SUMMARYChronic diseases, defined as conditions that persist for 1 or more years and require ongoing medical attention or impede daily life, represent an urgent public health challenge in the United States. In the last decade, fungal infections have garnered increased attention from public health officials and the media owing to the rapid and global rise of severe and antifungal-resistant infections. It is well-established that certain chronic diseases can increase the risk of invasive fungal infections. However, the inverse relationship-how fungal infections contribute to the development or exacerbation of chronic diseases-is less well studied. In this review, we summarize the current literature on the role of fungal infections in the development of chronic diseases, discussing pathophysiologic mechanisms and examining how chronic conditions can arise from the direct effects and sequelae of fungal infections. In addition, we discuss how the toxic effects of antifungal therapies can also contribute to the development of chronic disease states. Overall, our review highlights the significant yet underexplored role of fungal infections in the burden of chronic disease and emphasizes the need for further research, improved surveillance, increased public and healthcare awareness, and better access to diagnostics and treatments to address this issue.

SUMMARYMultidrug-resistant (MDR) bacterial infections continue to outpace therapeutic innovation, undermining the efficacy of conventional antibiotics and exposing the limitations of the current drug pipeline. In this review, we critically examine the translational viability of peptide-based antimicrobials and siderophore conjugates-two classes of therapeutics often promoted as next-generation solutions against MDR pathogens. Rather than reiterating their mechanistic promise, we dissect the structural assumptions that underpin their design and expose the clinical blind spots that have hindered their success. While peptides offer membrane disruption, intracellular targeting, and, in some cases, selective bacterial killing, their efficacy remains context-dependent and is frequently compromised by host-driven proteolysis, poor bioavailability, and limited tissue penetration. Similarly, siderophore-based conjugates exploit iron uptake systems for targeted delivery, yet depend on bacterial receptors that are variably expressed, easily suppressed, or genetically lost during infection. The failure of cefiderocol in specific clinical settings exemplifies the vulnerability of "Trojan horse" approaches to metabolic plasticity and ecological interference. This review highlights the need for a paradigm shift-from broad biochemical optimism to receptor-aware, pathogen-stratified, and pharmacologically grounded strategies. Reframing these modalities within their biological and clinical constraints offers a more realistic foundation for the development of actionable peptide- and siderophore-based therapies against resistant bacterial infections.

SUMMARYAntimicrobial resistance (AMR) is a public health threat that requires a coordinated and multi-sectoral approach. AMR is largely underexplored in Central Asia, a region shaped by the Soviet legacy. This narrative review aimed to synthesize evidence on the AMR landscape from articles published in five countries: Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, and Uzbekistan. A structured search of peer-reviewed and gray literature was conducted, covering AMR prevalence, consumption patterns, knowledge, awareness, practices, stewardship interventions, and AMR governance. Key findings revealed that all five countries in the region have retained the rigidly centralized public health system, which was formerly known as the Sanitary Epidemiological Service during the Soviet era. This has led to fragmented surveillance and poor AMR monitoring. Up to 70% of Enterobacterales spp. were resistant to third-generation cephalosporins, and up to 58% of Staphylococcus species exhibited macrolide resistance. Consumption of Watch group antibiotics ranged from 53% to 68%, with a broad preference for injectables. Self-medication was found to be common, with rates ranging between 26% and 40% among the general public. High levels of patient demand coincided with medical errors, affecting up to 80% of antibiotic prescriptions. Only a limited number of antimicrobial stewardship studies were found, highlighting the insufficient integration of stewardship practices into routine healthcare delivery. Central Asian countries continue to face significant challenges because of the persistence of poor surveillance, high antibiotic consumption, and inadequate implementation of AMS because of long-standing legacies and systemic weaknesses. Addressing these gaps demands structural reforms, integrated surveillance systems, targeted education, and robust stewardship programs as urgent priorities.

