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RECIDIVERENDE RESPIRATOIRE INFECTIES Paul van Spiegel, longarts Slotervaartziekenhuis 4 November 2010

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Page 1: RECIDIVERENDE RESPIRATOIRE INFECTIES · Severe CAP (PSI risk category V) No randomized double-blind placebo-controlled trials moxifloxacin 400 mg 1 dd iv/po. or penicillin 1 ME 6

RECIDIVERENDE RESPIRATOIRE INFECTIES

Paul van Spiegel, longarts

Slotervaartziekenhuis

4 November 2010

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  Mw B. 52jr, huisvrouw, gehuwd, 3 kinderen: bronchitis 3/jr, nu tweemaandelijks antibiotica nodig. Voor dagelijks wisselend productief hoesten al lang salbutamol/ipratropium.

  Niet meer na verkoudheden, vroeger altijd.

 Altijd produktieve ochtendhoest met veel sputum

  rookte pakje per dag >18e, 3 jaar geleden gestopt, chronische bronchitis verdween voorbijgaand meer gehoest; over na salbutamol/ipratropium

Casus: anamnese

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  Als kind kinkhoestpneumonie, daarna asthma tot 12e

  Vaak obstructieve neuslast

 Hoestbuien bij naar bed gaan en na opstaan; dan produktief

 GER? Tijdens zwangerschappen en nu rond ziekzijn terugkomend.

  Laatste jaar -10kg; inspanningsdyspnoe bij huishouden.

Casus: anamnese 2

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  Moe, hoestend (groen sputum), Temp 38,6; 68kg, 160cm,

 Huid- en Slmvlzn: atroof ruw keelaspect ov. ga; geen lymfklieren; Ah, p en RR nl

  Longauscultatie: bibasilair midinspir. crepiteren in overigens normaal ademgeruis.

Casus (Lich. onderzoek)

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  Bovenste luchtweg infecties (BLWI)

  verkoudheid   sinusitis   pharyngitis   (influenza)

  Lagere luchweg infecties (LLWI)

  bronchitis   pneumonie

Anatomisch onderscheid LWI

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  Meestal: viraal (rhinovirus, parainfluenza virus, coronavirus, adenovirus, respiratory syncytial virus, influenza virus)

  5–10 % pharyngitis: group A beta hemolytic

streptococci (GABHS) (group C beta hemolytic streptococci, Corynebacterium diphtheriae, Neisseria gonorrhoeae, Arcanobacterium haemolyticum, Chlamydia pneumoniae, Mycoplasma pneumoniae, herpes simplex virus)

  bacteriele superinfectie (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis)

BLWI

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  Antigene drift (mutation → geen immuniteit)   Transmissie door aerosol, druppel- en handcontact

BLWI (2)

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  Therapie: supportief

  Geen antibiotica (virale etiologie) tenzij:

  GABHS-pharyngitis: oraal amoxicilline of erythromycine bekort de duur met 1 tot 2 dagen   Matig tot ernstige acute sinusitis (S. Pneumoniae): amoxicilline or amoxicilline/clavulanaat

  Resolutie spontaan in 3-10 dagen

  Preventie: hygiene minimiseren expo

BLWI (3)

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Bronchitis Pneumonie

LRTI

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Acute bronchitis: productieve hoest; geen onderliggende longziekte, geen aanw. voor pneumonie/sinusitis

  Definitie Exacerbatie COPD/asthma/br.ectasis

  Acute: vaak viraal, geen antibiotica

  Ernstig ziek/COPD/asthma: H. Influenzae, S. Pneumoniae, M. Catharralis

  Doxycycline, amoxicilline (+ clavulanaat)

Bronchitis

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  Incidentie 8-15 per 1000 (♂♂ > ♀♀)

  Hoogste ratio bij jongsten en oudsten

  20% van de episoden leidt tot ziekenhuisopname

  Meest in de winter

  > 100 microbes (bacterien, virus, schimmels, parasieten) betrokken

Pneumonie: epidemiologie

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  Defect in gastheerweerstand   Ademhaling, slikken, hoest, GEReflux   sIgA, mucustransport, humorale en cellulaire immunieit   chron. ontsteking, remodelling   vicieuze cirkel: chron.bronchial sepsis

