Serological Protection Rates against TBEV Infection in Blood Donors from a Highly Endemic Region in Southern Germany.

BACKGROUND: Tick-borne encephalitis (TBE) is the most significant tick-borne disease in Europe and Asia, with more than 10,000 cases per year worldwide. A surge of reported TBE cases can be observed despite the availability of highly efficient vaccines. There is little known about the serological immune protection rate of the population in Germany. The seroprotection rate is defined as the presence of neutralizing antibodies. In contrast, the vaccination rate, as defined by public health agencies, may differ from the true protection rate in a population. MATERIALS AND METHODS: 2220 blood samples from inhabitants of the county Ortenaukreis in the Federal State of Baden-Württemberg in Germany were included in the study. These were tested for anti-TBEV IgG antibodies by an anti-TBEV-IgG-ELISA. Subsequently, all TBEV-IgG positive samples were confirmed for neutralizing antibodies in the micro serum neutralization assay. RESULTS: From the overall 2220 samples, 2104 were included in the comparison because of the selection of specific age groups (ages 20-69). In our sample size, we found an average serological protection rate (presence of neutralizing antibodies) of 57% (518/908) for the female blood donors and of 52% (632/1196) for the male blood donors. DISCUSSION: In this study, we present new findings on a highly endemic region in southern Germany. Additionally, we present current data regarding the serological TBEV protection rates in the Ortenaukreis in southern Germany and compare these with a dataset published by the RKI, which is based on vaccination reports of the primary care providers and health care insurers, and with a self-reporting study conducted by a vaccine manufacturer. Our results significantly exceed the official numbers of average active vaccination status by 23.2% for females and by 21% for males. This might indicate an even longer persistence of TBE-vaccination-induced antibody titers than previously assumed.

Tick-borne encephalitis virus IgG antibody surveillance: vaccination- and infection-induced seroprevalences, south-western Germany, 2021.

BackgroundThe exact epidemiology of tick-borne encephalitis virus (TBEV) infections is unknown because many TBEV infections have an influenza-like or asymptomatic course. Surveillance data are based on patients with any (predominantly neurological) symptoms that prompted diagnostic testing. Infection- and vaccine-induced antibodies against TBEV can be distinguished using an NS1 IgG ELISA.AimIn a seroprevalence study we aimed to investigate TBEV antibody prevalence, incidences, manifestation indices and potential protection rates in a highly endemic district in south-western Germany.MethodsWe analysed 2,220 samples from healthy blood donors collected between May and September 2021. The reported number of TBEV infections was provided on a sub-district level by the local public health authorities. Blood samples were first screened using a TBEV IgG ELISA. In a second step, all positive samples were further analysed with a recently established NS1 IgG ELISA. The presence of specific antibodies against TBEV (excluding cross-reacting antibodies against other flaviviruses) was confirmed by testing screening-positive samples with a microneutralisation assay.ResultsOf 2,220 included samples, 1,257 (57%) tested positive by TBEV IgG ELISA and 125 tested positive for infection-induced TBEV NS1 antibodies, resulting in a TBEV NS1 IgG seroprevalence at 5.6% in our population. The yearly incidence based on the NS1 ELISA findings resulted in 283 cases per 100,000 inhabitants.ConclusionUsing the TBEV NS1 IgG assay, we confirmed a manifestation index of ca 2% and a high incidence of predominantly silent TBEV infections (> 250/100,000/year), which exceeds the incidence of notified cases (4.7/100,000/year) considerably.

Decoding the Geography of Natural TBEV Microfoci in Germany: A Geostatistical Approach Based on Land-Use Patterns and Climatological Conditions.

