.

EuroNHID checklists for the assessment of high-level isolation units and referral centres for highly infectious diseases: results from the pilot phase of a European survey.

Healthcare settings have been identified as preferential for the transmission of many agents causing highly infectious diseases (HIDs). Infection control procedures strongly reduce the risk of transmission of HIDs in hospital settings, when adequately applied. The main objective of the European Network for Highly Infectious Diseases (EuroNHID), a network co-funded by the European Commission, is to assess the current capabilities for dealing with HIDs in Europe, specifically in the context of infection control and healthcare worker (HCW) safety, through conducting an on-the-field survey of high-level isolation units (HLIUs)/referral centres for the management of HIDs in participating countries. During the first year of the project's activities, specifically designed, evidence-based checklists were developed. This review introduces the EuroNHID checklists as a standard tool for the assessment of hospital capabilities concerning infection control and HCW safety in the management of patients with HIDs, and presents preliminary results from five HLIUs.

European concepts for the domestic transport of highly infectious patients.

Highly infectious diseases involve clinical syndromes ranging from single to multiorgan infections and pose a constant threat to the public. In the absence of a definite treatment for most causative agents, patients benefit from maximum supportive care as clinical conditions may deteriorate in the short term. Hence, following initial case identification and isolation, rapid transportation to a specialized treatment unit must be considered in order to minimize the risk of secondary infections, but this is limited by available infrastructure, accessible care en route and the patient's clinical condition. Despite the development of consensus curricula for the clinical management of highly infectious patients, medical transportation lacks a common European approach. This article describes, as examples, three current European concepts for the domestic relocation of highly infectious patients by ground vehicles and aircraft with respect to national legislation and geography.

A curriculum for training healthcare workers in the management of highly infectious diseases.

The SARS epidemic, the threat of bioterrorism, and recent examples of imported highly infectious diseases (HID) in Europe have all highlighted the importance of competent clinical and public health management of infectious disease emergencies. Although the European Union of Medical Specialists in Europe and the Infectious Diseases Society of America have developed curricula for training in infectious disease medicine, neither of those mentions training in the management of HIDs. The European Network for Infectious Diseases (EUNID, http://www.eunid.com) is a European Commission co-funded network of experts in HID management, created to help improve the preparedness for HID emergencies within Europe. One of EUNID's agreed tasks is the development of a curriculum for such a training. Between April 2005 and September 2006, EUNID developed a curriculum and accompanying training course on the basis of a questionnaire that was sent to all country representatives and discussion, followed by amendment of drafts shared through the project website, and a final consensus meeting. The resulting curriculum consists of a two-module course covering the core knowledge and skills that healthcare workers need to safely treat a patient who has, or who may have, an HID. The first module introduces theoretical aspects of HID management, including disease-specific knowledge, infection control, and the public health response, through didactic teaching and class-based discussion. The second module involves a "skill station" and a clinical scenario, and equips trainees with relevant practical skills, including the use of specialised equipment and teamwork practice in patient management. Together, the curriculum and course contribute to the creation of a common framework for training healthcare professionals in Europe, and although they are designed primarily for clinicians that are directly involved in patient care, they are relevant also to public health professionals and others who may be involved in HID management and emergency response.

First case of successful allogeneic stem cell transplantation in an HIV-patient who acquired severe aplastic anemia.

We report on the first successful allogeneic stem cell transplantation (SCT) in an HIV-infected patient with severe aplastic anemia (SAA) per- formed at a tertiary care institution. Highly active antiretroviral therapy (HAART) was administered until transplantation and restarted 34 days later with sustained virological response. The patient did however develop a rapid rise in HIV load during the interruption of HAART associated with an acute febrile illness. Due to the extended period between the onset of SAA until SCT, the posttransplant course was complicated by bacterial infections. Stage two skin GvHD, but no AIDS-defining opportunistic diseases were experienced. Neutrophils recovered to >0.5/nL on day +18 and the CD4 count reached 250/microL on day +71 and >500/microL on day +182. The patient is in good condition with an ECOG score of 0 twelve months after transplantation. This report demonstrates the feasibility of allogeneic stem cell transplantation in the HIV setting.