Methicillin-resistant Staphylococcus aureus (MRSA) is a significant problem in many healthcare systems. In Germany, few data are available on its economic consequences and, so far, no study has been performed using a large sample of real-life data from several hospitals. We present a retrospective matched-pairs analysis of mortality, length of stay, and cost of MRSA patients based mainly on routine administrative data from 11 German hospitals. Our results show that MRSA patients stay in hospital 11 days longer, exhibit 7% higher mortality, are 7% more likely to undergo mechanical ventilation, and cause significantly higher total costs ( 8,198).

IntroductionHospital-acquired pneumonia (HAP) often occurring as ventilator-associated pneumonia (VAP) is the most frequent hospital infection in intensive care units (ICU). Early adequate antimicrobial therapy is an essential determinant of clinical outcome. Organisations like the German PEG or ATS/IDSA provide guidelines for the initial calculated treatment in the absence of pathogen identification. We conducted a retrospective chart review for patients with HAP/VAP and assessed whether the initial intravenous antibiotic therapy (IIAT) was adequate according to the PEG guidelinesMaterials and methodsWe collected data from 5 tertiary care hospitals. Electronic data filtering identified 895 patients with potential HAP/VAP. After chart review we finally identified 221 patients meeting the definition of HAP/VAP. Primary study endpoints were clinical improvement, survival and length of stay. Secondary endpoints included duration of mechanical ventilation, total costs, costs incurred on the intensive care unit (ICU), costs incurred on general wards and drug costs.ResultsWe found that 107 patients received adequate initial intravenous antibiotic therapy (IIAT) vs. 114 with inadequate IIAT according to the PEG guidelines. Baseline characteristics of both groups revealed no significant differences and good comparability. Clinical improvement was 64% over all patients and 82% (85/104) in the subpopulation with adequate IIAT while only 47% (48/103) inadequately treated patients improved (p < 0.001). The odds ratio of therapeutic success with GA versus NGA treatment was 5.821 (p < 0.001, [95% CI: 2.712-12.497]). Survival was 80% for the total population (n = 221), 86% in the adequately treated (92/107) and 74% in the inadequately treated 'subpopulation (84/114) (p = 0.021). The odds ratio of mortality for GA vs. NGA treatment was 0.565 (p = 0.117, [95% CI: 0.276-1.155]). Adequately treated patients had a significantly shorter length of stay (LOS) (23.9 vs. 28.3 days; p = 0.022), require significantly less hours of mechanical ventilation (175 vs. 274; p = 0.001), incurred lower total costs (EUR 28,033 vs. EUR 36,139, p = 0.006) and lower ICU-related costs (EUR 13,308 vs. EUR 18,666, p = 0.003).Drug costs for the hospital stay were also lower (EUR 4,069 vs. EUR 4,833) yet not significant. The most frequent types of inadequate therapy were monotherapy instead of combination therapy, wrong type of penicillin and wrong type of cephalosporin.DiscussionThese findings are consistent with those from other studies analyzing the impact of guideline adherence on survival rates, clinical success, LOS and costs. However, inadequately treated patients had a higher complicated pathogen risk score (CPRS) compared to those who received adequate therapy. This shows that therapy based on local experiences may be sufficient for patients with low CPRS but inadequate for those with high CPRS. Linear regression models showed that single items of the CPRS like extrapulmonary organ failure or late onset had no significant influence on the results.C...

