2. Terapia antibiotica initiala influenteaza rezultatul clinic Source: Davey P et al. International Society of Pharmacoeconomics and Outcomes Research 2001 Rata de suces clinic P=0.007 (n=238) (n=56) Terapie antibiotica adecvata Terapie antibiotica inadecvata
3. În infecţiile severe, rata mortalităţii este determinat ă de terapia antibiotică iniţială
4. Pacienţi cu peritonită acută complicată (%), în relaţie directă cu terapia antibiotică de primă intenţie 0 5 10 15 20 25 30 35 40 45 50 Toţi pacienţii Re-intervenţii Abcese Suprainfecţia plagii operatorii Terapia adecvata Schimbată Terapie inadecvată (Mosdell et al ) Complicatiile sunt in relatie directa cu eficienta terapiei antibiotice initiale
8. R la β -lactamine, β -lactamaze – fenotip de R R R S S - Cefalo gen3 S R S R - Cefamicine R R S R - Cefalo gen2 R R R R S Cefalo gen1 R R S R R UreidoP R R S R R CarboxiP R R R - S Peniciline M R R R R R Peniciline A R R R R R Peni.G şi V dereprimate inductibile β –lactamaze cu spectru extins Cefalosporinaze Penicilinaz e BGN Penicilinaze S.aureus β -lactamine
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13. Parametri i farmacologici şi microbiologici AUC 24 C max (peak) AUIC 24 = AUC 24 / MIC T ½ MIC C m in Timp Timp sub CMI
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16. AUC CMI C max t T>CMI [C] Modelul prevenirii rezistentei
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18. Distribu ţ ia activit ăţ ii in vitro Num ă rul germenilor CMI (µg/mL) S I R Popula ţ ia bacterian ă S = Sensibil I = Intermediar R = Rezistent
19. Parametrii farmacodinamici ( in vivo ) 0 Concentration Timp (ore) AUC = Area under the concentration–time curve C max = Maximum plasma concentration PAE AUC:MIC T>MIC C max :MIC MIC
20. Probabilitatea dezvoltării rezisten ţ ei Thomas et al. Antimicrob Agents Chemother 1998;42:521–527 Probabilitatea de a r ă m â ne sensibile (%) AUC 0–24h :MIC 100 AUC 0–24h :MIC <100 Zile de la ini ţ irea terapiei 0 5 10 15 20 0 20 40 60 80 100 Rezulate de la 107 pacien ţ i cu i nfec ţ ii n osocomiale de t ract r espirator tratate diferit (ciprofloxacin, cefmenoxime, ceftazidime, ciprofloxacin plus piperacillin, ceftazidime plus tobramycin)
21. Farmacodinamica ceftazidimei 1 g ş i 2 g x3 /zi S. aureus MIC 0.1 10 100 1000 1 Concentra ţia (µg/m l ) 0 12 24 20 4 8 16 Tim pul (or e ) 2 g ceftazidim 1 g ceftazidim
SLIDE 26. Resistance cannot be made to disappear. But its effects can be minimised by less and better of antibiotics use, coupled to infection control and new pharmaceutical development.
SLIDE 2. Resistance is expensive financially and in terms of mortality and morbidity. Mosdell (ref.) compared rates of complications in peritonitis patients: (a) where the primary empirical therapy was active against all pathogens isolated; (b) where therapy was changed owing to isolation of resistant bacteria; and, (c) where inappropriate therapy was continued despite isolation of resistant bacteria. On every analysis, resistance increased the rates of complications, especially if in appropriate therapy was continued unchanged.