Background: Tickborne-encephalitis (TBE) is a potentially life-threating neurological disease that is mainly transmitted by ticks. The goal of the present study is to analyze the potential uniform environmental patterns of the identified TBEV microfoci in Germany. The results are used to calculate probabilities for the present distribution of TBEV microfoci in Germany based on a geostatistical model. Methods: We aim to consider the specification of environmental characteristics of locations of TBEV microfoci detected in Germany using open access epidemiological, geographical and climatological data sources. We use a two-step geostatistical approach, where in a first step, the characteristics of a broad set of environmental variables between the 56 TBEV microfoci and a control or comparator set of 3575 sampling points covering Germany are compared using Fisher's Exact Test. In the second step, we select the most important variables, which are then used in a MaxEnt distribution model to calculate a high resolution (400 × 400 m) probability map for the presence of TBEV covering the entire area of Germany. Results: The findings from the MaxEnt prediction model indicate that multi annual actual evapotranspiration (27.0%) and multi annual hot days (22.5%) have the highest contribution to our model. These two variables are followed by four additional variables with a lower, but still important, explanatory influence: Land cover classes (19.6%), multi annual minimum air temperature (14.9%), multi annual sunshine duration (9.0%), and distance to coniferous and mixed forest border (7.0%). Conclusions: Our findings are based on defined TBEV microfoci with known histories of infection and the repeated confirmation of the virus in the last years, resulting in an in-depth high-resolution model/map of TBEV microfoci in Germany. Multi annual actual evapotranspiration (27%) and multi annual hot days (22.5%) have the most explanatory power in our model. The results may be used to tailor specific regional preventive measures and investigations.

SARS-CoV-2 Seroprevalence among Health Care Workers-A Voluntary Screening Study in a Regional Medical Center in Southern Germany.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is associated with a potentially severe clinical manifestation, coronavirus disease 2019 (COVID-19), and currently poses a worldwide challenge. Health care workers (HCWs) are at the forefront of any health care system and thus especially at risk for SARS-CoV-2 infection due to their potentially frequent and close contact with patients suffering from COVID-19. Serum samples from 198 HCWs with direct patient contact of a regional medical center and several outpatient facilities were collected during the early phase of the pandemic (April 2020) and tested for SARS-CoV-2-specific antibodies. Commercially available IgA- and IgG-specific ELISAs were used as screening technique, followed by an in-house neutralization assay for confirmation. Neutralizing SARS-CoV-2-specific antibodies were detected in seven of 198 (3.5%) tested HCWs. There was no significant difference in seroprevalence between the regional medical center (3.4%) and the outpatient institution (5%). The overall seroprevalence of neutralizing SARS-CoV-2-specific antibodies in HCWs in both a large regional medical center and a small outpatient institution was low (3.5%) at the beginning of April 2020. The findings may indicate that the timely implemented preventive measures (strict hygiene protocols, personal protective equipment) were effective to protect from transmission of an airborne virus when only limited information on the pathogen was available.

The complex interplay of climate, TBEV vector dynamics and TBEV infection rates in ticks-Monitoring a natural TBEV focus in Germany, 2009-2018.

BACKGROUND: Tick-borne encephalitis (TBE) is the most important tick-borne viral disease in Eurasia and causes disease in humans and in a number of animals, among them dogs and horses. There is still no good correlation between tick numbers, weather conditions and human cases. There is the hypothesis that co-feeding due to simultaneous occurrence of larvae and nymphs may be a factor for the increased transmission of the virus in nature and for human disease. Based on long-term data from a natural TBEV focus, phylogenetic results and meteorological data we sought to challenge this hypothesis. METHODS: Ticks from an identified TBE natural focus were sampled monthly from 04/2009 to 12/2018. Ticks were identified and pooled. Pools were tested by RT-qPCR. Positive pools were confirmed by virus isolation and/or sequencing of additional genes (E gene, NS2 gene). Temperature data such as the decadal (10-day) mean daily maximum air temperature (DMDMAT) were obtained from a nearby weather station and statistical correlations between tick occurrence and minimal infection rates (MIR) were calculated. RESULTS: In the study period from 04/2009 to 12/2018 a total of 15,530 ticks (2,226 females, 2,268 males, 11,036 nymphs) were collected. The overall MIR in nymphs over the whole period was 77/15,530 (0.49%), ranging from 0.09% (2009) to 1.36% (2015). The overall MIR of female ticks was 0.76% (17/2,226 ticks), range 0.14% (2013) to 3.59% (2016). The overall MIR of males was 0.57% (13/2,268 ticks), range from 0.26% (2009) to 0.97% (2015). The number of nymphs was statistically associated with a later start of spring/vegetation period, indicated by the onset of forsythia flowering. CONCLUSION: There was no particular correlation between DMDMAT dynamics in spring and/or autumn and the MIR of nymphs or adult ticks detected. However, there was a positive correlation between the number of nymphs and the number of reported human TBE cases in the following months, but not in the following year. The hypothesis of the importance of co-feeding of larvae and nymphs for the maintenance of transmission cycle of TBEV in nature is not supported by our findings.

Knowledge, habits and attitudes towards TBE and other tick-borne diseases in German forestry trainees.

