Atovaquone microbiology
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Microbiology
Mechanism of Action
Atovaquone is a hydroxy-1,4-naphthoquinone, an analog of ubiquinone, with antipneumocystis activity. The mechanism of action against Pneumocystis jiroveci has not been fully elucidated. In Plasmodium species, the site of action appears to be the cytochrome bc1 complex (Complex III). Several metabolic enzymes are linked to the mitochondrial electron transport chain via ubiquinone. Inhibition of electron transport by atovaquone will result in indirect inhibition of these enzymes. The ultimate metabolic effects of such blockade may include inhibition of nucleic acid and ATP synthesis.
Activity In Vitro
Several laboratories, using different in vitro methodologies, have shown the IC50 (50% inhibitory concentration) of atovaquone against rat P. jiroveci to be in the range of 0.1 to 3.0 mcg/mL.
Drug Resistance
Phenotypic resistance to atovaquone in vitro has not been demonstrated for P. jiroveci. However, in 2 patients who developed Pneumocystis carinii pneumonia (PCP) after prophylaxis with atovaquone, DNA sequence analysis identified mutations in the predicted amino acid sequence of P. jiroveci cytochrome b (a likely target site for atovaquone). The clinical significance of this is unknown.[1]
References
Adapted from the FDA Package Insert.