Ali Saffaei

Infectious disease pharmacology continues to evolve at the intersection of therapeutic innovation, antimicrobial resistance, clinical optimization, and global health implementation. In this changing landscape, the field is increasingly required to connect mechanistic insight with clinically actionable, scalable, and globally relevant therapeutic strategies. The years following the acute phase of the COVID-19 pandemic have reinforced that pharmacological progress cannot be defined only by the discovery of new antimicrobial agents (Porta et al., 2024a). It also depends on understanding resistance at molecular and population levels, optimizing the use of existing therapies, developing regulatory and translational pathways for novel modalities, and ensuring that advances are relevant to neglected and difficult-to-treat infections.The evolution in pharmacology of infectious diseases: 2025The present Research Topic builds on the 2022 edition of "The evolution in pharmacology of infectious diseases", which captured a period shaped strongly by COVID-19, real-world therapeutic evidence, and antimicrobial optimization (Porta et al., 2024b). The 2025 collection extends that trajectory. Rather than centering on a single pandemic pathogen, it reflects a broader and more mature landscape in which infectious disease pharmacology is increasingly guided by resistance biology, pharmacokinetic/pharmacodynamic reasoning, therapeutic drug monitoring, host-directed approaches, chemoproteomic target discovery, and regulatory preparedness. Bringing together 10 articles from 76 researchers and attracting more than 100,000 total views and downloads at the time of writing (June 2026), this edition reflects sustained interest in infectious disease pharmacology as a multidisciplinary and globally relevant field.A major theme emerging from this collection is the need to understand antimicrobial resistance as a dynamic biological and translational challenge. Belay et al. (2024) reviewed major antibacterial resistance mechanisms, including target modification, reduced drug accumulation, enzymatic inactivation, biofilm formation, and horizontal gene transfer, while also emphasizing stewardship and next-generation antimicrobial strategies. This broad framework is complemented by Zhang et al. (2026), who examined drug-resistant Mycobacterium tuberculosis as a multifactorial problem involving genetic resistance, cell wall remodeling, metabolic adaptation, epigenetic regulation, and immune evasion. By connecting resistance mechanisms with the limitations of Bacillus Calmette-Guérin (BCG) and the promise of next-generation vaccine platforms, their contribution highlights the importance of integrating antimicrobial therapy with immunological prevention.The collection also advances conceptual thinking on resistance. Baquero et al. (2026) introduced antechokinetics as a framework for considering the intracellular kinetics of antimicrobial resistance molecules. By shifting attention from the movement of drugs alone to the movement, bioavailability, metabolism, and excretion of resistance biomolecules inside bacterial cells, this article opens a stimulating pharmacological perspective on how antibiotic action and resistance reactions may be studied together. At the translational and regulatory level, Fukaya-Shiba et al. (2025) addressed the development of phage therapy medicinal products for antimicrobial-resistant bacterial infections.Their analysis of quality control, manufacturing, non-clinical evaluation, clinical trial design, and Japan-specific regulatory considerations illustrates that innovation against resistance requires not only biological plausibility but also robust pathways toward standardized, safe, and timely patient access.A second theme is the optimization of existing anti-infective therapies through clinical pharmacology. Liu et al. (2025) integrated global Cryptococcus minimum inhibitory concentration distributions with pharmacokinetic/pharmacodynamic parameters for key antifungals, providing clinically relevant insights into induction, consolidation, and maintenance strategies for cryptococcal meningitis and meningoencephalitis. Tan et al. (2026) further emphasized the value of individualized antifungal management through a real-world, age-stratified analysis of isavuconazole therapeutic drug monitoring. Their findings suggest that pediatric patients, and selected elderly patients with factors such as intensive care admission or renal replacement therapy, may particularly benefit from exposure-guided dosing. Together, these studies underscore that antifungal pharmacology is moving toward a more nuanced model in which susceptibility data, tissue penetration, patient characteristics, and measured drug exposure are integrated into therapeutic decisions. This patient-centered approach is also evident in the review by Spanakis et al. (2025) on drug-drug interactions between antiretroviral therapy and cardiovascular drugs. As people living with HIV experience longer life expectancy and a growing burden of cardiovascular comorbidity, therapeutic success increasingly depends on managing complex polypharmacy. Their analysis highlights how pharmacological tools, interaction databases, and clinical judgment must converge to prevent adverse outcomes while preserving antiviral efficacy and cardiovascular protection.The third theme concerns therapeutic innovation for viral, neurological, and neglected tropical diseases. Bobat et al. (2025) reviewed the broad-spectrum therapeutic potential of 4-phenylbutyrate, a chemical chaperone that modulates endoplasmic reticulum stress and has been explored in ocular herpes simplex virus type 1 infection, HSV-1-associated neurological disease, and several systemic disorders. This contribution illustrates the continued relevance of drug repurposing and host-directed pharmacology, particularly where modulation of cellular stress pathways may provide benefit across infectious...

