Twice-weekly Pyrimethamine–sulfadoxine Effectively Prevents Pneumocystis carinii Pneumonia Relapse and Toxoplasmic Encephalitis in Patients with AIDS

Schürmann, Dirk; Bergmann, Frank; Albrecht, Helmut; Padberg, J.; Grünewald, Thomas; Behnsch, M.; Grobusch, Martin P.; Vallée, Marc; Wünsche, Thomas; Ruf, B.; Suttorp, Norbert

doi:10.1053/jinf.2000.0772

Cited by 33 publications

(20 citation statements)

References 42 publications

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“…However, cotrimoxazole has been reported to be ineffective at preventing Toxoplasma reactivation in a liver transplant recipient receiving antilymphocytic immunoglobulins for the treatment of acute graft rejection (4), suggesting that other prophylactic regimens could be used for severely immunocompromised patients. An alternative using pyrimethamine-sulfadoxine was proposed as a twice-weekly regimen for the prevention of P. jirovecii pneumonia and toxoplasmic encephalitis in HIV-infected patients (30) or as a onceweekly regimen for bone marrow transplant recipients (12). It is widely agreed that early diagnosis improves the prognosis of patients with disseminated toxoplasmosis, but diagnostic strategies differ from one country to another.…”

Section: Discussionmentioning

confidence: 99%

Correlation of Parasite Load Determined by Quantitative PCR to Clinical Outcome in a Heart Transplant Patient with Disseminated Toxoplasmosis

et al. 2010

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Disseminated toxoplasmosis is a life-threatening infection in transplant recipients, which results either from reactivation of latent infection or from organ-transmitted primary infection. Preventive measures and diagnostic screening methods differ between countries and are related to the seroprevalence of Toxoplasma spp. in the general population. Here we report a case of disseminated toxoplasmosis in a heart transplant recipient with previous immunity that occurred after cotrimoxazole prophylaxis for the prevention of Pneumocystis jirovecii pneumonia was stopped. Quantitative PCR proved useful for the diagnosis and monitoring of Toxoplasma infection. Decreasing parasitic burdens in sequential samples of cerebrospinal fluid, blood, and bronchoalveolar lavage fluid correlated with a favorable outcome and allowed modulation of the immunosuppressive drug regimen. The duration of anti-Toxoplasma treatment and the need for maintenance prophylaxis are discussed, as well as prophylaxis for solid-organ transplant recipients. Although a rare event in heart transplant recipients, Toxoplasma reactivation must be investigated promptly, since early treatment improves the prognosis.

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Section: Discussionmentioning

confidence: 99%

Correlation of Parasite Load Determined by Quantitative PCR to Clinical Outcome in a Heart Transplant Patient with Disseminated Toxoplasmosis

et al. 2010

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“…The insoluble material was filtered and the filtrate was washed with brine. The organic layer was dried over MgSO 4 and then concentrated. The crude product was dissolved in THF (76.0 mL) and was cooled to 0ºC.…”

Section: Nn-di-tert-butyl[(2-fluoro-4-nitro)benzylamino]dicarboxylatmentioning

confidence: 99%

“…The reaction mixture was stirred at 0ºC for 1 h followed by stirring at room temperature for 7 h. The reaction mixture was diluted with water and extracted with EtOAc. The organic layer was washed with brine and then dried over MgSO 4 . After concentration, the residue was purified by silica gel column chromatography (n-Hexane:EtOAc = 95:5) to give 6 (4.02 g, 55% for 2 steps): 1 7 mmol) and was stirred for 1 h at room temperature.…”

Section: Nn-di-tert-butyl[(2-fluoro-4-nitro)benzylamino]dicarboxylatmentioning

confidence: 99%

“…Toxoplasmosis is known to be one of the most prevalent parasitic infections of the central nervous system and causes severe congenital defects in unborn children of infected mothers as well as lethal encephalitis in immunocompromised patients such as acquired immunodeficiency syndrome (AIDS) [1][2][3]. Pyrimethamine is currently used in combination with sulfa drugs such as sulfadiazine in toxoplasmic infections [4,5]. This combination therapy targets enzymes of folate metabolism such as dihydrofolate reductase [6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

