Guideline-adherent initial intravenous antibiotic therapy for hospital-acquired/ventilator-associated pneumonia is clinically superior, saves lives and is cheaper than non guideline adherent therapy

<p>Abstract</p> <p>Introduction</p> <p>Hospital-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 guidelines</p> <p>Materials and methods</p> <p>We 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.</p> <p>Results</p> <p>We 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).</p> <p>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.</p> <p>Discussion</p> <p>These 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.</p> <p>Conclusion</p> <p>Guideline-adherent initial intravenous antibiotic therapy is clinically superior, saves lives and is less expensive than non guideline adherent therapy. Using a CPRS score can be a useful tool to determine the right choice of initial intravenous antibiotic therapy. the net effect on the German healthcare system per year is estimated at up to 2,042 lives and EUR 125,819,000 saved if guideline-adherent initial therapy for HAP/VAP were established in all German ICUs.</p

The use of a standardized PCT-algorithm reduces costs in intensive care in septic patients - a DRG-based simulation model

<p>Abstract</p> <p>Introduction</p> <p>The 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.</p> <p>Materials and methods</p> <p>We 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.</p> <p>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.</p> <p>Results</p> <p>We 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).</p> <p>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.</p> <p>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.</p> <p>Discussion</p> <p>Our 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 standard in PCT-based ABX. However the findings are based on data modelling. The algorithm will be implemented in 5-10 hospitals in 2012 and effects in clinical reality measured 6 months after implementation.</p> <p>Conclusion</p> <p>Managing sepsis with daily monitoring of PCT using our refined algorithm is suitable to save substantial costs in hospitals. Implementation in clinical routine settings will show how much of the calculated effect will be achieved in reality.</p

Clinical and economical improvements after introducing rapid identification of bacteria and early antibiotic susceptibility testing in sepsis and bloodstream infections. Results of the PHENOMENON study

Background: Sepsis and bloodstream infections pose severe challenges in intensive care. Early reliable diagnosis is the key to successful therapy. The objective of the study presented here was to investigate the clinical and economical effects of the new PhenoTM BC test, which allows bacteria identification (ID) and antimicrobial susceptibility testing (AST) in approximately 7 hours after a blood culture becomes positive (BC+).Methods: Historically controlled interventional study. Population: patients with BC+ and ICU admission. Inadequate initial antimicrobial therapy (IAT) is need of therapy change based on result. Prospectively the new test was used in addition. Primary endpoint: time-to-result in hours. Contribution margin (CM) i.e. revenue - costs was computed. All patients formed the intention-to-treat population (ITT). Patients with complete cost data formed the modified ITT group (mITT). CM results were calculated for mITT and PP. Further analyses: length-of-stay (LOS) and mortality.Results: 223 historical and 200 prospective patients were included. Time to result (ITT) was shortened by 51.1 hours (83 vs. 31.9; p<0.001). Overall savings (mITT) were 257,100 Euro (-301,264 Euro vs. -44,164 Euro). 143 of 181 (79%) patients had a test performed, 126 of 143 (88%) having a clinically useable result. 40 (32%) had IAT vs. 65 (29%) in the historic cohort. Median time to AST in PP was shortened by 61.7 hours (89.5 vs. 27.8; p<0.001). LOS was shortened 7 days (28 vs. 19; p=0.226) and mortality was 8% (40.5% vs. 32.5%; p=0.440) lower. Median CM +3,074.80 Euro per case (-2,350.50 Euro vs. +724.70 Euro; p=0.040). Conclusion: The new PhenoTM ID+AST test leads to faster and clinically meaningful results and saves money by shortening LOS on the ICU

Calculated initial parenteral treatment of bacterial infections: Sepsis

This is the eleventh chapter of the guideline "Calculated initial parenteral treatment of bacterial infections in adults - update 2018" in the 2nd updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience.Sepsis, defined as a life threatening organ dysfunction caused by a misregulated host response to an infection, is the third leading cause of death in Germany with a lethality rate of 30% to over 50%. An early, effective antimicrobial therapy is, next to infectious source control, the most important causal treatment option. It should be complemented by the mainly supportive measures of general intensive care therapy. Prior antimicrobial therapy, the patient's medical history (e.g. risk factors for multiresistant agents) and small-scale epidemiology are to be considered as part of the therapeutic and practical decisions. A modification of the often needed broad initial calculated combination therapy is desirable. In the future, prompt measurements of plasma concentrations of antiinfectives, especially for the sepsis patient with diverse and partly conflicting pathophysiological changes, will have great importance regarding efficacy, toxicity and resistance development. In order to apply those complex strategies in clinical routine, there is a requirement for a strong interdisciplinary collaboration between the intensive care unit, clinical infectiology, microbiology, and clinical pharmacology, ideally in the framework of a functional antimicrobial stewardship program.Dies ist das elfte Kapitel der von der Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) herausgegebenen S2k Leitlinie "Kalkulierte parenterale Initialtherapie bakterieller Erkrankungen bei Erwachsenen - Update 2018" in der 2. aktualisierten Fassung.Sepsis als die dritthäufigste Todesursache in Deutschland mit einer Letalität von 30 bis über 50% ist definiert als lebensbedrohliche Organdysfunktion, die durch eine fehlregulierte Wirtsantwort auf eine Infektion hervorgerufen wird. Die frühe, wirksame antimikrobielle Therapie stellt neben der Fokussanierung/-kontrolle die wichtigste kausale Behandlungsoption dar, ergänzt durch die allgemeine Intensivtherapie mit ihren vor allem supportiven Maßnahmen. Eine antimikrobielle Vortherapie, die Vorgeschichte des Patienten (z.B. Risikofaktoren für multiresistente Erreger) und die Kleinraumepidemiologie sollten unbedingt in die therapeutischen und praktischen Erwägungen einbezogen werden. Eine Modifizierung der zunächst oft breit notwendigen kalkulierten Kombinationstherapie ist anzustreben. In Zukunft wird der zeitnahen Plasmakonzentrationsbestimmung von Antiinfektiva gerade beim Sepsis-Patienten mit seinen vielfältigen, teils gegenläufigen pathophysiologischen Veränderungen eine herausragende Bedeutung im Hinblick auf Wirksamkeit, Toxizität und Resistenzentwicklung zukommen. Um diese komplexen Strategien im klinischen Alltag erfolgreich umsetzen zu können, bedarf es der engen Zusammenarbeit des Intensivmediziners/Klinikers mit der klinischen Infektiologie, der Mikrobiologie und der klinischen Pharmakologie, idealerweise im Rahmen eines funktionierenden Antimicrobial Stewardship Programmes