Clinical Predictive Model of Multidrug Resistance in Neutropenic Cancer Patients with Bloodstream Infection Due to Pseudomonas aeruginosa.

We aimed to assess the rate and predictive factors of bloodstream infection (BSI) due to multidrug-resistant (MDR) Pseudomonas aeruginosa in neutropenic cancer patients. We performed a multicenter, retrospective cohort study including oncohematological neutropenic patients with BSI due to P. aeruginosa conducted across 34 centers in 12 countries from January 2006 to May 2018. A mixed logistic regression model was used to estimate a model to predict the multidrug resistance of the causative pathogens. Of a total of 1,217 episodes of BSI due to P. aeruginosa, 309 episodes (25.4%) were caused by MDR strains. The rate of multidrug resistance increased significantly over the study period (P = 0.033). Predictors of MDR P. aeruginosa BSI were prior therapy with piperacillin-tazobactam (odds ratio [OR], 3.48; 95% confidence interval [CI], 2.29 to 5.30), prior antipseudomonal carbapenem use (OR, 2.53; 95% CI, 1.65 to 3.87), fluoroquinolone prophylaxis (OR, 2.99; 95% CI, 1.92 to 4.64), underlying hematological disease (OR, 2.09; 95% CI, 1.26 to 3.44), and the presence of a urinary catheter (OR, 2.54; 95% CI, 1.65 to 3.91), whereas older age (OR, 0.98; 95% CI, 0.97 to 0.99) was found to be protective. Our prediction model achieves good discrimination and calibration, thereby identifying neutropenic patients at higher risk of BSI due to MDR P. aeruginosa The application of this model using a web-based calculator may be a simple strategy to identify high-risk patients who may benefit from the early administration of broad-spectrum antibiotic coverage against MDR strains according to the local susceptibility patterns, thus avoiding the use of broad-spectrum antibiotics in patients at a low risk of resistance development.

[Antibiotic stewardship (ABS). Part 1: Basics]. / Antibiotic Stewardship (ABS). Teil 1: Grundlagen.

Against the background of increasing antimicrobial resistance, antibiotic stewardship (ABS) is an important measure to counteract the spread of resistant pathogens and multidrug resistance. For Germany and Austria, a comprehensive S3 guideline is available, which was last updated in 2018. The control of antibiotic or anti-infective use in hospitals should be guided by specialized ABS teams. At the hospital level, ABS also includes a structured ongoing analysis of local antibiotic use and resistance data. Recommendations for locally adapted therapy regimens should be derived and implemented from this data analysis. ABS consists of regular ward rounds ("ABS visits"), during which members of the ABS team review the indication, dosage, route of administration and duration of antimicrobial therapy at the bedside. Here, the key challenge is to save antibiotics without compromising the individual patient. Digitalization and artificial intelligence offer new options for ABS, while the adaption of inpatient concepts to outpatient care is also important.

[Antibiotic stewardship (ABS). Part 2: Application]. / Antibiotic Stewardship (ABS). Teil 2: Anwendung.

Antibiotic stewardship (ABS) is an important measure to counteract the spread of resistant pathogens and multidrug resistance. The most important ABS tools include the implementation of local guidelines, the development of a house-related list of anti-infective agents, regular ABS visits and practice-oriented internal training events. Effective strategies for therapy optimization include indication testing and therapy evaluation, dose optimization as well as determining an appropriate duration of therapy. Oralization of anti-infectives (sequence therapy) should be supported by consistent clinical criteria in in-house guidelines. The incidence of Clostridioides difficile infections (CDI) can be more than halved by restricting the so-called "4C antibiotics". Point-of-care tests help to minimize the use of antibiotics in the outpatient setting. Vaccination reduces the need for antibiotic therapy.

[Infectious diseases - a specialty of internal medicine]. / Infektiologie ­ ein Schwerpunkt der Inneren Medizin.

Infectious diseases have recently gained wide public interest. Emerging infections and rising rates of antibiotic resistance are determining this trend. Both challenges will need to be addressed in international and local collaborations between different specialties in medicine and basic science. Infectious diseases as a clinical specialty in this scenario is directly responsible for the care of patients with infectious diseases. Its involvement in the care of patients with complicated infections has proved to be highly effective. Antibiotic stewardship programmes are effective measures in slowing the development of antibiotic resistance and have been widely implemented. But antibiotic stewardship specialists should not be confused with or taken as an alternative to infectious disease experts. Infectious diseases requires appropriate and specific training. It mainly uses the instrumentarium of internal medicine. With the current challenges in modern medicine, infectious diseases in Germany should thus be upgraded from a subspecialty to a clinical specialty, ideally within Internal Medicine.

