Carbapenem-resistant gram-negative bacteria in Germany: incidence and distribution among specific infections and mortality: an epidemiological analysis using real-world data.

PURPOSE: Infections with carbapenem-resistant gram-negative bacteria (in Germany classified as 4MRGN) are a growing threat in clinical care. This study was undertaken to understand the overall burden of 4MRGN infections in Germany in the context of a Health Technology Appraisal (HTA) for Ceftazidime/Avibactam (CAZ/AVI). Besides, the incidences mortality was an endpoint of interest. METHODS: To assess infections with carbapenem-resistant gram-negative bacteria and related mortality, three different data sources have been used. From the German statistics office (DESTATIS) data have been retrieved to obtain the overall frequency these pathogens. Via two other databases, the German analysis database (DADB) and a Benchmarking of > 200 hospitals in a representative sample (BM-DB), the distribution of the infections and the mortality have been analyzed. RESULTS: DESTATIS data showed a total of 11,863 carbapenem-resistant gram-negative bacteria codings, of which 10,348 represent infections and 1515 carriers. The most frequent infections were complicated urinary tract infections (cUTI) (n = 2,337), followed by pneumonia (n = 1006) and intra-abdominal infections (n = 730). A considerable amount of patients had multiple infections in one hospital episode (n = 1258). In-hospital mortality was 18.6% in DADB and 14.3% in the BM-DB population, respectively. In cases with additional bloodstream infections, DADB mortality was correspondingly higher at 33.0%. DADB data showed an incremental mortality increase of 5.7% after 30 days and 10.0% after 90 days resulting in a cumulative 90 day mortality of 34.3%. CONCLUSIONS: Infections with carbapenem-resistant gram-negative bacteria are still rare (6.8-12.4 per 100,000) but show a significant increase in mortality compared to infections with more sensitive pathogens. Using different data sources allowed obtaining a realistic picture.

[Cost assessment for endoscopic procedures in the German diagnosis-related-group (DRG) system - 5 year cost data analysis of the German Society of Gastroenterology project]. / Kosten endoskopischer Leistungen der Gastroenterologie im deutschen DRG-System ­ 5-Jahres-Kostendatenanalyse des DGVS-Projekts.

Background In the German hospital reimbursement system (G-DRG) endoscopic procedures are listed in cost center 8. For reimbursement between hospital departments and external providers outdated or incomplete catalogues (e. g. DKG-NT, GOÄ) have remained in use. We have assessed the cost for endoscopic procedures in the G-DRG-system. Methods To assess the cost of endoscopic procedures 74 hospitals, annual providers of cost-data to the Institute for the Hospital Remuneration System (InEK) made their data (2011 - 2015; §â€Š21 KHEntgG) available to the German-Society-of-Gastroenterology (DGVS) in anonymized form (4873 809 case-data-sets). Using cases with exactly one endoscopic procedure (n = 274 186) average costs over 5 years were calculated for 46 endoscopic procedure-tiers. Results Robust mean endoscopy costs ranged from 230.56 € for gastroscopy (144 666 cases), 276.23 € (n = 32 294) for a simple colonoscopy, to 844.07 € (n = 10 150) for ERCP with papillotomy and plastic stent insertion and 1602.37 € (n = 967) for ERCP with a self-expanding metal stent. Higher costs, specifically for complex procedures, were identified for University Hospitals. Discussion For the first time this catalogue for endoscopic procedure-tiers, based on §â€Š21 KHEntgG data-sets from 74 InEK-calculating hospitals, permits a realistic assessment of endoscopy costs in German hospitals. The higher costs in university hospitals are likely due to referral bias for complex cases and emergency interventions. For 46 endoscopic procedure-tiers an objective cost-allocation within the G-DRG system is now possible. By international comparison the costs of endoscopic procedures in Germany are low, due to either greater efficiency, lower personnel allocation or incomplete documentation of the real expenses.

Treatment of MRSA pneumonia: Clinical and economic comparison of linezolid vs. vancomycin - a retrospective analysis of medical charts and re-imbursement data of real-life patient populations.