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Synthesis, biological evaluation and molecular modeling studies of N6-benzyladenosine analogues as potential anti-toxoplasma agents

Kim

Sharon

Chu

et al. 2007

Biochemical Pharmacology

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Toxoplasma gondii is an opportunistic pathogen responsible for toxoplasmosis. T. gondii is a purine auxotroph incapable of de novo purine biosynthesis and depends on salvage pathways for its purine requirements. Adenosine kinase (EC.2.7.1.20) is the major enzyme in the salvage of purines in these parasites. 6-Benzylthioinosine and analogues were established as "subversive substrates" for the T. gondii, but not for the human adenosine kinase. Therefore, these compounds act as selective antitoxoplasma agents. In the present study, a series of N 6 -benzyladenosine analogues were synthesized from 6-chloropurine riboside with substituted benzylamines & − solution phase parallel synthesis. These N 6 -benzyladenosine analogues were evaluated for their binding affinity to purified T. gondii adenosine kinase. Furthermore, the anti-toxoplasma efficacy and host toxicity of these compounds were tested in cell culture. Certain substituents on the aromatic ring improved binding affinity to T. gondii adenosine kinase when compared to the unsubstituted N 6 -benzyladenosine. Similarly, varying the type and position of the substituents on the aromatic ring led to different degrees of potency and selectivity as anti-toxoplasma agents. Among the synthesized analogues, N 6 -(2,4-dimethoxybenzyl) adenosine exhibited the most favorable anti-toxoplasma activity without host toxicity. The binding mode of the synthesized N 6 -benzyladenosine analogues were characterized to illustrate the role of additional hydrophobic effect and van der Waals interaction within an active site of T. gondii adenosine kinase by induced fit molecular modeling.

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“…The success of weekly administration of sulfadoxine-pyrimethamine in HIV-positive patients has been variable (37,151,163). Sulfadoxine-pyrimethamine has been effective and well tolerated in liver and cardiac transplant recipients (165).…”

Section: Other Agentsmentioning

confidence: 99%

Prevention of Infection Due toPneumocystisspp. in Human Immunodeficiency Virus-Negative Immunocompromised Patients

2004

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Pneumocystis infection in humans was originally described in 1942. The organism was initially thought to be a protozoan, but more recent data suggest that it is more closely related to the fungi. Patients with cellular immune deficiencies are at risk for the development of symptomatic Pneumocystis infection. Populations at risk also include patients with hematologic and nonhematologic malignancies, hematopoietic stem cell transplant recipients, solid-organ recipients, and patients receiving immunosuppressive therapies for connective tissue disorders and vasculitides. Trimethoprim-sulfamethoxazole is the agent of choice for prophylaxis against Pneumocystis unless a clear contraindication is identified. Other options include pentamidine, dapsone, dapsone-pyrimethamine, and atovaquone. The risk for PCP varies based on individual immune defects, regional differences, and immunosuppressive regimens. Prophylactic strategies must be linked to an ongoing assessment of the patient's risk for disease

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Twice-weekly Pyrimethamine–sulfadoxine Effectively Prevents Pneumocystis carinii Pneumonia Relapse and Toxoplasmic Encephalitis in Patients with AIDS

Cited by 33 publications

References 42 publications

Correlation of Parasite Load Determined by Quantitative PCR to Clinical Outcome in a Heart Transplant Patient with Disseminated Toxoplasmosis

Correlation of Parasite Load Determined by Quantitative PCR to Clinical Outcome in a Heart Transplant Patient with Disseminated Toxoplasmosis

Synthesis, biological evaluation and molecular modeling studies of N6-benzyladenosine analogues as potential anti-toxoplasma agents

Prevention of Infection Due toPneumocystisspp. in Human Immunodeficiency Virus-Negative Immunocompromised Patients

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