S5410 Acute Hepatitis During Dalbavancin Infusion: A Rare Adverse Reaction With Implications for Repeat Dosing

Introduction: Dalbavancin is an antibiotic approved for Gram-positive soft tissue infections, notably involving methicillin-resistant Staphylococcus aureus. It undergoes predominantly renal excretion with minimal hepatic metabolism. Clinically significant hepatotoxicity from dalbavancin is rare, occurring in fewer than 1% of treated patients. Rapid development of hepatitis soon after infusion has not been reported. Case Description/Methods: A 66-year-old man with a history of right rotator cuff repair developed right shoulder hardware-associated polymicrobial osteomyelitis. He underwent 2 debridements and a claviculectomy; cultures grew Escherichia coli, oxacillin-resistant coagulase-negative Staphylococcus, and oxacillin-sensitive Staphylococcus aureus. He began intravenous cefazolin and received the first of 2 planned dalbavancin infusions (1.5 g). Two days pre-infusion, labs were within normal limits (total bilirubin 1.5 mg/dL; aspartate aminotransferase (AST) 31 U/L; alanine aminotransferase (ALT) 21 U/L; alkaline phosphatase (ALP) 71 U/L). Three hours after the infusion, he experienced nausea and labs revealed AST 901 U/L, ALT 316 U/L, ALP 125 U/L, total bilirubin 1.2 mg/dL. He reported 3 days of fatigue that self-resolved. Two days later, AST declined to 140 U/L, ALT to 106 U/L, ALP to 88 U/L, and total bilirubin to 0.8 mg/dL. Hepatitis serologies and antinuclear antibody were negative. Liver tests normalized fully by 3 months. He subsequently completed therapy with cefazolin and linezolid and was placed on oral cefadroxil plus doxycycline suppression in view of retained hardware. Discussion: In pooled data from 2,120 adults across phase 1–3 studies, 17 patients (0.8%) developed post-baseline ALT elevations >3× upper limit of normal (ULN); within this group, 5 (0.2%) had ALT >10× ULN and 1 phase 1 subject exhibited ALT >20× ULN—each reversible on follow-up. These enzyme spikes were seen with both the single-dose (1.5 g) and 2-dose (1 g + 0.5 g one week apart) regimens, yet no study has specifically assessed outcomes when marked transaminase elevations arise after the initial 1.5 g infusion and a second 1.5 g dose is still administered. In this case likely mechanisms include immune-mediated hypersensitivity, similar to vancomycin-induced hepatotoxicity, although rate of cross-reactivity between dalbavancin and vancomycin appears to be very low to negligible. Given the growing adoption of the 2-dose dalbavancin (1.5 g) regimen—we recommend obtaining liver function tests prior to administration of any second dose on a routine basis, especially if symptoms occur during the first infusion.