Objectives: To supplement the data collected in randomized clinical trials, the present study in patients with methicillin resistant Staphylococcus aureus (MRSA) pneumonia was conducted to explore the clinical effectiveness of linezolid and vancomycin in a routine clinical setting. Further, the overall costs of the patients' stay in the intensive care unit (ICU) were compared. Methods: This was a retrospective analysis of medical and reimbursement data of adult patients who were treated for MRSA pneumonia with linezolid or vancomycin. Since the subjects were not randomly assigned to treatments, propensity score adjustment was applied to reduce a potential selection bias. Results: In total, 226 patients were included; 95 received linezolid and 131 received vancomycin as initial therapy for MRSA pneumonia. Switches to another antibiotic were observed in 4 patients (4.2%) receiving linezolid and in 23 patients (17.6%) receiving vancomycin (logistic regression analysis; odds ratio linezolid/vancomycin: 0.183; 95% confidence interval [CI]: 0.052-0.647; p<0.01). All-cause in-hospital mortality was also lower in patients receiving linezolid (22 patients [23.2%] vs. 54 patients [41.2%]) (logistic regression analysis; odds ratio linezolid/vancomycin: 0.351; 95% CI: 0.184-0.671; p<0.01). The analysis of the total costs of stay in ICU did not reveal any major differences between the two treatment groups (cost ratio linezolid/vancomycin: 1.29; 95% CI: 0.84-1.98; p=0.24). Conclusions: These findings confirm in a routine clinical setting that linezolid is a valuable therapeutic alternative to vancomycin for the treatment of MRSA pneumonia. However, prospective studies in real-life patient populations are warranted.

Invasive fungal infections in infants-focus on anidulafungin.

INTRODUCTION: Invasive fungal infection in pediatric intensive care units (PICU) is a rising challenge. Candida species are the most common microorganisms in these infections. Due to growing resistance against fluconazole, echinocandins are being used for the appropriate therapy. However, the recent IDSA guidelines recommend them only in cases where fluconazole or Amphotericin B cause treatment failure or are contraindicated. In a literature review, the importance of invasive fungal infections in PICU settings and the role of anidulafungin shall be examined. MATERIALS AND METHODS: Articles were retrieved form PubMed covering the years 2000-2012. Various search terms were used. Then the articles were clustered in different types like 'review,' 'pharmacokinetics,' 'case reports' and others. RESULTS: From 67 search results, 14 articles were selected. Of these, 7 were related to anidulafungin, while 7 were related to echinocandins or fungal infections in the PICU. Anidulafungin was examined in 4 PK/PD studies where a good safety profile was found. No serious adverse events occurred. The articles reporting risk factors show that central venous catheters, receipt of antibiotics, receipt of parenteral nutrition, and neutropenia are the most important independent risk factors for invasive fungal infections in PICU. Three reviews of antifungal agents show that echinocandins may be useful due to their safety profile; micafungin is the best examined one and further trials are needed. DISCUSSION: The published literature on invasive fungal infections in PICU settings has grown over the years. There are only a few articles, however, which are directly related to the use of anidulafungin in this setting. A most recent publication showed good PK/PD dynamics and a good safety profile for anidulafungin. So far, no RCT in the area of invasive candidiasis in infants and neonates has been published. A review of currently registered trials at ClinicalTrials.gov has shown one more trial related to PK/PD and two trials that investigate the use of anidulafungin or anidulafungin in combination with Voriconazole in pediatrics. CONCLUSION: The small body of existing literature on anidulafungin in infants shows success in treatment, no drug-related adverse events, and good pharmacodynamics. A dosing of 0.75 mg/kg/day or 1.5 mg/kg/day is as effective as 50 mg/day or 100 mg/day in adults. More trials on the use in clinical reality of PICU or NICU should follow.

Pharmaco-economic evaluation of antibiotic therapy strategies in DRG-based healthcare systems - a new approach.

The cost of treatments especially in conditions where multiresistant bacteria are involved are a major issue in times where in most developed countries in the world payment systems based on diagnoses-related-groups (DRG) are in place. There is great evidence that especially the length of stay in hospital (LOS), the time in the intensive care unit (ICU-days) and the hours of mechanical ventilation (HMV) are major cost drivers. - While established methods of pharmacoeconomical analyses focus on the efficiency of drugs from healthcare system perspective, these data are often not sufficient for improving treatment strategies in a given hospital context. - We developed a system that allows the analysis of patients with severe infections on the basis of routine data that is also used for reimbursement. These data contain a lot of information concerning the clinical conditions. By using the ICD-coding we developed an algorithm which allows the detection of patients with infections and gives information on the potential financial outcome of these patients. By using the analysis it is possible to identify subsets of infections and the patient records that had a potentially negative DRG-result, i.e. the costs are higher than the reimbursement. When identified the patient records undergo a peer review, where the clinical situation and the antibiotic therapy are reviewed by medical experts. In case simulations it is possible to find out if a different therapeutic approach, e.g. by different choices in initial (empirical) antibiotic treatment would have caused other outcomes. - Data driven analyses together with peer reviews of patient records are a useful tool to examine antibiotic treatment strategies and to establish changes that again can be reviewed on a regular basis. Doing this a continous improvement process can be established in hospitals which can lead to a better balance of clinical and economical outcomes in patients with severe infections. Moreover these analyses are helpful in assessing the literature on economical benefits of new therapies.

