Klaus Kaier

Effect of Availability of Transcatheter Aortic-Valve Replacement on Clinical Practice

BACKGROUND Since the adoption of transcatheter aortic-valve replacement (TAVR), questions have been raised about its effect on clinical practice in comparison with the effect of surgical aortic-valve replacement, which is considered the current standard of care. Complete nationwide data are useful in examining how the introduction of a new technique influences previous clinical standards. METHODS We analyzed data on characteristics of patients and in-hospital outcomes for all isolated TAVR and surgical aortic-valve replacement procedures performed in Germany from 2007 to 2013. RESULTS In total, 32,581 TAVR and 55,992 surgical aortic-valve replacement procedures were performed. The number of TAVR procedures increased from 144 in 2007 to 9147 in 2013, whereas the number of surgical aortic-valve replacement procedures decreased slightly, from 8622 to 7048. Patients undergoing TAVR were older than those undergoing surgical aortic-valve replacement (mean [±SD] age, 81.0±6.1 years vs. 70.2±10.0 years) and at higher preoperative risk (estimated logistic EuroSCORE [European System for Cardiac Operative Risk Evaluation], 22.4% vs. 6.3%, on a scale of 0 to 100%, with higher scores indicating greater risk and a score of more than 20% indicating high surgical risk). In-hospital mortality decreased in both groups between 2007 and 2013 (from 13.2% to 5.4% with TAVR and from 3.8% to 2.2% with surgical aortic-valve replacement). The incidences of stroke, bleeding, and pacemaker implantation (but not acute kidney injury) also declined. CONCLUSIONS The use of TAVR increased markedly in Germany between 2007 and 2013; the concomitant reduction in the use of surgical aortic-valve replacement was moderate. Patients undergoing TAVR were older and at higher procedural risk than those undergoing surgical aortic-valve replacement. In-hospital mortality decreased in both groups but to a greater extent among patients undergoing TAVR. (Funded by the Heart Center, Freiburg University.).

Two time-series analyses of the impact of antibiotic consumption and alcohol-based hand disinfection on the incidences of nosocomial methicillin-resistant Staphylococcus aureus infection and Clostridium difficile infection.

OBJECTIVE To determine the impact of antibiotic consumption and alcohol-based hand disinfection on the incidences of nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infection and Clostridium difficile infection (CDI). METHODS Two multivariate time-series analyses were performed that used as dependent variables the monthly incidences of nosocomial MRSA infection and CDI at the Freiburg University Medical Center during the period January 2003 through October 2007. The volume of alcohol-based hand rub solution used per month was quantified in liters per 1,000 patient-days. Antibiotic consumption was calculated in terms of the number of defined daily doses per 1,000 patient-days per month. RESULTS The use of alcohol-based hand rub was found to have a significant impact on the incidence of nosocomial MRSA infection (P< .001). The multivariate analysis (R2=0.66) showed that a higher volume of use of alcohol-based hand rub was associated with a lower incidence of nosocomial MRSA infection. Conversely, a higher level of consumption of selected antimicrobial agents was associated with a higher incidence of nosocomial MRSA infection. This analysis showed this relationship was the same for the use of second-generation cephalosporins (P= .023), third-generation cephalosporins (P= .05), fluoroquinolones (P= .01), and lincosamides (P= .05). The multivariate analysis (R2=0.55) showed that a higher level of consumption of third-generation cephalosporins (P= .008), fluoroquinolones (P= .084), and/or macrolides (P= .007) was associated with a higher incidence of CDI. A correlation with use of alcohol-based hand rub was not detected. CONCLUSION In 2 multivariate time-series analyses, we were able to show the impact of hand hygiene and antibiotic use on the incidence of nosocomial MRSA infection, but we found no association between hand hygiene and incidence of CDI.

