Foscarnet's double whammy: hypocalcemia and hypomagnesemia in lung transplant

SESSION TITLE: Chest Infections Case Report Posters 37 SESSION TYPE: Case Report Posters PRESENTED ON: 10/11/2023 12:00 pm - 12:45 pm INTRODUCTION: Foscarnet, also known as Foscavir, is a medication that inhibits various viral DNA polymerases by mimicking pyrophosphate. This drug is commonly prescribed to treat mucocutaneous herpes simplex virus and cytomegalovirus (CMV) infections in immunocompromised patients, including those with AIDS, who are resistant to acyclovir. In this report, we present a case of a patient with resistant CMV infection requiring foscarnet infusion, complicated by hypomagnesemia and hypocalcemia. CASE PRESENTATION: A 65-year-old female with a past medical history of bilateral orthotopic lung transplant (10/2019) maintained on everolimus, tacrolimus, and prednisone, complicated by rejection requiring anti-thymocyte globulin and subsequent CMV viremia and chronic kidney disease (CKD) related to chronic calcineurin inhibitor, was admitted for CMV gastritis. The patient's CMV infection was previously treated with intravenous ganciclovir and subsequently with foscarnet and leflunomide and maintained on oral maribavir with frequent monitoring of CMV viral load as an outpatient. The patient was found to have CMV gastritis on esophagogastroduodenoscopy with gastric biopsy notable for CMV DNA tissue viral load of 239,325 IU/mL, serum CMV viral load of 14,825 IU/mL on admission, which was up from 5,659 IU/mL two weeks prior. Subsequent resistance genotyping revealed UL97 and UL56 mutations which were linked to resistance to ganciclovir, letermovir, and maribavir. The patient was then started on a foscarnet infusion, which led to the development of paresthesia and muscle spasms. Laboratory workup was notable for hypocalcemia with an ionized calcium level of 0.77 mmol/L and a total calcium level of 6.4 mg/dL (down from a prior level of 1.27 mmol/L and 8.7 mg/dL, respectively) and hypomagnesemia with a level of 1.3 mg/dL (down from 2.2 mg/dL), requiring frequent administration of IV calcium gluconate, oral calcium supplementation with calcium acetate, along with magnesium replacement. Vitamin D-25 and 1-25 were within normal limits, but the patient's elevated parathyroid hormone (PTH) level of 790 was related to her CKD and appropriate stimulation of PTH from hypocalcemia. DISCUSSION: Foscarnet acts as a strong chelator of divalent cations due to its pyrophosphate analogue nature. When in solution, it can easily bind with calcium and magnesium to form complexes, and a direct correlation has been observed between low levels of ionized hypocalcemia and hypomagnesemia and increased circulating plasma concentrations of foscarnet. Although CNI (Calcineurin Inhibitor) is associated with hypomagnesemia, our patient has been on it for four years as part of her immunosuppressive regimen without any prior evidence of hypomagnesemia. The patient also has a history of CKD related to CNI use but maintained a normal calcium level before the foscarnet infusion. CONCLUSIONS: Our case study emphasizes the need to monitor magnesium and calcium levels in patients undergoing foscarnet infusion therapy. REFERENCE #1: Jacobson MA, Gambertoglio JG, Aweeka FT, Causey DM, Portale AA. Foscarnet-induced hypocalcemia and effects of foscarnet on calcium metabolism. J Clin Endocrinol Metab. 1991 May;72(5):1130-5. doi: 10.1210/jcem-72-5-1130. PMID: 1827127. REFERENCE #2: Huycke MM, Naguib MT, Stroemmel MM, Blick K, Monti K, Martin-Munley S, Kaufman C. A double-blind placebo-controlled crossover trial of intravenous magnesium sulfate for foscarnet-induced ionized hypocalcemia and hypomagnesemia in patients with AIDS and cytomegalovirus infection. Antimicrob Agents Chemother. 2000 Aug;44(8):2143-8. doi: 10.1128/AAC.44.8.2143-2148.2000. PMID: 10898688; PMCID: PMC90026. DISCLOSURES: No relevant relationships by Aravind Menon No relevant relationships by Waleed Mohammed No relevant relationships by Salem Vilayet