Winfried V. Kern

Mortality of S. aureus bacteremia and infectious diseases specialist consultation – A study of 521 patients in Germany

OBJECTIVES To evaluate the relationship between mortality of bloodstream infection due to Staphylococcus aureus and infectious diseases specialist consultation and other factors potentially associated with outcomes. METHODS A 6-year cohort study was conducted at a 1600-bed university hospital. Consecutive adult patients with S. aureus bacteremia were assessed using a standardised data collection and review form. A new infectious diseases service increased its consultations for S. aureus bacteremia from 33% of cases in 2002 to >80% in 2007. Infectious disease consultation and other factors potentially associated with in-hospital mortality were analysed by multivariate logistic regression. RESULTS A total of 521 patients were studied. All-cause in-hospital mortality was 22%, 90-day mortality was 32%. Factors significantly associated with in-hospital mortality in multivariate analysis were ICU admission (OR 5.8, CI 3.5-9.7), MRSA (OR 2.6, CI 1.4-4.9), age >/=60 years (OR 2.4, CI 1.4-4.2), a diagnosis of endocarditis (OR 2.8, CI 1.4-5.7), a non-fatal underlying disease/comorbidity according to the McCabe classification (OR 0.2, CI 0.1-0.4), and infectious disease specialist consultation (OR 0.6, CI 0.4-1.0). CONCLUSIONS These data suggest that outcome of S. aureus bacteremia may be improved by an expert consultation service.

Regional Variation in Outpatient Antibiotic Prescribing in Germany

Objective:According to recent surveys, outpatient antibiotic prescribing in Germany has been comparatively low among European countries. We assessed regional variation in outpatient antibiotic use within Germany both for overall use as well as for specific antibiotic drug classes.Methods:Prescription data for the year 2003 covering approximately 90% of the total population were analysed using the ATC/WHO defined daily dose (DDD) methodology. Data were expressed in DDD per 1,000 persons covered by the insurance and day (DID).Results:Outpatient antibiotic prescribing in 2003 was 13.6 DID and ranged between 9.2 and 17.9 DID in the different regions examined. Low consumption regions were eastern and southern states. High consumption areas were in the west near the French and Belgian border. This regional prescribing pattern was similar for children and adults. Penicillins were the most frequent prescribed drugs, but their use density showed a relatively large regional variation (factor 3.5), with relatively low prescription frequency in the eastern states. In almost all regions quinolones were used more often than trimethoprim–sulfamethoxazole.Conclusion:The regional variation in recent outpatient antibiotic prescribing in Germany is substantial. The relatively high antibiotic use in the western part of the country is remarkable, remains unexplained and requires further study.

Trends in Antibiotic Use at a University Hospital: Defined or Prescribed Daily Doses? Patient Days or Admissions as Denominator?

Background:Hospital antibiotic use can be measured by calculating daily doses as defined by the WHO/ATC index (DDD) divided by the number of patient or occupied bed days. We wondered whether changes in antibiotic use density over time at a university hospital using this data format are similar in order of magnitude when compared with a different, alternative dose definition and the number of admissions rather than the number of patient days as denominator.Methods:Data obtained from the hospital pharmacy for the medical and surgical services of a 1,000-bed university hospital for the period 1992 through 2003 were expressed both in daily doses per 100 patient days and daily doses per admission. A PDD dose definition (prescribed daily doses), defining doses that reflect the usually prescribed dose in adult hospitalized patients with normal renal function was compared with the WHO/ATC 2001 DDD dose definitions. The percent changes using the different data formats between two 3-year averages (1992–1994 and 2001–2003) were calculated.Results and Conclusion:The DDD/100 patient days data format overestimated antibiotic use density changes in this hospital both in medicine (81% vs 48%) as well as in surgery (69% vs 39%) when compared with PDD/100 patient days. Due to changes in the number of admissions and length of stay over the years, the percent change between the two periods expressed in doses per 100 patient days in addition differed substantially from that estimated by using the DDD per admission or PDD per admission data format. Studies evaluating the evolution of hospital antibiotic use need to address the limitations and adequacy of the different data formats.

