A 43-year-old woman comes to the emergency department due to low-grade fevers and malaise. She has a history of lung transplantation due to cystic fibrosis and had 2 episodes of cytomegalovirus (CMV) viremia over the past few months, which were treated with ganciclovir. Temperature is 37.6 C (99.7 F). Physical examination is unrevealing. Chest x-ray and urinalysis are negative for infection. Polymerase chain reaction testing for CMV in blood shows elevated CMV levels consistent with CMV viremia. Given the recurrent episodes of viremia, genotype analysis is performed and demonstrates ganciclovir-resistant CMV. The patient is started on an alternate intravenous antiviral agent. She develops hypocalcemia and hypomagnesemia. Which of the following agents is the most likely cause of these side effects?

Question

A 43-year-old woman comes to the emergency department due to low-grade fevers and malaise.  She has a history of lung transplantation due to cystic fibrosis and had 2 episodes of cytomegalovirus (CMV) viremia over the past few months, which were treated with ganciclovir.  Temperature is 37.6 C (99.7 F).  Physical examination is unrevealing.  Chest x-ray and urinalysis are negative for infection.  Polymerase chain reaction testing for CMV in blood shows elevated CMV levels consistent with CMV viremia.  Given the recurrent episodes of viremia, genotype analysis is performed and demonstrates ganciclovir-resistant CMV.  The patient is started on an alternate intravenous antiviral agent.  She develops hypocalcemia and hypomagnesemia.  Which of the following agents is the most likely cause of these side effects?

Quizplus · Accepted Answer

Foscarnet is a pyrophosphate analog that is sometimes used for ganciclovir-resistant cytomegalovirus (CMV) infections. Foscarnet can chelate calcium. Moreover, foscarnet-induced renal wasting of magnesium may lead to hypomagnesemia and a reduction in the release of parathyroid hormone, which contributes to the hypocalcemic state. Both hypocalcemia and hypomagnesemia can promote seizures. (Choice A) Major toxicities of acyclovir (used in some herpes simplex virus infections) include crystal nephropathy and neurotoxicity that manifests as delirium and/or tremor. (Choice B) Cidofovir, used in some cases of CMV retinitis, is associated with nephrotoxicity manifesting as proteinuria or elevated creatinine. (Choice D) Lamivudine is a nucleoside reverse transcriptase inhibitor (NRTI). Side effects are unusual with lamivudine, unlike other NRTIs. Lamivudine is occasionally associated with peripheral neuropathy and lactic acidosis. (Choice E) Sofosbuvir inhibits nonstructural protein 5B (NS5B), an RNA-dependent RNA polymerase needed for hepatitis C virus replication. Adverse effects associated with its use include fatigue and nausea. (Choice F) Valganciclovir is a ganciclovir prodrug and is unlikely to be useful against ganciclovir-resistant CMV. Ganciclovir is associated with severe neutropenia, which can be exacerbated by other bone-marrow suppressing agents (eg, zidovudine, trimethoprim-sulfamethoxazole). Educational objective: Foscarnet is an analog of pyrophosphate that can chelate calcium and promote nephrotoxic renal magnesium wasting. These toxicities can result in hypocalcemia and hypomagnesemia, which can cause seizures.

A 43-Year-Old Woman Comes to the Emergency Department Due to Low-Grade