The impact of antimicrobial drug consumption and alcohol-based hand rub use on the emergence and spread of extended-spectrum β-lactamase-producing strains: a time-series analysis

BACKGROUND The aim of this study was to explore the temporal relationship between the consumption of different antibiotics, alcohol-based hand disinfection and the incidence of nosocomial bacterial strains producing extended-spectrum beta-lactamases (ESBLs). METHODS Time-series analysis was performed based on monthly data available from January 2005 to October 2007. The incidence of nosocomial ESBL (cases/1000 patient-days) was regressed on the different antibiotic agents and the volume of alcohol-based hand rub orders. Antibiotic consumption was defined as monthly defined daily doses (DDD)/1000 patient-days, while alcohol-based hand rub was quantified in litres/1000 patient-days. RESULTS The multivariate analysis showed that using alcohol-based hand rub for hand disinfection had a significant influence on the ESBL incidence (P = 0.002). A higher volume of alcohol-based hand rub use was subsequently associated with a lower incidence of ESBL-producing strains. Additionally, the model showed that temporal increase in the use of third-generation cephalosporins (P = 0.022) and fluoroquinolones (P = 0.001) is, after a time lag of up to 3 months, followed by temporal variations in the incidence of nosocomial ESBLs. Furthermore, the incidence of patients admitted with ESBL was also shown to have an influence on the incidence of nosocomial ESBLs (P < 0.001). The final model explained 75% of the monthly variations in the incidence of nosocomial ESBLs. CONCLUSIONS The analysis identifies selective pressure caused by the use of different antimicrobial agents as a driving factor in the emergence and spread of ESBLs. Furthermore, the study confirms that hand disinfection is key to the prevention of nosocomial ESBLs.

Mortality associated with in-hospital bacteraemia caused by Staphylococcus aureus: a multistate analysis with follow-up beyond hospital discharge

OBJECTIVES The main objective was to study the impact of in-hospital bacteraemia caused by Staphylococcus aureus on mortality within 90 days after admission. We compared methicillin-resistant S. aureus (MRSA) with methicillin-susceptible S. aureus (MSSA). PATIENTS AND METHODS The study population consisted of adult residents of Tayside, Scotland, UK, from 1 January 2005 to 30 September 2006 who had a new admission to Ninewells Hospital between 1 July 2005 and 30 June 2006. All patients (n = 3132) in the same wards as the patients infected with S. aureus were included. We addressed key weaknesses in previous studies by using a cohort design and applying a multistate model, which addressed the temporal dynamics. Critically, the model recognized that death and discharge from the hospital are competing events and that delay in discharge independently increases the risk of death. RESULTS The cohort included 3132 patients, of whom 494 died within 90 days after admission, 34 developed MRSA bacteraemia and 26 MSSA bacteraemia in the hospital. In comparison with patients without S. aureus bacteraemia, the death hazard was 5.6 times greater with MRSA [95% confidence interval (CI) 3.36-9.41] and 2.7 times greater with MSSA bacteraemia (95% CI 1.33-5.39). After adjustment for co-morbidity, hospitalization, age and sex, the death hazard was 2.9 times greater with MRSA (95% CI 1.70-4.88) and 1.7 times greater with MSSA bacteraemia (95% CI 0.84-3.47). CONCLUSIONS Time-dependent models such as the proposed multistate model are necessary to address the temporal dynamics of admission, infection, discharge and death. The impact of S. aureus bacteraemia on mortality should be considered on two levels: the burden of disease, i.e. nosocomial infection with S. aureus bacteraemia, and the burden of resistance to methicillin.

Seasonal and ascending trends in the incidence of carriage of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella species in 2 German hospitals.