Background and Aims: Cutaneous leishmaniasis (CL) represents the most common form of leishmaniasis. It imposes a significant medical burden due to long‐lasting ulcers and disfiguring scars, underscoring the need for comprehensive CL control strategies, particularly in endemic regions. This study aims to classify atypical CL presentations for clinical practitioners. Additionally, we compiled and categorized original images from our clinical encounters with CL to create a clinical atlas enhancing the existing literature. Methods: A systematic search for atypical manifestations of Old World CL was conducted in June 2023 via the PubMed database, utilizing MeSH‐based keywords including leishmaniasis, atypical, manifestation, and characteristics. All of the records were included. Exclusion criteria included records published before the 20th century, non‐English articles, review articles, nonclinical studies (experimental and epidemiological), studies focusing on New World CL (based on the study geographical location), or focusing on Post‐Kala‐Azar leishmaniasis. Relevant articles were selected and assessed. Results: Based on the clinical manifestations described in the selected studies, articles were classified into the following categories: (a) subacute CL, (b) chronic CL, (c) CL associated with lymphatic involvement, (d) CL associated with an immunocompromised state, and (e) cutaneous leishmaniasis on special anatomical sites. Clinical, diagnostic, and therapeutic facets were subsequently explored. Conclusion: The diagnosis of leishmaniasis can be challenging. Given the broadening spectrum of differential diagnoses for CL in clinical settings, dermatologists, pediatric dermatologists, internists, infectious disease specialists, and pediatricians must be aware of this classification of atypical CL.

The coronavirus disease 2019 (CVOID-19) has varied clinical manifestations including mild to severe acute respiratory symptoms. Inflammasome complex and mitochondria play an important role in initiating inflammatory responses and could potentially be affected by this infection. To study the inflammasome and mitochondrial fission and fusion gene expression levels in COVID-19 patients, we designed this experiment. The inflammasome and mitochondrial gene expression profiles were determined by real-time polymerase chain reaction in the peripheral blood of 70 hospitalized CVOID-19 patients with mild to moderate symptoms (HOSP) and 30 ICU patients with severe symptoms (ICU) compared to 20 healthy controls (HC). The results indicated that the expression of the dynamin-related protein-1 was extremely suppressed in HOSP while it came back to the normal range in the ICU group. However, the expression of fission 1 protein had a non-significant increase in HOSP and a decrease in the ICU group. The mitofusin-1 and dominant optic atrophy genes showed high expression levels (10-fold) and (70-fold), respectively, in the HOSP group. However, mitofusin-2 significantly decreased in both groups. Although leucine-rich–containing family, pyrin domain–containing-3 (NLRP3) and apoptosis-associated speck-like protein containing a caspase activating and recruitment domain genes dramatically increased in both groups (10 and 4-fold), other inflammasome genes declined in both groups. Finally, Nuclear factor kappa-light-chain-enhancer of activate d B cells (NF-κB) extremely decreased, and Intreleukine-1 showed high expression in ICU patients (3-fold). CVOID-19 infection suppresses the fission genes and elevates the fusion gene expression in mitochondria, and it can cause activation of the inflammasome via the NLRP3 pathway.

The landscape of infectious diseases postpandemic: a pharmacological perspective The era post-2020 has marked a defining moment in the evolution of pharmacology, with a particular emphasis on infectious diseases (Baker et al., 2022). This period has been characterized by the relentless global campaign against COVID-19 and the emergence of a spectrum of other infectious pathogens (Tabish, 2020). It was during this time that the field of pharmacology experienced an unprecedented amalgamation of global research endeavors and the development of innovative therapeutic solutions. The research conducted in these years has not only paved the way for groundbreaking therapeutic strategies but has also illustrated the extraordinary capacity for resilience and innovation within the scientific community (Rijs and Fenter, 2020). These advancements, born out of necessity in the face of global health crises (Betz et al., 2023), have reshaped the landscape of infectious disease treatment and prevention. This editorial offers an insightful examination and analysis of the significant advancements in the field of infectious diseases from 2022 to 2023, specifically focusing on how these developments have transformed our approaches to combating such diseases. At the heart of this exploration is an overview of 15 pivotal articles featured in our Research Topic. These articles, contributed by 120 distinguished experts worldwide, represent a critical blend of knowledge, combining a range of expert insights and discoveries. This collective wisdom is crucial for developing innovative strategies to treat infectious diseases and significantly enhances our methods for addressing global health challenges. Additionally, this editorial delves into the interplay between pathogens and recent advances in drug development, highlighting how this period has served as both a rigorous test of scientific resolve and a catalyst for notable progress in medical science. By exploring the dynamic relationship between emerging diseases and pharmacological innovations, it underscores how this era has been challenging yet instrumental in driving substantial advancements in the evolution of the medical field.

