. . . "5.1\tFarmakodynamick\u00E9 vlastnosti"@cs . . . "Farmakoterapeutick\u00E1 skupina: Fluorochinolony, ATC k\u00F3d: J01MA02\nMechanizmus \u00FA\u010Dinku:\nCiprofloxacin je fluorochinolov\u00E9 antibiotikum, to znamen\u00E1, \u017Ee p\u016Fsob\u00ED inhibi\u010Dn\u011B na oba bakteri\u00E1ln\u00ED enzymy, topoizomer\u00E1zu II (DNA-gyr\u00E1zu) a topoizomer\u00E1zu IV, kter\u00E9 jsou pot\u0159ebn\u00E9 pro replikaci, transkripci, opravu a rekombinaci bakteri\u00E1ln\u00ED DNA.\nVztah FK/FD:\n\u00DA\u010Dinnost z\u00E1vis\u00ED hlavn\u011B na vztahu mezi maxim\u00E1ln\u00ED s\u00E9rovou koncentrac\u00ED (Cmax) a minim\u00E1ln\u00ED inhibi\u010Dn\u00ED koncentrac\u00ED (MIC) ciprofloxacinu vzhledem k p\u0159\u00EDslu\u0161n\u00E9mu mikroorganizmu a na vztahu mezi plochou pod k\u0159ivkou (AUC) a MIC.\nMechanizmus rezistence:\nIn vitro rezistence na ciprofloxacin se m\u016F\u017Ee vyvinout postupn\u00FDm procesem mutac\u00ED c\u00EDlov\u00E9ho m\u00EDsta u obou topoizomer\u00E1z , topoizomer\u00E1zy II (DNA gyr\u00E1zy) a topoizomer\u00E1zy IV. V\u00FDsledn\u00FD stupe\u0148 zk\u0159\u00ED\u017Een\u00E9 rezistence mezi ciprofloxacinem a jin\u00FDmi fluorochinolony je prom\u011Bnliv\u00FD. Jednotliv\u00E9 mutace nemus\u00ED m\u00EDt za n\u00E1sledek klinickou rezistenci, ale n\u00E1sobn\u00E9 mutace obvykle za n\u00E1sledek klinickou rezistenci na mnoho aktivn\u00EDch l\u00E1tek nebo na v\u0161echny aktivn\u00ED l\u00E1tky v r\u00E1mci skupiny maj\u00ED.\nNepropustnost a/nebo mechanizmus rezistence efluxn\u00ED pumpy \u00FA\u010Dinn\u00E9 l\u00E1tky m\u016F\u017Ee m\u00EDt prom\u011Bnliv\u00FD efekt na citlivost na fluorochinolony, kter\u00E1 z\u00E1vis\u00ED na fyziochemick\u00FDch vlastnostech r\u016Fzn\u00FDch \u00FA\u010Dinn\u00FDch l\u00E1tek v r\u00E1mci skupiny a afinit\u011B transportn\u00EDch syst\u00E9m\u016F pro danou \u00FA\u010Dinnou l\u00E1tku. V\u0161echny in vitro mechanizmy rezistence jsou b\u011B\u017En\u011B pozorov\u00E1ny v klinick\u00FDch izol\u00E1tech. Mechanizmy rezistence, kter\u00E9 inaktivuj\u00ED dal\u0161\u00ED antibiotika, nap\u0159\u00EDklad permea\u010Dn\u00ED bari\u00E9ry (b\u011B\u017En\u00E9 u Pseudomonas aeruginosa ) a effluxn\u00ED mechanizmus, mohou ovlivnit citlivost na ciprofloxacin. Byla zaznamen\u00E1na rezistence zprost\u0159edkovan\u00E1 plazmidem k\u00F3dovan\u00E1 pomoc\u00ED gen\u016F qnr.