Tick-borne encephalitis (TBE) is an occupational hazard for forestry workers. We measured knowledge levels, misbeliefs, and vaccination rates in forestry trainees in order to tailor specific measures aimed at reducing occupational TBE incidence. A paper-based survey was performed at a central training site for forestry workers in the state of Baden-Wuerttemberg. The questionnaire contained items regarding vaccination status against tick-borne encephalitis virus (TBEV), self-reported tick-borne diseases, knowledge of and attitudes towards tick-borne disease, and practices in the context of ticks and tick bites. All trainees in the period June-December 2018 were surveyed. Statistical analyses were conducted using Mann-Whitney-Rank sum test and one-way ANOVA tests. Two-hundred-twenty-five trainees participated in the survey. Almost all (>99%) were aware of living in a TBE high-risk area. Eighty-three percent of respondents were vaccinated in line with current recommendations. Seventeen percent had no effective vaccination status. Twenty-seven percent believed that ticks can transmit only TBEV and Borrelia spp. Sixty-two percent knew that TBEV infections can be fatal. Only 8% of respondents use tick repellents and only 17% wear long sleeves and pants. Trainees who graduated from a six and (eight or) nine secondary school (Realschule and Abitur respectively) had more knowledge on ticks and tick-borne disease compared to graduates from a five year school (Hauptschule) (p = 0.002 and p = 0,037 respectively). Overall, the TBE vaccination rate is not high enough in this high-risk occupational group. We identified gaps in knowledge and practices that could have an impact on TBE incidence in this group if addressed. Further epidemiological research is needed on knowledge, attitudes, and practices in different high-risk populations.

Tick-borne encephalitis virus infections in Germany. Seasonality and in-year patterns. A retrospective analysis from 2001-2018.

BACKGROUND: Little is known regarding the changing seasonality of infections with the tick-borne encephalitis virus (TBEV) and the incidence of the resulting disease over the last two decades. Seasonal patterns have to our knowledge not previously been systematically investigated and are poorly understood. We investigate emerging seasonal changes in clinical aspects like potentially increasing hospitalization during the year, variations in clinical symptoms and disease severity during the season and seasonal dynamics of fatal outcomes. MATERIAL AND METHODS: TBEV infection became a notifiable disease in Germany in 2001. We used the national reporting dataset spanning from 2001-2018, provided by the Robert Koch-Institute (RKI). There were general epidemiological variables available, including "symptom onset", "age" and "sex". Furthermore, several variables documented disease severity. These included "CNS symptoms", "myelitis", "fatal outcome" and "hospitalization". Potential factors influencing the occurrence of CNS symptoms, myelitis, hospitalizations and fatal outcome were analyzed using logistic regression models. Linear trends, including the "time point in year" at which TBEV infection related symptoms were detected, were tested using calendar year as a continuous covariate. In addition, seasonal trends and age and sex specific differences were exploratively tested for non-linear effects using restricted cubic splines with knot locations based on Harrell's recommended percentiles. Finally, the dynamic relationship between in-seasonal trends year of detection, sex and age was tested using interaction terms. RESULTS: 6,073 TBEV infection cases from 2001-2018 were included in our analysis. We find that from 2001-2018 TBEV infections are reported 0.69 days earlier each year (p<0.001). There was no detectable seasonal variation regarding the occurrence of fatal outcome, CNS and myelitis. However, there was a significant changing trend regarding hospitalizations over the course of the year: The risk for hospitalization increases until August, decreases again from October on. CONCLUSION: We present epidemiological evidence that the TBE season in Germany has shifted to start earlier over the last years, beginning approximately 12 days earlier in 2018 than it did in 2001. There are seasonal patterns regarding a higher risk of hospitalization during August.

A headache with surprising outcome: first case of brucellosis caused by Brucella suis biovar 1 in Germany.

In July 2018, brucellosis was diagnosed in a German patient without a travel history to regions endemic for Brucella. Microbiological analysis, including whole-genome sequencing, revealed Brucella suis biovar 1 as the etiologic agent. Core-genome-based multilocus sequence-typing analysis placed the isolate in close proximity to strains originating from Argentina. Notably, despite a strong IgM response, the patient did not develop Brucella-specific IgG antibodies during infection. Here, we describe the clinical course of infection, the extensive epidemiological investigations, and discuss possible routes of transmission.

