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General survey of trimethoprim combinations in the treatment of urinary tract infections

Allgemeine Übersicht über Trimethoprim-Kombinationen in der Behandlung von Harnwegsinfektionen

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Summary

The properties of trimethoprim (TM), reviewed here, show it to be an excellent antimicrobial agent in its own right. However, with very few exceptions, TM has been made available clinically only in combination with a sulphonamide, usually sulphamethoxazole (SMX). We present evidence to suggest that the decision so to restrict the availability of TM was mistaken. Synergy between TM and SMX can be shown clearly in vitro, but there is no evidence from clinical trials that it plays a significant therapeutic role in urinary infections. Also, there is no evidence that combining the two antibiotics suppresses the emergence of resistance. Recently, sulphonamides other than SMX have been proposed as partners for TM, mainly on pharmacokinetic grounds. Compounds other than sulphonamides may also be logical partners for TM: we have made extensive studies on TM + rifampicin, for instance, and have obtained excellent results in certain clearly-defined patient groups. Only clinical trials of these new combinations will reveal whether they are superior to TM/SMX. There is already sufficient evidence to suggest that TM alone will be as effective as, and more acceptable than, TM/SMX. We propose that further large-scale clinical trials with TM alone be carried out, both to treat acute urinary infections and in prophylaxis.

Zusammenfassung

Die hier besprochenen Eigenschaften von Trimethoprim (TM) zeigen, daß es für sich allein ein vorzügliches antimikrobielles Mittel ist. Jedoch ist TM mit sehr wenigen Ausnahmen klinisch nur in Verbindung mit einem Sulfonamid, für gewöhnlich Sulfamethoxazol (SMX) zur Verfügung gestellt worden. Wir stellen Faktoren vor, aus denen geschlossen werden kann, daß es falsch war, die Verfügbarkeit von TM so einzuschränken. Der Synergismus zwischen TM und SMX kann in vitro eindeutig nachgewiesen werden, doch gibt es aus klinischen Untersuchungen keine Beweise dafür, daß er bei Harnwegsinfektionen eine wesentliche therapeutische Rolle spielt. Auch kann nicht bewiesen werden, daß die Kombination der beiden Antibiotika die Resistenzentwicklung vermindert. In jüngerer Zeit wurden vorwiegend aus pharmakokinetischen Gründen andere Sulfonamide als SMX als Partner für TM vorgeschlagen. Außer Sulfonamiden können auch andere Verbindungen sinnvolle Partner für TM sein. Wir haben beispielsweise ausgedehnte Untersuchungen an TM + Rifampicin durchgeführt und bei bestimmten klar umrissenen Patientengruppen ausgezeichnete Ergebnisse erzielt. Nur klinische Untersuchungen über diese neuen Kombinationen werden klären, ob sie dem TM/SMX überlegen sind. Es gibt bereits genügend Belege für die Annahme, daß TM allein ebenso wirksam sein wird wie TM/SMX und zugleich zufriedenstellender. Wir machen den Vorschlag, daß weitere umfangreiche klinische Versuche mit TM allein zur Behandlung von akuten Harnwegsinfektionen und zur Prophylaxe durchgeführt werden.

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  1. Department of Microbiology, Royal Free Hospital, Pond Street, Hampstead, NW3, London, United Kingdom

    W. Brumfitt &  J. M. T. Hamilton-Miller

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Brumfitt, W., Hamilton-Miller, J.M.T. General survey of trimethoprim combinations in the treatment of urinary tract infections. Infection 7 (Suppl 4), S388–S393 (1979). https://doi.org/10.1007/BF01639018

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