Antonio Boccazzi Clinica Pediatrica 2.a - Milano
-
Upload
randall-hopkins -
Category
Documents
-
view
192 -
download
7
description
Transcript of Antonio Boccazzi Clinica Pediatrica 2.a - Milano
![Page 1: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/1.jpg)
Antonio BoccazziClinica Pediatrica 2.a - Milano
![Page 2: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/2.jpg)
![Page 3: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/3.jpg)
DRUG RESISTANCEPharmacological aspects
• Minimize the time that suboptimal drug levels arepresent by thoughful attention to dosing.
• Clinicians need to consider pharmacodynamic andpharmacokinetic properties when choosing an antibiotictherapy
• Choosing the right dose and dose interval may becritical to achieving optimal clinical responses andpreventing the emergence of resistant pathogens.
J.J. Schentag, 1998; D.G. Burgess, 1999
![Page 4: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/4.jpg)
Terapia empirica
Terapia ragionata
Terapia a casaccio
![Page 5: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/5.jpg)
![Page 6: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/6.jpg)
![Page 7: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/7.jpg)
STA AUMENTANDO L’IMPORTANZA
DI MYCOPLASMA PN. ??
L’ESEMPIO DELL’ENCEFALITE
![Page 8: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/8.jpg)
Mycoplasma Pneumoniae: The Most Common Cause of Pediatric Encephalitis?Posted 01/02/2008William T. Basco, Jr, MD, FAAPAuthor InformationPediatric Encephalitis: What Is the Role of Mycoplasma Pneumoniae?Christie LJ, Honarmand S, Talkington DF, et alPediatrics. 2007;120:305-313
![Page 9: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/9.jpg)
Abbiamo bisogno dei chinoloni in pediatria ?
![Page 10: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/10.jpg)
![Page 11: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/11.jpg)
![Page 12: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/12.jpg)
![Page 13: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/13.jpg)
![Page 14: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/14.jpg)
![Page 15: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/15.jpg)
![Page 16: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/16.jpg)
RESISTENZA DI S.PNEUMONIAE “PORTATO”
IN NASOFARINGE IN ITALIA (242 ceppi – 2799 bambini)
25,97,6 5,9 9,1
56,344,6 52,1
60,4
0
20
40
60
80
100
< 2 2-5 > 5 totale
PENICILLINA MACROLIDE
Marchisio et al, Emerg Infect Dis,2002
anni
![Page 17: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/17.jpg)
1992-98Pre-vax SP
2000-2003Post-vax SP
S.pneumoniae 48% 31%
Pen-I 16% 13%
Pen-R 9% 6%
Vax-types 70% 36%
Vax-related types 8% 32%
H.influenzae 41% 56%
B.la pos 56% 64%
Vaccino anti-pneumococco e modificazione dell’etiologia di OMA
Block S. Pediatr Infect Dis J sept. 04 pag.829
![Page 18: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/18.jpg)
1995-7 1998-2000 2001-03(vax anti-SP)
Timpanocentesi in OMA persistente o fallimenti terapeutici
16.2% 16.1% 12.3%
MEF SP 48% 44% 31%
H.flu
38% 43% 51%
*
*****
Riduzione del 24% in 2001-03 vs altri periodiRiduzione p=0.017Incremento p=0.012
Incremento di SP Pen-S p=0.17
Casey and Pichichero, Pediatr Infect Dis J Sept 04, pag 824
Vi sono novità nell’etiologia dell’OMA ?
![Page 19: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/19.jpg)
IN ARRIVO
ALLARGAMENTO SIEROTIPI DI SP
VAX ANTI-H.FLU non CAPSULATO
![Page 20: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/20.jpg)
![Page 21: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/21.jpg)
![Page 22: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/22.jpg)
Pharmacological aspects for emergenceof resistance
PHARMACOKINETIC
•Insufficient antibiotic concentration at thesite of infection
PHARMACODYNAMIC
• Unsuitable dose
•Too long intervals between administrations
•Short treatment duration
![Page 23: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/23.jpg)
Rohde, Chhatwal, Kaplan, 2004
Continuation of the ingestion process
![Page 24: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/24.jpg)
/R
GABHS INTERNALIZATION
![Page 25: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/25.jpg)
BiofilmSociomicrobiologia
Pseudomonas aeruginosaStaph aureusHaemophilus influenzaeS.Pneumoniae
possono formare biofilmche sono inattaccabili da
• anticorpi• fagociti• antibiotici
![Page 26: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/26.jpg)
![Page 27: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/27.jpg)
![Page 28: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/28.jpg)
![Page 29: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/29.jpg)
![Page 30: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/30.jpg)
![Page 31: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/31.jpg)
Where are Biofilms to be found in chronic/recurrent
infections?