Phylogenetics of tick-borne encephalitis virus in endemic foci in the upper Rhine region in France and Germany.

OBJECTIVE: Tick-borne encephalitis (TBE) caused by the tick-borne encephalitis virus (TBEV) is the most important tick-borne arboviral disease in Europe and Asia. The Upper Rhine Valley is thought to be the very western border of TBEV distribution in Europe. The aim of our study was to identify natural foci and isolate TBEV from ticks, to determine the prevalence of TBEV in local tick populations and to study the phylogenetic relatedness of circulating TBEV strains in this region. MATERIAL AND METHODS: Ticks were collected between 2016, 2017 and 2018 by flagging. TBEV was isolated from collected ticks and phylogenetic analyses were performed. Minimal infection rates (MIR) of the collected ticks were calculated. RESULTS: At 12 sampling sites, a total of 4,064 Ixodes ticks were collected in 2016 and 2017 -(and one single collection 2018). 953 male, 856 female adult ticks and 2,255 nymphs were identified. The MIR rates were 0,17% (1/595) for Schiltach (Germany) and 0,11% (1/944) for Foret de la Robertsau (France), respectively. Overall, the three newly described TBEV strains, isolated in the years 2016 and 2017 from the Upper Rhine Valley have no close phylogenetic relation and show a genetic relationship with strains from eastern Europe. The 2018 TBEV strain from Aubachstrasse (Germany), however, is closely related to the TBEV found in Schiltach (Germany). CONCLUSION: In conclusion, we demonstrate, to our knowledge for the first time, the phylogenetic relations of the newly isolated TBEV strains on both sides of the upper Rhine river.

Five cases of vector-borne Francisella tularensis holarctica infections in south-western Germany and genetic diversity.

Tularemia is a rare zoonotic disease in Germany. Francisella tularensis has been isolated previously from ticks in southern Germany underscoring the importance of ticks (Ixodes ricinus) in tularemia transmission, but there have been only few reports from this region with single cases or small case series of tick-borne transmissions of tularemia. We report five cases of non-game animal associated tularemia diagnosed from 2010 to 2016 in southwestern Germany - Baden-Wuerttemberg. Our case series and molecular typing (MLVA) results add published clinical experience to this underdiagnosed disease and consolidate previous findings regarding tick-borne transmission of tularemia and phylogenetic diversity in Germany.

Pediatric antibiotic stewardship: successful interventions to reduce broad-spectrum antibiotic use on general pediatric wards.

PURPOSE: Antibiotic stewardship programs (ASP) optimize antibiotic usage and combat antibiotic resistance of bacteria. The objective of this study was to assess the impact of specific ASP interventions on antibiotic consumption in general pediatric wards. METHODS: We conducted a prospective study to compare a pre-intervention (Sept.-Dec. 2014) and post-intervention (Sept.-Dec. 2015) period. An ASP bundle was established including (1) infectious diseases (ID) ward rounds (prospective-audit-with-feedback), (2) ID consultation service, (3) internal guidelines on empiric antibiotic therapy. Medical records on four general pediatric wards were reviewed daily to analyze: (1) antibiotic consumption, (2) antibiotic dosage ranges according to local guidelines, and (3) guideline adherence for community-acquired pneumonia (CAP). RESULTS: Antibiotic prescribing for 273 patients (pre-intervention) was compared to 263 patients (post-intervention). Antibiotic prescription rate did not change (30.6 vs. 30.5%). However, overall days-of-therapy and length-of-therapy decreased by 10.5 and 7.7%, respectively. Use of cephalosporins and fluoroquinolones decreased by 35.5 and 59.9%, whereas the use of penicillins increased by 15.0%. An increase in dosage accuracy was noted (78.8 vs. 97.6%) and guideline adherence for CAP improved from 39.5 to 93.5%. Between the two study periods, no adverse effects regarding length of hospital stay and in-hospital mortality were observed. CONCLUSIONS: Our data demonstrate that implementation of an ASP was associated with a profound improvement of rational antibiotic use and, therefore, patient safety. Considering the relatively short observation period, the long-term effects of our ASP bundle need to be further investigated.

Implementing an intensified antibiotic stewardship programme targeting daptomycin use in orthopaedic surgery: a cost-benefit analysis from the hospital perspective.

