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GoiniaEncontro Nacional Infeces Respiratrias e Tuberculose

Alexandre Pinto CardosoMd PhDProfessor Pneumologia Fac. Medicina UFRJDiretor Diviso de Tisio-Pneumologia Coordenador Unidade de Pesquisa ClnicaIDT/HUCFF/UFRJ

Bronquiectasias FibrocsticaMedicamentos disponveisMedicamentos necessrios

Epidemiologia das Doenas Epidemiologia das Doenas Pulmonares Obstrutivas CrnicasPulmonares Obstrutivas CrnicasJaneiro 2008 a Setembro 2011Janeiro 2008 a Setembro 2011

Fonte: Ministrio da Sade - Sistema de Informaes Hospitalares do SUS (SIH/SUS)

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Pneumonia 282198 767126 1012795 515376 246512DPOC 28736 94165 170188 197421 53328Asma 76212 335629 159131 110042 55726Bronquiectasia 1133 2895 3472 1408 1701

Internaes por Regio e por Lista de Morbidade

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Influenza [gripe] Pneumonia Bronquite enfisema e outr

doen pulm obstr crn

Asma Bronquiectasia

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5,4

5,8

3

7,4

Mdia de permanncia por lista de morbidade do CID 10

Bronquiectasias Fibrocstica

Alteraes da depurao mucociliar so crticasna patogenia da bronquiectasia e no tratamento

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Hiptese do crculo vicioso na patogenia da bronquiectasia

Lapa e Silva and Cole 1989. Am J resp. Mol. Biology

Modelo experimental de bronquiectasias em ratos

Lapa e Silva et al. Am J Respir Cell Mol Bio 1989,1, 197

TratamentoBronquiectasias

Farmacolgico Antibiticos

Anti-inflamatrios

Drogas Hiper

osmolar

Mucolticos

Outros Fisioterapia

Respiratria

Rehabilitao

Educao e

suporte

emocional

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Hiptese do crculo vicioso na patogenia da bronquiectasia

Lapa e Silva and Cole 1989. Am J resp. Mol. Biology

Novo nicho ecolgico

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BRONQUIECTASIAS Etiologia Infeces S. pneumoniae 10,6%H. influenzae 30,1%P. aeruginosa 30,9%BGN 13,0% (moraxella)Mycobacterium 22,0%Staphylo ureus 17,0%Aspergillus 4,9% Macfarlane 2010 Thorax

Short and Long Term Antibiotic treatment Reduces Airway and Systemic Inflammation in Non-Cystic Fibrosis BronchiectasisJames D Chalmers1, Maeve P Smith2, Brian J McHugh3, Cathy

Doherty4, John R Govan5 and Adam T Hill6

385 pacientes /12 meses / Gentamicina /nebulizao

15 tratados ATB venoso Excerbao

35 ATB venoso sem exacerbao

Marcadores sorolgicos: ICAM I, VICAM I

Published ahead of print on June 28, 2012, doi: 10.1164/rccm.201203-0487OC Am. J. Respir. Crit. Care Med. June 28, 2012 rccm.201203-0487OC

Short and Long Term Antibiotic treatment Reduces Airway and Systemic Inflammation in Non-Cystic Fibrosis BronchiectasisJames D Chalmers1, Maeve P Smith2, Brian J McHugh3, Cathy

Doherty4, John R Govan5 and Adam T Hill6

In stable patients, there was a direct relationship between airway bacterial load and markers of airway inflammation (p

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Antibiticos

Exacerbao Venosos Orais Inalatrios Combinao

Colonizao Orais Inalados Venosos*

Critrios Exacerbao

Critrios ExacerbaoO Donnel , CHEST 1998

Mudana da produo do catarroAumento da dispnia

Aumento da tosseFebre

Aumento do ChiadoMoleza, fadiga,letargia ou

reduo exerciciosReduo da funo pulmonar

Novo infiltrado radiolgicoMudana na ausculta pulmonar

Pelo menos 4 destes

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EXACERBAO.

1) Obter amostra de escarro antes de iniciar tratamento

2). Antibitico emprico estratificar riscos para pseudomonas.