  Microbiele virulentie:   Ciliostatische eigenschappen   Kapsels   Productie van IgA splijtende proteasen   Resistentie tegen fagocytaire killing

  Overvloed aan microben

Pneumonie: pathogenese

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Pneumonie: pathologie

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Aetiologie pneumonie

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Aetiology (2): extramuraal

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Aetiology (3): intramuraal

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Aetiology (4): ICU

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Severity index

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Severity index (2)

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  Severe CAP (PSI risk category V)   No randomized double-blind placebo-controlled trials

  moxifloxacin 400 mg 1 dd iv/po. or   penicillin 1 ME 6 dd iv and ciprofloxacin 400 mg 2 dd iv / 500 mg 2 dd po. or   penicillin 1 ME 6 dd iv and erytromycin 500 mg 4 dd iv. or   ceftriaxon 2000 mg 1 dd iv / cefotaxim 1000 mg 4 dd iv and erytromycin 500-1000 mg 4 dd iv.

Therapie

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  Moderately severe CAP (PSI risk category III-IV)   penicillin 1*106 MU 4dd i.v.   amoxicillin 1g 4dd i.v.

  In case of penicillin allergy: cefuroxim 750 mg 3 dd iv, cefotaxim 1000 mg 4 dd iv, ceftriaxon 2000 mg 1 dd iv, moxifloxacin 400 mg 1 dd

iv/po

Therapie (2)

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  Mild CAP (PSI risk category I-II)   amoxicillin 500-750 mg 3-4dd p.o.   doxycyclin 100 mg 1dd1 p.o. (first dose 200 mg)

  2nd choice: feniticillin 500 mg 4dd p.o.

Therapie (3)

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CCiirriioonn

Treatment (4)

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  Geen associatie tussen comorbiditeit (COPD, diabetes mellitus, alcoholisme, roken) and specific pathogens

  Uitgezonderd:

  Aspiratie (enteriobacteriaceae/anaeroben waarsch.); switch amoxicilline naar amoxicillin-clavulanate   Post-influenza pneumonie (S. Aureus waarsch.); behandel vlgs richtlijn, maar ß-lactam moet wel S. Aureus dekken (flucloxacillin)   Aangetoonde kolonisatie met Pseudomonas spp.; behandel vlgs richtlijn + toevoegen anti-pseudomonas antibioticum (ceftazidim/ciprofloxacin)

Comorbiditeit

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  Early switch from i.v. to oral as soon as clinical improvement occurs is safe and cost-effective

  Contra-indications for oral therapy:

  S. Aureus pneumonia   Pseudomonas spp. pneumonia   non-drained lung empyema/abscess   disturbed GI-absorption

  Duration of therapy:

  7 days of treatment = 10 days of treatment   one study shows 3d amoxicillin therapy in mild to moderate-severe CAP is not inferior

Therapeutische dilemmas

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  Atypische pneumonie:

  legionella, mycoplasma, chlamydophila   clinical presentation, lab and chest X-ray not helpful   treatment 10-21 days

  Cochrane review 2007: “No benefit of survival or clinical efficacy was shown to empirical atypical coverage in hospitalized patients with CAP.”

 Vaak samen met pneumococcen

Therapeutische dilemmas (2)

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CCiirriioonn

Contents

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Pulmonary and Systemic Inflammation in COPD Exacerbations

Systemic inflammation

Bronchoconstriction oedema, mucus

Expiratory flow limitation

Cardiovascular comorbidity

Exacerbation symptoms

Dynamic hyperinflation

Inflamed COPD airways

Greater airway inflammation

Viruses Bacteria Pollutants

EFFECTS

TRIGGERS

Reprinted from The Lancet, 370, Wedzicha JA, Seemungal TA, COPD exacerbations: defining their cause and prevention, 786-796, Copyright 2007, with permission from Elsevier.

