Ertapenem in Hidradenitis Suppurativa: A Review of Antimicrobial Effects and a Proposed Immunomodulatory Role

Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disorder characterized by recurrent nodules, abscesses, and sinus tract formation, driven by dysregulated innate immunity and microbial dysbiosis. Intravenous ertapenem has emerged as a therapeutic option for severe, refractory HS, with clinical studies consistently demonstrating meaningful improvements in pain, drainage, inflammatory markers, and quality of life. While these benefits have traditionally been attributed to ertapenem’s broad-spectrum antimicrobial activity against the polymicrobial anaerobic flora of HS lesions, the rapid onset of clinical improvement and inconsistent anaerobic suppression observed during treatment suggest that additional mechanisms may be at play. Emerging mechanistic evidence from studies of carbapenems in non-HS experimental systems suggests that this drug class may influence host inflammatory pathways through effects on cytokine signaling, endotoxin release, neutrophil and macrophage activation, and NF-κB inhibition. Additionally, ertapenem’s unusually high plasma protein binding, particularly to acute-phase reactants elevated in HS such as haptoglobin and fibrinogen, may further influence drug distribution and immune signaling within inflamed tissues. This review examines the antimicrobial and emerging immunomodulatory properties of ertapenem and explores how these convergent mechanisms may explain its clinical efficacy in severe HS, while highlighting stewardship considerations and directions for future research. Methods: A structured search of PubMed/MEDLINE was conducted from database inception through 1 May 2026 using terms related to hidradenitis suppurativa, ertapenem, carbapenems, antimicrobial activity, immunomodulation, inflammatory signaling, innate immune cells, and pharmacokinetics. During revision, a targeted literature update through 1 September 2026 was performed to incorporate newly published and reviewer-requested studies. Eligible clinical, microbiologic, pharmacologic, and mechanistic studies were screened by title, abstract, and full text and synthesized narratively.