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Antibiotic therapy of postoperative sepsis,Markus A. Weigand Department of Anesthesiology and Intensive Care Medicine Justus-Liebig-University Gieen University Hospital Gieen and Marburg Campus Gieen,Hit hard and early Preferred antibiotics in severe sepsis Combination therapy Duration of antibiotic therapy Use of antibiotic diversity Conclusion,Time is the critical factor,Rivers et al. 2001 Early goal-dircted therapy“ ScVO270% reduces mortality by 15%,Kumar et al. 2006 Each hour of delay in antimicrobial administration was associated with a decrease in survival of 5 10%,6 h,Kumar A et al. ICAAC, 2007: L-477,Critical role of adequate antibiotic therapy,Hit hard and early Preferred antibiotics in severe sepsis Combination therapy Duration of antibiotic therapy Use of antibiotic diversity Conclusion,Wong PF et al. Cochrane Database Syst Rev 2005 Antibiotic regimens for secondary peritonitis of gastrointestinal origin in adults,No specific recommendations can be made,No recent randomized trial for patients with severe sepsis,Increasing Resistance for E. Coli,G.-T.E.S.T. 1 vs. G.-T.E.S.T. 2; Kresken M et al. Chemother J 2008; 17(5):205-226;,Resistant strains (%),Some guidelines recommend a combination therapy in severe sepsis Aminoglykosides, Chinolones, Tigecycline Only in patients with risk factors or with proven infections with MDR-bacteria guidelines uniformerly recommend combinations with Vancomycin, Linezolid, Daptomycin or Tigecycline,Ceftazidime oder Cefepime + Metronidazole Piperacillin + Beta-Lactamase inhibitor Imipenem, Meropenem or Doripenem,Recommended drug groups for empirical antibiotic treatment of severe nosocomial infections,Hit hard and early Preferred antibiotics in severe sepsis Combination therapy Duration of antibiotic therapy Use of antibiotic diversity Conclusion,Pat. without Shock,Pat. with Shock,Pseudomonas Bacteraemia,There was no difference in 28 day mortality between the combination and monotherapy groups (CI: 0.78-1.42; p=0.74),In patients with severe septic shock and in patients with MDR Pseudomonas a combination therapy might be of advantage,Hit hard and early Preferred antibiotics in severe sepsis Combination therapy Duration of antibiotic therapy Use of antibiotic diversity Conclusion,Duration of antibiotic therapy 8 vs. 15 days for ventilator-associated pneumonia,No difference in mortality, recurrent infections, ventilation- and organ failure free days and length of stay but more antibiotic free days in the 8-day course group,Chastre J et al. JAMA 2003; 290:2588-2598,Duration of antibiotic therapy 8 vs. 15 days for ventilator-associated pneumonia,Although patients with VAP caused by non-fermenting gram negative bacilli, including pseudomonas aeruginosa, did not have more unfavorable outcomes when antimicrobial therapy lasted only 8 days, they did have a higher pulmonary recurrence rate compared with those receiving 15 days of treatment (40.6 vs. 25.4%),Chastre J et al. JAMA 2003; 290:2588-2598,Hit hard and early Preferred antibiotics in severe sepsis Combination therapy Duration of antibiotic therapy Use of antibiotic diversity Conclusion,ESBL (%) ICUs UKG,Klebsiella,Unbalanced antibiotic use - Collateral damage,Cephalosporins Chinolons Carbapenems Penicillins -Lactamase-inhibitor,Penicillins are generally viewed as the antibiotics with the least selection pressure,Enterococci/VRE MRSA ESBL-producers Enterobacteriaceae (Chinolon-resistant) Acinetobacter MDR Stenotrophomonas Klebsiella MDR Clostridium difficile Pseudomonas MDR,mod. according to Sandiumenge A, et al. J Antimicrob Chemother. 2006;57:1197-1204.,PS: Patient specific PP: Prioritization of an antibiotic group RP: Restriction MP: Mixing,Nursing facilities High age Concomitant disease (e.g. multimorbidity) Immundodeficiency Malnutrition Chron. Skin and skin-structure infections Previous hospital stay within the last 3 month Previous antibiotic therapy within the last 3 month Prolonged ICU stay,Kaye KS et al. Infect Dis Clin N Am 2004;18:467-511; Sandiumenge et al. J AC 2006;57:1197-1204; Alter MJ. In: Hospital Epidemiology and Infection Control, 3rd edition, 2004; Geisel R, Schmitz FJ in Praktische Krankenhaushygiene und Umweltschutz, 3. Auflage; Springer Verlag; Panknin HT. Intensiv 2004; 12: 296-297, Thieme,Risk factors for antimicrobial resistance,New antibiotics for gramnegative bacteria,?,Tigecycline, Aminoglykoside Colistin+Rifampicin, Doripenem?,Treatment of severe complicated infections with Tigecycline,Drug use evaluation in 70 patients of a surgical ICU,Patient characteristics 70 patients with severe sepsis or septic shock 45% of patients with an age 65 years 51% of patients with comorbidities (57% with renal replacement therapy) Mean APACHE-II-Score 27, SAPS-Score 56, SOFA-Score 12,Swoboda et al JAC, Januar 2008; 61:729-733,Results and conclusion 8 patients with tigecyline first-line therapy 64% second-line-therapy with tigecycline in combination with other antibiotics Mortality rate was 30%. Tigecycline can be used safely and effective in this patient population,Linezolid (Tigecyclin CAP),Linezolid Alternatives Vancomycin (+ Rifa, Fo