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...

Infections in intensive care unit (ICU) patients like severe pneumonia, e.g. nosocomial (NP) and community-acquired pneumonia (CAP), or septicemia must be treated promptly and effectively because of the ensuing high mortality. Treatment is thus empirical and starts before the results of microbiological cultures are known. The risk factors affecting mortality include severity of illness, virulence of etiologic pathogens and the use of inappropriate antibiotic therapy. Several studies have shown that modifying initially inadequate therapy, according to microbiological results, does not result in a better outcome. Due to this, antibiotic treatment requires agents which have an appropriate spectrum covering the likely pathogens causing these infections. In critically ill patients, the need for empirical first-line treatment covering a broad spectrum of Gram-negative and Gram-positive bacteria, as recommended in international guidelines (e.g. those of the American Thoracic Society or the Infectious Diseases Society of America), is justified in the presence of resistant organisms commonly documented in these patients. To choose an appropriate, initial antibiotic regimen, local and national resistance data have to be considered. With respect to new German resistance trends in Gram-negative and Gram-positive bacteria, the Paul Ehrlich Society of Chemotherapy has recently published guidelines for the treatment of infections in hospitalized patients. Especially in ICU patients with severe pneumonia (NP or CAP) or septicemia and risk factors like underlying diseases, antibiotic pretreatment or mechanical ventilation, agents with an appropriate spectrum encompassing Pseudomonas aeruginosa as well as other Gram-negative bacteria like Escherichia coli, Klebsiella spp., Enterobacter spp. and Gram-positive bacteria (e.g. Staphylococcus aureus, pneumococci and streptococci) are recommended as treatment of choice. Combination therapy with an anti-pseudomonal β-lactam and a fluoroquinolone or an aminoglycoside are recommended for these patients to provide the necessary spectrum of activity and to prevent the emergence of resistant organisms. On the other hand, clinical trials and meta-analyses have shown the efficacy, tolerability and cost-effectiveness of monotherapy regimens even in critically ill and immunocompromised patients. Conclusion: Appropriate β-lactam antibiotics recommended in international and German guidelines for the treatment of severe CAP, NP and septicemia, either as monotherapy or as combination therapy, are the 4th generation cephalosporin cefepime, the carbapenems imipenem and meropenem, and the acylamino-β-lactamase inhibitor combination piperacillin-tazobactam.

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 ...

This large prospective non-interventional study investigated the effects of tigecycline either as single agent or in combination with other antimicrobial agents in 1,025 patients treated in clinical routine at German hospitals. Sixty-five percent of the patients had APACHE II scores >15, indicating high overall disease severity. Complicated intra-abdominal infections (cIAI) or complicated skin and skin tissue infections (cSSTI) were the most common indications, with Staphylococcus aureus, Enterococcus faecium and Escherichia coli being the most frequently isolated pathogens. Clinical success was reported at the end of tigecycline therapy in 74.2% of the total population, in 75.4% of the cIAI and in 82.2% of the cSSTI patients. The subpopulation (28.0% of the patients) infected with multidrug-resistant pathogens (methicillin-resistant S. aureus, extended-spectrum β-lactamase producers and vancomycin-resistant enterococci) were treated with similar success rates as the overall population. Tigecycline was generally well tolerated. Drug-related adverse events (AEs) were reported in 7.7% of the total population; 2.5% had serious AEs mostly attributable to inefficacy of therapy or deterioration of the disease. Mortality rates were consistent with the types of infection and severity of illness. There was no indication of excessive mortality associated with tigecycline as had been suggested in previously performed meta-analyses. In this large non-interventional study performed in the clinical routine setting, tigecycline achieved favorable clinical success rates in a patient population with high severity of illness and a high prevalence of multidrug-resistant pathogens and showed a good safety and tolerability profile.

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We conclude that SAPS II is applicable to CCU patients in our unit.

Background: Only few data are available on the efficacy of tigecycline in critically ill patients. Methods: This prospective, multicenter, non-interventional study investigated the efficacy and safety of tigecycline in hospitalized, severely ill patients with complicated intra-abdominal infections (cIAI) and/or complicated skin and soft tissue infections (cSSTI). Documentation included diagnosis, clinical findings, Acute Physiology and Chronic Health Evaluation II score, laboratory assessments, surgery, clinical outcomes, and adverse events. Results: Six hundred and fifty-six patients (mean Acute Physiology and Chronic Health Evaluation II score 19.1) with cIAI (41%), cSSTI (16%), multiple infection sites (13%) and/or other severe infections (31%) received tigecycline – 51% as monotherapy – due to failure of previous antibiotics (55%) or since resistant pathogens were suspected or proven (45%); clinical cure/improvement rates were 75, 82, 76 and 67% for cIAI, cSSTI, other severe infections and multiple infection sites, respectively. Drug-related adverse events occurred in 6.7% of patients. Conclusions: The efficacy and safety of tigecycline was demonstrated in a population of severely ill patients with complicated infections.

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