Antibiotika-Verordnungen aus der Sicht des Hygienikers: Antibiotika-Resistenz Prof. Dr. Uwe Frank Department für Infektiologie Krankenhaus- und Umwelthygiene Universitätsklinikum Heidelberg

Antibiotika-Verordnungen in Deutschland 2009 Schröder H, WIdO 2010

Schröder H, WIdO 2010

Antibiotika-Verordnungen aus der Sicht des Hygienikers 1:3 Regel: Rd. 1/3 aller Krankenhauspatienten erhalten zu irgendeinem Zeitpunkt ein Antibiotikum im Krankenhaus Rd. 1/3 (bis ½) aller Antibiotikagaben = nicht indiziert Rd. 1/3 aller chirurg. Antibiotika-Prophylaxen = unangemessen Rd. 1/3 des Arzneimittelbudgets = Antibiotika Bis 1/3 des Arzneimittel-Budgets (10-30%) kann mit Hilfe eines Antibiotic Stewardships eingespart werden Rd. 1/3 der Krankenhauspatienten, die ein Antibiotikum erhalten, leiden an einer nosokomialen Infektion → Aktive Surveillance von Krankenhausinfektionen → Infektions-Kontrolle 4

Moderne Medizin ist nicht denkbar ohne Antibiotikaverordnungen.... Hüftersatz Organtransplantation Krebs-Chemotherapie Intensivmedizin Frühgeborenen-Intensivpflege

...aber Antibiotika-Verordnungen begünstigen auch die Antbiotika-Resistenzentwicklung in Krankenhäusern Kaier K, Hagist C, Frank U et al. Infect Control Hosp Epidemiol 2009;30(4):346-352

Bronzwaer S. L. et al., Emerging Infectious Diseases 2002; 8 (3): 278–282 Pneumokokken-Resistenz versus ambulante Betalaktam-Verbräuche

Einfluss von Azithromycin und Clarithromycin Therapie auf die pharyngeale Besiedlung mit Macrolid-resistenten Streptokokken n 74 72 Malhotra-Kumar S. et al., Lancet 2007; 369: 482 – 490

Wie entstehen Antibiotika-resistente Erreger? Neue resistente Bakterien Mutationen XX Empfindliche Bakterien Resistenzgen-Transfer (z.B. ESBL, AG, SMX) (z.B. FQ) Resistente Bakterien Bacteria have evolved numerous mechanisms to evade antimicrobial drugs. Chromosomal mutations are an important source of resistance to some antimicrobials. Acquisition of resistance genes or gene clusters, via conjugation, transposition, or transformation, accounts for most antimicrobial resistance among bacterial pathogens. These mechanisms also enhance the possibility of multi-drug resistance. (qnr-Gen: FQ)

Selektion resistenter Bakterienstämme Resistente Stämme Mehrheit Antibiotika Exposition x Resistente Stämme Minderheit x Once resistant strains of bacteria are present in a population, exposure to antimicrobial drugs favors their survival Reducing antimicrobial selection pressure is one key to preventing antimicrobial resistance and preserving the utility of available drugs for as long as possible

Teufelskreis ”Antibiotikatherapie” Erreger Therapie Resultat Pneumokokken Penicillin E. coli E. coli Ampicillin Klebsiella Klebsiella Cefuroxime Enterobacter Enterobacter Pipera/Genta. Pseudomonas Pseudomonas Cefta/Tobra Candida spp. Candida spp. Amphotericin-B Taubheit + Niereninsuffiz.

Antibiotika-Resistenz: Präventions-Strategien Empfindlicher Erreger Resistenter Erreger Erreger Infektion Verhüte Transmission Infektions- Verhütung Antibiotika-Gabe Antibiotika-Resistenz Once a pathogen produces infection, antimicrobial treatment may be essential However, antimicrobial use promotes selection of antimicrobial-resistant strains of pathogens As the prevalence of resistant strains increases in a population, subsequent infections are increasingly likely to be caused by these resistant strains Fortunately, this cycle of emerging antimicrobial resistance/multidrug resistance can be interrupted Preventing infections in the first place will certainly reduce the need for antimicrobial exposure and the emergence and selection of resistant strains Effective diagnosis and treatment will benefit the patient and decrease the opportunity for development and selection of resistant microbes; this requires rapid accurate diagnosis, identification of the causative pathogen, and determination of its antimicrobial susceptibility Optimizing antimicrobial use is another key strategy; optimal use will ensure proper patient care and at the same time avoid overuse of broad-spectrum antimicrobials and unnecessary treatment Finally, preventing transmission of resistant organisms from one person to another is critical to successful prevention efforts Korrekte Diagnose + Therapie Rationaler Einsatz

Antibiotika-Resistenz: CDC-Präventions-Strategien Campaign to Prevent Antimicrobial Resistance in Healthcare Settings Antibiotika-Resistenz: CDC-Präventions-Strategien Verhüte Infektionen! Diagnostiziere + therapiere korrekt! Verwende AB rational ! Verhüte Transmission ! These 4 strategies—preventing infection, diagnosing and treating infection effectively, using antimicrobials wisely, and preventing transmission—form the framework for the CDC’s Campaign to Prevent Antimicrobial Resistance Clinicians and their patient care partners hold the solution to integrating these strategies into daily practice and optimizing the care and safety of all patients

CDC: Gebote zur Resistenzkontrolle 12 Vermeide Übertragung 11 Isoliere den Erreger 10 Beende die Therapie zeitig 9 Vermeide Vancomycin 8 Behandle Infektion, nicht Kolonisation 7 Behandle Infektion, nicht Kontamination 6 Beachte lokale Epidemiologie 5 Kontrolliere Antibiotikagebrauch 4 Frage Experten 3 Ziele auf den Erreger 2 Entferne Katheter! 1 Impfe! VERMEIDE TRANSMISSION VERWENDE ANTIBIOTIKA KLUG DIAGNOSTIZIERE UND BEHANDLE EFFIZIENT VERHÜTE INFEKTIONEN On the questionnaire, clinicians reported those campaign steps that would have the most barriers to implementaion and preventing antimicrobial resistance. The three most frequently indicated steps were „Practice antimicrobial control“, „Treat infection, not colonization“, and „Stop treatment, when infection is cured“. The two most frequently indicated strategies were „“Use antibiotics wisely“ and „Prevent infection“. Centers for Disease Contol 2002

Antibiotika-Resistenz: Die Bombe ist scharf!