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La terapia antibiotica in età pediatrica Lo stato dell’arte ? Risorse non rinnovabili?. Antonio Boccazzi Clinica Pediatrica Milano. Increase in antibiotic use. Increase risk of inappropriate use. Limited treatment alternatives more antibiotics increased mortality.

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slide1

La terapia antibiotica

in età pediatrica

Lo stato dell’arte ?

Risorse non rinnovabili?

Antonio Boccazzi

Clinica Pediatrica

Milano

slide4

Increase inantibiotic use

Increase risk of inappropriate use

  • Limited treatment alternatives
    • more antibiotics
    • increasedmortality

Increase inresistant strains

  • Increasedhospitalisation
    • more antibiotics
  • Ineffective empirictherapy
    • increased morbidity
    • more antibiotics
strategies for empirical outpatient antibacterial therapy
Strategies for empirical outpatient antibacterial therapy
  • Unnecessary and inappropriate use of antibacterials contributes to resistance
  • To minimize the threat of resistance, the right drug should be administered at the right dose and duration
  • Antibacterials should rapidly eradicate the infecting pathogen at the site of infection
  • Appropriate use may increase the use of some ‘optimal’ agents, but will decrease the use of ‘sub-optimal’ agents
  • Emerging scientific principles (PK/PD) should be applied to all new and existing antibacterials

Adapted from: Ball et al. J Antimicrob Chemother 2002; 49:31–40

slide6

Problemi aperti e di gravità

  • in peggioramento:
  • Meticillino-R
  • Vanco-Ivanco-R
  • Penicillino-R
  • Comparsa di ESBL
  • Resistenza ai macrolidi
slide7

Quali patologie comportano un elevato

  • utilizzo di antibiotici nell’ambulatorio
  • Del Pediatra di Famiglia
  • (spesso non giustificato)
  • Faringotonsillite
  • OMA
  • Influenza e sindromi influenzali
  • Bronchiolite
  • Bcp

Sindromi febbrili

slide8

FARINGOTONSILLITE

EPIDEMIOLOGIA

ITALIA

18.000.000 pazienti/anno

50% età pediatrica (5-15 aa.)

1a causa di consumo di antibiotici

Mazzaglia G. e coll.; 1999

slide9

Per OMA: utilizzo della vigile attesa

Per FGT: attenzione alla

identificazione dei

casi ad etiologia streptococcica

Terapie brevi

antibioticoterapia della fta
Antibioticoterapia della FTA

Terapia breve

mancata

giorni eradicazione

Cefuroxime axetil (Mehra, 1998) 5 12,0%

Cefaclor (Catania, 1999) 5 9,3%

Cefprozil (Doyle, 1992) 5 10,9%

Cefpodoxime proxetil (Portier, 1994) 5 4,0%

Cefixime (Adam, 1995) 5 15,9%

Ceftibuten (Boccazzi, 1999) 5 13,8%

Amoxicillina (Cohen, 1996) 6 16,3%

slide11

-lactams

macrolides

trimethoprim/ sulphamethoxazole

100

80

Green = S.pneumoniae-associated AOM

Orange = H. influenzae- associated AOM

60

40

20

0

0

20

40

60

80

100

For -lactams, a serum concentration profile with a ‘Time above MIC’ 40% is required to achieve 85% bacteriological cure

Bacteriological cure (%)

‘Time Above MIC’ (% of dosing interval)

Craig & Andes. Pediatr Infect Dis J 1996;15:255–259

slide13

Ricordare:

L’impiego della switch therapy

parenterale-orale nelle BCP

slide14

Caveat:

La terapia di associazione

macrolide+beta lattamico

nelle Bcp

slide17
ASL MILANO

Valutazione prescrizioni

2004 e 2005

slide19

In tutte le infezioni ambulatoriali

(eccetto le IVU) non è possibile

Identificare l’agente etiologico

Approccio empirico al trattamento

slide20

Approccio empirico

  • Disegnare il miglior trattamento in base a:
  • Etiologia e meccanismi di R
  • Caratteristiche pK-pD
  • Rischio di induzione di R
  • Tollerabilità
  • Compliance
  • Costo
s pneumoniae 848 trend of penicillin resistance in italy
S.pneumoniae (848)Trend of penicillin-resistance in Italy

%R

PROTEKT ITALY (2002)

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

main resistance of aom pathogens in italy
MAIN RESISTANCE OF AOM PATHOGENS IN ITALY
  • Streptococcus pneumoniae = resistance to penicillin (15%) and macrolides (35%)
  • Haemophilus influenzae = resistance to amoxicillin (20%)
  • Moraxella catarrhalis = resistance to amoxicillin (80%)
  • Streptococcus pyogenes = resistance to macrolides (20-30%)
slide24

Vaccino anti-pneumococco e modificazione dell’etiologia di OMA

Block S. Pediatr Infect Dis J sept. 04 pag.829

slide26

Farmaco

Dose

pen S

MIC90(mg/L)/

T>MIC (%)

Pen I

MIC90(mg/L)/

T>MIC (%)

Co-Amoxiclav

Cefaclor

Cefuroxime

Cefixime

Ceftibuten

Cefpodoxime

500 mg x3

500mg x3

500 mg x2

400 x1

400 x1

200x2

0.125/ 113.8

1/49.3

0.25/73.1

1/48.1

8/19.9

0.125/112.6

1/65

16/11.8

2/43.1

16/0

16/9.9

1/52.6

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

slide27

Farmaco

Dose

b-lattamasi +

MIC90(mg/L)/

T>MIC (%)

b-lattamasi -

MIC90(mg/L)/

T>MIC (%)

CoAmoxiclav

Cefaclor

Cefuroxime

Cefixime

Ceftibuten

Cefpodoxime

500 mg x3

500mg x3

250 mg x2

400 x1

400 x1

200x2

1/65

32/2.4

2/43.1

0.25/81.5

0.25/69.9

0.25/92.6

1/65

16/11.8

2/43.1

0.25/81.5

0.25/69.9

0.25/92.6

Tempo in cui le concentrazioni rimangono sopra la MIC in H. influenzae di vari antibiotici betalattamici orali

R Auckenthaler . JAC- 2000

slide28

Farmaco

Dose

b-lattamasi +

MIC90(mg/L)/

T>MIC (%)

Co-Amoxiclav

Cefaclor

Cefuroxime

Cefixime

Ceftibuten

Cefpodoxime

500 mg x3

500mg x3

250 mg x2

400 x1

400 x1

200x2

0.25/97.5

1/49.3

2/43.1

0.5/64.8

4/29.9

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

slide34

Amoxicillin and acute otitis media

Effect of betalactamase production by H. influenzae

on bacteriological failure rates

Dagan R & Leibovitz E, The Lancet Infect Dis, 2002

slide35

Acute otitis media in children

T > MIC and bacteriological eradication rates

after 3-5 days of treatment

Dagan R & Leibovitz E, The Lancet Infect Dis, 2002