Cefalosporíny v ambulantnej praxi. Pavol Jarčuška Klinika pre infekčné choroby FNLP a LF UPJŠ Košice
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1 Cefalosporíny v ambulantnej praxi Pavol Jarčuška Klinika pre infekčné choroby FNLP a LF UPJŠ Košice Košice, Synlab,
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3 Od čoho závisí kolonizácia potencionálne patogénnymi mikroorganizmami?
4 Od čoho závisí kolonizácia potencionálne patogénnymi mikroorganizmami? 1. epidemiologická situácia 2. imunitné mechanizmy hostiteľa 3. Fyziologická baktericídna obrana hostiteľa fyziologická mikroflóra a bakteriocíny
5 Normálna flóra má významnú protektívnu úlohu Nazofaryng zdravých detí je kolonizovaný relatívne nepatogénnymi aeróbnymi (napr. -hemolytické streptokoky) a anaeróbnymi mikróbmi (napr. Peptostreptococcus anaerobius). -hemolytické streptokoky majú významnú protektívnu úlohu sú schopné zabraňovať osídleniu nazofaryngu rôznymi patogénmi, vrátane Str.pneumoniae, -hemolytických streptokokov a Staph. aureus. Brook I: Ped.Inf.Dis.J.,1998,17,8, Supplement:S62-67.
6 Vplyv antibiotík na kolonizáciu nazofaryngu
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13 Streptococcus pyogenes Najčastejší patogén tonzilitídy a detských kožných infekcií Vynikajúca citlivosť na penicilín a na betalaktámové ATB Rezistencia na makrolidy (M, MLSb) Rezistencia na linkozamidy (MLSb)
14 Sreptococcus pyogenes Citlivosť na ATB
15 Streptococcus pyogenes - paradoxy Vo svete a v SR v posledných rokoch pozorovaná nižšia klinická účinnosť a nižšia mikrobiologická účinnosť penicilínu V SR sa prakticky nevyskytujú poststreptokokové komplikácie
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23 Teória Koadherencie zvýšenej adherencie S.pyogenes Koagregácie väčšieho počtu kmeňov S.pyogenes
24 Koadherencia S.pyogenes a M. catarrhalis LaFointaine, Infect Immun, 2004
25 Koagregácia S.pyogenes a M. catarrhalis LaFointaine, Infect Immun, 2004
26 Pneumónia SR ročne hlásených až prípadov pneumónie SR ročne hospitalizovaných cca prípadov 2007 hospitalizovaných pacientov, mortalita 8,5% viac ako 80% prípadov úmrtia vo vekovej skupine starších ako 60 rokov SR nízka penetrácia očkovania IDSA/ATS guidelines 4 skupiny + skórovacie systémy (CURB, PORT, PSI)
27 Košturiak, 2009
28 Proporcia úmrtí v (%) Komunitná pneumónia v dospelosti 30 Distribúcia úmrtnosti hospitalizovaných pacientov s CAP v závislosti na veku % % % % 9.57% % 1.31% 1.26% 1.18% Vek Adaptované podľa Ewig S, et al. Thorax 2009;64: CAP = community-acquired pneumonia. v komunite získaná pneumónia Slide Ewig S, et al. New perspectives on Community-Acquired Pneumonia in 388,406 patients. Results from a nationwide mandatory performance measurement program in healthcare quality. Thorax. 2009;64:
29 CAP u dospelých pacientov 5 Distribúcia hlavných respiračných patogénov podľa veku Vek < 65 rokov 65 rokov p Počet pacientov n = 1,298 n = 1,349 value Počet detegovaných patogénov n = 271 n = 268 Streptococcus pneumoniae 42.10% 43.30% 0.85 Gram-negative bacily 3.70% 7.10% 0.17 Staphyloccocus aureus 1.50% 2.20% 0.74 Hemophilus influenzae 4.80% 3.40% 0.53 Chlamydia pneumoniae 1.10% 0% 0.26 Mycoplasma pneumoniae 14.00% 0.70% Legionella spp % 17.50% 0.87 Respiratory syncytial virus 1.80% 3.70% 0.29 Influenza virus A 5.90% 14.90% CAP = community-acquired pneumonia. Podľa Kothe H et al. Eur Respir J. 2008;32: Slide Kothe H et al. Outcome of Community-Acquired Pneumonia: influence of age, residence status and antimicrobial treatment. Eur Respir J. 2008; 32:
