OKUŽBE SKLEPOV IN KOSTI

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1 OKUŽBE SKLEPOV IN KOSTI Lotrič Furlan Stanka Klinika za infekcijske bolezni in vročinska stanja, Univerzitetni klinični center Ljubljana

2 AKUTNO VNETJE SKLEPA Povzročitelji: bakterije virusi glive mikobakterije, borelije lymske borelioze

3 Starost Povzročitelj 3 mesece Staphylococcus aureus Streptococcus agalactiae po Gramu negativne črevesne bakterije Candida 3 mesece 5 let Staphylococcus aureus Streptococcus pyogenes Kingella kingae Haemophilus influenzae tipa b > 5 let Staphylococcus aureus Streptococcus pyogenes > 15 let Staphylococcus aureus Staphylococcus epidermidis Streptococcus spp. Pseudomonas aeruginosa Serratia marcescens Escherichia coli Anaerobne bakterije Neisseria gonorrhoeae (pri spolno aktivnih osebah)

4 - Razsoj bakterij po krvi - širjenje vnetja iz okuženih tkiv in kosti - vnos bakterij v sklep pri poškodbah, operaciji, aplikaciji zdravila,

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7 Revmatološki priročnik za družinskega zdravnika

8 DIFERENCIALNA DIAGNOZA reaktivni artritis, Lymski artritis, degenerativne spremembe sklepov, protin, pseudoprotin, sinovijske hondromatoze, juvenilni idiopatski artritis, zlomi, tumorji.. težave pri starostnikih (predhodno antibiotično zdravljenje, degenerativne spremembe, protin,.)

9 Zdravljenje septičnega artritisa Za zdravljenje septičnega artritisa so potrebni veliki odmerki parenteralnih antibiotikov, izkušnje s peroralnim zdravljenjem so skope; Pri nas 3 tedne i.v., izjema streptoki, H. influenzae (2 tedna), > 3 tedne P. aeruginosa nekateri priporočajo vsaj 14 dnevno parenteralno zdravljenje, nato 2-4 tedensko peroralno zdravljenje, če lahko glede na povzročitelja in antibiogram izberemo antibiotik z dobro peroralno absorbcijo (kinoloni, amoksicilin, klindamicin, linezolid) QUIBA

10 Priporočila za antibiotično zdravljenje septičnega artritisa glede na povzročitelja Razmaz po Gramu Antibiotik izbire (parenteralno) Druge možnosti (parenteralno) Trajanje zdravljenja (tedni) Grampozitivni koki v skupinah občutljivi za meticilin (Staphylococcus aureus, KNS) flukloksacilin 2g / 4 ali 6 h cefazolin 2 g / 8 h ali klindamicin 600 do 900 mg / 8 h 3 Grampozitivni koki v skupinah proti meticilinu odporni (MRSA, KNS ) vankomicin 1g / 12 h linezolid 600 mg / 12 h daptomycin 6mg/kg t.t. 3 Grampozitivni koki v verižicah (Streptococcus spp.) penicilin G 4 mil. IE / 4 h cefazolin 2 g / 8 h ali klindamicin 600 do 900 mg / 8 h 2 Gramnegativni bacili (enterobakterije, Haemophilus influenzae *) ceftriakson 2g / 24 h ali cefotaksim 2 g / 8 h ciprofloksacin 400 mg / 12 h Pseudomonas aeruginosa cefepim 2 g / 12 h ali ceftazidim 2 g / 8 h ali piperacilin/tazobaktam 4,5g/8h + gentamicin 5 mg/kg / 24 h 3-4 Ni vidnih bakterij v razmazu flukloksacilin 2g / 4 ali 6 h ali ceftriakson 2 g / 24 h ali cefotaksim 2 g / 8 h 3 MRSA proti meticilinu odporen Staphylococcus aureus. KNS koagulazno negativni stafiloki. *Bolnike z artritisom, ki ga povzroča H. influenzae zdravimo dva tedna. QUIBA 4 tedne, najmanj 2 tedna i.v. 2* - 3

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13 1. Klinični primer 41 letni moški, samski, 3x tedensko službeno potuje v tujino - Nevrogeni mehur po infarktu hrbtenjače Th3-5, samokateterizacija - V zadnjih 3 mesecih 3x zdravljen zaradi okužbe sečil (amoksicilin, nitrofurantoin) Sedanja bolezen: dan pred sprejemom oteklo, boleče D koleno, gibljivost zavrta; izbrani zdravnik opravil punkcijo kolena, aplikacija kortikosteroida; laboratorijski izvidi SR 50 mmhg, L 14,5x 109/L, CRP 105 mg/l -