In vitro susceptibility to 19 agents other than ß-lactams among third-generation cephalosporin-resistant Enterobacteriaceae recovered on hospital admission.

Objectives: As part of the multicentre Antibiotic Therapy Optimisation Study, MIC values of 19 non-ß-lactam agents were determined for third-generation cephalosporin-resistant Escherichia coli , Klebsiella species and Enterobacter species (3GCREB) isolates collected in German hospitals. Methods: A total of 328 E. coli , 35 Klebsiella spp. (1 Klebsiella oxytoca and 34 Klebsiella pneumoniae ) and 16 Enterobacter spp. (1 Enterobacter aerogenes and 15 Enterobacter cloacae ) isolates were submitted to broth microdilution antimicrobial susceptibility testing with the MICRONAUT system. MICs of fluoroquinolones (levofloxacin and moxifloxacin), aminoglycosides (gentamicin, tobramycin, amikacin, streptomycin, neomycin and paromomycin), tetracyclines (tetracycline, minocycline and tigecycline), macrolides (erythromycin, clarithromycin and azithromycin) and miscellaneous agents [trimethoprim/sulfamethoxazole, chloramphenicol, nitrofurantoin, colistin and fosfomycin intravenous (iv)] were determined and reviewed against 2016 EUCAST breakpoints. Results: The MIC of levofloxacin was >2 mg/L for 128 of 328 E. coli and 8 of 35 Klebsiella spp., but only 1 of 16 Enterobacter spp. Rates of resistance to trimethoprim/sulfamethoxazole were high (>70%), except for Enterobacter spp. Rates of resistance to colistin and fosfomycin iv were still low. About 20% of the tested isolates were resistant to chloramphenicol. Only 1 (of 328) E. coli isolate had an MIC of amikacin >16 mg/L and only 33 of 328 E. coli and 1 of 35 Klebsiella spp. had an MIC of tobramycin >4 mg/L, whereas average gentamicin MICs were in general more elevated. A tigecycline MIC >2 mg/L was only found for 1 of 16 Enterobacter spp., but in none of the E. coli or Klebsiella spp. isolates. Conclusions: Our study gives insight into previously unreported non-ß-lactam MIC distributions of 3GCREB isolates.

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 ß-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.

PEPDar: A randomized prospective noninferiority study of ritonavir-boosted darunavir for HIV post-exposure prophylaxis.

OBJECTIVES: PEPDar compared the tolerability and safety of ritonavir-boosted darunavir (DRV/r)-based post-exposure prophylaxis (PEP) with the tolerability and safety of standard of care (SOC). The primary endpoint was the early discontinuation rate among the per-protocol population. METHODS: PEPDar was an open-label, randomized, multicentre, prospective, noninferiority safety study. Subjects were stratified by type of event (occupational vs. nonoccupational, i.e. sexual) and were randomized to receive DRV/r plus two nucleoside reverse transcriptase inhibitors (NRTIs) or SOC PEP. Twenty-two private or university HIV clinics in Germany participated. Subjects were ≥ 18 years old and had documented or potential HIV exposure and indication for HIV PEP. They initiated PEP not later than 72 h after the event and were HIV negative. RESULTS: A total of 324 subjects were screened, the per-protocol population was 305, and 273 subjects completed the study. One hundred and fifty-five subjects received DRV/r-based PEP and 150 subjects received ritonavir-boosted lopinavir (LPV/r)-based PEP for 28-30 days; 298 subjects also received tenofovir/emtricitabine. The early discontinuation rate in the DRV/r arm was 6.5% compared with 10.0% in the SOC arm (P = 0.243). Adverse drug reactions (ADRs) were reported in 68% of DRV/r subjects and 75% of SOC subjects (P = 0.169). Fewer DRV/r subjects (16.1%) had at least one grade 2 or 3 ADR compared with SOC subjects (29.3%) (P = 0.006). All grades of diarrhoea, nausea, and sleep disorders were significantly less frequent with DRV/r, while headache was significantly more frequent. No HIV seroconversion was reported during follow-up. CONCLUSIONS: Noninferiority of DRV/r to SOC was demonstrated. DRV/r should be included as a standard component of recommended regimens in PEP guidelines.

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.

[Management of Adult Community-acquired Pneumonia and Prevention - Update 2016]. / Behandlung von erwachsenen Patienten mit ambulant erworbener Pneumonie und Prävention - Update 2016.

