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Κινολόνες Άγγελος Πεφάνης Παθολόγος – Λοιμωξιολόγος Παθολογική Κλινική ΓΝΝΘΑ «Η Σωτηρία», Αθήνα

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Κ ινολόνες. Άγγελος Πεφάνης Παθολόγος – Λοιμωξιολόγος Παθολογική Κλινική ΓΝΝΘΑ «Η Σωτηρία», Αθήνα. Κινολόνες : Ομάδα Ι (1962…..). Περιορισμένου φάσματος Ν αλιδιξικό οξύ Σ ινοξασίνη. Φθόριοκινολόνες. Το επόμενο σημαντικό βήμα ήταν η τοποθέτηση φθορίου στη θέση 6 με - PowerPoint PPT Presentation

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NorfloxacinCiprofloxacinOfloxacinLevofloxacinMoxifloxacinPrulifloxacin

A (penicillins, cephalosporins, glycopeptides) (macrolides, tetracyclines,aminoglycosides, oxazolidinones) DNA (fluoroquinolones)

(sulfonamides, trimethoprim) Gram (-) IV Gram(+)9Antimicrobials disrupt bacterial function by interfering with a number of important cellular processes. These include inhibition of: cell wall synthesis (eg -lactam antibiotics such as penicillins, cephalosporins and glycopeptides) protein synthesis (eg macrolides, tetracyclines, aminoglycosides and oxazolidinones) DNA replication (eg fluoroquinolones inhibit DNA gyrase, the enzyme responsible for supercoiling DNA).Other antimicrobial mechanisms include interference with the cytoplasmic membrane (eg polymixin) and metabolic transformations in the cytoplasm (eg sulfonamides).

DNA- (gyrA, gyr B) IV (parC, parE) DNA , . gram + . 7 gram +10

. . Efflux pumps. : DNA , o IV .

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Drlica K et al, Current Topics in Medicinal Chemistry 2009

Gram(-) (: Cipro)Gram(+) ( ) ()H Gram (+) :

H H :Legionella pneumophila, Mycoplasma pneumoniae, Chlamydophila spp, Mycoplasma hominis, Ureaplasma urealyticum

J Antimicrob Chemother 2003;51S: n vitro . tuberculosis (MIC90) 0,5 - 4,0 mg/l 1,0 - 2,0mg/l 1,0mg/l 0,12 - 0,5mg/l

Moxifloxacin Ethambutol I

/PK/PD Cmax g/mlT (h) (%) N400 po1.53.350234500 po400 IV2.44.645-670358300400 po400 IV4.65.54-56>95195190500 po500 IV5.76.46-86-89911694400 po400 IV4.54.411-128-158843-Eur J Clin Microbiol Infect 2003;22:203 Antimicrob Agents Chemother 2000;44:2600 , * , , , , O* *

* : * * : MIC 90 (g/ml) Streptococcus pneumoniae

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0.12 (g/ml) (g/ml) (g/ml)

1.9 + 0.13.0 + 1.05

13.4 + 3.5

4.110.927.7

3.220.756.7 :

:: 500mg/24h, Cl < 50ml/min, : Cl 8 10 () > 10 ( )Forrest et al. Antimicrob Agents Chemother 1993;37:10731081 : PD (%)020406080100062.562.5125125250250500>500AUC/MICM26

QT moxifloxacin (Torsades de pointes) . : , Mg - : quinidine, procainamide - : amiodarone, sotalol

Bolon MK, Infect Dis Clin North Am 2009

Shakeri Nejad K & Stahlmann R, Expert Opin Pharmacother 2006

Shakeri Nejad K & Stahlmann R, Expert Opin Pharmacother 2006

(1-2%):

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Heidelbaugh JJ, et al. J Fam Practice 2014;62:191

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G-6-PD

( ) Heidelbaugh JJ, et al. J Fam Practice 2014;62:191

178.179 pts on FQ vs same on Amoxicillin (RRD) : - FQ: n = 96 (0.054%) vs - AMOX: n = 46 (0.026%) HR 2.07 (1.45 - 2.96) Hazard Ratio: Cip (3.2) > Levo (2.4) > Moxi (2.0) > Oflo (1.1) 35 (14-57)

Clostridium difficile and FQ 027 Clostridium difficile (p=0,001).

027.