BACKGROUND: Hospital antibiotic stewardship (ABS) programmes offer several evidence-based tools to control prescription rates of antibiotics in different settings, influence the incidence of nosocomial infections and to contain the development of multi-drug-resistant bacteria. In the context of endoprosthetic surgery, however, knowledge of core antibiotic stewardship strategies, comparisons of costs and benefits of hospital ABS programmes are still lacking. MATERIALS AND METHODS: We identified a high daptomycin use for the treatment of methicillin-sensitive staphylococcal infections as a potential target for our ABS intervention. In addition, we endorsed periprosthetic tissue cultures for the diagnosis of PJI. Monthly antibiotic use data were obtained from the hospital pharmacy and were expressed as WHO-ATC defined daily doses (DDD) and dose definitions adapted to local guidelines (recommended daily doses, RDD), normalized per 1000 patient days. The pre-intervention period was defined from February 2012 through January 2014 (24 months). The post-intervention period included monthly time points from February 2014 to April 2015 (15 months). For a basic cost-benefit analysis from the hospital perspective, three cost drivers were taken into account: (1) the cost savings due to changes in antimicrobial prescribing; (2) costs associated with the increase in the number of cultured tissue samples, and (3) the appointment of an infectious disease consultant. Interrupted time-series analysis (ITS) was applied. RESULTS: Descriptive analysis of the usage data showed a decline in overall use of anti-infective substances in the post-intervention period (334.9 vs. 221.4 RDDs/1000 patient days). The drug use density of daptomycin dropped by -75 % (51.7 vs. 12.9 RDD/1000 patient days), whereas the utilization of narrow-spectrum penicillins, in particular flucloxacillin, increased from 13.8 to 33.6 RDDs/1000 patient days. ITS analysis of the consumption dataset showed significant level changes for overall prescriptions, as well as for daptomycin (p < 0.001) and for narrow-spectrum penicillins (p = 0.001). The total costs of antibiotic consumption decreased by an estimated € 4563 per month (p < 0.001), and around 90 % of these savings were linked to a decrease in daptomycin consumption. Overall, the antibiotic stewardship programme was beneficial, as monthly cost savings of € 2575 (p = 0.005) were achieved. INTERPRETATION: In this example of large endoprosthetic surgery department in a community-based hospital, the applied hospital ABS programme targeting daptomycin use has shown to be feasible, effective and beneficial compared to no intervention.

Diagnosis of prosthetic joint infections using UMD-Universal Kit and the automated multiplex-PCR Unyvero i60 ITI(®) cartridge system: a pilot study.

BACKGROUND: Prosthetic joint infections (PJI) are associated with high morbidity and costs. Various efforts have been made to improve the diagnosis of PJI over the past years, but only few studies have assessed the diagnostic utility of nucleic acid amplification test (NAAT) techniques in this context. Here, we report our experience with a commercial 16S rRNA gene PCR and an automated multiplex-PCR cartridge system in identifying pathogens causing PJI. MATERIALS AND METHODS: A prospective single-centre study was performed including 54 patients with either septic or aseptic prosthetic joint replacement or surgical revision between February 2012 and April 2013. Conventional cultures of periprosthetic tissue samples were compared with the results of broad-range 16S rRNA gene real-time PCR (UMD-Universal Pathogen DNA Extraction and PCR Analysis, Molzym GmbH, Germany) and the multiplex-PCR Unyvero ITI(®) cartridge system (U-ITI; Curetis AG, Germany). Conventional culture and broad-range 16S rRNA gene real-time PCR were performed on all samples. U-ITI was used in a subgroup of 28 cases including all culture-positive cases. The agreement of the results from the methods was assessed. RESULTS: Of 54 cases, seven were culture-positive. Broad-range 16S rRNA gene real-time PCR gave 6, U-ITI 3 concordant positive results. Of the 47 culture-negative samples, 46 were also negative by broad-range 16S rRNA gene real-time PCR resulting in a 96 % (52/54) agreement between 16S rRNA gene PCR and culture. Of the 21 culture-negative samples analysed with U-ITI, 20 gave negative results, including the single 16S rRNA gene PCR-positive/culture-negative specimen. The rate of agreement between U-ITI and culture results was 82 % (23/28). CONCLUSION: This pilot study gave no indication of superiority of the used NAATs over conventional culture methods for the microbiological diagnosis of PJI. Drawbacks are susceptibility to contamination in the case of 16S rRNA gene real-time PCR, labour-intensive DNA extraction and limited pathogen panel in the case of the multiplex cartridge PCR system. More prospective trials are needed to evaluate the diagnostic performance of NAATs and their impact on the clinical management of PJI.