Colonization with third-generation cephalosporin-resistant Enterobacteriaceae on hospital admission: prevalence and risk factors

OBJECTIVES The objectives of this study were to prospectively assess the rectal carriage rate of third-generation cephalosporin-resistant Enterobacteriaceae (3GCREB) in non-ICU patients on hospital admission and to investigate resistance mechanisms and risk factors for carriage. METHODS Adult patients were screened for 3GCREB carriage at six German tertiary care hospitals in 2014 using rectal swabs or stool samples. 3GCREB isolates were characterized by phenotypic and molecular methods. Each patient answered a questionnaire about potential risk factors for colonization with MDR organisms (MDROs). Univariable and multivariable risk factor analyses were performed to identify factors associated with 3GCREB carriage. RESULTS Of 4376 patients, 416 (9.5%) were 3GCREB carriers. Escherichia coli was the predominant species (79.1%). ESBLs of the CTX-M-1 group (67.3%) and the CTX-M-9 group (16.8%) were the most frequent β-lactamases. Five patients (0.11%) were colonized with carbapenemase-producing Enterobacteriaceae. The following risk factors were significantly associated with 3GCREB colonization in the multivariable analysis (P < 0.05): centre; previous MDRO colonization (OR = 2.12); antibiotic use within the previous 6 months (OR = 2.09); travel outside Europe (OR = 2.24); stay in a long-term care facility (OR = 1.33); and treatment of gastroesophageal reflux disease (GERD) (OR = 1.22). CONCLUSIONS To our knowledge, this is the largest admission prevalence study of 3GCREB in Europe. The observed prevalence of 9.5% 3GCREB carriage was higher than previously reported and differed significantly among centres. In addition to previously identified risk factors, the treatment of GERD proved to be an independent risk factor for 3GCREB colonization.

Outcomes of Invasive Infection due to Vancomycin-Resistant Enterococcus faecium during a Recent Outbreak

Background:Earlier reports have shown a high mortality of invasive infection due to vancomycin-resistant Enterococcus faecium (VREF). Most of these studies have been conducted in US hospitals prior to the advent of newer VREF-active antimicrobials, and the reported poor outcomes have been explained by the limited choices for effective antimicrobial therapy.Patients and Methods:A total of 25 cases of invasive VREF infection were seen during an outbreak in a tertiary care hospital. Patient characteristics and outcomes were evaluated by a structured retrospective chart review and descriptive analysis.Results:Severe underlying diseases such as leukemia not in remission (86%) were highly prevalent among patients with invasive VREF infection. Fifty-two percent of underlying diseases and/or comorbidities were considered according to the McCabe classification as rapidly fatal. Most patients had received high-dose cytotoxic chemotherapy, and many were neutropenic at the onset of VREF infection. Concomitant infection due to other organisms was found in 48% of the patients. All patients had received extensive antibiotic treatment prior to the onset of VREF infection. Resistance to linezolid was observed in four cases. Overall survival at day 30 was 48%. Four deaths were considered to be directly related to VREF infection.Conclusion:Invasive VREF infection during this outbreak was confined to patients with severe underlying comorbidity. The mortality of VREF infection remained high, despite treatment with newer VREF-active antibiotics such as linezolid and quinupristin–dalfopristin.

Dynamics of Schistosoma haematobium egg output and associated infection parameters following treatment with praziquantel in school-aged children

