LM, a 32-year-old male, presented to the ED with 4-day history of fever, chills, generalized weakness, and abdominal pain. Rapid diagnostics results 24 hours after admission within LM's blood cultures revealed Candida glabrata. The antimicrobial stewardship team decided to therefore add Mycamine to his empiric regimen antimicrobial regimen of piperacillin/tazobactam.

PMH: HIV

Labs from most recent visit:

CD4+ T-cell count 189 cells/mm³ (Normal 500-1600 cells/mm³)

HIV-1 RNA viral load 40,567 copies/mL (Goal < 200 copies/mL for virologic suppression)

Current medications:

Biktarvy 1 tablet PO QD

Septra 1 DS tablet PO QD

After a few days of treatment, LM’s blood cultures confirmed the initial rapid diagnostic PCR findings of Candida glabrata. His most recent blood cultures were negative and LM’s symptoms have resolved with good source control. The physician determined that LM is ready for discharge, however, he needs recommendation for an antifungal agent to finish out LM’s course. During his hospital stay, LM also expressed that he is currently having transportation issues due to a recent car wreck. The team is considering a possible transition to Rezzayo. 

Which of the following statement(s) is/are correct regarding Rezzayo? Select all that apply.

A. Rezzayo is dosed as 400 mg IV once on Day 1, then 200 mg IV once daily beginning on Day 2 for a total duration of 14 days

B. It is indicated in adult patients who have limited or no alternative options for the treatment of candidemia and invasive candidiasis

C. Rezzayo may increase the metabolism of Biktarvy resulting in poor clinical outcomes 

D. It may cause infusion-related reactions, such as flushing or sensation of warmth 

E. Once reconstituted with sterile water for injection, it may be given IV push over 5 minutes for ease of administration

Answer with Rationale

Candida species are yeasts that exist primarily as small, unicellular, thin-walled, ovoid cells that reproduce by budding. They normally live harmlessly on skin, genitals, & GI tract but can cause invasive disease under certain conditions, like immune suppression or antibacterial use. Most cases arise from our host flora, not external sources, and can cause both mucocutaneous infections (affecting skin, nails, mucous membranes) & systemic infections (like bloodstream infections, endocarditis, brain infections). Invasive fungal infections (IFIs), which include candidemia, are a major cause of morbidity and mortality in immunocompromised patients. Eight Candida species (C. albicans, C. tropicalis, C. parapsilosis, C. krusei, C. dublinensis, C. guilliermondii, C. lusitaniae, and C. glabrataI) have been flagged as clinically important pathogens in human disease. Risk factors for IFIs include exposure to broad-spectrum antibacterial therapies, recent major surgery (especially abdominal), immunosuppressive diseases/medications, necrotizing pancreatitis, dialysis, and total parenteral nutrition (TPN) therapy. Candidemia is the 4^th most common bloodstream infections in US hospitals. Prompt and appropriate treatment is crucial, as it comes with high economic burden and risk of mortality, as well as prolonged length of stay.

Answer A is incorrect. Unlike other echinocandins that require once-daily dosing, Rezzayo is dosed once weekly. The correct dosing regimen is 400 mg once on Day 1, then 200 mg once weekly beginning on Day 8 for up to 4 doses.

Answer B is correct. Rezzayo is a semi-synthetic echinocandin that works by inhibiting the 1,3-β-D-glucan synthase enzyme complex present in fungal cell walls. This results in inhibition of the formation of 1,3-β-D-glucan in many fungi, including Candida spp. There are a number of effective echinocandins that are FDA-approved for Candida spp. but Rezzayo may have a role in certain patients (like our case) due to special need for a once weekly option. 

Answer C is incorrect. Rezzayo is not a substrate of CYP enzymes or drug transporter systems. In addition, it is also not an inhibitor or inducer of common drug metabolizing by CYP enzymes or transporter systems. As of currently, no significant drug-drug interaction has been identified.

Answer D is correct. Rezzayo is typically infused over approximately one hour at a rate of ~250 mL/hr. Infusion-related reactions have been observed in clinical trials with Rezzayo. If these reactions occur, slow or pause the infusion and restart at a lower rate.

Answer E is incorrect. Each Rezzayo vial must be reconstituted with 9.5 mL of sterile water for injection (SWFI), not normal saline, to yield a concentration of 20 mg/mL. It is swirled gently to dissolve the white to pale yellow cake or powder. Shaking the vial should be avoided to minimize foaming. The solution should be clear to pale yellow after dissolution. The reconstituted solution is NOT for direct injection however and must be diluted before intravenous infusion over approximately one hour.

Generic/Brand: Micafungin (Mycamine), Bictegravir/Emtricitabine/Tenofovir Alafenamide (Biktarvy), Trimethoprim/Sulfamethoxazole (Septra), Rezafungin (Rezzayo)

NAPLEX Core Competencies Covered:

• 1.2 – From patients: treatment adherence, or medication-taking behavior; chief complaint, medication history, medical history, family history, social history, lifestyle habits, socioeconomic background
• 2.1 – Pharmacology, mechanism of action, or therapeutic class
• 2.2 – Commercial availability; prescription or non-prescription status; brand, generic, or biosimilar names; physical descriptions; or how supplied

• 4 – Drug dosing or dosing adjustments; duration of therapy

• 3.5 – Drug route of administration, dosage forms, or delivery systems
• 3.7 – Adverse drug effects, toxicology, or overdose
• 3.8 – Drug interactions
• 5.5 – Instructions or techniques for drug administration