Atovaquone

Publication Title: 
The Journal of Antimicrobial Chemotherapy

The anticryptosporidial activity of four macrolides alone and in combination with other antimicrobial agents was investigated against ten clinical isolates of Cryptosporidium parvum recovered from stools of AIDS patients. The susceptibility tests were performed by inoculation of the protozoa on to cell monolayers and determining the parasite count after 72 h incubation at 37 degrees C.

Author(s): 
Giacometti, A.
Cirioni, O.
Scalise, G.
Publication Title: 
Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences

Antimarial drug resistance develops when spontaneously occurring parasite mutants with reduced susceptibility are selected, and are then transmitted. Drugs for which a single point mutation confers a marked reduction in susceptibility are particularly vulnerable. Low clearance and a shallow concentration-effect relationship increase the chance of selection.

Author(s): 
White, N.
Publication Title: 
Antimicrobial Agents and Chemotherapy

The interactions of artemisinin with atovaquone, quinine, and mefloquine were investigated in three Plasmodium falciparum strains (strains F-32, FCR-3, and K-1) by an in vitro culture assay. The parasites were cultured for 48 h in the presence of different concentrations and proportions of two drugs at a time in a checkerboard design. The response parameters were determined, and the sums of the fractional inhibitory concentrations (sigmaFICs) of the drug combinations were calculated for different degrees of inhibition (50% effective concentration [EC50], EC90, and EC99).

Author(s): 
Gupta, S.
Thapar, M. M.
Wernsdorfer, W. H.
Bjorkman, A.
Publication Title: 
Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America

In an open-label trial carried out on the northwest border of Thailand, 1596 patients with uncomplicated multidrug-resistant falciparum malaria were randomly assigned to receive atovaquone-proguanil, atovaquone-proguanil-artesunate, or artesunate-mefloquine and were followed up for 42 days. All 3 regimens were highly effective and well tolerated. Fever duration and parasite clearance times were significantly shorter among patients who received artesunate (P<.001).

Author(s): 
van Vugt, Michèle
Leonardi, Elisabetta
Phaipun, Lucy
Slight, Thra
Thway, Kyaw Lay
McGready, Rose
Brockman, Alan
Villegas, Leopoldo
Looareesuwan, Sornchai
White, Nicholas J.
Nosten, François
Publication Title: 
Antimicrobial Agents and Chemotherapy

A modified fixed-ratio isobologram method for studying the in vitro interactions between antiplasmodial drugs is described. This method was used to examine the interactions between atovaquone, proguanil, and dihydroartemisinin. The interaction between atovaquone and proguanil was synergistic against atovaquone-sensitive strains K1 and T996; however, there was a loss of synergy against atovaquone-resistant strain NGATV01 isolated after Malarone (the combination of atovaquone and proguanil) treatment failure.

Author(s): 
Fivelman, Quinton L.
Adagu, Ipemida S.
Warhurst, David C.
Publication Title: 
The Journal of Infectious Diseases

BACKGROUND: There is no safe, practical, and effective treatment for pregnant women infected with multidrug-resistant Plasmodium falciparum. METHODS: We recruited pregnant Karen women in the second or third trimesters of pregnancy who had uncomplicated falciparum malaria for a randomized, open-label trial with a restricted sequential trial design of 7 days of supervised quinine (SQ7) versus 3 days of artesunate-atovaquone-proguanil (AAP). RESULTS: Eight-one pregnant women entered the study between December 2001 and July 2003; 42 were treated with SQ7 and 39 were treated with AAP.

Author(s): 
McGready, Rose
Ashley, Elizabeth A.
Moo, Eh
Cho, Thein
Barends, Marion
Hutagalung, Robert
Looareesuwan, Sornchai
White, Nicholas J.
Nosten, François
Publication Title: 
The American Journal of Tropical Medicine and Hygiene

Combinations are set to become the mainstay in treatment and prophylaxis of malaria due to Plasmodium falciparum. Various antimalarials have been implicated in cardiotoxicity via prolongation of the QTc interval. Atovaquone-proguanil is an effective and increasingly popular antimalarial choice when used alone or with artesunate in areas of drug resistance. We report the results of an investigation carried out on the Thai-Burmese border in 42 patients randomized to receive either atovaquone-proguanil or atovaquone-proguanil-artesunate for three days.

Author(s): 
Gupta, Ravindra K.
van Vugt, Michèle
Paiphun, Lucy
Slight, Thra
Looareesuwan, Sornchai
White, Nicholas J.
Nosten, François
Publication Title: 
The FEBS journal

Despite intensive research extending back to the 1930s, when the first synthetic antimalarial drugs made their appearance, the repertoire of clinically licensed formulations remains very limited. Moreover, widespread and increasing resistance to these drugs contributes enormously to the difficulties in controlling malaria, posing considerable intellectual, technical and humanitarian challenges.

Author(s): 
Hyde, John E.
Publication Title: 
Malaria Journal

BACKGROUND: The emergence of Plasmodium falciparum resistant to most currently used antimalarial drugs is the major problem in malaria control along the Thai-Myanmar and Thai-Cambodia borders. Although artemisinin-based combination therapy has been recommended for the treatment of multidrug-resistant falciparum malaria, these combinations are not available for some people, such as travelers from North America.

Author(s): 
Khositnithikul, Rommanee
Tan-Ariya, Peerapan
Mungthin, Mathirut
Publication Title: 
Antimicrobial Agents and Chemotherapy

Pafuramidine is a novel orally active antimalarial. To identify a combination partner, we measured the in vitro antimalarial activities of the active metabolite, DB75, with amodiaquine, artemisinin, atovaquone, azithromycin, chloroquine, clindamycin, mefloquine, piperaquine, pyronaridine, tafenoquine, and tetracycline. None of the drugs tested demonstrated antagonistic or synergistic activity in combination with pafuramidine.

Author(s): 
Purfield, Anne E.
Tidwell, Richard R.
Meshnick, Steven R.

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