\nSpektrum antibakteri\u00E1ln\u00ED aktivity:\nBreak pointy odd\u011Bluj\u00EDc\u00ED citliv\u00E9 kmeny od kmen\u016F s intermedi\u00E1rn\u00ED citlivost\u00ED a tyto od rezistentn\u00EDch kmen\u016F:\nDoporu\u010Den\u00ED EUCAST\n\tMikroorganizmy\n\tCitliv\u00E9\n\tRezistentn\u00ED\n\tEnterobakterie \n\tS \u2264 0.5 mg/l\n\tR > 1 mg/l\n\tPseudomonas \n\tS \u2264 0.5 mg/l\n\tR > 1 mg/l\n\tAcinetobacter \n\tS \u2264 1 mg/l\n\tR > 1 mg/l\n\tStaphylococcus spp .1\n\tS \u2264 1 mg/l\n\tR > 1 mg/l\n\tHaemophilus influenzae a\nMoraxella catarrhalis\n\tS \u2264 0.5 mg/l\n\tR > 0,5 mg/l\n\tNeisseria gonorrhoeaee\n\tS \u2264 0.03 mg/l\n\tR > 0,06 mg/l\n\tNeisseria meningitidis\n\tS \u2264 0.03 mg/l\n\tR > 0,06 mg/l\n\tBreak pointy nevzta\u017Eiteln\u00E9 k t\u0159\u00EDd\u00E1m *\n\tS \u2264 0.5 mg/l\n\tR > 1 mg/l\n1 Staphylococcus spp. \u2013 Break pointy pro ciprofloxacin odpov\u00EDdaj\u00EDc\u00ED terapii s vysok\u00FDmi d\u00E1vkami.\n* Break pointy nevzta\u017Eiteln\u00E9 k t\u0159\u00EDd\u00E1m byly ur\u010Deny zejm\u00E9na na z\u00E1klad\u011B \u00FAdaj\u016F PK/PD a nejsou z\u00E1visl\u00E9 na distribuci MIC jednotliv\u00FDch druh\u016F. Jsou ur\u010Deny pouze pro druhy, pro kter\u00E9 specifick\u00E9 Break pointy nebyly ur\u010Deny a ne pro takov\u00E9 druhy, pro kter\u00E9 testy citlivosti nejsou doporu\u010Dov\u00E1ny.\nPrevalence z\u00EDskan\u00E9 rezistence vybran\u00FDch druh\u016F se m\u016F\u017Ee li\u0161it geograficky a \u010Dasov\u011B. Je vhodn\u00E1 informace o lok\u00E1ln\u00ED rezistenci, zejm\u00E9na pokud se jedn\u00E1 o l\u00E9\u010Dbu z\u00E1va\u017En\u00FDch infekc\u00ED. V nezbytn\u00FDch p\u0159\u00EDpadech, kdy lok\u00E1ln\u00ED prevalence rezistence je takov\u00E1, \u017Ee prosp\u011B\u0161nost l\u00E1tky je p\u0159inejmen\u0161\u00EDm u n\u011Bkter\u00FDch typ\u016F infekc\u00ED sporn\u00E1, je t\u0159eba po\u017E\u00E1dat o radu experta.\nZa\u0159azen\u00ED p\u0159\u00EDslu\u0161n\u00FDch druh\u016F podle citlivosti na ciprofloxacin (druhy Streptococcus viz bod 4.4)\n\tDRUHY V\u011AT\u0160INOU CITLIV\u00C9\n\tAerobn\u00ED grampozitivn\u00ED mikroorganizmy\nBacillus anthracis (1)\n\tAerobn\u00ED gramnegativn\u00ED mikroorganizmy\nAeromonas spp.\nBrucella spp.\nCitrobacter koseri\nFrancisella tularensis\nHaemophilus ducreyi\nHaemophilus influenzae*\nLegionella spp.\nMoraxella catarrhalis*\nNeisseria meningitidis\nPasteurella spp.\nSalmonella spp. *\nShigella spp. *\nVibrio spp.\nYersinia pestis\n\tAnaerobn\u00ED mikroorganizmy\nMobiluncus\n\tDal\u0161\u00ED mikroorganizmy\nChlamydia trachomatis ($)\nChlamydia pneumoniae ($)\nMycoplasma hominis ($)\nMycoplasma pneumoniae ($)\n\tDRUHY, U KTER\u00DDCH SE M\u016E\u017DE REZISTENCE VYVINOUT\n\tAerobn\u00ED grampozitivn\u00ED mikroorganizmy\nEnterococcus faecalis ($)\nStaphylococcus spp. * (2)\n\tAerobn\u00ED gramnegativn\u00ED mikroorganizmy\nAcinetobacter baumannii+\nBurkholderia cepacia+*\nCampylobacter spp. +*\nCitrobacter freundii*\nEnterobacter aerogenes\nEnterobacter cloacae*\nEscherichia coli*\nKlebsiella oxytoca\nKlebsiella pneumoniae*\nMorganella morganii*\nNeisseria gonorrhoeaee*\nProteus mirabilis*\nProteus vulgaris*\nProvidencia spp.