The present guideline provides a new and updated concept of treatment and prevention of adult patients with community-acquired pneumonia. It replaces the previous guideline dating from 2009.The guideline was worked out and agreed on following the standards of methodology of a S3-guideline. This includes a systematic literature search and grading, a structured discussion of recommendations supported by the literature as well as the declaration and assessment of potential conflicts of interests.The guideline has a focus on specific clinical circumstances, an update on severity assessment, and includes recommendations for an individualized selection of antimicrobial treatment as well as primary and secondary prevention.

Implementing an intensified antibiotic stewardship programme targeting cephalosporin and fluoroquinolone use in a 200-bed community hospital in Germany.

BACKGROUND: Prescription of third-generation cephalosporins and fluoroquinolones has been linked to an increasing incidence of gram-negative bacteria producing extended-spectrum beta-lactamases, methicillin-resistant Staphylococcus aureus and nosocomial infection with Clostridium difficile. Antibiotic stewardship (ABS) programmes offer evidence-based tools to control antibiotic prescription rates and thereby influence the incidence of nosocomial infection and contain the development of multidrug-resistant bacteria, but there is limited experience with such programmes at community hospitals. METHODS: We implemented an ABS programme at a 200-bed community hospital and aimed at a > 30 % reduction of cephalosporin and fluoroquinolone consumption within 1 year. Pharmacy data were obtained to estimate hospital-wide drug use density expressed in WHO-ATC-defined daily doses (DDD) or hospital-adapted recommended daily doses (RDD) per 1,000 patient days. The effect of the ABS intervention on drug use density was analysed using interrupted time-series analysis for the periods between January 2011 and March 2013 as pre-intervention, and between April 2013 and March 2014 as post-intervention period. The CDI incidence was calculated based on microbiology laboratory data. RESULTS: Cephalosporin use (measured in RDD/1,000 patient days) decreased by 33 %, and fluoroquinolone use decreased by 31 %, respectively. Interrupted time-series analysis confirmed significant changes in the drug use density trends for both cephalosporins and fluoroquinolones after the intervention as well as for total antibiotic use that decreased by 11 % while no significant effect was noted for CDI incidence rates. CONCLUSION: ABS programmes can be effective in community hospitals and may help establish ecologically advantageous antibiotic strategies when needed.

α-Defensins partially protect human neutrophils against Panton-Valentine leukocidin produced by Staphylococcus aureus.

UNLABELLED: α-Defensins produced by neutrophils are important effector molecules of the innate immune system. In addition to their microbicidal effects, α-defensins have the ability to neutralize bacterial toxins. Panton-Valentine leukocidin (PVL) is the hallmark of community-acquired methicillin-resistant Staphylococcus aureus. Staphylococcus aureus that produce PVL are responsible for severe diseases, including necrotizing pneumonia. Polymorphonuclear neutrophils (PMNs) are the target cells of PVL action. The goal of this study was to elucidate the effect of a group of α-defensins known as the human neutrophil peptides (HNPs) on the interactions between LukS-PV and LukF-PV, which compose PVL, and human PMNs. We observed that HNPs bound to both subunits of PVL and significantly decreased PVL pore formation in PMNs, with a maximum inhibition of 27%. When various HNP molecules were tested individually under the same conditions, we observed that HNP3, but not HNP1 or 2, decreased pore formation. Similarly, HNP3 significantly decreased PVL-induced PMN lysis, with a maximum inhibition of 31%. Interestingly, HNPs did not affect LukS-PV LukF-PV oligomerization, LukS-PV LukF-PV binding to PMNs or calcium influx induced by PVL in PMNs. Our results suggest that HNP3 partially protects neutrophils against PVL by interfering with the conformational changes of PVL required to form a functional pore. SIGNIFICANCE AND IMPACT OF THE STUDY: Panton-Valentine leukocidin (PVL) is a pore-forming toxin produced by Staphylococcus aureus, responsible for neutrophil damage and key player of severe staphylococcal diseases. Antimicrobial peptides produced by neutrophils (HNP1-3) neutralize several other bacterial cytotoxins. We examined the impact of human neutrophil peptides (HNPs) on PVL cytotoxicity against human neutrophils and we found that HNPs bind to both LukS and LukF components of PVL, thereby inhibiting pore formation and neutrophil lysis. Our results suggest that HNP3 may impair PVL conformational changes required to form a functional pore and provide insight into the pathogenesis of PVL-related staphylococcal infection, with potential impact on the disease outcome.

[New antibacterial agents on the market and in the pipeline]. / Neue Antibiotika auf dem Markt und in Entwicklung.

