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Beurteilung der Resistenzentwicklung als Faktor für die Einschränkung therapeutischer Möglichkeiten

Limitation of antibacterial chemotherapy due to development of resistance

  • Nebenwirkungsprofile Bei Antibakteriell Wirksamen Chemotherapeutika
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Zusammenfassung

Das breite Spektrum der zur Verfügung stehenden Substanzen und die hohe Aktivität neu entwickelter Chemotherapeutika läßt eine allgemein gestiegene Sicherheit in der Chemotherapie erkennen. Für einzelne Substanzgruppen sind jedoch Trends in der Resistenzentwicklung erkennbar. Dazu gehört die Entstehung von Breitspektrumresistenz durch schrittweise Veränderung plasmidcodierter β-Laktamasen (z. B. TEM oder SHV). Kombination verschiedener Gene für Aminoglykosid-modifizierende Enzyme auf einzelnen Plasmiden trägt zur Vielfachresistenz gegenüber Aminoglykosidantibiotika bei. Für die in Enterokokken neu entdeckte Resistenz gegenüber Glykopeptidantibiotika, die als Reservemittel (Methicillin-resistenteStaphylococcus aureus) und für bestimmte Indikationen (Pseudomembranöse Enterocolitis) bisher uneingeschränkt zur Verfügung standen, besteht ebenso wie für die beschriebenen Substanzen die Gefahr der Ausbreitung auf verschiedene Spezies. Trotz der fehlenden Transferierbarkeit der 4-Chinolon-Resistenz zeichnet sich aber auch bei einigen Spezies(Staphylococcus aureus undPseudomonas aeruginosa) eine Veränderung der Resistenzsituation ab, ohne daß es Hinweise auf neuartige Resistenzmechanismen gibt. Statistich gesicherte Dokumentation der Resistenzentwicklung mit validierten Methoden sowie einheitliche Bewertungskriterien nach international festgelegten Breakpoints sind notwendig, um allgemeine Trendänderungen zu erkennen und von lokalen Ereignissen zu unterscheiden. Konsequenterweise muß der Einsatz neuentwickelter Substanzen sorgfältig kontrolliert werden.

Summary

From the microbiological point of view a variety of highly active compounds has contributed to improved efficacy of antibacterial chemotherapy during the last few decades. In some cases, however, resistance has increased due to different molecular mechanisms. Resistance to the new generation of broad-spectrum β-lactams is in the cases of TEM and SHV enzymes based upon the stepwise acquisition of point mutations within the structural gene. Multiresistance to aminoglycosides is caused by a combination of different genes coding for aminoglycoside modifying enzymes on transferable plasmids. Resistance to glycopeptides has recently been detected in enterococci and is due to a new mechanism of resistance. These substances have so far had unlimited activity against methicillin-resistantStaphylococcus aureus and have been widely used for treatment of pseudomembranous colitis. While all the three mechanisms of resistance mentioned above are transferable among different strains, no evidence exists so far for transferable resistance to 4-quinolones. However, forS. aureus andPseudomonas aeruginosa an increase of resistance has been reported. The underlying mechanisms seem to be unchanged. The detection of global changes in the development of resistance and the discrimination of these changes from local events requires recording of statistically significant data obtained with approved methods and evaluation of the data with standardized international breakpoints. Consequently, the use of new agents should be controlled efficiently.

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  1. Institut für Medizinische Mikrobiologie der Universität, An der Immenburg 4, W-5300, Bonn, Germany

    P. Heisig &  B. Wiedemann

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  1. P. Heisig
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  2. B. Wiedemann
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Heisig, P., Wiedemann, B. Beurteilung der Resistenzentwicklung als Faktor für die Einschränkung therapeutischer Möglichkeiten. Infection 19 (Suppl 1), S47–S51 (1991). https://doi.org/10.1007/BF01644735

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