Newer antibiotics for drug-resistant Gram-negative infections in immunocompromised hosts: from pivotal trials to high-risk practice
Abstract
Newer antibiotics have expanded treatment options for drug-resistant Gram-negative infections, but registration evidence is dominated by syndrome-based trials and post-approval evidence by heterogeneous observational cohorts. Translation to immunocompromised patients remains uncertain because profound neutropenia, transplantation, cell-targeted therapy, organ dysfunction, impaired source control, and limited immune-mediated clearance change both the probability and consequences of treatment failure. This critical narrative Review integrates 27 pivotal-trial protocol identifiers included in a predefined evidence map, immune-phenotype-specific cohorts, contemporary guidance, pharmacokinetic/pharmacodynamic evidence, and treatment-emergent resistance reports for a bounded core set of newer agents first authorized in the United States or European Union between 2014 and 2025, including newer β-lactam/β-lactamase-inhibitor combinations, cefiderocol, sulbactam-durlobactam, aztreonam-avibactam, and selected non-β-lactams. Fifteen of 27 pivotal protocols explicitly excluded at least one major immune phenotype or threshold; 11 had unresolved immune-host enrollment, and one enrolled immunocompromised patients but pooled distinct immune phenotypes. None reported comparative outcomes resolved to a defined immune phenotype. Phenotype-specific post-approval evidence was concentrated in hematological malignancy/profound neutropenia and solid-organ transplantation, whereas direct…
Read the paper
Related studies
- Penicillins for Treatment of Pneumococcal Pneumonia: Does In Vitro Resistance Really Matter?
- Thiophenes—Naturally Occurring Plant Metabolites: Biological Activities and In Silico Evaluation of Their Potential as Cathepsin D Inhibitors
- Inhalable Mannosylated Rifampicin–Curcumin Co-Loaded Nanomicelles with Enhanced In Vitro Antimicrobial Efficacy for an Optimized Pulmonary Tuberculosis Therapy
- Development and validation of microbial bioassay for quantification of Levofloxacin in pharmaceutical preparations
- GC-MS Analysis and Biomedical Therapy of Oil from n-Hexane Fraction of Scutellaria edelbergii Rech. f.: In Vitro, In Vivo, and In Silico Approach
- Propranolol, chlorpromazine and diclofenac restore susceptibility of extensively drug-resistant (XDR)-Acinetobacter baumannii to fluoroquinolones
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.