3). Antibiticos emprico devemos ajustar de acordo com a cultura de escarro.

Clinical Microbiology and Infection 2011 European Society of Clinical Microbiology and Infectious

Diseases, CMI, 17 (Suppl. 6), E1E59

BRONQUIECTASIAS

Rico de agudizao p/ Pseudomonas :

Uso recente de ATB

Hospitalizao Recente

Doena Grave

Prvio isolamento de Pseudomonas aeruginosa

VEF1 menor que 60 % ( ?)

Clinical Microbiology and Infection 2011 European

Society of Clinical Microbiology and Infectious Diseases,

CMI, 17 (Suppl. 6), E1E59

Recomendaes Teraputicas

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Antibiticos

Emprico Amoxilina 500 TID Co-amoxi TID lactamase

CiprofloxacinaBID(Pseudomonas)

CombinaoDependendo da cepa

Comentrios Durao

CurtoXLongo Sensibilidade da

cultura Medicamentos IV

IMPACTO DA INFECO CRNICA

IMPACTO CLNICO

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POLVERINO 2011

Critrios para tratamento continuado com Atb e drogas imunomoduladoras

Pacientes com 3 exacerbaes por ano que necessitaram antibiticos,ou significante morbidade (C)

Modulao da cargabacteriana Ciclos de antibioticoterapia VO

Antibitico inalatrio (NBZ/p)

Contnuo ou intermitente

Uso prolongado de Macroldeos*

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Prtica no nova

PROFILAXIA ANTIBIOTICOS ORAIS Currie et al 1989 Amoxicilina 3g TID/32

semanas Hill SL 1990 Amoxicilina inalada 10

semanas Raynor et al1994 Ciprofloxacino >90 dias

TOBRAMICINA INALATRIA AJRCCM 2000,162:481-482

AUSENCIA DE PSEUDOMONAS NO ESCARRO 35 % EM 6

SEMANAS FUNO PULMONAR IGUAL

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Am J Respir Crit Care Med. 2011 Feb 15;183(4):491-9. Epub 2010 Sep24.A randomized controlled trial of nebulized gentamicin in non-cysticfibrosis bronchiectasis.Murray MP, Govan JR, Doherty CJ, Simpson AJ, Wilkinson TS, Chalmers JD, Greening AP, Haslett C, Hill AT.

METHODS: Sixty-five patients were randomized to

either twice-daily nebulized gentamicin, 80 mg, or nebulized 0.9% saline, for 12 months.

All were reviewed at three-monthlyintervals during treatment and at 3 months' follow-up.

GENTAMICINA

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An Optimized Inhaled Ciprofloxacin Formulation DRCFI (Dual Release Ciprofloxacin For Inhalation) Enhances Antibiotic LungConcentrations And Antimicrobial Effect In Non-CF Bronchiectasis(Non-CF BE), [Publication Page: A3659 ATS 2012 San Francisco

D.J. Serisier1, D. Bilton2, T. De Soyza3, I. Gonda41Brisbane, QLD/AU, 2London/UK, 3Newcastle/UK, 4Hayward, CA/USORBIT-1 and ORBIT-2 study group

CFI (Ciprofloxacin for inhalation) [ARD-3100] -Lipoquin andDRCFI (Dual release ciprofloxacin for inhalation) [ARD-3150] -Pulmaquin are once daily inhaled liposomal ciprofloxacinformulations.In addition to the liposomal formulation in CFI, DRCFI alsocontains free ciprofloxacin solution that produces an initialhigh peak of ciprofloxacin followed by prolongedciprofloxacin concentrations in the lung.

An Optimized Inhaled Ciprofloxacin Formulation DRCFI (Dual Release Ciprofloxacin For Inhalation) Enhances Antibiotic LungConcentrations And Antimicrobial Effect In Non-CF Bronchiectasis(Non-CF BE), [Publication Page: A3659 ATS 2012 San Francisco

In addition to the liposomal formulation in CFI, DRCFI also contains free ciprofloxacin solution thatproduces an initial high peak of ciprofloxacinfollowed by prolonged ciprofloxacin concentrationsin the lung. DRCFI also achieves high and sustainedairway concentrations with once-daily dosing in non-CF BE patients .