Multiresistant bacteria and current therapy - the economical side of the story.

UNLABELLED: Severe infections with multiresistant bacteria (MRB) are a medical challenge and a financial burden for hospitals. The adequate antibiotic therapy is a key issue in multiresistant bacteria management. Several major cost drivers have been identified. Remarkably drug acquisition costs are not necessarily included. Most significant are the length of stay in hospital, the hours of mechanical ventilation and the time treated on an intensive care unit. - In a systematic review of the literature the following aspects were investigated: - Do generic treatment strategies contribute in cost savings? - Are there specific results for recent antibiotics? - Early adequate and effective antimicrobial treatment, switch from i.v. to oral therapy, adjusted duration of therapy and adherence to guidelines have been found to be successful strategies. - Looking at specific antibiotics, the best evidence for cost-effectiveness is found for Linezolid in treatment of cSSTI as well as in HAP. Daptomycin shows good economic results in bloodstream infections, so possibly being a cost-effective alternative to vancomycin. Looking at tigecycline the published data show neither higher costs nor savings compared to imipeneme. Doripenem as one of the newest therapy options has proven to be highly cost-saving in HAP when compared with imipenem. However, most analyses are based on pharmacoeconomic modelling rather than on directly analysing trial data or real life clinical populations. - CONCLUSION: Using modern antibiotics in whole is not more expensive than using established therapies. Modern antibiotics are cost-effective and sometimes even cost-saving. This is especially true if an effective therapy is initiated as early as possible.

The significance of laboratory testing for the German diagnosis-related group system--the systematic evaluation of comorbidities of relevance to case reimbursement and continued development of the DRG Watchdog software.

The launch of the G-DRG system version 2004 made it necessary to update our former studies on the importance of laboratory testing (Clin Lab 2002;48:327-333). Using a systematic search algorithm, we established a total of 2,828 comorbidities, the ICD coding of which has a positive effect on case reimbursement, thus helping to secure hospital revenue. 62% of these comorbidities were found to depend exclusively or predominantly on laboratory testing. On average, one such comorbidity can be said to influence approximately 100 DRGs (range 2 to 226). In order to gain a clearer idea of the practical benefit of such "hits", amounting to several 100,000s, we selected about 5% of them for illustration with a computer program called DRG Watchdog. This program shows just how much additional reimbursement can be achieved for a specific DRG upon the ICD coding of a specific comorbidity. The program is freely available on the Internet at www.trillium.de and enjoys more than 100 search runs per day.

Detection and documentation of DRG-relevant comorbidities using laboratory tests.

Germany will soon begin per case payment by DRG, and preparations are in progress in most hospitals and insurance companies. The Academic Teaching Hospital Munich-Schwabing in Munich decided to explore coding strategies by considering the impact of diagnoses that could be detected by pathology tests. An Australian database was analysed. We detected "discriminating" diagnoses--that is, diagnoses that could be found in level A or B DRGs, and not in the respective lower severity DRG. After isolating 584 diagnoses, they were rated by a laboratory specialist, to determine whether they could be proved by pathology tests. 187 diagnoses were selected in this way. In the next step, theoretical cases were generated and grouped. 157 diagnoses were found to produce a switch to a higher DRG. The diagnoses, the DRGs and the respective laboratory tests were then arranged in a small MS-Excel program to allow comfortable browsing. The overall success rate of 84% shows that laboratory medicine can contribute to correct coding for DRGs.

Impact of laboratory testing on DRG coding and reimbursement--results of a data base research.

We filed an Australian data base with about 7 million well-documented clinical cases for comorbidities, which can be proven, supported or excluded by laboratory testing and which have an impact on DRG reimbursement. The result was a list of 123 DRGs being shifted to a higher severity level by documenting one out of 157 complications. For better visualization of the more than 4,000 combinations, we developed a computer program, which allows the laboratory to develop its own diagnostic pathways for these complications in a simple Excel format.