Antimicrobial peptides (AMPs) are short protein fragments that function as an innate immune response across diverse life forms. Structurally, AMPs exhibit diverse configurations, including α-helical, β-sheet, mixed, and random-coil forms, enabling a variety of mechanisms to combat pathogens. The mechanisms of action of AMPs encompass membrane disruption and inhibition of critical cellular processes, highlighting their broad-spectrum activity against bacteria, fungi, viruses, and parasites. AMP activity extends to anti-tumor and anti-HIV activities, further emphasizing their therapeutic potential. Purifying AMPs from natural sources can be challenging due to posttranslational processing. Fortunately, chemical synthesis has the advantage of producing high yield and pure AMPs, but the reaction efficiency diminishes as the molecular weight of peptides increases. Advances in computational tools and curated databases have further accelerated AMP discovery and engineering. While commercially available AMP-based antibiotics and in vivo efficacy against multidrug-resistant bacteria demonstrate their clinical relevance, several limitations still hinder the widespread use of AMPs such as low stability and toxicity to human cells. This review provides a comprehensive overview of AMP origins, characteristics, mechanisms, applications, and future prospects in combating infectious diseases with a particular focus on the clinical applicability of AMPs and their prospects as potent alternative to traditional antibiotics.

Biofilm-associated infections pose a significant challenge in clinical settings due to their increased resistance to antibiotics and evasion of host immune responses. These infections are responsible for a large proportion of chronic and recurrent infections, leading to prolonged hospital stays, increased healthcare costs, and elevated morbidity and mortality rates. Vancomycin, a glycopeptide antibiotic, has long been a cornerstone in the treatment of infections caused by Gram-positive bacteria, particularly methicillin-resistant Staphylococcus aureus (MRSA). In addition, vancomycin-resistant Enterococcus (VRE) represents an important group of biofilm-forming pathogens, further complicating treatment strategies. However, its efficacy against biofilms remains a subject of ongoing research and debate. The ability of vancomycin to target biofilm-embedded bacteria is often hindered by multiple resistance mechanisms, including poor antibiotic penetration, metabolic adaptation of biofilm-associated cells, and the presence of persister cells. The aim of this review is to evaluate vancomycin’s antibiofilm activity by examining its mechanism of action, pharmacokinetics, effectiveness, limitations, and potential strategies to enhance its therapeutic outcomes. Several novel approaches have been explored to augment vancomycin’s antibiofilm activity, including combination therapies, adjuvant strategies, and nanotechnology-based drug delivery systems. Understanding these factors is crucial for optimizing therapeutic strategies and overcoming the persistent challenge of biofilm-related infections. This review synthesizes current evidence and highlights areas requiring further research to enhance vancomycin’s efficacy against biofilm-associated infections.

Burkholderia pseudomallei, a gram-negative facultative intracellular bacterium, is the causative agent of melioidosis, a life-threatening infectious disease endemic to tropical and subtropical regions, particularly Southeast Asia and Northern Australia. Key risk factors such as diabetes, alcoholism, and socioeconomic challenges were identified as major contributors to disease susceptibility and treatment outcomes in melioidosis. Globally, melioidosis accounts for approximately 89,000 deaths annually and poses a significant public health concern, particularly in resource-limited settings. B. pseudomallei exhibits remarkable environmental resilience, thrives in soil and water, and is intrinsically resistant to various antibiotics. Its pathogenicity is mediated by diverse virulence factors, including type III and VI secretion systems, a protective capsule, lipopolysaccharide (LPS), and BimA-mediated actin-based motility, which facilitate intracellular survival, immune evasion, and systemic dissemination. This bacterium can cause a wide spectrum of clinical manifestations ranging from localized skin infections to severe septicemia, pneumonia, and neurological involvement. In certain cases, B. pseudomallei may persist in a latent state for years and reactivation is often triggered by immunosuppression. The treatment of melioidosis is challenging because of its intrinsic antibiotic resistance, necessitating a two-phase approach: an intensive phase with intravenous antibiotics, such as ceftazidime or meropenem, followed by a prolonged eradication phase using trimethoprim-sulfamethoxazole. However, relapse remains a concern, particularly in patients with poor adherence to the therapy. Preventive strategies, particularly in endemic regions, focus on minimizing environmental exposure through protective measures and safe water practices. Despite advancements in therapeutic approaches, there is an urgent need for novel treatment strategies, including bacteriophage therapy and vaccine development, to enhance melioidosis prevention and control. Understanding the complex pathogenic mechanisms of B. pseudomallei is essential to improve its clinical management and reduce its global burden.

Pandoraea species are emerging multidrug-resistant pathogens increasingly associated with respiratory tract infections, particularly in cystic fibrosis patients. Despite their growing clinical relevance, these bacteria are underrepresented in the scientific literature. This review aims to consolidate existing evidence regarding Pandoraea species as emerging multidrug-resistant pathogens, with a focus on their taxonomy, diagnostic methodologies, antimicrobial resistance mechanisms, and treatment challenges. By identifying gaps in current therapeutic strategies and the limited clinical outcome data, this review underscores the necessity of advancing research into innovative interventions, such as bacteriophages, antimicrobial peptides, and combination therapies, to enhance patient management and infection control. A comprehensive literature search was conducted using PubMed and Google Scholar, employing relevant keywords to identify case reports, clinical studies, and in vitro research related to Pandoraea infections, resistance mechanisms, and therapeutic strategies. Our findings reveal a significant lack of comprehensive data on therapeutic approaches, particularly concerning bacteriophages, antimicrobial peptides, and combination antibiotic therapies. Furthermore, clinical data on treatment efficacy remain sparse, with the majority of evidence stemming from in vitro studies rather than real-world clinical settings. This review emphasizes the urgent need for further research to address these knowledge deficits and to develop effective therapeutic interventions against Pandoraea infections.

Klebsiella pneumoniae is a major opportunistic pathogen responsible for a wide range of hospital- and community-acquired infections, including respiratory tract infections, urinary tract infections, meningitis, and liver abscesses. Among its emerging forms, hypervirulent K. pneumoniae (hvKp) has gained global attention due to its heightened virulence and ability to cause severe infections in healthy individuals. hvKp differs from classical K. pneumoniae (cKp) in its clinical presentation, often causing metastatic infections, liver abscesses without biliary disease, and multiple-site involvement. Despite initial antibiotic susceptibility, the recent convergence of hvKp virulence traits with antimicrobial resistance genes—especially those conferring multidrug resistance (MDR) and carbapenem resistance—poses a serious therapeutic challenge. This review highlights the epidemiological and clinical distinctions between hvKp and cKp, emphasizing the limitations of current diagnostic markers like the string test. Furthermore, it explores novel therapeutic strategies beyond conventional antibiotics, focusing on promising alternatives such as bacteriophage therapy and antimicrobial peptides (AMPs). Several phages, including PSKP16, vB_Kpn_F13, and phage cocktails, have demonstrated potent activity against hvKp strains, including biofilm-forming and carbapenem-resistant isolates. Likewise, AMPs such as Osmin, AA139-nanoformulations, and scorpion venom-derived Cm38 show efficacy in preclinical models. These emerging approaches hold potential to combat the rising threat of hvKp, especially strains that are extensively drug-resistant. Continued research and investment are essential to translate these findings into clinical practice and ensure effective management of hypervirulent and resistant K. pneumoniae infections.