Successful alternative treatment of extensively drug-resistant tuberculosis in Argentina with a combination of linezolid, moxifloxacin and thioridazine

Abstract

The combination of linezolid, moxifloxacin and thioridazine is recommended for compassionate use in specialized centres with expertise in the management of XDR-TB.

The Accepted “Clinical Interaction Model”: A Special Case of Reality

“…Reduction of the dose of both revealed a synergistic activity between the antibiotic and the non-antibiotic [53]. Similar synergistic effects have been observed between thioridazine in combination with antibiotics for treating extensively drug-resistant infections of pulmonary tuberculosis [54,55].…”

“…Yes [39,40,[55][56][57][58][59][60][61] Can pathogenicity and virulence be reduced by means of psychotherapeutics and/or other non-antibiotics and their analogues? Yes [62][63][64][65][66] Can the synergy between psychotherapeutics and "classical" antibiotics/chemotherapeutics be expoited (for example to reduce the dose)?…”

Totally Drug Resistant Tuberculosis can be treated with thioridazine in combination with antibiotics to which the patient was initially resistant.

“…Given that tuberculosis is essentially an intracellular infection, the question of whether thioridazine, the equal to chlorpromazine as an in vitro tubercular agent [3], has similar intracellular activity against multi-drug resistant Mycobacterium tuberculosis, was soon investigated and shown to promote the killing of intracellular multi-drug resistant Mycobacterium tuberculosis by non-killing human macrophages at a concentration that was close to that initially used to treat a freshly diagnosed case of pyschosis [5]. Thioridazine has been shown to cure the mouse of an antibiotic susceptible [6] and multi-drug resistant [7] infections and most recently, shown to cure patients infected with extensively drug resistant strains of Mycobacterium tuberculosis when used in combination with antibiotics to which the patients were initially resistant [8]. When used as monotherapy, thioridazine has been reported to significantly improve the XDR TB patient´s quality of life and has been recommended to be used as a salvage drug for therapy of the XDR TB patient [9].…”

“…Because the killing of the bacterium is independent of the antibiotic status of the bacterium, the use of thioridazine for therapy of the XDR and now, the TDR TB patient is expected to be successful. Given that unlike the life-long therapy of the psychotic patient, the use of thioridazine for therapy of these antibiotic resistant infections is expected to be in terms of months [8] rather than years, the negative side effects produced by thioridazine, albeit, infrequent, are expected to be far less frequent. Given that at this time, there are no drugs known to cure the TDR TB infected patient, and thioridazine when used as described herein is safe, and very cheap, it must at this time be considered for therapy of the XDR TB patient.…”

Advances in Personalised Treatment of Multi-drug Resistant Tuberculosis

“…As an example, the phenothiazine thioridazine (TZ), used as a neuroleptic in humans, inhibits efflux pumps of Mtb [20] as well as the Ca ++ and K + pumps of the macrophage [21] and at relevant clinical drug concentrations enhances the killing activity of the human macrophage against phagocytosed Mtb [21]. Because TZ alone [22] and in combination with anti-TB drugs inhibits the in vitro replication of Mtb [23], Abbate and his group successfully treated 18 XDR-TB patients with a combination of TZ and antibiotics to which the infective strains were initially resistant to [24]. That TZ alone and in combination with anti-TB drugs cures MDR-TB infections has also been confirmed in murine models [25][26][27][28].…”