[How to do: Blood culture]. / Abnahme von Blutkulturen.

The detection of living microorganisms in the blood of a patient is of major diagnostic and prognostic importance. Blood cultures are the goldstandard in the diagnosis of BSIs (bloodstream infections). The "How to do: Blood culture collection" article provides a step-by-step approach to this method. The importance of obtaining blood cultures, indications and common pitfalls are explained in this teaching manuscript.

Hospital use of systemic antifungal drugs: a multi-center surveillance update from Germany.

BACKGROUND: The consumption of antifungal agents increased over the last decade, resulting in the development of resistant organisms and causing a significant pharmaco economic burden. Antifungal drugs are widely used for the treatment of systemic fungal infections and high-risk patients, especially with severe hematological or oncological conditions. Up to date, there are no reliable and systematically reported data on the consumption of antifungal substances on a nationwide level available. The presented study gives an update to the previously published multicenter study investigating antifungal consumption in different settings from five university hospital centers in Germany from 2001 to 2003. METHODS: Consumption data for systemic antifungal drugs were obtained through the hospital pharmacies for 2001-2003 and 2008-2011 regarding the medical and surgical services of five university hospital centers in Germany (A-E). Drug use densities were calculated as yearly RDDs/100 patient days. These calculations were performed for the surgical and medical services, and independently for surgical and medical ICUs, as well as for the hematology-oncology services. RESULTS: We report an increased utilization of systemic antifungal drugs in both study periods. The mean drug use density (mean value of all 5 hospitals) in the medical services increased by 24% between 2001 and 2003. In 2011, this value was 37% above the level from 2001 (12.4 RDD/100 patient days in 2001, 15.4 RDD/100 patient days in 2003, 17.0 RDD/100 patient days in 2011). The 4-year average drug use density (2008-2011) of medical services ranged between 11.6 RDD/100 patient days (hospital E) and 23.8 RDD/100 patient days (hospital A). Drug use densities were in medical intensive care units 29.4 RDD/100 patient days and hematology-oncology services 49.9 RDD/100 patient days. CONCLUSIONS: Despite the variability of the prescribing patterns between the tertiary hospitals, the presented pharmaco-epidemiological data are a cornerstone for the initiation and implementation of effective antifungal stewardship programmes and might serve as important benchmarking information for other hospitals with similar structures and baseline settings.

Implementation of an intensified antibiotic stewardship programme targeting third-generation cephalosporin and fluoroquinolone use in an emergency medicine department.

INTRODUCTION: Early initiation of antimicrobial treatment for acute infection is an important task in the emergency department (ED) with a likely impact on the hospital-wide antibiotic use pattern. We implemented an antibiotic stewardship (ABS) programme focused on non-trauma emergency patients at a large university hospital centre targeting broad-spectrum cephalosporin and fluoroquinolone use. METHODS: Guidelines and focused discussion groups emphasised reduced prescription of third-generation cephalosporins and fluoroquinolones and encouraged penicillins. Antibiotic consumption expressed as monthly drug density in WHO-Anatomical Therapeutic Chemical defined and locally recommended daily doses (DDD and RDD) per 100 patient days was analysed before (January 2008 to October 2011) and after starting the intervention (January 2012 to October 2013). We performed a before-and-after uncontrolled interventional study using interrupted time-series (ITS) analysis in one ED to investigate ABS intervention-related effects in a quasiexperimental research setting. RESULTS: The mean monthly total antibiotic use density declined from 111 RDD (138 DDD) per 100 patient days before the intervention to 86 RDD (128 DDD) per 100 patient days after starting the intervention. Among the different antibacterial drug classes, the consumption of third-generation cephalosporins showed the largest reduction and dropped significantly by -68% between preintervention and postintervention periods. Using the RDD dataset, ITS confirmed a highly significant postintervention change in level of third-generation cephalosporins (-15.2, 95% CI (-24.08 to -6.311)) and a corresponding increase in the use of aminopenicillin/betalactamase inhibitor formulations (+6.6, 95% CI (4.169 to 9.069)). The drug use densities for fluoroquinolones and for overall antibiotics declined, however, the postinterventional level changes missed statistical significance--overall (95% CI (-39.99 to 0.466), fluoroquinolones 95% CI (-11.72 to 4.333)). CONCLUSIONS: An intensified ABS programme using non-restrictive tools targeting third-generation cephalosporin and fluoroquinolone use in the setting of a large academic hospital emergency medicine department is feasible and effective. The intervention may serve as a model for other emergency medicine departments at hospitals with a similar structure and baseline situation.