In placebo-controlled studies in non- CF BE, bothformulations produced statistically significantreductions in P. aeruginosa (PA) colony forming units(CFUs), but DRCFI produced greater and more sustained reductions.

D.J. Serisier1, D. Bilton2, T. De Soyza3, I. Gonda41Brisbane, QLD/AU, 2London/UK, 3Newcastle/UK, 4Hayward, CA/USORBIT-1 and ORBIT-2 study group

An Optimized Inhaled Ciprofloxacin Formulation DRCFI (Dual Release Ciprofloxacin For Inhalation) Enhances Antibiotic LungConcentrations And Antimicrobial Effect In Non-CF Bronchiectasis(Non-CF BE), [Publication Page: A3659 ATS 2012 San Francisco

A 24 week study of once daily DRCFI (3 cycles of 4 weeks ontreatment and 4 weeks off) confirmed significant reductions of PA CFUs after each treatment cycle, as well as a significantdifference in median time to first pulmonary exacerbation (DRCFI 134 days vs placebo 58 days, p=0.046).

DRCFI also produced excellent safety profiles with no significantchanges in FEV1 and no significant adverse effects.

The optimization of inhaled ciprofloxacin formulation from CFI toDRCFI has resulted in improved airway antibiotic concentrationand retention characteristics and antimicrobial efficacy in PA-colonized non-CF BE.

D.J. Serisier1, D. Bilton2, T. De Soyza3, I. Gonda41Brisbane, QLD/AU, 2London/UK, 3Newcastle/UK, 4Hayward, CA/USORBIT-1 and ORBIT-2 study group

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NOVAS DROGAS INALADAS

Erradicao Pseudomonas

Torax 2010

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Respir Med. 2012 Mar;106(3):356-60. Epub 2011 Dec 26.Outcomes of Pseudomonas eradication therapy in patients with non-cystic fibrosis bronchiectasis.White L, Mirrani G, Grover M, Rollason J, Malin A, Suntharalingam J.SourceRespiratory Department, Royal United Hospital, Combe Park, Bath, BA1 3NG, United Kingdom

. Eradication therapy involved intravenous antibiotics (n = 12), intravenous antibiotics followed by oral ciprofloxacin (n = 13) or ciprofloxacin alone (n = 5), combined with 3 months of nebulised colistin.

Pseudomonas was initially eradicated from sputum in 24 patients (80.0%). 13/24 patients remained Pseudomonas-free and 11/24 were subsequently reinfected(median time 6.2 months).

Respir Med. 2012 Mar;106(3):356-60. Epub 2011 Dec 26.Outcomes of Pseudomonas eradication therapy in patients with non-cystic fibrosis bronchiectasis.White L, Mirrani G, Grover M, Rollason J, Malin A, Suntharalingam J.SourceRespiratory Department, Royal United Hospital, Combe Park, Bath, BA1 3NG, United Kingdom

Exacerbation frequency was significantly reduced from 3.93 per year pre-eradication and 2.09 post-eradication (p = 0.002).

.

This study demonstrates that Pseudomonas can be eradicated from a high proportion of patients, which may lead to prolonged clearance and reduced exacerbation rates. This important outcome requires confirmation in a prospective

Macrolideos Ao no biofilme produzido por

pseudomonas (iasl,rhl) Retarda a maturao in vitro

Propriedades antiinflamatrias

Reduz a produao de NfK

Reduz produo de Mucina (MUC5AC)

Azitromicina 500 2X semana trs meses

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Cymbala et al Treat RespirMed

2005 4(2)-117

MACROLDEOS

AZITROMICINA 2 X SEMANA/12 PACIENTES/

REDUO DE EXACERBAES, REDUO VOLUME SECREO

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CORTICOIDES INALADOS

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GoiniaEncontro Nacional Infeces Respiratrias e Tuberculose

Alexandre Pinto CardosoMd PhDProfessor Pneumologia Fac. Medicina UFRJDiretor Diviso de Tisio-Pneumologia Coordenador Unidade de Pesquisa ClnicaIDT/HUCFF/UFRJ

Bronquiectasias FibrocsticaMedicamentos disponveisMedicamentos necessrios

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Medicamentos necessrios

Farmacolgico Antibiticos

Antibiticos inalados

Anti-inflamatriosCorticoide inalados+Agonistas adrenrgicos

Drogas Hiper osmolar

Mucolticos

Outros Fisioterapia

Respiratria

Rehabilitao

Educao e

suporte

emocional

RIO 2016Esperamos por voce!