Context:: Fungal infections are very common, and several medications are used to treat them. Azoles are prescribed widely to treat fungal infections. In addition to therapeutic effects, any drug can be accompanied by side effects in patients. One of the most important complications in this regard is liver injury. Therefore, hepatotoxicity induced by azole antifungal drugs were reviewed in this study. Evidence Acquisition:: English scientific papers were evaluated to review the effects of hepatotoxicity by azole antifungal agents, and the related studies' results were summarized using a table. The systematic search was implemented on electronic databases, including PubMed, Google Scholar, and Science Direct. Original articles and review articles that were published before April 1, 2022, were included in the study. Those articles without available full text or non-English articles were excluded. Also, articles that reported pediatric data were excluded. Results:: Most studies have reported the effects of hepatotoxicity by azole antifungal agents, and their mechanisms have been described. Conclusions:: Clinical evaluations regarding the hepatotoxicity of antifungal agents provided in the literature were reviewed. Therefore, it is recommended to prescribe these drugs with caution in high-risk patients suffering from liver diseases, and patients should be monitored for hepatotoxicity. However, more research is needed to evaluate the hepatotoxicity of azole antifungal agents and select appropriate drugs according to cost-effectiveness and the side effects' profiles, relying on lower incidence of this liver complication.

Purpose: Vancomycin is a narrow therapeutic window glycopeptide antibiotic that acts against Gram-positive bacteria. As it is renally eliminated, therapeutic drug monitoring is recommended for vancomycin, especially in case of kidney function alteration. Augmented renal clearance (ARC), defined as a creatinine clearance of more than 130 ml/min, is a risk factor for sub-therapeutic concentrations of vancomycin. This study aimed to evaluate the vancomycin pharmacokinetics following the administration of two different regimens in ARC patients.Methods: A randomized clinical trial (IRCT20180802040665N1) was conducted on patients in need of vancomycin therapy. Eight hours of urine was collected and 56 patients divided into two groups with creatinine clearance of more than 130 ml/min were included in the study. The first group received 15 mg/kg of vancomycin every 12 h and the second group 15 mg/kg every 8 h. After four doses, the peak and trough concentrations were measured from two blood samples. The primary outcome was the percentage of patients who attainted AUC more than 400. The occurrence of acute kidney injury also was evaluated after seven days.Results: The mean age of patients in the every 12 h and every 8 h groups was 44.04 ± 16.55 and 42.86 ± 11.83 years, respectively. While neurosurgical issues were the most common causes of hospitalization, central nervous infections were the most common indications for vancomycin initiation. Urinary creatinine clearance was 166.94 ± 41.32 ml/min in the every 12 h group and 171.78 ± 48.56 ml/min in the every 8 h group. 46.42% of patients in the every 12 h group and 82.14% of patients in the every 8 h group attained AUC/MIC of more than 400 mg × hr/L. None of the patients in the every 12 h group reached more than 15 mcg/ml concentration. At the 7-day follow-up, 10.7% patients in the BD group and 28.6% patients in the TDS group developed acute kidney injury (p = 0.089).Conclusion: Administration of vancomycin at a dose of 15 mg/kg every 8 h is associated with higher pharmacokinetic attainment in ARC patients. The occurrence of acute kidney injury also was not significantly higher in this therapeutic regimen. AUC/MIC monitoring is necessary in this population.

The development of a safe and effective vaccine is essential to protect populations against coronavirus disease 2019 (COVID‐19). There are several vaccine candidates under investigation with different mechanisms of action. In the present study, we have evaluated the safety and immunogenicity of a recombinant receptor‐binding domain (RBD)‐based protein subunit vaccine (Noora vaccine) against COVID‐19 in adults. This Phase 1 trial is a randomized, double‐blind, placebo‐controlled study to evaluate the safety and immunogenicity of the recombinant RBD‐based protein subunit vaccine (Noora vaccine) against COVID‐19 in healthy adults volunteers. Eligible participants were included in this study after evaluating their health status and considering the exclusion criteria. They were then randomized into three groups and received three doses of vaccine (80 µg, 120 µg, and placebo) on Days 0, 21, and 35. Primary outcomes including solicited, unsolicited, and medically attended adverse events were recorded during this study. Secondary outcomes including the humoral and cellular immunity (including anti‐RBD IgG antibody and neutralizing antibody) were measured on Days 0, 21, 28, 35, 42, and 49 by using the ELISA kit and the Virus Neutralization Test (VNT) was performed on day 49. Totally 70 cases were included in this Phase 1 trial and 60 of them completed the study. Safety assessments showed no severe adverse events. Local pain at the vaccine injection site occurred in 80% of the vaccinated volunteers. Induration and redness at the injection site were the other adverse reactions of this vaccine. There was no significant difference between the studied groups regarding adverse reactions. Anti‐RBD IgG antibody and neutralizing antibody assessment showed significant seroconversion in comparison to the placebo group (80%, and 100% respectively, p < 0.001). The cellular immunity panel also showed mild to moderate induction of TH1 responses and the VNT showed 78% of seroprotection. The results of this Phase 1 trial showed acceptable safety without serious adverse events and significant seroconversions in the humoral and cellular immunity panel. The dose of 80 µg is an appropriate dose for injection in the next phases of the trial.