14 1. Klinični primer (nadaljevanje) Hospitalizacija: znaki vnetja D kolena, CRP>300 mg/l, L 13,3, DKS: 85 % segment Punkcija sklepa: L 119x109/L, nevtro gran 83% Rtg kolena: bp Mikrobiološke preiskave: - gramski razmaz: po Gramu negativni diplokoki - hemokulture: neg - PCR: N. gonorrhoeae Empirično zdravljenje: flukloksacilin 2 g/6 ur i.v., nato ceftriakson 1g /24 ur 7 dni 2x izpiranje kolena, artroskopska lavaža, ceftriakson 1g/dan i.v. 7 dni (dnevna bolnišnica) Dg: Gonartritis desno, Gonokokna okužba desnega kolena

15 PCR (širokospektralni evbakterijski PCR) dokazujemo prisotnost bakterij s pomnoževanj gena 16S rrnk prednosti: boljša občutljivost (55-96%), specifičnost % hitrejši rezultat slabosti: ne moremo dokazati občutljivosti oziroma odpornosti bakterij na antibiotike, ocena težja, lažno pozitiven dopolnilna metoda bakterijski kulturi, če je negativna oz pri bolnikih, ki so že dobili antibiotik oz. za bakterije, ki rabijo posebna gojišča ali pa zaradi majhne koncentracije bakterij

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17 OKUŽBE KOSTI povzročajo bakterije, redko glive prizadene vse starostne skupine pri otrocih polovica osteomielitisov do 5 leta starosti akutni, kronični

18 Klasifikacija osteomielitisov (po Waldvoglu - glede na način nastanka okužbe) hematogeni osteomielitis (pri otrocih, pri odraslih redko) osteomielitis, ki nastane zaradi neposrednega širjenja vnetja iz sosednjih tkiv ali neposrednega vnosa klic - pri osebah z normalno prekrvljenostjo ali z moteno prekrvljenostjo

19 2. Klinični primer 82 letna bolnica: arterijska hipertenzija, osteoporoza, po mastektomiji zaradi ca dojk (1968, 1975), po radioterapiji, po holecistektomiji, zlom kolka 2005 (osteosinteza) Sedanja bolezen: D rama jo boli 14 dni, T do 39 C, mrzlica, oslabela Hospitalizacija: D rama otekla, koža pordela, topla - L 20,2x109/L, CRP 315 mg/l, DKS pomik v levo 18 % nesegm, Punkcija sklepa: moten, PVT L 31,9x 109/L, nevtrof granul 92 % Mikrobiološke preiskave: - Gramski razmaz: po Gramu pozitivni koki v verižicah - Hemokulture: S. disgalactiae-equisimilis G - Punktat rame: S. disgalactiae-equisimilis G - Prisotnost kristalov v punktatu: neg

20 2. Klinični primer (nadaljevanje) Izkustveno zdravljenje: flukloksacilin i.v., po prejemu izvidov kristalni penicilin 4 mil IE/4 h i.v. 2x artroskopska lavaža, klinično in laboratorijsko ni izboljšanja, ortoped predlaga MR D ramena MR (19. dan): Artritis glenohumeralno z večjim izlivom in sinovitisom tudi v burzi, erozivni osteitis glavice humerusa, osteitis proksimalne metadiafize humerusa, 2 kostna fragmenta ob malem tuberklu, popolna destrukcija hrustanca v sklepu, stanje po rupturi tetiv mišic rotatorne manšete Operacija (24. dan): resekcija burze in ostankov rotatorne manšete, sinovektomija; postoperativni potek brez zapletov Antibiotično zdravljenje: 67 dni, 47 dni po operaciji Trajanje hospitalizacije: 68 dni Dg: Septični artritis desne rame (S. dysgalactiae), Akutni hematogeni osteomielitis desne nadlahtice

21 Diagnostika, zdravljenje, izbira antibiotika, način aplikacije pomembno je dokazati povzročitelja (kri, biopsija, brisi) izkustveno zdravljenje predpišemo samo, če je bolnik febrilen, septičen, prizadet praviloma zdravimo usmerjeno glede na osamljene povzročitelje če je povzročitelj, dobro občutljiv za antibiotik z dobro biološko uporabnostjo, lahko že od začetka zdravimo per os peroralni betalaktamski antibiotiki (protistafilokokni, cefalosporini), ki imajo slabšo biološko uporabnost, se ne priporočajo za peroralno zdravljenje se priporočajo kinoloni, klindamicin, linezolid kombinacija z rifampicinom! Zimmerli W, Sendi P. Orthopedic biofilm infections. APMS 2017; 125:

22 Osteomielitis (trajanje zdravljenja) Akutni osteomielitis: vsaj 2 tedna i.v, nato per os do skupno 6-12 tednov Kronični osteomielitis: vsaj 2 tedna i.v., 3-6 mesecev per os, do normalizacije laboratorijskih izvidov (SR, CRP)

23 Antibiotično zdravljenje osteomielitisa Povzročitelj Najprimernejši antibiotik in odmerek Druge možnosti Staphylococcus aureus flukloksacilin 2g/4-6 ur iv cefazolin 2 g/8 ur iv MRSA vankomicin 1 g /12 ur iv linezolid 600 mg/12 ur iv ali po ali teikoplanin 12mg/kg/12ur (5 odmerkov), nato na 24 ur ali daptomicin 6-10 mg/kgtt/24 ur Streptococcus spp. penicilin G 4 mil. IE /4-6 ur iv cefotaksim 2g/8 ur i. ali ceftriakson 2 g/24 ur iv Enterobakterije ciprofloksacin 400 mg/12 ur iv nato ceftriakson 2 g/24 ur iv ali cefotaksim 2 g /8 ur iv 750 mg/12 ur po ali levofloksacin 750 mg /24 ur po Pseudomonas cefepim 2g/8 ur aeruginosa tazobaktamom 4,5 g/8 ur posvetu z infektologom Enterokoki penicilin G 4 mil. IE /4-6 ur iv ali vankomicin 1g12 ur gentamicin 1g/kgTT/8 ur ampicilin 2g/4 1g/kgTT/8 ur iv ali piperacilin s ciprofloksacin 400 mg12 ur iv nato 750 mg12 ur po ur gentamicin

24 Hematogeni osteomielitis pri odraslih infekcijski spondilodiscitis (vertebralni osteomielitis)

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26 Algoritem preiskav pri bolniku s sumom na spondilodiscitis

27 Osteomielitis: občutljivost in specifičnost slikovnih preiskav Smids C, et al. Infection 2017; 45: Preiskava Občutljivost (%) Specifičnost (%) Scintigrafija skeleta Scintigrafija z označenimi levkociti MRI PET/CT

28 SPONDILODISCITIS IDSA 2015 We recommend a total duration of 6 weeks of parenteral or highly bioavailable oral antimicrobial therapy for most patients with bacterial NVO (strong, low). Empirično zdravljenje le v primeru, če je bolnik septičen, prizadet, ogrožen

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31 Spondilodiscitis: trajanje antibiotičnega zdravljenja Empirično zdravljenje (bolnik septičen, prizadet) kužnine flukloksacilin 2g/4-6 ur + ciprofloksacilin 400 mg/12 ur Nato glede na povzročitelja in antibiogram MSSA, MSSS: flukloksacilin 2g/4-6 ur najmanj 2 tedna, nato levofloksacin 750 mg/24 ur + rifampin 450 mg/12 ur

32 Ali lahko skrajšamo parenteralno zdravljenje (najmanj 2 tedna)??? Krajše parenteralno zdravljenje se ne priporoča: - starost > 75 let - MRSA okužbah - kronična ledvična bolezen - epiduralni absces - nedrenirani abscesi - multirezistentne okužbe

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37 Literatura Chokkalingam S, et al. Diagnosing acute monoarthritis in adults: a practical approach for the family physician. Am Fam Physician 2003; 68: Ross JJ. Septic arthritis of native joints. Infect Dis Clin N Am 2017; 31: Berbari EF, et al. Clinical practice guidelines for the diagnosis and treatment of native vertebral osteomyelitis in adults. CID 2015; 61: Murillo O, Lora-Tamayo J. Pyogenic vertebral osteomyelitis and antimicrobial therapy: It is not just the lenth, but also the choice. CID 2016; 62: Zimmerli W, Sendi P. Orthopedic biofilm infections. APMS 2017; 125: Babouee FB, et al. Is switching to an oral antibiotic regimen safe after 2 weeks of intravenous treatment for primary bacterial vertebral osteomyelitis? BMC Infect Dis 2014; 14:

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