Chiefs’ Inquiry Corner — 8/2/2021

August 2, 2021

Chief residents of the NYU Langone Internal Medicine Residency give quick-and-easy, evidence-based answers to interesting questions posed by house staff, both in their clinics and on the wards.

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 Methotrexate blocks nucleic acid synthesis by inhibiting folic acid activation via dihydrofolate reductase. Leucovorin, also known as folinic acid, is folic acid in its active (reduced) form, so it allows nucleic acid synthesis to proceed even in the presence of methotrexate. Although available in different formulations, intravenous is preferred in the setting of methotrexate toxicity and should be started promptly. Methotrexate becomes increasingly polyglutamated; the longer it stays in the cell, the polyglutamated methotrexate becomes less susceptible to reversal with leucovorin. Methotrexate and serum creatinine levels require at least daily monitoring; leucovorin should continue until the methotrexate level falls below 0.05 micromolar. Since the rate of methotrexate elimination is dependent on urine output, hydration and urinary alkalinization should also be optimized along with leucovorin therapy.

References: StatPearls Leucovorin  
  The live-attenuated zoster vaccine (Zostavax) was previously found to have >70% efficacy in preventing illness in patients 50-59 years old. However, in patients >60 years efficacy went down to about 50% and >70 years about 30%. There is evidence also supporting waning levels of immunity within 5-7 years. The newer recombinant subunit vaccine Shingrix was approved by the FDA in October 2017, and the Zostavax is no longer available in the United States as of November 2020. Patients who received Zostavax should still receive the new recombinant subunit Shingrix vaccine.  Vaccine efficacy of recombinant Shingrix was shown to be >95% in all age groups. The Singrix vaccine should be given at least 8 weeks after the Zostavax. As a reminder, patients >50 years or older are eligible.

References: Efficacy of an Adjuvanted Herpes Zoster Subunit Vaccine in Older Adults  
  Only 5-10% of people infected with Mycoplasma will develop pneumonia. Detection of Mycoplasma DNA does not confirm a current infection. DNA may be detectable after organisms are no longer viable and a patient’s symptoms have resolved or may represent co-infection. Serologic tests lack both sensitivity and specificity. Levels of serum IgM increase shortly after infection and will decline, but they may persist for several months. Levels of IgG may remain detectable at some level for the rest of a patient’s life. The gold standard for serologic diagnosis requires detection of a fourfold rise in IgG titers when comparing acute and convalescent serum samples. That being said, PCR from a nasopharyngeal swab, sputum, or bronchoalveolar lavage is the test of choice when available. Overall, don’t forget that community acquired pneumonia often requires empiric treatment without a known organism, but these tools can be additional aids. Another fun fact — Mycoplasma are among the smallest living organisms that can live independently in nature! Antibodies also cross-react with RBCs. Coombs + anemia can be commonly detected in these patients.

References: Stat Pearls Mycoplasma Pneumonia