Roxithromycin in the treatment of lyme disease-update and perspectives

Summary

Spirochaetal infections have been successfully treated with penicillin; more recently, erythromycin has been used in cases with known penicillin allergy. The discovery of the spirochaeteBorrelia burgdorferi and the elaboration of a new generation of macrolides with properties that differ from older macrolides have led to new ways of treating spirochaetal disease with these compounds. This paper presents data on thein vitro andin vivo efficacy of a combination of roxithromycin and co-trimoxazole againstB. burgdorferi. In vitro (checkerboard technique;B. burgdorferi strain B31; modified BSK II medium) it was found that while roxithromycin showed excellent efficacy againstB. burgdoferi (MIC 0.031 mg/l), co-trimoxazole had no effect. However, the combination of both chemotherapeutics led to a minor synergistic effect, decreasing the MIC for roxithromycin by one dilution step at concentrations of co-trimoxazole from 256 to 8 mg/l. In addition, a clearly reduced growth of microorganisms was seen at concentrations of roxithromycin as low as 0.015 mg/l in combination with 256 to 4 mg/l co-trimoxazole, when compared to the positive controls. Most interestingly, however, the motility ofB. burgdorferi was markedly reduced even when the two drugs were combined at very low concentrations. In anin vivo, non-randomised, open, prospective pilot study it was found that of 17 patients, with confirmed late Lyme borreliosis (stage II/III), treated with combined roxithromycin (300 mg b.i.d.) and co-trimoxazole for 5 weeks, 13 (76%) recovered completely by the end of treatment, and four continued to have symptoms on follow-up at 6 and 12 months. This success rate is similar to that seen with i.v. penicillin and ceftriaxone. It appears that the reduced motility ofB. burgdorferi makes the pathogen mor accessibile to the immune system.

Zusammenfassung

Es wird über diein vitro- undin vivo- Wirksamkeit einer Kombination von Roxithromycin und Co-trimoxazol gegenBorrelia burgdorferi berichtet.In vitro zeigte sich, daß Roxithromycin über eine ausgezeichnete Wirksamkeit gegenüberB. burgdorferi verfügt, Co-trimoxazol war jedoch unwirksam. Die Kombination beider Chemotherapeutika führt zu einem geringen synergistischen Effekt u.z., um eine Verdünnungsstufe bei einer Co-trimoxazol-Konzentration von 256/8mg/1. Bei einer 0.015 mg/l Roxithromycin-Konzentration in Kombination mit 256/4 mg/l zeigte sich in Vergleich zu positiven Kontrollen ein eindeutig reduziertes Wachstum der Mikroorganismen. Die Motilität war sogar eindeutig reduziert, wenn beide Substanzen nur sehr niedrige Konzentrationen aufwiesen. Bei einer offenen prospektiven Pilot-Studie, bei 17 Patienten mit einer gesicherten Borreliose in Stadium II/III, die mit einer Kombination von Roxithromycin (300 mg b.i.d.) 5 Wochen behandelt wurden, waren danach 13 ausgeheilt, vier hatten weiterhin Symptome nach 6 bis 12 Monaten. Das Ergebnis entspricht der einer i.v. Penizillin-oder Ceftriaxon-Behandlung.