ENT: Pharyngotonsillitisitis, acute otitis media, rhino-sinusitis, otitis media with effusion, cholesteatoma
ENT DEVICE-ASSOCIATED INFECTIONS:
Tympanostomy tubes; endotracheal tubes Costerton et al., Science, 2002; Chole et al., Arch. Otolaryngol. Head & Neck Surg., 2003; Post et al., Curr. Opin. Otolaryngol. Head & Neck Surg., 2004
![Page 32: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/32.jpg)
Bacterial biofilms in adults with chronic sinusitisundergoing sinus surgery
Present in 14 of 18 specimens
Sanderson AR, Laryngoscope 2006
![Page 33: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/33.jpg)
Hall-Stoodley L et al, JAMA 2006; 296:202
![Page 34: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/34.jpg)
![Page 35: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/35.jpg)
![Page 36: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/36.jpg)
Farmaco Dose pen S
MIC90(mg/L)/
T>MIC (%)
Pen IMIC90(mg/
L)/T>MIC (%)
Co-AmoxiclavCefaclorCefuroximeCefiximeCeftibutenCefpodoxime
500 mg x3500mg x3500 mg x2
400 x1400 x1200x2
0.125/ 113.81/49.3
0.25/73.11/48.18/19.9
0.125/112.6
1/6516/11.82/43.116/0
16/9.91/52.6
Tempo in cui le concentrazioni rimangono sopra la MIC in S. pneumoniae penicillino sensibile (pen S) o penicillino intermedio (pen I) di vari antibiotici betalattamici orali
R Auckenthaler . JAC- 2000
![Page 37: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/37.jpg)
Farmaco
Dose
b-lattamasi +MIC90(mg/L)/
T>MIC (%)
b-lattamasi -MIC90(mg/L)/
T>MIC (%)
CoAmoxiclavCefaclorCefuroximeCefiximeCeftibutenCefpodoxime
500 mg x3500mg x3250 mg x2
400 x1400 x1200x2
1/6532/2.42/43.1
0.25/81.50.25/69.90.25/92.6
1/6516/11.82/43.1
0.25/81.50.25/69.90.25/92.6
Tempo in cui le concentrazioni rimangono sopra la MIC in H. influenzae di vari antibiotici betalattamici orali
R Auckenthaler . JAC- 2000
![Page 38: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/38.jpg)
Farmaco
Dose
b-lattamasi +MIC90(mg/L)/
T>MIC (%)
Co-AmoxiclavCefaclorCefuroximeCefiximeCeftibutenCefpodoxime
500 mg x3500mg x3250 mg x2
400 x1400 x1200x2
0.25/97.51/49.32/43.1
0.5/64.84/29.9
0.5/72.6
Tempo in cui le concentrazioni rimangono sopra la MIC in M.catarrhalis di vari antibiotici betalattamici orali
R Auckenthaler . JAC- 2000
![Page 39: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/39.jpg)
Farmaco
Dose
MIC90(mg/L)/
T>MIC (%)
Co-AmoxiclavCefaclorCefuroximeCefiximeCeftibutenCefpodoxime
500 mg x2500mg x3250 mg x2
400 x1400 x1200x2
OK
Tempo in cui le concentrazioni rimangono sopra la MIC in S. pyogenes di vari antibiotici betalattamici orali
![Page 40: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/40.jpg)
MEF concentrations of azithromycin in total or free cell fraction
C+ C-
BAS 0 0
4h 0.38 + 0.24 0.11 + 0.04
12h 0.9 + 0.3 0.12 + 0.08
24h 1.05 + 0.3 0.23 + 0.12
Scaglione et al 1998
![Page 41: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/41.jpg)
CefiximeRapporto MEF/MIC90 (media volte)
C+ C-
H.influenzae
Bla neg 4.8 12.8
Bla pos 2.4 6.4
M.catarrhalis 2.4 6.4
S.pneumoniae
Pen-S 2.4 6.4
Pen-I 0.3 0.8
Cmax MEF 1.2 mg/L + 0.6 SD (C+) e 3.2 mg/L + 1.4 SD (C-) (10)C+ titolata con componente cellulare MEFC- titolata senza componente cellulare MEF
Boccazzi et al, 2003
![Page 42: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/42.jpg)
S.pyogenes (1056) Evolution of macrolide-resistance in Italy
0
5
10
15
20
25
30
35
40
45
1993 1995 1996 1997 1998 1999 2000 2002
*
*
*
*
* two studies. Schito et al., JAC, 1997; Varaldo et al., CID, 1999; Crotti, Medori and D’Annibale, GIMMOC 2001; Rondini, GIMMOC 2001; Schitot et al.,GIMMOC, 2003
PROTEKT
ITALY (2002)
%R
![Page 43: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/43.jpg)
S.pneumoniae (848)Trend of penicillin-resistance in Italy
0
5
10
15
20
25
1992 1995 1996 1997 1998 1999 2000 2001 2002
H-LL-L