ObjectiveNosocomial or more exactly, hospital-acquired (HAP) and ventilator-associated pneumonia (VAP) are frequent conditions when treating intensive care unit (ICU) patients that are only exceeded by central line-associated bloodstream infections. In Germany, approximately 18,900 patients per year suffer from a VAP and another 4,200 from HAP. We therefore reviewed the current guidelines about HAP and VAP, from different sources, regarding the strategies to address individual patient risks and medication strategies for initial intravenous antibiotic treatment (IIAT).Material and methodsWe conducted an analysis of the recent guidelines for the treatment of HAP. The current guidelines of the American Thoracic Society, the treatment recommendations of the Paul-Ehrlich-Gesellschaft (PEG), the guidelines from the British Society for Antimicrobial Chemotherapy, the VAP guideline of the Canadian Critical Care trials group, as well as the new German S3-guideline for HAP were examined.ResultsAll guidelines are based on grading systems that assess the evidence underlying the recommendations. However, each guideline uses different grading systems. One common aspect of these guidelines is the risk assessment of the patients for decision making regarding IIAT. Most guidelines have different recommendations depending on the risk of the presence of multidrug resistant (MDR) bacteria. In guidelines using risk assessment, for low-risk patients (early onset, no MDR risk) aminopenicillins with beta-lactamase inhibitors (BLI), second or third generation cephalosporins, quinolones, or ertapenem are recommended. For patients with higher risk, imipenem, meropenem, fourth generation cephalosporins, ceftazidime or piperacillin/tazobactam are recommended. The PEG recommendations include a combination therapy in cases of very high risk (late onset, MDR risk, ICU, and organ failure) of either piperacillin/tazobactam, dori-, imi- or meropenem or cefepime or ceftazidime with ciprofloxacin, levofloxacin, fosfomycin or an aminoglycoside. For the treatment of HAP caused by methicillin-resistant Staphylococcus aureus (MRSA), either linezolid or vancomycin is recommended. With regard to the ZEPHyR-trial, linezolid has shown higher cure rates but, no difference in overall survival. Economic analyses show the relevance of guideline-adherent IIAT (GA-IIAT). Besides significantly better clinical outcomes, patients with GA-IIAT cause significantly lower costs (€28,033 versus (vs) €36,139) (P=0.006) and have a shorter length of stay in hospital (23.9 vs 28.3 days) (P=0.022).ConclusionWe conclude that most current treatment guidelines take into account the individual patient risk and that the correct choice of IIAT affects clinical as well as economical outcomes.

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.ConclusionUsing 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.

IntroductionThe management of bloodstream infections especially sepsis is a difficult task. An optimal antibiotic therapy (ABX) is paramount for success. Procalcitonin (PCT) is a well investigated biomarker that allows close monitoring of the infection and management of ABX. It has proven to be a cost-efficient diagnostic tool. In Diagnoses Related Groups (DRG) based reimbursement systems, hospitals get only a fixed amount of money for certain treatments. Thus it's very important to obtain an optimal balance of clinical treatment and resource consumption namely the length of stay in hospital and especially in the Intensive Care Unit (ICU). We investigated which economic effects an optimized PCT-based algorithm for antibiotic management could have.Materials and methodsWe collected inpatient episode data from 16 hospitals. These data contain administrative and clinical information such as length of stay, days in the ICU or diagnoses and procedures. From various RCTs and reviews there are different algorithms for the use of PCT to manage ABX published. Moreover RCTs and meta-analyses have proven possible savings in days of ABX (ABD) and length of stay in ICU (ICUD). As the meta-analyses use studies on different patient populations (pneumonia, sepsis, other bacterial infections), we undertook a short meta-analyses of 6 relevant studies investigating in sepsis or ventilator associated pneumonia (VAP). From this analyses we obtained savings in ABD and ICUD by calculating the weighted mean differences. Then we designed a new PCT-based algorithm using results from two very recent reviews. The algorithm contains evidence from several studies. From the patient data we calculated cost estimates using German National standard costing information for the German G-DRG system.We developed a simulation model where the possible savings and the extra costs for (in average) 8 PCT tests due to our algorithm were brought into equation.ResultsWe calculated ABD savings of -4 days and ICUD reductions of -1.8 days. our algorithm contains recommendations for ABX onset (PCT ≥ 0.5 ng/ml), validation whether ABX is appropriate or not (Delta from day 2 to day 3 ≥ 30% indicates inappropriate ABX) and recommendations for discontinuing ABX (PCT ≤ 0.25 ng/ml).We received 278, 264 episode datasets where we identified by computer-based selection 3, 263 cases with sepsis. After excluding cases with length of stay (LOS) too short to achieve the intended savings, we ended with 1, 312 cases with ICUD and 268 cases without ICUD. Average length of stay of ICU-patients was 27.7 ± 25.7 days and for Non-ICU patients 17.5 ± 14.6 days respectively. ICU patients had an average of 8.8 ± 8.7 ICUD.After applying the simulation model on this population we calculated possible savings of € -1, 163, 000 for ICU-patients and € -36, 512 for Non-ICU patients.DiscussionOur findings concerning the savings from the reduction of ABD are consistent with other publications. Savings ICUD had never been economically evaluated so far. our algorithm is able to possibly set a new ...