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AECOPD Richtlijn Diagnostiek en Behandeling van COPD 2010

EXACERBATIE 1.   >Dyspnoe 2.   >Sputum volume 3.   >Sputum purulentie 4.  >Hoesten

ETIOLOGIE LWI Luchtverontreiniging >Longwater (Hartfalen) Pijn Rx incompliantie 30% onbekend

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AECOPD

EXACERBATIE 1.   >Dyspnoe 2.   >Sputum volume 3.   >Sputum purulentie 4.  >Hoesten

ETIOLOGIE LWI Luchtverontreiniging >Longwater (Hartfalen) Pijn 30% onbekend

•  LICHT –  Extra Rx, thuis, geen

interventie arts •  MATIG ERNSTIG

–  Extra Rx, thuis, huisarts, of tfn longpoli

•  ERNSTIG (opname) –  >Dy MRC 5, orthopneu –  AH>25/min –  HF>110min –  >hulpAHspiergebruik –  O2sat<92%

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AECOPD

EXACERBATIE 1.   >Dyspnoe 2.   >Sputum volume 3.   >Sputum purulentie 4.  >Hoesten

ETIOLOGIE LWI Luchtverontreiniging >Longwater (Hartfalen) Pijn 30% onbekend

•  LICHT –  Extra Rx, thuis, geen

interventie arts •  MATIG ERNSTIG

–  Extra Rx, thuis, huisarts, of tfn longpoli

•  ERNSTIG (opname) –  >Dy MRC 5, orthopneu –  AH>25/min –  HF>110min –  >hulpAHspiergebruik –  O2sat<92%

•  EXTRA Rx: 1. Luchtwegverwijders 2. Prednisolon 30mg 7-14d 3. Antibiotica ??

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AECOPD

EXACERBATIE 1.   >Dyspnoe 2.   >Sputum volume 3.   >Sputum purulentie 4.  >Hoesten

ETIOLOGIE LWI Luchtverontreiniging >Longwater (Hartfalen) Pijn 30% onbekend

•  LICHT –  Extra Rx, thuis, geen

interventie arts •  MATIG ERNSTIG

–  Extra Rx, thuis, huisarts, of tfn longpoli

•  ERNSTIG (opname) –  >Dy MRC 5, orthopneu –  AH>25/min –  HF>110min –  >hulpAHspiergebruik –  O2sat<92%

EXTRA Rx: 1. Luchtwegverwijders 2. Prednisolon 30mg 7-14d 3. Antibiotica ??

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AECOPD: Potentieel Pathogene Microben

Viruses •  Influenza •  Parainfluenza •  Respiratory syncytial virus

(RSV) •  Human metapneumomia

virus •  Picornaviruses •  Coronavirus •  Adenovirus

Bacteria •  Common

– Haemophilus influenzae – Moraxella catarrhalis – Streptococcus pneumoniae

– Staphylococcus aureus •  Common in Severe Disease

– Pseudomonas aeruginosa – Gram-negative bacilli

•  Rare – Chlamydia pneumoniae – Mycoplasma pneumoniae – Legionella spp

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Sputumkleur bij AECOPD Hans Daniels, longarts VUMC, Thesis 2010

Sputum color reported by patients is not a reliable marker of the presence of bacteria in acute exacerbations of COPD

Geen infectie Infectie

Patiënt Gevalideerde sputum kleurenkaart

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Sputumkleur bij AECOPD

Sputum color reported by patients is not a reliable marker of presence of bacteria in acute exacerbations of COPD

Patiënt Bacteriën aanwezig

51%

65%

p= 0.041

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Sputumkleur bij AECOPD

Dr Hans Daniels, longarts Thesis 2010 VUMC

Sputum color reported by patients is not a reliable marker of the presence of bacteria in acute exacerbations of COPD

Patiënt Kleurenkaart Bacteriën aanwezig

51%

65%

p= 0.041

32%

82%

p< 0.001

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Sputumkleur bij AECOPD

Dr Hans Daniels, longarts Thesis 2010 VUMC

Sputum color reported by patients is not a reliable marker of the presence of bacteria in acute exacerbations of COPD

Kleurenkaart  Pa,ënt  

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  Geen additioneel effect bij lichte exacerbaties behandeld met stootkuur prednisolon (Sachs, 1995)

  Bij infectiekliniek (>38,5 en malaise) of COPD III/IV:

 Risicofactoren ernstig beloop?  ( >65j, AH>30/min, RR<90mmHg, desorientatie, nierinsuff., e/o Legionella kans):

Ambulant: doxycycline, amoxicilline, of ander breedspectrumAB tot 72u na normaliseren temp.