After some years of stagnation there have been several new successful developments in the field of antibacterial agents. Most of these new developments have been in conventional antibacterial classes. New drugs among the beta-lactam agents are methicillin-resistant Staphylococcus aureus (MRSA) active cephalosporins (ceftaroline and ceftobiprole) and new combinations of beta-lactam with beta-lactamase inhibitors (ceftolozane/tazobactam, ceftazidime/avibactam, imipenem/relebactam and meropenem/RPX7009). New developments can also be observed among oxazolidinones (tedizolid, radezolid, cadazolid and MRX-I), macrolides/ketolides (modithromycin and solithromycin), aminoglycosides (plazomicin), quinolones (nemonoxacin, delafloxacin and avarofloxacin), tetracyclines (omadacycline and eravacycline) as well as among glycopeptides and lipopeptides (oritavancin, telavancin, dalbavancin and surotomycin). New agents in a very early developmental phase are FabI inhibitors, endolysines, peptidomimetics, lipid A inhibitors, methionyl-tRNA synthetase inhibitors and teixobactin.

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

PURPOSE: Simple, 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. METHODS: Based 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. RESULTS: Of 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. CONCLUSIONS: A 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.

Expression of the sweat-derived innate defence antimicrobial peptide dermcidin is not impaired in Staphylococcus aureus colonization or recurrent skin infections.

Antimicrobial peptides are an integral part of innate immunity, and contribute to the protection of human skin from Staphylococcus aureus colonization and infection. We sought to investigate whether the expression of the eccrine sweat-derived staphylocidal antimicrobial peptide dermcidin might influence S. aureus colonization or recurrent skin and soft-tissue infections (SSTIs). Eccrine sweat was collected from 18 patients with recurrent S. aureus SSTIs, 28 patients who were intermittent or permanent S. aureus carriers, and 32 noncarriers. Expression and proteolytic degradation of dermcidin was investigated using ELISA and surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF-MS). We found no significant differences in the overall amount or the proteolytic degradation pattern of dermcidin-derived peptides between healthy noncarriers, intermittent and permanent carriers, and patients with recurrent S. aureus SSTIs. S. aureus colonization or recurrent SSTIs do not seem to be associated with diminished dermcidin expression in eccrine sweat.

Occurrence and trends of Clostridioides difficile infections in hospitalized patients: a prospective multi-centre cohort study in six German university hospitals, 2016-2020.

BACKGROUND: For Clostridioides difficile infections (CDIs) in Germany no longitudinal multi-centre studies with standardized protocols for diagnosing CDI are available. Recent evaluations of general surveillance databases in Germany indicate a downward trend in CDI rates. We aimed to describe the actual burden and trends of CDI in German university hospitals from 2016 to 2020. METHODS: Our study was a prospective multi-centre study covering six German university hospitals. We report the data in total, stratified by year, by medical specialty as well as by CDI severity. Multi-variable regression analyses were performed to assess risk factors for severe CDI. RESULTS: We registered 3780 CDI cases among 1,436,352 patients. The median length of stay (LOS) of CDI cases was 20 days (interquartile range 11-37) compared with a general LOS of 4.2 days. In-hospital all-cause mortality in CDI patients was 11.7% (N = 444/3780), while mortality attributed to CDI was 0.4% (N = 16/3761). CDI recurrence rate was comparatively low at 7.2%. The incidence density of severe healthcare-associated healthcare onset (HAHO)-CDI showed a significant decrease from 2.25/10,000 patient days (pd) in 2016 to 1.49/10,000 pd in 2020 (trend calculation P=0.032). CONCLUSIONS: Compared with a European point-prevalence study in 2013/2014, where overall CDI incidence density was 11.2 cases/10,000 pd in Germany (EUCLID), we see in our study halved overall CDI rates of 5.6 cases/10,000 pd in 2020. Our study shows current data on the distribution of CDI cases in German university hospitals and thus provides international comparative data on the key indicators of CDI.

Development and validation of potential structure indicators for evaluating antimicrobial stewardship programmes in European hospitals.