BackgroundPraziquantel is the drug of choice in preventive chemotherapy targeting schistosomiasis. Increasing large-scale administration of praziquantel requires monitoring of drug efficacy to detect early signs of development of resistance. Standard protocols for drug efficacy monitoring are necessary. Here, we determined the optimal time point for praziquantel efficacy assessment against Schistosoma haematobium and studied the dynamics of infection parameters following treatment.MethodsNinety school-aged children from south Côte d’Ivoire with a parasitologically confirmed S. haematobium infection were treated with a single oral dose of praziquantel (40 mg/kg) and followed up for 62 days post-treatment. Urine samples were collected on 23 schooldays during this period and were subjected to visual examination (macrohaematuria), urine filtration and microscopy (S. haematobium eggs) and reagent strip testing (microhaematuria, proteinuria and leukocyturia).ResultsObserved cure and egg reduction rates were highly dependent on the time point post-treatment. Egg reduction rates were high (>97%) in weeks 3–9 post-treatment. Cure rates were highest in weeks 6 (92.9%) and 9 (95.0%) post-treatment. The prevalence of infection-associated parameters decreased after treatment, reaching a minimum of 2.4% in weeks 5 (proteinuria) and 7 (leukocyturia) post-treatment, and 16.3% at the end of week 8 (microhaematuria). Macrohaematuria disappeared between weeks 3 and 6 post-treatment.ConclusionsFor monitoring praziquantel efficacy against S. haematobium, we recommend that the cure rate is assessed at week 6 post-treatment. The egg reduction rate can be evaluated earlier, from day 14 post-treatment onwards. Reagent strips are a useful additional tool for evaluating treatment outcomes in areas with high endemicity, preferably at weeks 5 and 6 post-treatment. The delayed decrease of microhaematuria confirms that lesions in the urinary tract persist longer than egg excretion post-treatment.

Selection of hospital antimicrobial prescribing quality indicators: a consensus among German antibiotic stewardship (ABS) networkers

PurposeSimple, valid, and evidence-based indicators to measure the quality of antimicrobial prescribing in acute-care hospitals are urgently needed and increasingly requested by policymakers. The aim of this study was to develop new consensus quality indicators (QIs) for hospital antibiotic stewardship (ABS) and infection management which will be further evaluated for internal quality management and external quality assessment in Germany.MethodsBased on an extensive literature review, the Austrian–German hospital ABS Guideline Committee and selected members of the German ABS Expert Network discussed and drafted a list of 99 potential indicators for hospitals that reflect structural prerequisites for ABS (35 items), ABS core activities (18 items), additional ABS measures (5 items), and process of care indicators (both generic and disease-specific—12 and 29 items, respectively). Questionnaires were mailed to German ABS experts and healthcare professionals with further education in ABS. Participants scored (on a nine-point Likert scale) relevance (clinical, ecological/resistance, economical/expenses) and presumed practicability (six categories: clarity of definition, effort to collect data, barrier to implementation, verifiability, suitability for external quality assessment, quality gap), taking into account their local work environment. The scores were processed according to the RAND/UCLA appropriateness method, and QIs were judged relevant if the median (clinical + ecological and/or economical) scores were >6. The indicators thus assessed to be potentially relevant were then filtered according to their practicability. Highly relevant QIs with borderline practicability scores and items with disagreements and overlapping areas were re-discussed in a final multidisciplinary panel consensus workshop convened in November 2012.ResultsOf the 340 questionnaires that were mailed, 75 questionnaires were completed and returned. Of 99 initially proposed items, 32 were excluded due to insufficient scores. Of the remaining 67 items, 21 structural and 21 process of care QIs were finally selected, including four QIs with high clinical and ecological but limited economical relevance, and three QIs with high clinical and economical but limited ecological relevance. Among the selected QIs, efforts to collect data and implementation barriers were scored as suboptimal in many cases.ConclusionsA catalog of consensus structural and process of care ABS-QIs was established. These should undergo further pilot and feasibility studies in the German hospital healthcare sector. The panelists were most critical regarding resource use/complexity issues and presumed implementation barriers. How this may limit applicability of QIs remains to be determined.

