Neue Antibiotika zur Therapie von Atemwegsinfektionen

Zusammenfassung

Der Bedarf an neuen Antibiotika ist aufgrund vielfältiger Resistenzentwicklungen groß. Die Resistenz bei Streptococcus pneumoniae gegenüber Makroliden und Penicillinen wird in den USA bereits auf über 30 % beziffert. Die Zulassung neuer Antibiotika, insbesondere solche mit neuem Wirkmechanismus, ist seit vielen Jahren rückläufig, so dass in Zukunft mit einem Mangel an wirksamen Therapieoptionen gerechnet werden muss. Neue Substanzen mit guter In-vitro-Aktivität gegenüber Pneumokokken haben sich nicht in allen Fällen als klinisch unbedenklich erwiesen, wie es zum Beispiel für mehrere Chinolone zutrifft. Ebenso konnte Daptomycin, ein Lipopeptid mit neuartigem Wirkprinzip, aufgrund der Deaktivierung durch Surfactant bei Atemwegserkrankungen nicht überzeugen. Etabliert haben sich bei den Chinolonen Levofloxacin und Moxifloxacin, das seit 2002 auch als i. v.-Zubereitung zur Verfügung steht. Bei den Ketoliden sind Telithromycin (nur oral) und bei den Azaliden Azithromycin (seit 2005 auch als i. v.-Zubereitung) im Handel. Linezolid ist das bisher einzige zugelassene Oxazolidinon. Im Laufe des Jahres 2006 ist in Deutschland mit der Zulassung eines neuen Tetracyclinderivats (Tigecyclin) zu rechnen. Als neues Carbapenemen wurde Ertapenem im Jahr 2003 zugelassen, ein weiteres Antibiotikum aus dieser Gruppe, Doripenem, befindet sich noch in der klinischen Entwicklung.

Abstract

The need for new antibiotics is ongoing in view of manifold resistance developments. The resistance of Streptococcus pneumoniae against macrolides and penicillins in the USA already amounts to more than 30 %. The approval of new antibiotics, particularly those with a new mode of action, has been decreasing over the past years which is anticipated to result in a lack of resourceful therapy options in the future. Some new substances with good in vitro activity against S. pneumoniae have turned out to raise safety issues as shown for a number of quinolones. Likewise daptomycin, a lipopeptide with a new mechanism of action, did not show satisfying results due to its inactivation by surfactant. Established quinolones are levofloxacin and moxifloxacin, the latter being available as i. v. formulation since 2002. For ketolides, telithromycin (oral) and for azalides azithromycin (since 2005 as i. v. formulation) are available for antimicrobial therapy. Linezolid is the only approved oxazolidinone. Tigecycline, a tetracycline derivate, will be approved in 2006 in Germany. The latest approval regarding carbapenems was ertapenem in 2003, while doripenem, a new antibiotic from this group, is still under clinical development.

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