Evidence that rifampicin can be used safely for non-tuberculous diseases.

Abstract

The incidence of primary resistance to rifampicin in Mycobacterium tuberculosis has been analysed in countries where rifampicin is restricted to use for treating tuberculosis and in countries where its use is not restricted. There is no evidence that rifampicin-resistant M tuberculosis strains are more common where the use of the drug is unrestricted. Resistance to rifampicin is less common than is resistance to streptomycin or to isoniazid. We can thus see no danger of producing resistant strains of M tuberculosis if rifampicin therapy is used for short periods for non-tuberculous infections. The problem of resistant mutants arising in the non-tuberculous species being treated is overcome by combining rifampicin with trimethoprim.Rifampicin has a uniquely wide spectrum of antimicrobial activity, which includes Grampositive and Gram-negative organisms as well as Mycobacterium tuberculosis.' Because of this, in a relatively early phase of the clinical use of this antibiotic for non-tuberculous indications, rifampicin was employed alone in infections of the chest2 and urinary tract.3 4 However, the observation that in these circumstances resistant mutants were rapidly selected caused the use of monotherapy with rifampicin in non-tuberculous infections to fall into disrepute.As a logical means of overcoming this problem, a combination of rifampicin and trimethoprim was envisaged, based on a "double blockade" type of approach. The basic assumptions were confirmed in a series of microbiological studies,5 6 which indicated both the existence of synergism between the two compounds and the prevention of the selection of resistant mutants. The situation concerning fears for the development of resistance in M tuberculosis7 as a result of rifampicin/trimethoprim being used was summarised in a provocative editorial.8 Since then, the pharmacokinetic properties of the combination9 10 and its clinical effectiveness" have been evaluated, and confirmed the encouraging preclinical evidence. A further and most important part of the development of the combination has been, and continues to be,

Short-Course, High-Dose Rifampicin Achieves Wolbachia Depletion Predictive of Curative Outcomes in Preclinical Models of Lymphatic Filariasis and Onchocerciasis

“…Because elevated rifampicin dosages for filariasis cure are predicted in a 1–2 week dose exposure time frame, this is unlikely to result in resistant strains of M tuberculosis (TB), as there is no evidence for rifampicin resistance occurrence when administered for short periods of time 73 , 74 .…”

Rifampicin in periprosthetic joint infections: where do we stand and where are we headed?

“…This resistance is known to occur if rifampicin is used as monotherapy or when treating infections with a very high bacterial load [9]. In 1980, Acocella et al reported that the incidence of rifampicinresistant tuberculosis strains was not higher in countries where rifampicin was frequently used in comparison with countries with a restrictive use of rifampicin and therefore concluded that this fear was unjustified [10]. Nowadays, it is a common antibiotic prescribed for foreign body-materialrelated infections, including PJI.…”

“…In vitro studies demonstrate that resistance to rifampicin easily develops when used as monotherapy, in particular when the bacterial load is high [44]. This phenomenon is illustrated in a clinical study demonstrating that inadequate surgical debridement and inadequate induction therapy with intravenous antimicrobials resulted in a higher odds of developing rifampicin-resistant strains [10]. However, if a thorough surgical debridement with adequate bacterial load reduction is performed followed by rifampicin combination therapy, the occurrence of rifampicin resistance is probably very unlikely.…”

Rifampicin for Non-Tuberculous Infections?

“…First, epidemiological evidence has been adduced [4,5] to show that no more primary resistance is found in strains of M. tuberculosis isolated in countries where RIF is freely available than in countries where it is used only in combined therapy for tuberculosis.…”