Reply to Raoult

To the Editor—We read with interest the letter from Professor Raoult in this edition of Clinical Infectious Diseases and appreciate the experience and perspective that he brings to this debate [1]. However, the suggestion that we were advocating an abandonment of older antibiotics in order to use newer molecules is not accurate. In the supplement published recently in Clinical Infectious Diseases [2], a series of experiments were described which could serve as proof-of-concept as to how to evaluate drug combinations (linezolid, faropenem, and moxifloxacin). Although the supplement described the evaluation of the 3 drugs linezolid, faropenem, and moxifloxacin, using hollow fiber models together with pharmacokinetic modeling, we were not suggesting that these were the only drugs that should be evaluated. Instead, as outlined in the final article in the supplement, we were proposing a comprehensive approach to the development of new regimens for the treatment of tuberculosis in children that could systematically evaluate all available drugs, in all available combinations [3]. We were not suggesting any restriction to the drugs tested, and the medicines suggested by Professor Raoult, namely the antileprosy drugs clofazimine, minocycline, and the sulfonamides, would certainly be part of any list of drugs included in a comprehensive evaluation of regimen combinations. As suggested, these pharmacophores have proven efficacy against Mycobacterium leprae and would be early drugs to consider. In fact, both clofazimine and tetracycline have already been examined in the system, with publications forthcoming. As regimens are developed for children, all molecules are being looked at, including the antileprosy compounds. The approach is not one of either/or but a comprehensive look at new and old. Their final inclusion in a regimen would be dependent on demonstration of efficacy, synergy or additivity, penetration into anatomic sites most commonly affected by tuberculosis in children, and the toxicity of the compounds. We agree that only by using a comprehensive approach, without forgetting the lessons of the past, are we likely to develop the most effective treatment to help children with tuberculosis.

Note

Potential conflicts of interest. All authors: No potential conflicts. The authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

References

Author notes