Microarray-Based Genotyping and Clinical Outcomes of Staphylococcus aureus Bloodstream Infection: An Exploratory Study

The clinical course of Staphylococcus aureus bacteremia varies extensively. We sought to determine the relationship between genetic characteristics of the infecting pathogen and clinical outcomes in an exploratory study. In two study centers, 317 blood culture isolates were analyzed by DNA microarray and spa genotyping. By uni- and multivariate regression analyses associations of genotype data with 30-day all-cause mortality, severe sepsis/septic shock, disseminated disease, endocarditis, and osteoarticular infection were investigated. Univariate analysis showed significant association between S. aureus genes/gene-clusters or clonal complexes and clinical endpoints. For example CC15 was associated with 30-day mortality and CC22 with osteoarticular infection. In multivariate analysis methicillin resistance (mecA, OR 4.8 [1.43–16.06]) and the beta-lactamase-gene (bla, OR 3.12 [1.17–8.30]) remained independently associated with 30-day mortality. The presence of genes for enterotoxins (sed/sej/ser) was associated with endocarditis (OR 5.11 [1.14–18.62]). Host factors such as McCabe classification (OR 4.52 [2.09–9.79] for mortality), age (OR 1.06 [1.03–1.10] per year), and community-acquisition (OR 3.40 [1.31–8.81]) had a major influence on disease severity, dissemination and mortality. Individual genotypes and clonal complexes of S. aureus can only partially explain clinical features and outcomes of S. aureus bacteremia. Genotype-phenotype association studies need to include adjustments for host factors like age, comorbidity and community-acquisition.

Converting habits of antibiotic prescribing for respiratory tract infections in German primary care--the cluster-randomized controlled CHANGE-2 trial.

BackgroundWith an average prescription rate of 50%, in German primary care antibiotics are still too frequently prescribed for respiratory tract infections. The over-prescription of antibiotics is often explained by perceived patient pressure and fears of a complicated disease progression. The CHANGE-2 trial will test the effectiveness of two interventions to reduce the rate of inappropriate antibiotic prescriptions for adults and children suffering from respiratory tract infections in German primary care.Methods/DesignThe study is a three-arm cluster-randomized controlled trial that measures antibiotic prescription rates over three successive winter periods and reverts to administrative data of the German statutory health insurance company AOK. More than 30,000 patients in two regions of Germany, who visit their general practitioner or pediatrician for respiratory tract infections will be included. Interventions are: A) communication training for general practitioners and pediatricians and B) intervention A plus point-of-care testing. Both interventions are tested against usual care. Outcome measure is the physicians’ antibiotic prescription rate for respiratory tract infections derived from data of the health insurance company AOK. Secondary outcomes include reconsultation rate, complications, and hospital admissions.DiscussionMajor aim of the study is to improve the process of decision-making and to ensure that patients who are likely to benefit from antibiotics are treated accordingly. Our approach is simple to implement and might be used rapidly among general practitioners and pediatricians. We expect the results of this trial to have major impact on antibiotic prescription strategies and practices in Germany, both among general practitioners and pediatricians.Trial registrationThe study is registered at the Current Controlled Trials Ltd (ISRCTN01559032)

Differential activity of innate defense antimicrobial peptides against Nocardia species

BackgroundMembers of the genus Nocardia are ubiquitous environmental saprophytes capable to cause human pulmonary, disseminated and cutaneous nocardiosis or bovine mastitis. Innate immunity appears to play an important role in early defense against Nocardia species. To elucidate the contribution of antimicrobial peptides (AMPs) in innate defense against Nocardia, the activity of human α-defensins human neutrophil peptides (HNPs) 1-3, human β-defensin (hBD)-3 and cathelicidin LL-37 as well as bovine β-defensins lingual and tracheal antimicrobial peptides (LAP, TAP) and bovine neutrophil-derived indolicidin against four important Nocardia species was investigated.ResultsWhereas N. farcinica ATCC 3318 and N. nova ATCC 33726 were found to be susceptible to all investigated human and bovine AMPs, N. asteroides ATCC 19247 was killed exclusively by neutrophil-derived human α-defensins HNP 1-3 and bovine indolicidin. N. brasiliensis ATCC 19296 was found to exhibit complete resistance to investigated human AMPs and to be susceptible only to bovine indolicidin.ConclusionSelected AMPs are capable to contribute to the first line of defense against Nocardia, yet, susceptibility appears to vary across different Nocardia species. Obtained results of neutrophil-derived AMPs to possess the broadest antinocardial spectrum are remarkable, since nocardiosis is characterized by a neutrophil-rich infiltrate in vivo.