\nPseudomonas aeruginosa*\nPseudomonas fluorescens\nSerratia marcescens*\n\tAnaerobn\u00ED mikroorganizmy\nPeptostreptococcus spp.\nPropionibacterium acnes\n\tINHERENTN\u00CD REZISTENTN\u00CD ORGANIZMY\n\tAerobn\u00ED grampozitivn\u00ED mikroorganizmy\nActinomyces\nEnteroccus faecium\nListeria monocytogenes\n\tAerobn\u00ED gramnegativn\u00ED mikroorganizmy\nStenotrophomonas maltophilia\n\tAnaerobn\u00ED mikroorganizmy\nKrom\u011B v\u00FD\u0161e uveden\u00FDch\n\tDal\u0161\u00ED mikroorganizmy\nMycoplasma genitalium\nUreaplasma urealitycum\n\t* Klinick\u00E1 \u00FA\u010Dinnost byla prok\u00E1z\u00E1na pro citliv\u00E9 izol\u00E1ty ve schv\u00E1len\u00FDch klinick\u00FDch indikac\u00EDch\n+ M\u00EDra rezistence \u2265 50\u00A0% v jedn\u00E9 nebo v\u00EDce zem\u00EDch EU\n($): P\u0159irozen\u00E1 st\u0159edn\u00ED citlivost neexistuje-li z\u00EDskan\u00FD mechanizmus rezistence\n(1): Byly provedeny studie s experiment\u00E1ln\u00EDmi zv\u00ED\u0159ec\u00EDmi infekcemi zp\u016Fsoben\u00FDmi inhalac\u00ED spor Bacillus anthracis ; tyto studie uk\u00E1zaly, \u017Ee antibiotika podan\u00E1 brzy po expozici zabr\u00E1nila vzniku onemocn\u011Bn\u00ED, jestli\u017Ee l\u00E9\u010Dba vedla ke sn\u00ED\u017Een\u00ED po\u010Dtu spor v organizmu pod infek\u010Dn\u00ED d\u00E1vku. U lid\u00ED je doporu\u010Den\u00E9 pou\u017Eit\u00ED prim\u00E1rn\u011B d\u00E1no citlivost\u00ED, zji\u0161\u0165ovanou in vitro, a tak\u00E9 experiment\u00E1ln\u00EDmi daty z\u00EDskan\u00FDmi u zv\u00ED\u0159at a v limitovan\u00E9m mno\u017Estv\u00ED u lid\u00ED. L\u00E9\u010Dba ciprofloxacinem pod\u00E1van\u00FDm v d\u00E1vk\u00E1ch 500 mg 2x denn\u011B po dobu 2 m\u011Bs\u00EDc\u016F je u lid\u00ED pova\u017Eov\u00E1na jako dostate\u010Dn\u00E1 ochrana p\u0159ed infekc\u00ED vyvolanou antraxem. O\u0161et\u0159uj\u00EDc\u00EDm l\u00E9ka\u0159\u016Fm je doporu\u010Deno sezn\u00E1mit se s n\u00E1rodn\u00EDmi a /nebo mezin\u00E1rodn\u00EDmi konven\u010Dn\u00EDmi dokumenty, kter\u00E9 se vztahuj\u00ED k l\u00E9\u010Db\u011B infekce antraxu.\n(2): S. aureus rezistentn\u00ED na meticilin se obvykle projevuje ko-rezistenc\u00ED na fluorochinolony.\nM\u00EDra rezistence na meticilin je mezi v\u0161emi druhy stafylokok\u016F p\u0159ibli\u017En\u011B 20 a\u017E 50\u00A0%; ve zv\u00FD\u0161en\u00E9 m\u00ED\u0159e je pozorov\u00E1na zejm\u00E9na v nemocni\u010Dn\u00EDm prost\u0159ed\u00ED.\n"@cs . . . . . . . . . . "005.001" . . . . . . . . . . . .