Felmingham et al., JAC, 1996; Felmingham et al., JAC, 2000; Marchese et al., MDR 2001; Marchese et al., SIM Congress, 2002; Schito et al., ICAAC, 2003
PROTEKT ITALY (2002)
%R
![Page 44: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/44.jpg)
S. pneumoniaeS. pneumoniaeTrend Trend della eritromicino-resistenza indella eritromicino-resistenza in ItaliaItalia
0
5
10
15
20
25
30
35
40
45
1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002
Felmingham et al., JAC, 1996; Felmingham et al., JAC, 2000; Marchese et al., MDR 2001; Marchese et al., SIM Congress, 2002
PROTEKT PROTEKT ITALIA ITALIA (2002)(2002)
%R
![Page 45: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/45.jpg)
Percentuale di ceppi resistenti a:Percentuale di ceppi resistenti a:
Fenotipo (n,Fenotipo (n, %%) ) EE SXTSXT TE TE LEV LEV
PenS (461,PenS (461, 83,583,5) ) 34,934,9 34,534,5 25,625,6 0,2 0,2
PenI (68,PenI (68, 12,312,3) ) 50,050,0 41,241,2 42,642,6 0 0
PenR (23,PenR (23, 4,24,2)) 43,543,5 87,087,0 26,126,1 0 0
Correlazione tra resistenza (%) di 4 antibiotici nei Correlazione tra resistenza (%) di 4 antibiotici nei tre differenti fenotipi di tre differenti fenotipi di S. pneumoniaeS. pneumoniae (552 ceppi) (552 ceppi) in Italia nel 2000in Italia nel 2000
eritromicinaeritromicina ((EE),), cotrimossazolocotrimossazolo ((SXTSXT),), tetraciclinatetraciclina ((TETE), levofloxacina), levofloxacina ((LEVLEV))
![Page 46: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/46.jpg)
Dead Bugs Don’t Mutate C.W. Stratton, 2003
![Page 47: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/47.jpg)
Drlica e Schmitz, 2002
Mutant prevention concentration (MPC)
Definizione
Concentrazione minima di antibiotico in grado di prevenire la crescita di ceppi batterici resistenti (inoculo in piastra di 1010 batteri)
Fornisce informazioni sul possibile sviluppo di resistenza
![Page 48: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/48.jpg)
Time post-administration
MIC
MPC
Ser
um o
r tis
sue
drug
con
cent
ratio
n
Mutant Selection Window (MSW)
MSW
Above MPC – both susceptible and first-step resistant cells inhibited – no selective amplification of resistance subpopulation.
MSW - susceptible cells inhibited.- first step resistant cells not inhibited.- selective amplification of resistant subpopulation
Sub MIC – neither susceptible nor first-step resistant mutants inhibited – no selective amplification of resistant subpopulation.
Blondeau et al, 2004, J.Chemo
![Page 49: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/49.jpg)
Wise 1999, Blondeau et al. 2001, Hansen et al. 2002, Hansen et al. 2003
Correlazione tra le concentrazioni sieriche di Correlazione tra le concentrazioni sieriche di moxifloxacina e levofloxacina ed MPC vs moxifloxacina e levofloxacina ed MPC vs S.S. pneumoniaepneumoniae
8
7
6
5
4
3
2
1
01 6 12 18 24
Moxifloxacina8
7
6
5
4
3
2
1
01 6 12 18 24
Levofloxacina
MPC90=2ug/ml
MIC90=0,25ug/ml
Finestradi selezione dei mutanti
MPC90=8ug/ml
MIC90=1ug/ml
Finestradi selezione dei mutanti
Cmax=5,7ug/ml
Ore Ore
Cmax=4,5ug/ml
![Page 50: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/50.jpg)
Iannini, Tillotson 2001
Correlazione tra sviluppo di resistenze in Correlazione tra sviluppo di resistenze in P. P. aeruginosaaeruginosa e utilizzo di levofloxacina e e utilizzo di levofloxacina e ciprofloxacinaciprofloxacina
0
120
60
80
20
Uso
(%
)
Ospedale di Danbury (Danbury, USA)
64
84
74
78
70
Sensi
bili
tà (
%)
98 98 98 98 99 99 99 99 00 00 00 00 01 01 0101 02 03 04 01 02 03 04 01 02 03 04 01 02 03
100
40
82
66
68
72
76
80
Ciprofloxacina sensibilitàCiprofloxacina uso Levofloxacina uso
![Page 51: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/51.jpg)
Uso di fluorochinoloni e sviluppo di resistenza Uso di fluorochinoloni e sviluppo di resistenza vsvs S. pneumoniae S. pneumoniae (USA)(USA)
Pneum
oco
cchi co
n r
idott
a s
usc
ett
ibili
tà a
i FQ
s (%
)
1988 1999 2000 2001
4
5
6
3
2
1
0
35
30
25
20
Pre
scri
