Christopher G. Bunick

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.

Biologics and Janus kinase (JAK) inhibitors have transformed the management of atopic dermatitis (AD), yet some patients experience early worsening of disease activity during treatment initiation. In clinical trials, these events are typically recorded as treatment‐emergent adverse events (TEAEs), most commonly coded as “atopic dermatitis”. We conducted a structured narrative review of phase 3 randomized trials evaluating approved systemic therapies for AD used in combination with background topical therapy. Trials of dupilumab, lebrikizumab, tralokinumab, nemolizumab, upadacitinib, and abrocitinib, including AD UP, JADE COMPARE, LIBERTY AD CHRONOS, ECZTRA 3, ARCADIA 1 and 2, and ADhere were included. Study design characteristics, background topical protocols, rescue therapy rules, dermatitis‐related TEAEs reported during the first 16 weeks of treatment were extracted from published data. Dermatitis TEAEs varied widely, ranging from 1% to 29% in treatment arms and 3% to over 41% in placebo groups. Substantial heterogeneity existed in baseline disease severity, topical therapy requirements, rescue allowances, and whether worsening was protocol‐defined or captured through investigator‐reported MedDRA coding. Because TEAEs labeled as atopic dermatitis may reflect natural disease variability, reporting conventions, or protocol factors rather than direct drug effects, cross‐trial comparisons should be interpreted cautiously. Clinicians are reminded to counsel patients that transient worsening may occur and emphasize the importance of adherence to adjunctive topical therapy. Standardized definitions of AD‐related adverse events are needed to improve interpretability across future trials.

Introduction Head and neck atopic dermatitis (AD) is difficult to treat. We evaluated the efficacy of upadacitinib versus placebo in patients with head and neck AD in a post hoc analysis of Measure Up 1 (NCT03569293) and Measure Up 2 (NCT03607422). Methods Patients with head and neck AD (overall and stratified by baseline head and neck Eczema Area and Severity Index [EASI]) received upadacitinib 15 mg, upadacitinib 30 mg, or placebo. Efficacy assessments included achievement of stringent targets (head and neck EASI ≤ 0.3 [almost clear], EASI 90 [near-complete clearance], EASI 100 [complete clearance], and patient-reported outcomes [PROs]) through week 16. Results At week 16, more patients achieved head and neck EASI ≤ 0.3, EASI 90, and EASI 100 with upadacitinib 15 mg (46.8%, 41.9%, 29.1%) and upadacitinib 30 mg (58.0%, 56.5%, 42.4%) versus placebo (13.5%, 11.5%, 9.0%), respectively. Similar patterns, including PRO outcomes, were observed across head and neck AD severity subgroups. Total EASI head and neck median percentage reduction from baseline at week 16 was 87.8% for upadacitinib 15 mg and 96.3% for upadacitinib 30 mg. Conclusions Upadacitinib substantially improved skin and PRO outcomes in patients with head and neck AD, including those with moderate or severe baseline involvement. Trial Registration ClinicalTrials.gov Measure Up 1 (NCT03569293) and Measure Up 2 (NCT03607422).

The tetracycline class of antibiotics is widely used for treating bacterial diseases including Lyme disease, anthrax, acne vulgaris, and pneumonia. Using a series of high-resolution cryo-electron microscopy (cryo-EM) structures, we show that tetracyclines can simultaneously target the mRNA decoding center in the 30S subunit and the nascent peptide exit tunnel (NPET) in the 50S subunit of the bacterial ribosome. Among the tested tetracyclines, Doxycycline was distinct in its ability to dimerize and bind the NPET at multiple locations. Structural comparison of Doxycycline, Minocycline, and Sarecycline bound to the Escherichia coli and Cutibacterium acnes 70S ribosome revealed species-specific differences affecting drug interaction and occupancy. Our results reveal a dual site mechanism of action for tetracyclines and provide a structural basis for rational design of narrow spectrum tetracyclines to overcome the rising threat of antibiotic resistance.

Biologic-associated conjunctivitis represents a clinically meaningful adverse effect in patients with atopic dermatitis (AD), with...

Biologic therapies have reshaped treatment of atopic dermatitis, yet most available agents target only one cytokine or receptor and many patients still do not reach minimal disease activity. Data from real-world practice shows that most individuals treated with current monospecific biologics fail to achieve Eczema Area and Severity Index 90 (EASI 90), clear or almost clear global assessments, or itch scores of 0 or 1. Janus kinase inhibitors reach higher clearance and itch targets because they concurrently block multiple cytokine pathways, exposing an efficacy gap and prompting development of multi-specific biologics. This review links atopic dermatitis endotypes and neuroimmune itch pathways to emerging multi-target designs and provides a focused overview of the growing pipeline of bispecific and trispecific antibodies, nanobody constructs, and antibody cocktails. Agents discussed include NM26-2198 (JNJ-5939), PX128, PX130, ZL-1503, BBT001, ATTO-002, PF-07264660, PF-07275315, GB12-09, APG279 (APG777+APG990), Galvokimig (UCB9741), Donzakimig (UCB1381), TRIV-509, TRIV-573, SAR443765 (Lunsekimig), CM512, ATI-052, and ZW1572. Early clinical data suggest the potential for faster improvement, reliable itch control, and longer dosing intervals. This review highlights the potential for shifting treatment options in atopic dermatitis.

Rademikibart (CBP-201) is a human monoclonal antibody with higher binding affinity to IL-4Rα compared to dupilumab. Dupilumab is a first-generation interleukin-4 receptor alpha (IL-4Rα) inhibitor for treating IL-4Rα-dependent inflammatory disorders, including several dermatologic and respiratory conditions. Rademikibart, however, demonstrated better inhibition of STAT6 intracellular signaling in vitro and similar potency in inhibiting both IL-4 induced TARC release and IL-4 induced B cell activation. To further characterize the molecular function of rademikibart and its differentiation from dupilumab, we determined the crystal structure of the rademikibart fragment antigen binding (Fab) bound to IL-4Rα at 2.71 Å resolution and compared this to the 2.82 Å resolution structure of dupilumab Fab bound to IL-4Rα. The rotation angle between dupilumab and rademikibart bound to IL-4Rα is 54.88°. This rotation enables the binding epitopes of rademikibart, but not dupilumab, on IL-4α to overlap more closely with the conserved binding interface naturally utilized by IL-4 and IL-13 cytokines. Molecular dynamics (MD) studies on rademikibart and dupilumab bound to IL-4Rα examined the stability of the complexes and effects of amino acid mutations on receptor complex formation. MD simulations demonstrated that the third interface loop (residues 145 to 153 in domain 2) of IL-4Rα interacts directly with rademikibart, which is absent in the dupilumab/IL-4Rα complex. This finding is confirmed by increased hydrogen bond interactions at the interface between rademikibart and IL-4Rα, demonstrating superior binding energy for rademikibart. Through analysis of the x-ray crystallography structures, MD-equilibrated structures, and computational point-mutation analysis of rademikibart, we identified residue Y50 and R55 of the light chain and R97, R99, and Y101 of the heavy chain of rademikibart as key residues interacting with IL-4Rα's third interface loop. Our data provides a molecular and structural rationale for the enhanced IL-4Rα inhibition by rademikibart over dupilumab, confirming rademikibart as an optimized second-generation IL-4Rα inhibitor.