Adherence to an antibiotic stewardship bundle targeting Staphylococcus aureus blood stream infections at a 200-bed community hospital.

PURPOSE: Bacteremia with Staphylococcus aureus (SAB) is a serious clinical condition and is associated with a high mortality, ranging from 20 to 40 %. Different trials from tertiary referral hospitals demonstrate that infectious disease consultation and adherence to standard of care indicators reduce the high mortality. Data from <250-bed general hospitals are lacking in this context. METHODS: Patient cases at a community 200-bed general hospital with documented SAB were retrospectively analyzed from January 2010 to March 2013 regarding defined standard of care indicators. In April 2013, an antibiotic stewardship bundle approach was implemented targeting SAB. Follow-up was available until December 2013. Adherence to the different components of the bundle was analyzed. RESULTS: There were 64 cases of SAB reported. After exclusion of five cases, 39 cases were included in the pre-intervention period and 20 patients in the post-intervention period. Mean average bundle adherence increased from a baseline score of 0.8-3.7 (p < 0.001) in the post-intervention period, whereas in-hospital mortality decreased significantly (44 vs. 10 %, p < 0.001) despite or even because the absolute number of detected cases of SAB increased substantially after the intervention was initiated. CONCLUSION: Although we were unable to identify whether the bundle, one of its components, or procedural improvements are responsible for the success of the intervention, our study indicates that the applied approach is feasible and is accompanied by a significant reduction of in-hospital mortality in the secondary care setting. The intervention may serve as a model for other hospitals with similar structures and baseline situations.

Feasibility and impact of an intensified antibiotic stewardship programme targeting cephalosporin and fluoroquinolone use in a tertiary care university medical center.

BACKGROUND: Restricted use of third-generation cephalosporins and fluoroquinolones has been linked to a reduced incidence of hospital-acquired infections with multidrug-resistant bacteria. We implemented an intensified antibiotic stewardship (ABS) programme in the medical service of a university hospital center aiming at a reduction by at least 30% in the use of these two drug classes. METHODS: The ABS programme was focused on the 300-bed medical service. Prescription of third-generation cephalosporins was discouraged, whereas the use of penicillins was encouraged. Monthly drug use density was measured in WHO-ATC defined and locally recommended daily doses (DDD and RDD) per 100 patient days, to evaluate trends before (01/2008 to 10/2011) and after starting the intervention (1/2012 to 3/2013). The effect was analysed using interrupted time-series analysis with six non-intervention departments as controls. RESULTS: Following initiation of the ABS intervention, overall antibiotic use in the medical service declined (p < 0.001). There was a significant intervention-related decrease in the use of cephalosporins and fluoroquinolones (p < 0.001) outperforming the decreasing baseline trend. Trend changes observed in some of the control departments were smaller, and the difference between trend changes in the medical service and those in control departments were highly significant for overall use and cephalosporin use reductions (p < 0.001) as well as for the increasing use of penicillins (p < 0.001). Mean use density levels (in RDD per 100 patient days) dropped for cephalosporins from 16.3 to 10.3 (-37%) and for fluoroquinolones from 17.7 to 10.1 (-43%), respectively. During the same period, the use of penicillins increased (15.4 to 18.2; 18%). The changes in expenditures for antibiotics in the medical service compared to control services minus programme costs indicated initial net cost savings likely to be associated with the programme. CONCLUSION: An intensified ABS programme targeting cephalosporin und fluoroquinolone use in the setting of a large academic hospital is feasible and effective. The intervention may serve as a model for other services and hospitals with a similar structure and baseline situation.

Mycobacterium genavense specific mesenteritic syndrome in HIV-infected patients: a new entity of retractile mesenteritis?

Abdominal mesenteritis is a rare and poorly understood gastroenterological disease. Here, we report on two identical cases of Mycobacterium genavense associated retractile mesenteritis in HIV-positive patients. A literature search retrieved only few small retrospective studies, which characterize the clinical course of this seldom infection. We propose a pathogen-specific syndrome of retractile mesenteritis in HIV-positive patients linked to Mycobacterium genavense infection on the basis of our clinical observation and literature meta-analysis with duodenal wall thickening, central mesenterial mass and vascular complications.