zioni per
10
00
pazi
enti
per
IR*
0
15
10
5
Ciprofloxacina Levofloxacina
20021998199719961995199419931989
0.9 1.2 1.6 1.4 3.4
n=1934(45)
n=1531(33)
n=1601(34)
n=1527(30)
*IR: Infezioni Respiratorie
![Page 52: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/52.jpg)
Comparative MIC distribution for azalide/macrolide compounds against clinical isolates of S. pneumoniae
(n=178).Drug Concentration (ug/ml)
Compound <0.031 0.063 0.125 0.25 0.5 1 >2
Azithromycin 12 58 68 11 1 2 26
(BP <0.5/ug/ml) (16%)
Clarithormycin 120 31 1 1 1 5 19
(BP <0.25 ug/ml) (14%)
Erythromycin 8 89 46 7 0 1 25
(BP <0.25 ug/ml) (15%)
Telithromycin 331 11 15 8 4 3
(n=372) (<1%)Blondeau et al, Nurnberg Germany Sept/04:ECCMID, 2005
![Page 53: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/53.jpg)
Comparative RPC distribution for azalide/macrolide compounds against clinical isolates of S. pneumoniae
(n=178).Drug Concentration (ug/ml)
Compound <0.125 0.25 0.5 1 >2-8
Azithromycin 1 9 38 50 80
(BP <0.5/ug/ml) (73%)
Clarithromycin 79 44 14 11 30
(BP <0.25 ug/ml) (23%)
Erythromycin 18 60 41 22 37
(BP <0.25 ug/ml) (33%)
Telithromycin 208 16 14 (7 isolates >0.5ug/ml)
(n=245)Blondeau et al, Nurnberg Germany Sept/04:ECCMID, 2005
![Page 54: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/54.jpg)
PAESETasso di
prescrizione antibiotica
Incidenza per 100.000 p.a.
OLANDA 31% 3.8
NORVEGIA 67% 3.5
DANIMARCA 76% 4.2
USA 96% 2.0
INGHILTERRA 99% 1.2
Correlazione tra prescrizione antibiotica nell’OMA e incidenza
della mastoidite acuta
Van Zuijlen, 2001
![Page 55: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/55.jpg)
IL PUZZLE
DELL’ANTIBIOTICOTERAPIA
ANTIBIOTICO
SITO
BATTERI
+
MIC
PAZIENTEPAZIENTE
![Page 56: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/56.jpg)
![Page 57: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/57.jpg)
![Page 58: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/58.jpg)
![Page 59: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/59.jpg)
![Page 60: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/60.jpg)
![Page 61: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/61.jpg)
![Page 62: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/62.jpg)
![Page 63: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/63.jpg)
![Page 64: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/64.jpg)
![Page 65: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/65.jpg)
![Page 66: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/66.jpg)
![Page 67: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/67.jpg)
![Page 68: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/68.jpg)
![Page 69: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/69.jpg)
![Page 70: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/70.jpg)
![Page 71: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/71.jpg)
Role of Bacterial Interference and beta-Lactamase-Producing Bacteria in the Failure of Penicillin to Eradicate Group A Streptococcal Pharyngotonsillitis
Brook, Itzhak MD, MSc; Gober, Alan E. MDFrom the Departments of Pediatrics, Georgetown and George Washington UniversitiesSchools of Medicine, Washington, DC.
Archives of Otolaryngology-Head & Neck Surgery 121(12), December 1995, pp 1405-1409
![Page 72: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/72.jpg)
Archives of Otolaryngology-Head & Neck Surgery 121(12), December 1995, pp 1405-1409
![Page 73: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/73.jpg)
Archives of Otolaryngology-Head & Neck Surgery 121(12), December 1995, pp 1405-1409
![Page 74: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/74.jpg)
Archives of Otolaryngology-Head & Neck Surgery 121(12), December 1995, pp 1405-1409
![Page 75: Antonio Boccazzi Clinica Pediatrica 2.a - Milano](https://reader033.fdocuments.in/reader033/viewer/2022061423/56813050550346895d95fd2e/html5/thumbnails/75.jpg)