Opame: Volgens SWAB-rl voor pneumonie

  Als onvoldoende verbetering na 2-4d prednisolon: Amoxicilline/clavulanaat of op geleide van sputumkweek

Antibiotica bij AECOPD Richtlijn Diagnostiek en Behandeling van COPD 2010

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AECOPD: Recommended Antimicrobial Therapy

Oral Treatment (No particular order)

Alternative Oral Treatment

(No particular order)

Parenteral Treatment

(No particular order)

Group A

Patients with only one cardinal symptom should not receive antibiotics If indication then: β-lactam (penicillin, ampicillin/amoxicillin), tetracycline, trimethoprim/ sulfamethoxazole

β-lactam/β-lactamase inhibitor (Co-amoxiclav) Macrolides (azithromycin, clarithromycin, roxithromycin) Cephalosporins (2nd or 3rd generation) Ketolides (telithromycin)

Group B

β-lactam/β-lactamase inhibitor (Co-amoxiclav)

Fluoroquinolones (gemifloxacin, levofloxacin, moxifloxacin)

β-lactam/β-lactamase inhibitor (Co-amoxiclav, ampicillin/sulbactam) Cephalosporins (2nd or 3rd

generation) Fluoroquinolones (levofloxacin, moxifloxacin)

Group C

In patients at risk for pseudomonas infections: Fluoroquinolones (ciprofloxacin, levofloxacin - high dose)

Fluoroquinolones (ciprofloxacin, levofloxacin - high dose) or β-lactam with P aeruginosa activity

Group A: Mild exacerbation, no risk factors for poor outcome Group B: Moderate exacerbation with risk factor(s) for poor outcome Group C: Severe exacerbation with risk factors for P aeruginosa infection

From the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2008. Available from: http://www.goldcopd.org.

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  Know your bugs!

  Know your epidemiology!

  Short course of AB is safe

  Atypical coverage only in severely ill

 Met dank aan Maarten Limper, AIOS Interne Geneesk Slotervaartziekenhuis

Take home message

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Recidiverende Respiratoire Infecties

•  Geconditioneerde luchtwegen –  COPD –  Asthma –  Bronchiectasis –  Restafwijkingen (fibroserend e/o holtevormend, stenosen)

•  MK-pneumonie •  Destroyed lung

•  Chronische aspiratie –  GER/dysfagie/Zenker’s divertikel –  ETOH/MDA –  Neurologisch lijden

•  Onderliggend systemische aandoening –  Mucoviscoidose , primaire ciliaire dyskinesie –  Noninfectieus: vasculitis, organiserende pneumonie, BAC –  Secundaire immuundeficientie (HIV, beenmergzktn) –  Primaire ImmDef (CVID, hypogammaglob, IgGsubkl.en MBL)

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BRONCHIECTASIS: Vicious Circle Hypothesis Chronic Bronchial Sepsis

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BRONCHIECTASIS: Management

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For whom the bell tolls… Hemmingway

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  SWAB guidelines 2005: therapy of Community-acquired Pneumonia (www.swab.nl)   IDSA guidelines 2000 (www.idsa.com)   Shefet D et al: Empiric antibiotic coverage of atypical pathogens for community acquired pneumonia in adults: COCHRANE-review   Li JZ et al: Efficacy of short-course antibiotic regimens for community-acquired pneumonia: a meta-analysis. Am J Med (2007)120; 783-790   Cunha BA: The atypical pneumonias: clinical diagnosis and importance. Clin Microbiol Infect (2006) 12; 12-24   Lode HM: Managing community-acquired pneumonia: a European perspective. Res Med (2007) 101; 1864-1873   El Moussaoui R et al: Effectiveness of discontinuing antibiotic treatment after three days versus eight days in mild to moderate-severe community acquired pneumonia. BMJ (2006) 332; 1355-62

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