SUMMARYInvasive fungal diseases cause severe illness and death in immunocompromised patients. Antifungal use is increasingly common, as is fungal diagnostic testing. However, these efforts have not been guided by traditional stewardship efforts akin to those used for bacterial infections. Fungal diagnostic stewardship can have a significant impact on the care of vulnerable patients, including decreasing unnecessary testing while increasing appropriate testing and improving testing strategies to reduce diagnostic errors. In this review, we discuss the most frequently used fungal diagnostic assays for molds and dimorphic fungal infections, their diagnostic performance for these organisms in immunocompromised hosts, and strategies to improve diagnostic stewardship and ultimately patient outcomes.

SUMMARYIatrogenic central nervous system mold infections (ICNSMIs) are rare and occur as sporadic complications of neurosurgical procedures or device insertions. However, recent outbreaks have been reported in outpatient settings, following epidural injections with contaminated medicines. We conducted a comprehensive literature review of studies published without date restrictions through July 2025 on ICNSMIs. We identified 905 cases of such infections, with 4% occurring in non-outbreak settings and 96% associated with five documented outbreaks. In both non-outbreak and outbreak settings, infections were more common after spinal/epidural injections, with contaminated medicines or supplies being the primary source. Due to their angioinvasive tendencies, ICNSMI caused by Fusarium solani and Aspergillus species had a higher frequency of stroke/intracranial hemorrhage (P = 0.011), aneurysm formation (P = 0.012), and resulted in higher mortality compared with ICNSMI caused by other molds (P < 0.001). ICNSMI, as a result of catheter-associated fungemia, was very rare (only one case). Strategies to identify ICNSMI in exposed individuals during an outbreak have included (i) symptom-driven lumbar puncture, (ii) screening lumbar puncture regardless of symptoms, and (iii) screening brain MRI regardless of symptoms. Measurement of (1→3)-β-D-glucan in cerebrospinal fluid was a valuable tool to diagnose ICNSMI preemptively. Outcomes of ICNSMI following neurosurgical procedures were poor (90-day mortality of 35%) and depended on the route of inoculation, mold species, timing of diagnosis, and prompt initiation of appropriate antifungal therapy in combination with source control. Patients with ICNSMI often suffered long-term neurologic sequelae, even with the most optimal management strategies.

SUMMARYParatransgenesis employs insect-associated bacteria to deliver antipathogen effectors and is an emergent complementary strategy for vector control. This review synthesizes current evidence for Serratia species as paratransgenic vehicles, combining mechanistic insights into effector molecules (e.g., scorpine, MP2, multi-fusion constructs, and the naturally secreted antimalarial lipase AmLip), with comparative evidence on colonization, transmission, and efficacy. Serratia strains (e.g., AS1, Su_YN1) demonstrate rapid dissemination in laboratory populations and potent reductions in Plasmodium development (reported oocyst inhibition in laboratory studies ranging from ~60% to >90% for specific effectors). We critically examine biosafety, genetic stability, and ecological factors and propose a minimum evidence package and translational roadmap comprising multigeneration stability assays, horizontal gene transfer monitoring, non-target impact assessments, and community and regulatory engagement to responsibly advance Serratia-based paratransgenesis toward field evaluation. This comparative framing integrates Serratia-focused detail with the broader paratransgenesis literature to clarify both its promise and remaining knowledge gaps.

SUMMARYHemodialysis catheter-related bloodstream infections (CRBSIs), primarily driven by microbial colonization and biofilm formation, represent a major cause of morbidity and mortality in patients with end-stage renal disease. Key pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa employ sophisticated virulence mechanisms, including microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) and quorum-sensing (QS) systems, to establish resilient biofilms. Surface modification technologies-encompassing antibacterial coatings, antithrombotic modifications, antibiofilm technologies, surface topological optimization, and tip design innovations-offer promising "anti-colonization" strategies to prevent infections. Notably, while tunneled and non-tunneled catheters exhibit distinct biofilm dynamics and clinical risk profiles, emerging multifunctional coatings demonstrate the potential for enhancing long-term catheter safety and performance. However, the clinical translation of these innovations requires overcoming challenges related to biocompatibility, long-term durability, and scalable manufacturing, necessitating interdisciplinary collaboration.