This study describes the development of structure indicators for hospital antimicrobial stewardship programmes and pilot validation across European hospitals. A multi-disciplinary panel from four European countries developed structure indicators in three steps: identification and listing of indicators, remote ranking of indicators using multi-criteria scoring, selection of indicators in a face-to-face consensus meeting. Additionally, the top-ten indicators were identified as a minimal set of key indicators. A survey was sent to the directors of antimicrobial stewardship programmes in European hospitals. The yes/no answers for the indicators were transformed into numbers in order to calculate the total scores. A list of 58 indicators was selected and categorised into the following topics: antimicrobial stewardship services (12 items), tools (16 items), human resources and mandate (6 items), health care personnel development (4 items), basic diagnostic capabilities (6 items), microbiological rapid tests (2 items), evaluation of microbiological drug resistance data (3 items), antibiotic consumption control (5 items) and drug use monitoring (4 items). The indicator scores, reported by 11 pilot hospitals from five European countries, ranged from 32 to 50 (maximum score = 58) and from 5 to 10 points (maximum score = 10) for, respectively, the complete and the top-ten list. An international panel selected 58 potential structure indicators, among which was a minimal set of ten key structure indicators, that could be useful for assessment of the comprehensiveness and resource-intensity of antimicrobial stewardship programmes. There was significant heterogeneity among participating centres with regard to their score for structural components of effective antimicrobial stewardship.

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.

[Management of patients with EHEC/HUS. Lessons and perspectives from clinical infectious disease specialists]. / Versorgung und Behandlung von EHEC/HUS-Patienten. Erfahrungen und Perspektiven aus infektiologischer Sicht.

The 2011 EHEC/HUS outbreak created uncertainty regarding the previous recommendations of withholding antibiotic therapy and regarding rational measures for prevention of invasive meningococcal disease after treatment with the monoclonal antibody eculizumab. For both these areas, an expert panel of the German Society for Infectious Diseases in cooperation with representatives of other learned societies and health institutions has drafted and consented guidelines that were published online on 1 June 2011 (i.e., ~10 days after the peak of the epidemic) and 4 June 2011. A summary of the guidelines in English was made available online on 4 June 2011. The time until ad hoc guidelines are made publicly available should and can be shortened in similar scenarios in the future. To this end-among other things-scientific societies in Germany linked to infectious diseases and medical microbiology have established a permanent working group called AFIM. This working group will facilitate timely identification and appointment of experts and expert panels, and will make use of new ways of rapid and effective sharing and dissemination of knowledge and ad hoc guidelines in the medical community and public domain if needed. In the case of disease outbreaks, immediate telephone conferences among all professionals involved, close cooperation between institutions and expert groups, and avoidance of premature unconsented information and press releases will be critical. We expect that proceeding in this way will also have a major impact on proper planning, professional design, and adequate analysis of clinical studies and endpoints appropriate for the outbreak situation.

[Surveillance of antibiotic consumption : clarification of the "definition of data on the nature and extent of antibiotic consumption in hospitals according to § 23 paragraph 4 sentence 2 of the IfSG"]. / Antibiotika-Verbrauchs-Surveillance : Ausführungen und Erläuterungen zur Bekanntmachung "Festlegung der Daten zu Art und Umfang des Antibiotika-Verbrauchs in Krankenhäusern nach § 23 Abs. 4 Satz 2 IfSG"

According to § 23 paragraph 4 of the German Infection Prevention Act (IfSG; July 2011), hospitals and clinics for ambulatory surgery are obliged to establish a continuous monitoring system of antibiotic consumption. This is aimed at contributing to an optimization of antibiotic prescription practices in order to confine the development and spread of resistant pathogens. The general requirements (restricted to hospitals) on the method and extent of data collection are provided by the national public health institution after discussion with representatives of various professional societies (Robert Koch-Institut, Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 59, 2013). The article aims to clarify these specifications and to provide background details. In agreement with national and European surveillance systems, the Anatomical Therapeutic Chemical (ATC)/Defined Daily Dose (DDD) classification system recommended by the WHO should be used as reference standard. Antibiotic consumption should be expressed as the number of DDDs per 100 patient days and per 100 admissions. The categories of antimicrobials and hospital organizational units to be monitored and the time intervals in which analyses should be conducted are determined. Furthermore, various approaches of data assessment are described.

[Colistin : renaissance of an old antibiotic?]. / Colistin : Ein altes Antibiotikum in neuem Glanz?

Owing to its activity against multidrug-resistant gram-negative bacteria, colistin (like other older antibiotics) is experiencing a surprising resurgence. In the 50 years following its discovery, little effort was put into studying its dosing and pharmacodynamic properties. Recent data have been filling the gaps, and individualized dosing recommendations targeting an optimal AUC/MIC ratio have been published. According to these data, pharmacokinetic targets will clearly be missed without exceeding the currently recommended dosages. Even the highest doses studied so far do not universally result in sufficient drug levels. Therefore, colistin remains a last-resort drug which should be used in combination with other antibiotics only. Regardless of the presence of resistance, carbapenems seem to be the most promising combination partners.