: 24% !!Mascart G, et al. Eur J Clin Microbiol Infect Dis 2013;32:1177-82. 20 - 30 The use of quinolones during the first trimester of pregnancy does not appear to represent an increased risk for major malformations recognized after birth, stillbirths, preterm births or low birth weight.Bar-Oz B, et al. Eur J Obstet Gynecol Reprod Biol. 2009;143:75-8.

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; - - (CAP) CAP :

Rello J. Annals of Intensive Care 2011;1:48he pathogen spectrum covered by fluoroquinolones is considered unnecessarily broad in low-risk pneumonia Thiem U et al, Drugs Aging 2011

: 44 Helicobacter pyloriAmerican College of Gastroenterology guideline on the management of Helicobacter pylori infection.

Omeprazole (20 mg bid) + Levofloxacin (500 mg bid) + Amoxicillin (1 g bid), for 10 days is more effective and better tolerated than bismuth quadruple therapy BQT. Am J Gastroenterol 2007;102:1808-25. 1 24 10-3-2014 : 37,5C . . , : , , . 4 , . ; 1 () 9 .

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IDSA Clinical Practice Guideline for Acute Bacterial Rhinosinusitis (ABRS) in Children and AdultsChow AW, et al.Clin Infect Dis 2012;54(8):e72112Initial empirical therapy of ABRSFirst-line (Daily Dose)

ChildrenAmoxicillin-clavulanate 45 mg/kg/day, PO, bid

AdultsAmoxicillin-clavulanate 500 mg/125 mg, PO, tid, or 875 mg/125 mg, PO, bidRespiratory Fluoroquinolone vs a b-lactamA b-lactam agent (amoxicillin/clavulanate) rather than a respiratory fluoroquinolone is recommended for initial empiric antimicrobial therapy of ABRS

weak, moderateEfficacy of Fluoroquinolones compared to a b-lactam for the treatment of acute bacterial rhinosinusitis

Karageorgopoulos DE, et al. CMAJ 2008; 178:84554. 1 () 10 . . ; ; - 1 2

>30%

(, ) - Chow AW, et al. Clin Infect Dis 2012;54(8):e72112Second line antimicrobial regimens for ABR in adults

2 60 , 35p/y ( : FEV1 = 45%) 2 = 37,3 C 1 ; ; ; 60 , 35p/y ( : FEV1= 45%) 2 = 37,3 2 ; > 1

FEV1 4 ;/

/: 875/125 mg x 2 500/125 mg x 3 /: 750 mg x 2: 400 mg x 1: 500 mg x 1: 500 mg x 2 ( Pseudomonas aeruginosa. ) P. aeruginosa Enterobacteriaceae FEV1 < 35% ( ) 3 70 2, :

38,5C 24

3 () :

: 100/60 : 100/ : 36/

3 () Ht: 38%, WBC: 13.000 (85% ) PLT: 100.000 : 60mg/dl, Cr: 1,4 mg/dl : pH: 7.46, PO2: 60, PCO2: 30/ : .

;Primary care summary of the BTSGuidelines for the management of CAP in adults: 2009 updateLevy ML, et al. Prim Care Resp J 2010; 19: 21-27. CAP

; A : 3, 4, 5, (strong recommendation - level I) - + (strong recommendation - level I)

- CefotaximeCeftriaxone Ampicillin Ertapenem ( )

(ATS IDSA 2007) FQ : ( ) , .

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CAP CAP, - ( , ).

Mortensen EM. Critical Care 2006, 10:R8 p = 0.004 : Fluoroquinolone-resistant TB was most closely associated with prolonged or recurrent use of these antibiotics for infections where TB initially was not suspected.

Receipt of quinolones for more than 10 days, particularly more than 60 days before the diagnosis of tuberculosis, was associated with a high risk of fluoroquinolone-resistant Tb.Bernardo J. Am J Respir Crit Care Med 2009;180:88-289.

Devasia RA, et al. Am J Respir Crit Care Med 2009;180:365-370.

OXI M. tuberculosis

M. tuberculosis DNA , .CID, 2009:48:1361-3CID 2009; 48:135460 3/148 FQ-R M. tuberculosis : DNA gyr A M. tuberculosis AAC 2014; PMID 24419347 9/770 eligible studiesMean delay in diagnosis of TBC in FQ group: 19 days (CI 95%, 10.8-27.2), p35 : - x 10-14 x 10-14

The Sanford Guide to Antimicrobial Therapy, 2007 Ciprofloxacin: 500mg x 2 x 28 Levofloxacin: 500 x 1 x 28

960 mg x 2 x 1-3

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: 2014