30 Mortalita na CAP, ktoré sú vyvolané enterobaktériami (EB) Definitívne a indeterminované 6 Vybrané demografické a klinické údaje u pacientov s a bez EB Počet vzoriek (n = 3,009) Vzorky bez EB/PA (n = 1,833) Definitívne EB (n = 67) Indeterminované EB (n = 172)* Vek (roky) 60 ± ± ± ± 14 Ošetrovateľská starostlivosť Cchronické srdcové zlyhanie 8% 2% 19% 10% 19% 14% 46% 25% Ochorenie CNS 12% 5% 33% 12% Diabetes mellitus 17% 13% 30% 24% 30 dňová mortalita 7.3% 4.5% 20.9% 7% * Celkom 172 (81%) z 212 izolátov EB bolo hodnotených ako indeterminované. CAP = community-acquired pneumonia;; PA = Pseudomonas aeruginosa. Podľa Baum H, et al. Eur Respir J. 2010;35(3): von Baum H et al. Community-Acquired Legionella Pneumonia: New Insights from the German Competence Network for Community Acquired Pneumonia. Eur Respir J. 2010;35(3): Slide 30
31 Kombinačná terapia vs. monoterapia rizikoví pacienti závažná bakterieická pneumónia u rizikových pacientov 225 pacientov (99 monoterapia, ost. min 2 ATB) Pneumonia severity index rovnaký v oboch skupinách (rizikový nad 90) mortalita výrazne vyššia v skupine s monoterapiou (P =.02, odds ratio, 3.0 [95%konfidenčný interval ]) prediktívny mortalitný index u pacientov s monoterapiou bol 6,4 [95%konfidenčný interval ,7]) Monotherapy May Be Suboptimal for Severe Bacteremic Pneumococcal Pneumonia G. W. Waterer; G. W. Somes,; R. G. Wunderink, Arch Intern Med. 2001;161:
32 Skupina II: Ambulantní pacienti, s kardiopulmonálnym ochorením a/alebo iným modifikujúcim faktorom 1,2 Organizmus Streptococcus pneumoniae (vrátane DRSP) Mycoplasma pneumoniae Chlamydia pneumoniae Zmiešané infekcie (baktéria plus atypický patogén alebo vírus) Haemophilus influenzae Črevné gramnegatívne baktérie Respiračné vírusy Rôzne Moraxella catarrhalis, Legionella sp., aspirácia (anaeróby), Mycobacterium tuberculosis, endemické plesne Liečba 3 Betalaktám (orálny cefixím, cefuroxim, ceftibutém, cefprozil amoxicillin vo vysokej dávke, amoxicillin/klavulanát alebo parenterálny ceftriaxon nasledovaný orálnym cefixímom) plus Makrolid alebo Doxycyklín 4 alebo antipneumokokový fluorochinolón (používaný samostatne) 5
33 Odporúčanie pre sekvenčnú ATB liečbu. Al-Eidan F A et al. J. Antimicrob. Chemother. 1999;44:
34 Spotreba cefalosporínov v 25 EU krajinách
35 Ako účinkujú betalaktámové ATB sú medzi nimi rozdiely?
36 Mechanizmus účinku betalaktámov 1. -lactam sa viaže na PBP 2. Inhibícia syntézy bunkovej steny 3. Smrť bunky
37 Štruktúra peptidoglykanu
38 5. Farmakokinetika a farmakodynamika Prediktory eradikácie baktérií Time > MIC AUC24/MIC MIC MIC 50% Penicilíny Cefalosporíny Erytromycín Klarithromycín Chinolóny Aminoglycozidy Azithromycín
39 Bacteriological cure (%) Korelácia medzi time above MIC 90 a eradikáciou baktérií S. pneumoniae (červené) a H. influenzae (modré) Otitis media Sinusitis Time Above MIC (% of dosing interval) Slide no 39
40 Percento citlivých kmeňov na jednotlivé cefalosporíny podľa PK/PD breakpointov PK/PD breakpoint S.pneumoniae H.influenzae M.catarrhalis (µg/ml) n=1760 n=1919 n=204 Cefuroxime Cefprozil Cefixime Cefaclor Loracarbef Jacobs et al. ICAAC 1999
41 Take home message CFX Infekcie HCD farmakokinetika Pneumónie Pk PD, enterobaktérie, kombinovaná liečba Uroinfekcie ženy, rezistentné kmene
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