BACKGROUND Extended-spectrum ß-lactamase (ESBL)-producing strains of bacteria have become a major public health concern. In the present study, the incidence of carriage of ESBL-producing strains was analyzed for general trends and seasonality. METHODS Monthly data on ESBL-producing strains were collected retrospectively at 2 large university hospitals in Germany. The mean monthly temperatures for the 2 settings were collected from Germanys national meteorological service. Multivariable time series analyses were performed to explain variations in the monthly incidence densities of carriage of ESBL-producing bacteria (number of cases involving ESBL-producing Escherichia coli and/or Klebsiella species per 1,000 patient days). For the final models, we incorporated variables for the ascending linear trends and other variables representing the mean monthly temperature. RESULTS Our models demonstrated that there was an increasing trend in the incidences of carriage of ESBL-producing bacteria. In addition, the incidences of carriage of all ESBL-producing bacteria responded positively to the mean temperature, meaning that during the summer, more cases involving ESBL-producing bacteria were detected than during the winter. The same methodology was also applied to the incidence of methicillin-resistant Staphylococcus aureus carriage, but no association was found with the mean temperature. CONCLUSIONS In the present study, we demonstrated that the monthly incidence of carriage of ESBL-producing bacteria was highly correlated with the mean monthly temperature, a fact that should be considered in experimental studies as an additional parameter influencing the incidence of ESBL-producing bacteria.

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

BackgroundRestricted 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.MethodsThe 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.ResultsFollowing 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.ConclusionAn 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.

Bed occupancy rates and hospital-acquired infections--should beds be kept empty?

There is growing evidence that bed occupancy (BO) rates, overcrowding and understaffing influence the spread of hospital-acquired infections (HAIs). In this article, a systematic review of the literature is presented, summarizing the evidence on the adverse effects of high BO rates and overcrowding in hospitals on the incidence of HAIs. A Pubmed database search identified 179 references, of which 44 were considered to be potentially relevant for full-text review. The majority (62.9%) focused on methicillin-resistant Staphylococcus aureus-associated infection or colonization. Only 12 studies were found that provided a statistical analysis of the impact of BO on HAI rates. The median BO rate of the analysed studies was 81.2%. The majority of studies (75%) indicated that BO rates and understaffing directly influence the incidence of HAIs. Only three studies showed no significant association between BO rates and the incidence of HAIs. Interestingly, only one of the included studies detected a seasonal trend in the BO rate. The present review shows an association between BO rates and the spread of HAIs in various settings. Because the evidence on this topic is limited, we conclude that further research is needed in order to analyse the rationale of a threshold BO rate, because keeping beds empty is comparatively costly.

Early identification of individuals at high risk for cerebral infarction after aneurysmal subarachnoid hemorrhage: the BEHAVIOR score

Cerebral infarction (CI) is a crucial complication of aneurysmal subarachnoid hemorrhage (SAH) associated with poor clinical outcome. We aimed at developing an early risk score for CI based on clinical characteristics available at the onset of SAH. Out of a database containing 632 consecutive patients with SAH admitted to our institution from January 2005 to December 2012, computed tomography (CT) scans up to day 42 after ictus were evaluated for CIs. Different parameters from admission up to aneurysm treatment were collected with subsequent construction of a risk score. Seven clinical characteristics were independently associated with CI and included in the Risk score (BEHAVIOR Score, 0 to 11 points): Blood on CT scan according to Fisher grade ≥ 3 (1 point), Elderly patients (age ≥ 55 years, 1 point), Hunt&Hess grade ≥ 4 (1 point), Acute hydrocephalus requiring external liquor drainage (1 point), Vasospasm on initial angiogram (3 points), Intracranial pressure elevation > 20 mm Hg (3 points), and treatment of multiple aneurysms (‘Overtreatment’, 1 point). The BEHAVIOR score showed high diagnostic accuracy with respect to the absolute risk for CI (area under curve = 0.806, P < 0.0001) and prediction of poor clinical outcome at discharge (P < 0.0001) and after 6 months (P = 0.0002). Further validation in other SAH cohorts is recommended.

Predictors and impact of early cerebral infarction after aneurysmal subarachnoid hemorrhage

Cerebral infarction is a frequent and serious complication of aneurysmal subarachnoid hemorrhage (SAH). This study aimed to identify independent predictors of the timing of cerebral infarction and clarify its impact on disease course and patients’ outcome.

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.