Feature Reviews in Antibiotic Therapy for Infectious Diseases 2026

Dear Colleagues,

Antibiotic therapy is facing an unprecedented convergence of scientific, clinical, and structural challenges. Foremost among these are the rapid global expansion of antimicrobial resistance (AMR), the slow and fragile innovation pipeline for new antibacterial agents, and persistent gaps in diagnostic capacity and surveillance. Together, these factors threaten the effectiveness of antibiotics as a cornerstone of modern medicine.

High levels of resistance to key antibiotic classes—including third-generation cephalosporins, fluoroquinolones, and carbapenems—are now widely reported in many regions of the world. These resistance patterns increasingly affect common and clinically significant pathogens, such as Enterobacteriales, Pseudomonas sp., Salmonella spp., and Acinetobacter spp., complicating the management of both community-acquired and healthcare-associated infections. The spread of multidrug-resistant and extensively drug-resistant organisms has narrowed therapeutic options, increased reliance on last-line agents, and contributed to worse clinical outcomes.

Despite the growing burden of AMR, the global antibacterial development pipeline remains limited. Fewer than 60 traditional antibiotics are currently in clinical development, and only a small fraction fulfill accepted innovation criteria, such as representing new antibiotic classes or targeting novel bacterial pathways. Most agents are incremental derivatives of existing compounds (“me-too” drugs), providing modest improvements in pharmacokinetics or tolerability but limited advances against the most problematic resistant organisms. This stagnation reflects powerful economic and regulatory disincentives: antibiotic development is scientifically complex, costly, and high risk, while expected financial returns are constrained by short treatment durations, stewardship requirements, and the imperative to reserve new agents for limited use.

At the same time, deficiencies in diagnostic infrastructure continue to undermine optimal antibiotic use. In many healthcare settings worldwide, access to rapid, affordable microbiological diagnostics and antimicrobial susceptibility testing remains inadequate. As a result, clinicians are frequently compelled to initiate empiric broad-spectrum therapy, delay de-escalation, and extend treatment courses beyond what is clinically necessary. Weak laboratory capacity and incomplete surveillance systems further limit the availability and reliability of local and global AMR data, impairing evidence-based guideline development and situational awareness.

While novel antimicrobial agents and alternative therapeutic strategies—including long-acting antibiotics, β-lactam/β-lactamase inhibitor combinations, and nontraditional approaches—offer promise for selected patients, their optimal clinical positioning remains uncertain. Questions regarding resistance selection pressure, real-world effectiveness, safety in diverse populations, and cost-effectiveness continue to challenge their integration into routine practice.

In this context, the goal of this Special Issue is not only to review emerging therapies but also to reaffirm the foundational principles of optimal antibiotic prescribing. These include accurate diagnosis, appropriate empiric selection, timely reassessment, de-escalation based on microbiological data, and individualized treatment duration. This Specail Issue highlights the critical role of antimicrobial stewardship programs, multidisciplinary collaboration, and education in preserving antibiotic effectiveness.

Importantly, this collection of feature reviews recognizes a fundamental biological reality: bacteria possess an extraordinary evolutionary capacity, refined over billions of years, that consistently challenges human innovation. While advances in genomics, artificial intelligence, and data science may accelerate drug discovery and optimize clinical decision-making, they are unlikely to fully outpace bacterial adaptation and the emergence of new resistance mechanisms. Sustainable progress will therefore depend not only on innovation but also on responsible antibiotic use, strengthened diagnostics and surveillance, and coordinated global action.

By integrating scientific advances with clinical pragmatism and stewardship principles, this Special Issue aims to provide clinicians, researchers, and policymakers with a comprehensive and realistic framework for antibiotic therapy in infectious diseases as we move toward 2026 and beyond.

Dr. Karolina Akinosoglou
Dr. Mehran Monchi
Guest Editors

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• antibiotic resistance
• antibiotic therapy
• infectious diseases
• novel antimicrobial agents
• alternative therapeutic strategies
• antibiotic prescribing
• antimicrobial stewardship