Summary
Resistance to fluoroquinolone antibacterials has emerged in a limited form, largely amongst certain specific species and often restricted to single clones of these pathogens. Mediated by chromosomal mutation, the major mechanisms are alterations in gyrase subunits and reduced penetration associated with decreased outer membrane protein production. Resistance is most commonly seen to emerge amongst pathogens with higher than average initial MICs, particularly affected species beingPseudomonas aeruginosa and the staphylococci. Resistance is more likely to be encountered when such pathogens are exposed to concentrations at or below the MIC, which may result either from underdosage, the presence of the organism in a sequestered site, e.g. bone or prostate, or from confounding factors such as the presence of pus, indwelling prostheses or interactions which reduce absorption from the gastrointestinal tract. Repetitive use of these agents and continued use of fluoroquinolone precursors, such as nalidixic acid, may also contribute to resistance emergence. Most resistance is appearing amongst hospitalised patients and much of the apparent burden reflects horizontal cross-infection of many patients by a single resistant clone. There is very limited data linking increasing community use of fluoroquinolones with resistance emergence amongst pathogens such asEscherichia coli. In the main, the emergence of resistance can be anticipated and perhaps prevented or avoided for the sorts of risk groups and pathogens described. The use of adequate dosage by appropriate routes of administration in suitable patients and implementation of surveillance procedures for those at risk will minimise such problems. Policies for the effective use of these valuable agents should be part of everyday practice in hospitals.
Zusammenfassung
Die Resistenzentwicklung gegen Fluorochinolone beschränkt sich weitgehend auf bestimmte Spezies, von denen oft nur einzelne Klone betroffen sind. Durch chromosomale Mutation bedingt sind die wesentlichen Resistenzmechanismen Veränderungen in Untereinheiten der Gyrase und verminderte Penetration aufgrund verminderter Produktion von Proteinen der äußeren Membran. Man sieht die Resistenz meist bei Erregern, bei denen die initialen MHK-Werte über dem Durchschnitt liegen, vor allem sindPseudomonas aeruginosa und Staphylokokken betroffen. Man findet die Resistenz eher, wenn solche Erreger Konzentrationen um den MHK-Wert oder darunter ausgesetzt werden, was eine Folge von zu niedriger Dosierung sein kann, oder die Erreger befinden sich in einer abgeschlossenen Region wie Knochen oder Prostata, oder aber es liegen andere Faktoren vor wie die Anwesenheit von Eiter, implantierte Prothesen oder Faktoren, die zu einer Verminderung der Resorption aus dem Gastrointestinaltrakt führen. Wiederholte Anwendung dieser Substanzen, Gebrauch in der Tierzucht und kontinuierlicher Gebrauch von Vorläufersubstanzen der fluorierten Chinolone wie Nalidixinsäure können auch zur Resistenzentwicklung beitragen. Die meisten Fälle von Chinolonresistenz finden sich bei hospitalisierten Patienten und in vielen Fällen besteht eine horizontale Infektionsausbreitung bei vielen Patienten mit einem einzigen resistenten Klon. Es gibt nur wenige Daten, die einen zunehmenden Gebrauch der fluorierten Chinolone im niedergelassenen Bereich mit der Resistenzentwicklung bei Erregern wieEscherichia coli aufzeigen. Im wesentlichen kann die Resistenzentwicklung vorhergesehen werden, und vielleicht ist es möglich, sie für die beschriebenen Risikogruppen und Erreger zu verhüten oder zu vermeiden. Der Gebrauch adäquater Dosen und Applikationsformen bei den richtigen Patienten und die Einbeziehung von Überwachungsmaßnahmen für die Risikopersonen ist in der Lage, solche Probleme auf ein Minimum einzuschränken. Methoden für die wirksame Anwendung dieser wertvollen Substanzen sollten Teil der Routinepraxis in den Krankenhäusern sein.
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Ball, P. Bacterial resistance to fluoroquinolones: Lessons to be learned. Infection 22 (Suppl 2), S140–S147 (1994). https://doi.org/10.1007/BF01793579
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DOI: https://doi.org/10.1007/BF01793579