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Dansk Lungemedicinsk Selskab har repræsentanter i Danmarks Lungeforening og indgår i Dansk Selskab for Intern Medicin (DSIM) samt European Respiratory Society.

fb artDansk Lungemedicinsk Selskab har mere end 10 stående udvalg indenfor f.eks. telemedicin, retningslinjer m.m. og deltager med repræsentanter i forskellige udvalg under Sundhedsstyrelsen. Foreningen af Yngre Lungemedicinere, som repræsenterer næste generation af lungemedicinske speciallæge, er organiseret under Dansk Lungemedicinsk Selskab.

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Næste Årsmøde: 29-30. november, 2019. Odense | Invitation | Tilmelding | Program | Dagsorden generalforsamling

Emner: Lungecancer, hoste, allergi m.m.

 

The efficacy and safety of inhaled antibiotics for theThe efficacy and safety of inhaled antibiotics for thetreatment of bronchiectasis in adults: a systematic reviewand meta-analysis

Professor: Jens-Ulrik Stæhr Jensen 

Artikel link | DOI | PubMed | Journal: Lancet Respir Med I Dato: 2019 Okt

Kommentar til artiklen:

Patienter med bronkiektasier har høj risiko for bakterielle lungeinfektioner, ofte kompliceret af at det er særlige bakterier som kan være svære at behandle. Eksempler på sådanne bakterier, som leder til komplekse problemer er Pseudomonas aeruginosa, Stenotrophomonas maltophilia og Achromobaster xylosoxidans. Behandlingstilbuddene til bronkiektasi-patienter med sådanne Gram negative infektioner, har indtil for nylig været begrænsede idet f.eks. azithromycins antibakterielle effekt er indenfor det Gram positive spektrum. Adskillige randomiserede kontrollerede studier (RCT) har undersøgt forskellige inhalerede antibiotika til bronkiektasi-patienter, men i flere af disse, ikke så store studier, har man blot set ”tendenser” til bedre outcomes, som f.eks. i ORBIT-3, RESPIRE-2, AIR-BX1 og AIR-BX2.

Resultaterne fra de tilgængelige RCT´er er nu analyseret samlet i en dygtigt gennemført meta-analyse, hvilket giver en del afklaring: Inhalerede antibiotika reducerer antallet af exacerbationer 0·81 (0·67–0·97), mængden af bakterier pr. gram sputum og er generelt veltålte, om end nogle patienter får bivirkninger. Omvendt er der hverken klinisk- eller statistisk signifikant effekt på symptombyrden.

Resistens-problematik er altid tungtvejende ved overvejelser om at sætte patienter i langtidsprofylakse med antibiotika, og således også med inhaleret antibiotika. Således står denne behandlingsoption tilbage som en mulighed der kan overvejes hos bronkiektasi-patienter der har mange exacerbationer, primært med Gram negative bakterier i luftvejssekret, og hvor andre behandlingsmuligheder ikke har givet tilfredsstillende resultat. I sådanne tilfælde kan man forvente en moderat, men klinisk relevant effekt i at reducere frekvensen af exacerbationer og som de fleste patienter tåler. På Gentofte Hospital opstarter vi sådan en behandling under en kort indlæggelse på et døgn for at observere for bivirkninger (primært astma-anfald) og for at sikre at patienten har lært at tage medicinen. 

Abstract

Background

Although use of inhaled antibiotics is the standard of care in cystic fibrosis, there is insufficient evidenceBackground Although use of inhaled antibiotics is the standard of care in cystic fibrosis, there is insufficient evidenceto support use of inhaled antibiotics in patients with bronchiectasis not due to cystic fibrosis. We aimed to assess theefficacy and safety of inhaled antibiotics for the long-term treatment of adults with bronchiectasis and chronicrespiratory tract infections.

Methods

We did a systematic review and meta-analysis of all randomised controlled trials of inhaled-antibiotic use inadult patients with bronchiectasis and chronic respiratory tract infections. Eligible publications were identified bysearching MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov. Randomised controlled trials of inhaled antibiotics were included if the patients were adults with stablebronchiectasis diagnosed by CT or bronchography, the trials had treatment a duration of at least 4 weeks, and theiroutcomes met at least one of the endpoints of interest. Studies in cystic fibrosis were excluded. Efficacy endpointsassessed were bacterial load, bacterial eradication from sputum, frequency of exacerbations, time to first exacerbation,proportion of patients with at least one exacerbation, frequency of severe exacerbations, quality of life, change inFEV1, 6-min walk distance, mortality, adherence to treatment, and sputum volume; safety endpoints were adverseevents and bacterial resistance in sputum. Each study was independently reviewed for methodological quality usingthe Cochrane risk of bias tool. Random-effects meta-analysis was used to pool individual studies. Heterogeneity wasassessed using I². The review is registered on PROSPERO, number CRD42019122892.

Findings

16 trials (n=2597 patients) were included for analysis. The mean reduction of colony forming units per g ofsputum with inhaled antibiotics was –2·32 log units (95% CI –3·20 to –1·45; p<0·0001). Bacterial eradication wasincreased with inhaled antibiotic therapy (odds ratio [OR] 3·36, 1·63 to 6·91; p=0·0010). Inhaled antibiotics significantlyreduced exacerbation frequency (rate ratio 0·81, 0·67 to 0·97; p=0·020). Time to first exacerbation was significantlyprolonged with inhaled antibiotics (hazard ratio 0·83, 0·69 to 0·99; p=0·028). The proportion of patients with at leastone exacerbation decreased (risk ratio 0·85, 0·74 to 0·97; p=0·015). There was a significant reduction in the frequencyof severe exacerbations (rate ratio 0·43, 0·24 to 0·78; p=0·0050). The scores for neither the Quality of Life Bronchiectasis questionnaire nor St George’s Respiratory Questionnaire improved above the minimal clinically important difference.The relative change in FEV1 was a deterioration of 0·87% predicted value (–2·00 to 0·26%; p=0·13). Other efficacyendpoints were reported in only few studies or had few events. There was no difference in treatment-emergent adverseeffects (OR 0·97, 0·67 to 1·40; p=0·85) or bronchospasm (0·99, 0·66 to 1·48; p=0·95). Emergence of bacterialresistance was evident at the end of the treatment period (risk ratio 1·91, 1·46 to 2·49; p<0·0001).

Interpretation

Inhaled antibiotics are well tolerated, reduce bacterial load, and achieve a small but statisticallysignificant reduction in exacerbation frequency without clinically significant improvements in quality of life inpatients with bronchiectasis and chronic respiratory tract infections.