CONGRESSO BRASILEIRODE PNEUMOLOGIA E TISIOLOGIA

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Drugs Today (Barc). 2012 May;48(5):339-51.Inhaled antibiotics for lower respiratory tract infections: focus on ciprofloxacin.

Arch Bronconeumol. 2011 Jun;47 Suppl6:19-23.[Inhaled antibiotics in the treatment of noncystic fibrosis bronchiectasis]

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i. The study discussed in this paper demonstrates that long-term therapy with inhaled gentamicin can eradicate the infection or reduce the bacterial load, decrease the risk of subsequent infections and improve the quality of life in patients with non-CF bronchiectasis with a minimal risk of side effects.

2011 Informa UK, Ltd

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Am J Respir Crit Care Med. 2011 Feb 15;183(4):491-9. Epub 2010 Sep24.A randomized controlled trial of nebulized gentamicin in non-cysticfibrosis bronchiectasis.Murray MP, Govan JR, Doherty CJ, Simpson AJ, Wilkinson TS, Chalmers JD, Greening AP, Haslett C, Hill AT.

MEASUREMENTS AND MAIN RESULTS:

At each review the following were assessed: quantitative and qualitative sputumbacteriology;

sputum purulence and 24-hour volume; FEV(1), FVC, and forced expiratory flow, midexpiratory phase; exercise capacity;

Leicester Cough Questionnaire and St. George's Respiratory Questionnaire; and exacerbation frequency.

Fifty-seven patients completed the study

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Am J Respir Crit Care Med. 2011 Feb 15;183(4):491-9. Epub 2010 Sep24.A randomized controlled trial of nebulized gentamicin in non-cysticfibrosis bronchiectasis.Murray MP, Govan JR, Doherty CJ, Simpson AJ, Wilkinson TS, Chalmers JD, Greening AP, Haslett C, Hill AT.

. At the end of 12 months' treatment, comparedwith the saline group, in the gentamicin groupthere was reduced sputum bacterial density with 30.8% eradication in those infected with

Pseudomonas aeruginosa and 92.8% eradicationin those infected with other pathogens;

less sputum purulence (8.7% vs. 38.5%; P < 0.0001); greater exercise capacity (510 [350-690] m vs. 415 [267.5-530] m; P = 0.03);

and fewer exacerbations (0 [0-1] vs. 1.5 [1-2]; P < 0.0001) with increased time to first exacerbation(120 [87-161.5] d vs. 61.5 [20.7-122.7] d; P = 0.02)

Am J Respir Crit Care Med. 2011 Feb 15;183(4):491-9. Epub 2010 Sep 24.A randomized controlled trial of nebulized gentamicin in non-cystic fibrosisbronchiectasis.Murray MP, Govan JR, Doherty CJ, Simpson AJ, Wilkinson TS, Chalmers JD, Greening AP, Haslett C, Hill AT.

The gentamicin group had greater improvements in Leicester Cough Questionnaire (81.4% vs. 20%; P < 0.01) and St. George's Respiratory Questionnaire (87.5% vs. 19.2%; P < 0.004) score.

No differences were seen in 24-hour sputum volume, FEV(1), FVC, or forced expiratory flow, midexpiratory phase.

No P. aeruginosa isolates developed resistance to gentamicin. At follow-up, all outcome measures were similar to baseline.

Conclusions: Regular, long-term nebulized gentamicin is of significant benefit in non-cystic fibrosis bronchiectasis but treatmentneeds to be continuous for its ongoing efficacy.

Clinical trial registered with www.clinicaltrials.gov (NCT 00749866).