SUMMARYInquilinus limosus is a nonfermentative Gram-negative rod that has been reported as an emergent pathogen, particularly in chronic respiratory diseases. I. limosus was first isolated from the airways of a lung transplant patient suffering from cystic fibrosis (CF). As I. limosus is almost exclusively recovered from the airways of CF patients, its identification may be challenging for non-CF specialists. Indeed, I. limosus is mainly isolated from the airways of CF patients, and its pathogenesis and treatments are still debated. We have extensively reported and reviewed the different clinical cases described in the literature, the identification methods used, and the antimicrobial susceptibility testing performed. Therefore, we provide here an exhaustive description of the phenotypic features and antimicrobial susceptibilities of I. limosus. Only seven I. limosus genomes are currently available in public databases. These genomes are not fully assembled and therefore allow only partial genomic analyses, which could not unveil antimicrobial resistance determinants or virulence factors. They are approximately 7 Mb in size and encode between 6,036 and 7,483 genes. Given that the available genomes are incomplete, our genomic analyses are still limited and would undoubtedly benefit from further fully sequenced and annotated genomes to provide additional information on the antibiotic resistance and pathogenesis of I. limosus. We anticipate that our review will be a starting point for more genome sequencing studies, as well as epidemiological studies, to provide additional information on I. limosus for better management of patients.

SUMMARYThe global resurgence of drug-resistant tuberculosis (DR-TB) presents a formidable challenge to public health, driven by a complex interplay of mycobacterial evolution, dynamics and outcomes of host-pathogen interactions and systemic gaps in diagnosis and treatment strategies. This comprehensive review delineates the multifactorial basis of antimicrobial resistance (AMR) in Mycobacterium tuberculosis (Mtb), integrating molecular, immunological, and pharmacological perspectives to inform next-generation strategies for effective TB control. We reconceptualize TB as a dynamic clinical spectrum-ranging from asymptomatic infection to overt disease-shaped by granuloma biology and bacterial adaptation. This spectrum underpins both diagnostic ambiguity and therapeutic failure, particularly in the context of phenotypic drug tolerance/resistance to current anti-TB drugs. We discuss Mtb's intrinsic and extrinsic resistance mechanisms, including the lipid-rich cell envelope, efflux systems, and enzymatic drug modification, which are compounded by acquired mutations that disrupt drug activation, alter targets, and confer cross-resistance. These adaptations are further potentiated by granuloma-induced pharmacokinetic heterogeneity and host-induced metabolic quiescence. We highlight the emerging role of therapeutic drug monitoring and pharmacokinetic/pharmacodynamic modeling in optimizing individualized therapy, particularly for novel regimens incorporating bedaquiline, pretomanid, and linezolid. Moreover, we underscore the diagnostic limitations in detecting heteroresistance and early-stage disease, advocating for expanded deployment of advanced and targeted molecular diagnostic modalities. Finally, we propose a paradigm shift toward integrated, precision-based TB management, leveraging host-directed therapies, biofilm-disrupting agents, and real-time pharmacokinetics-guided dosing to preempt resistance emergence and improve clinical outcomes. This review provides a translational framework for addressing the biological and operational complexities of DR-TB in the era of AMR.

SUMMARYTuberculosis (TB) remains a major infectious disease threatening global health. An estimated 2 billion people worldwide are infected with Mycobacterium tuberculosis (Mtb), and 5-10% of those with latent infection will develop active TB. Despite the success of existing anti-TB drugs in controlling transmission, significant challenges remain, including long treatment durations, severe side effects, suboptimal treatment adherence, and inevitable drug resistance. Even newly developed drugs may fail to keep pace with the rising number of drug-resistant cases. Moreover, these treatments do not adequately address persistent lung dysfunction after cure. A primary reason for these therapeutic challenges in TB management may be that all current anti-TB drugs are solely aimed at achieving antibacterial, bacteriostatic, or bactericidal efficacy, which neglects the critical role of host cellular responses during disease progression. Future strategies should explore the potential of cell-based therapies, an area that has received limited attention in previous reviews. From the perspective of cell therapy, this article comprehensively reviews key clinical studies, animal models, and in vitro experiments from recent decades that utilized cells or cytokines for TB treatment, providing clinicians and researchers with a unique perspective and support for developing more integrated therapeutic strategies toward ending TB.