Invasive fungal infections are on the rise. Echinocandins are a relatively new class of antifungal drugs that act by inhibition of a key enzyme necessary for integrity of the fungal cell wall. Currently there are three available agents: caspofungin, micafungin and anidulafungin.While the individual echinocandin antifungals have a different spectrum of licensed indications, basically all of them are available for the treatment of candidemia and invasive candidiasis. Antifungal treatment modalities basically include in therapy for suspected or proven infection and prophylaxis. All three drugs are comparatively expensive. Therefore a systematic review of the literature was performed to investigate the following aspects:• General aspects of cost-effectiveness in the treatment of invasive fungal infections• Cost-effectiveness of the treatment with the above-mentioned antifungals• Cost-effectiveness in two settings: therapy and prophylaxisEarly initiation of antifungal therapy, adjustment after availability of microbiological results, duration of therapy, success and occurrence of severe complications (e.g renal failure) are the most important cost drivers in antifungal therapy.Considering the specific antifungals, for caspofungin the best evidence for cost-effectiveness is found in treatment of invasive candidiasis and in empiric therapy of suspected infections. Favourable economic data are available for micafungin as a cost-effective alternative to LAmB for prophylaxis in patients with hematopoietic stem cell transplantation (HSCT). For anidulafungin, cost-effectiveness was demostrated in a pharmacoeconomic model. Net savings - yet not significant - were observed in a retrospective chart review of 234 patients. Generally, however, most analyses are still based on pharmacoeconomic modelling rather than direct analysis of trial data or real-life clinical populations.As an overall conclusion, using caspofungin, micafungin, or anidulafungin is not more expensive than using other established therapies. Micafungin has proven to be cost-effective in prophylaxis if the local fungal epidemiology indicates a high level of resistance to fluconazole. Switch strategies involving early initiation of broadly active therapy with switch to cheaper alternatives according to microbiology results and clinical status and early initiation of an appropriate therapy have been proven to be cost-efficient independent of the antifungal agent.

By extrapolating these findings CDAD not only harms patients but generates a yearly cost burden of 464 million € for the German healthcare system including a loss of 197 million € for German hospitals. To the authors' opinion sufficient measures against CDAD should include pre hospital risk reduction programs, introduction of effective therapeutic and hygienic strategies in hospitals as well as improvements in documentation for these cases to support further developments of the German DRG system.

We describe a prototype implementation of a semantic filtering capability added to an existing XML-based publish and subscribe infrastructure. An ontology is used to provide vocabulary for expressing both 1) the semantic annotations that characterize the published documents and 2) the subscriptions specifying the class of documents to be routed to a given client. A description logic (DL) classifier is used to determine which subscribers an incoming document is routed to. We outline the key elements of the ontology for the battlefield domain and give some sample annotations and subscriptions. This is the basis for describing a number of scenarios showing how this filtering capability could be used practice. We critically analyze the suitability of a DL language and reasoner in general, and the particular implementation choices (DAML+OIL, FaCT and OilEd) for performing this task. A key result of the work is to demonstrate the importance of testing semantics-based technologies on practical problems. We discovered a number of new and interesting areas for future work, which in turn can direct the focus of the research community.