Dose-escalation, phase I/II study of azithromycin and pyrimethamine for the treatment of toxoplasmic encephalitis in AIDS

Jacobson, Jeffrey M.; Hafner, Richard; Remington, Jack S.; Farthing, Charles; Holden‐Wiltse, Jeanne; Bosler, Edward M.; Harris, Carol; Jayaweera, Dushyantha; Roque, C.; Luft, Benjamin J.

doi:10.1097/00002030-200103300-00007

Cited by 62 publications

(27 citation statements)

References 21 publications

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“…Interestingly, there was no improvement of efficacy at doses higher than 900 mg of azithromycin per day. In fact, adverse effects were apparent when azithromycin was used at 1,500 mg per day (67). Pyrimethamine plus azithromycin at a lower azithromycin dose (500 mg/day) may also be effective during induction therapy, but the interpretation of the study is limited by a very small sample size (68).…”

Section: Immunocompromised Patientsmentioning

confidence: 99%

Treatment of Toxoplasmosis: Historical Perspective, Animal Models, and Current Clinical Practice

et al. 2018

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SUMMARYPrimary infection is usually subclinical, but cervical lymphadenopathy or ocular disease can be present in some patients. Active infection is characterized by tachyzoites, while tissue cysts characterize latent disease. Infection in the fetus and in immunocompromised patients can cause devastating disease. The combination of pyrimethamine and sulfadiazine (pyr-sulf), targeting the active stage of the infection, is the current gold standard for treating toxoplasmosis, but failure rates remain significant. Although other regimens are available, including pyrimethamine in combination with clindamycin, atovaquone, clarithromycin, or azithromycin or monotherapy with trimethoprim-sulfamethoxazole (TMP-SMX) or atovaquone, none have been found to be superior to pyr-sulf, and no regimen is active against the latent stage of the infection. Furthermore, the efficacy of these regimens against ocular disease remains uncertain. In multiple studies, systematic screening for infection during gestation, followed by treatment with spiramycin for acute maternal infections and with pyr-sulf for those with established fetal infection, has been shown to be effective at preventing vertical transmission and minimizing the severity of congenital toxoplasmosis (CT). Despite significant progress in treating human disease, there is a strong impetus to develop novel therapeutics for both the acute and latent forms of the infection. Here we present an overview of toxoplasmosis treatment in humans and in animal models. Additional research is needed to identify novel drugs by use of innovative high-throughput screening technologies and to improve experimental models to reflect human disease. Such advances will pave the way for lead candidates to be tested in thoroughly designed clinical trials in defined patient populations.

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Section: Immunocompromised Patientsmentioning

confidence: 99%

Treatment of Toxoplasmosis: Historical Perspective, Animal Models, and Current Clinical Practice

et al. 2018

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“…When not able to use any of the above regimens, a combination of pyrimethamine/atovaquone may be a useful alternative (26). Pyrimethamine/azithromycin is an inferior regimen (27). A minimum of 4–6 weeks of therapy is recommended.…”

Section: Literature Reviewmentioning

confidence: 99%

Donor‐transmitted toxoplasmosis in liver transplant recipients: a case report and literature review

Assi

Rosenblatt

Marshall

2007

Transplant Infectious Dis

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Transmission of toxoplasmosis via liver transplantation is extremely uncommon. Here we report the case of a 52-year-old male liver transplant recipient who on day 32 post transplant developed pneumonia followed by respiratory failure. Donor-transmitted toxoplasmosis was confirmed as the etiology by both serologic and molecular testing. We also review all previously published cases of toxoplasmosis in the English-language adult liver transplant literature.

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“…Pyrimethamine (as above) plus clarithromycin 1 g twice daily [III]. Pyrimethamine (as above) plus azithromycin 600–1800 mg/day [III] (Jacobsen et al. , 2001).…”

Section: Treatmentmentioning

confidence: 99%

Guidelines for the diagnosis and management of neurological complications of HIV infection

Portegies

Solod

Cinque

et al. 2004

Euro J of Neurology

103

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The spectrum of neurological complications of HIV‐infection has remained unchanged through the years, but its epidemiology changed remarkably as a result of the introduction of highly active antiretroviral therapy (HAART). Guidelines for the diagnosis and treatment of cerebral toxoplasmosis, cryptococcal meningitis, progressive multifocal leukoencephalopathy, CMV encephalitis, CMV polyradiculomyelitis, tuberculous meningitis, primary CNS lymphoma, HIV dementia, HIV myelopathy and HIV polyneuropathy are given with a grading of evidence and recommendations.

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Dose-escalation, phase I/II study of azithromycin and pyrimethamine for the treatment of toxoplasmic encephalitis in AIDS

Cited by 62 publications

References 21 publications

Treatment of Toxoplasmosis: Historical Perspective, Animal Models, and Current Clinical Practice

Treatment of Toxoplasmosis: Historical Perspective, Animal Models, and Current Clinical Practice

Donor‐transmitted toxoplasmosis in liver transplant recipients: a case report and literature review

Guidelines for the diagnosis and management of neurological complications of HIV infection

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