TY - JOUR
T1 - Activity of phenothiazines against antibiotic-resistant Mycobacterium tuberculosis
T2 - a review supporting further studies that may elucidate the potential use of thioridazine as anti-tuberculosis therapy
AU - Amaral, Leonard
AU - Kristiansen, Jette E.
AU - Viveiros, Miguel
AU - Atouguia, Jorge
PY - 2001/5/1
Y1 - 2001/5/1
N2 - The in vitro and in vivo anti-mycobacterial activities of a number of phenothiazine compounds are reviewed. These compounds, normally employed for the management of psychosis, inhibit the growth in vitro of Mycobacterium tuberculosis at concentrations that are significantly greater than those that can safely be achieved in a patient harbouring these infections. Nevertheless, one of these phenothiazines, chlorpromazine, is concentrated by human macrophages to 10-100 times its concentration in plasma, and has activity against mycobacteria that have been phagocytosed by these cells. Phenothiazines have significant in vitro activity against susceptible, polydrug- and multidrug-resistant strains of M. tuberculosis, as well as enhancing the activity of some agents employed for first-line treatment. Because thioridazine, the very mild anti-psychotic agent whose most common side effect is drowsiness, has equal anti-tuberculosis properties in vitro to chlorpromazine, we recommend that thioridazine be studied as an adjuvant to the four- or five-drug regimens employed for the management of a freshly diagnosed tuberculosis infection of unknown antibiotic susceptibility, at least during the period required for the assessment of antibiotic susceptibility. Because it also enhances the activity of rifampicin and streptomycin, antibiotics that frequently have adverse effects, additional studies evaluating the use of thioridazine as an adjuvant may eventually allow a reduction in the dosages of these antibiotics and result in a decreased frequency of adverse effects. It is important to note that whereas the management of patients with thioridazine for periods in excess of many months will result in the appearance of some undesirable side effects, its use for a limited period of 2-3 months should not produce side effects that are more severe than simple drowsiness. Nevertheless, further in vitro and in vivo studies are essential before thioridazine may be recommended for the management of select cases of pulmonary tuberculosis.
AB - The in vitro and in vivo anti-mycobacterial activities of a number of phenothiazine compounds are reviewed. These compounds, normally employed for the management of psychosis, inhibit the growth in vitro of Mycobacterium tuberculosis at concentrations that are significantly greater than those that can safely be achieved in a patient harbouring these infections. Nevertheless, one of these phenothiazines, chlorpromazine, is concentrated by human macrophages to 10-100 times its concentration in plasma, and has activity against mycobacteria that have been phagocytosed by these cells. Phenothiazines have significant in vitro activity against susceptible, polydrug- and multidrug-resistant strains of M. tuberculosis, as well as enhancing the activity of some agents employed for first-line treatment. Because thioridazine, the very mild anti-psychotic agent whose most common side effect is drowsiness, has equal anti-tuberculosis properties in vitro to chlorpromazine, we recommend that thioridazine be studied as an adjuvant to the four- or five-drug regimens employed for the management of a freshly diagnosed tuberculosis infection of unknown antibiotic susceptibility, at least during the period required for the assessment of antibiotic susceptibility. Because it also enhances the activity of rifampicin and streptomycin, antibiotics that frequently have adverse effects, additional studies evaluating the use of thioridazine as an adjuvant may eventually allow a reduction in the dosages of these antibiotics and result in a decreased frequency of adverse effects. It is important to note that whereas the management of patients with thioridazine for periods in excess of many months will result in the appearance of some undesirable side effects, its use for a limited period of 2-3 months should not produce side effects that are more severe than simple drowsiness. Nevertheless, further in vitro and in vivo studies are essential before thioridazine may be recommended for the management of select cases of pulmonary tuberculosis.
KW - Tuberculostatic agent
KW - Chlorpromazine
KW - Desipramine
KW - Ethambutol
KW - Isoniazid
KW - Levomepromazine
KW - Methdilazine
KW - Methylene blue
KW - Neuroleptic agent
KW - Phenothiazine derivative
KW - Promethazine
KW - Pyrazinamide
KW - Rifampicin
KW - Streptomycin
KW - Thioridazine
KW - Trifluoperazine
UR - http://www.scopus.com/inward/record.url?scp=0035010729&partnerID=8YFLogxK
UR - https://academic.oup.com/jac/article/47/5/505/858497
U2 - 10.1093/jac/47.5.505
DO - 10.1093/jac/47.5.505
M3 - Review article
C2 - 11328759
AN - SCOPUS:0035010729
SN - 0305-7453
VL - Vol. 47
SP - 505
EP - 511
JO - Journal of Antimicrobial Chemotherapy
JF - Journal of Antimicrobial Chemotherapy
IS - n.º 5
ER -