Antimicrobial activity of phenothiazines.
Multidrug-resistant Mycobacterium tuberculosis (MDRTB) and antibiotic-resistant Plasmodium falciparum are the major global lethal infections accounting for over 4 million deaths per year. Methicillin-resistant Staphylococcus aureus (MRSA) is the major global nosocomial infection and resistance to vancomycin is evident and may become common. This review provides the scientific and medical basis that support the use of one particular group of compounds, the phenothiazines, and in particular thioridazine, for the management of the above antibiotic-resistant infections. Because thioridazine, a relatively mild neuroleptic as compared to its parental compound chlorpromazine, kills intracellular MDRTB and MRSA at clinical concentrations, its use for the management of these infections may be considered. The review also discusses the activity of phenothiazines against protozoa and parasites, the mechanisms by which phenothiazines promote their antimicrobial effects, their potential for regulating efflux pumps that are a cause for mono or multidrug resistance, as well as their potential for the therapy of problematic infections caused by bacteria that have acquired plasmid-antibiotic-resistant genes.
Amaral
Leonard
L
Unit of Mycobacteriology/UPMM/Instituto de Higiene e Medicina Tropical/Universidade de Lisboa, 1394-008 Lisbon, Portugal. lamaral@ihmt.unl.pt
Viveiros
Miguel
M
Molnar
Joseph
J
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D004351:Drug Resistance / Q000187:drug effects*; D006801:Humans; D010640:Phenothiazines / Q000494:pharmacology* / Q000627:therapeutic use*; D013881:Thioridazine / Q000494:pharmacology / Q000627:therapeutic use
D000890:Anti-Infective Agents; D010640:Phenothiazines; D013881:Thioridazine