A boy is delivered via spontaneous vaginal delivery at 39 weeks gestation to a woman, gravida 1 para 0. The boy is vigorous with a strong cry, requiring no interventions after delivery except for warming and drying. APGAR scores are 8 and 9 at 1 and 5 minutes, respectively. Head circumference measures

Question

A boy is delivered via spontaneous vaginal delivery at 39 weeks gestation to a woman, gravida 1 para 0.  The boy is vigorous with a strong cry, requiring no interventions after delivery except for warming and drying.  APGAR scores are 8 and 9 at 1 and 5 minutes, respectively.  Head circumference measures <10th percentile, and the placenta has numerous calcifications.  Serology is consistent with congenital toxoplasmosis.  As part of treatment, he is prescribed a combination of pyrimethamine and sulfadiazine.  Which of the following best describes the reason for using multiple drugs during this patient's treatment?

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11ec160b_3c39_92d1_9249_a5379f6fc970_MD0001_00 Toxoplasma gondii is a ubiquitous protozoan that rarely causes illness in healthy individuals but can cause severe infection in immunocompromised patients or those with congenital infection. Symptomatic congenital disease is often marked by intracranial calcification, hydrocephalus, chorioretinitis, jaundice, and/or thrombocytopenia. Early treatment with sulfadiazine and pyrimethamine reduces neurologic and retinal sequalae. Sulfadiazine and pyrimethamine work synergistically to inhibit protozoal DNA synthesis by blocking 2 steps necessary for the formation of tetrahydrafolate (THF), a cofactor needed for synthesis of purine nucleic acids. Sulfadiazine inhibits dihydropteroate synthase, a microbial enzyme that generates dihydropteroate, which is converted to dihydrofolic acid. Pyrimethamine inhibits dihydrofolate reductase, an enzyme that converts dihydrofolic acid to THF. Sulfadiazine does not impair host DNA synthesis because dihydropteroate synthase is not found in human cells. In contrast, pyrimethamine partially impairs host DNA synthesis because dihydrofolate reductase generates THF in host cells. However, leucovorin (folinic acid), a derivative of THF that does not require conversion by dihydrofolate reductase, is usually administered with pyrimethamine to provide a bypass substrate for the generation of host purine nucleic acids. (Choice A) Patients are often treated with 2 different classes of antimicrobial medications to broaden the coverage of potential pathogens. Sulfadiazine and pyrimethamine both block the same metabolic pathway, so the combination is less useful for empiric antimicrobial therapy. (Choice B) Gentamicin is often administered with an agent that targets the bacterial cell wall (eg, ampicillin, vancomycin) to allow gentamicin to enter the intracellular space. Use of sulfadiazine with pyrimethamine does not alter intracellular penetration. (Choice C) Bacterial resistance can occur due to the production of an inactivating enzyme (eg, beta-lactamase). Administration of an agent that inhibits the enzyme (eg, clavulanic acid) can often restore the effect of the antibiotic (eg, amoxicillin). (Choice D) Probenecid blocks the renal tubular excretion of most beta-lactam antibiotics, which can increase their serum level. Sulfadiazine and pyrimethamine are not used together to alter renal excretion. Educational objective: Congenital toxoplasmosis is treated with sulfadiazine plus pyrimethamine. These medications work synergistically to inhibit formation of tetrahydrafolate, a necessary cofactor for purine nucleotide synthesis.

A Boy Is Delivered Via Spontaneous Vaginal Delivery at 39