Antibiotics

Objective: Vulvovaginal candidiasis (VVC) is a common condition in clinical practice, and the absence of standardized diagnostic criteria based solely on clinical findings remains a challenge. This study aimed to evaluate the distribution of Candida species, antifungal susceptibility patterns, recurrence rates, and clinical factors associated with recurrent disease. Methods: This retrospective study included 345 VVC episodes from 325 patients in whom Candida species were isolated from vaginal cultures. Demographic and clinical characteristics, identified Candida species, antifungal susceptibility test results, and recurrence patterns were analyzed. Associations with recurrent VVC were evaluated using univariable analyses and multivariable Firth penalized logistic regression. Results: Candida albicans was the most frequently isolated species, accounting for 85.2% (n = 294) of cases, followed by C. glabrata (9.6%; n = 33) and C. krusei (1.7%; n = 6). Fluconazole susceptibility patterns did not differ significantly between patients with ≥3 recurrent episodes and those with <3 recurrent episodes (p = 0.493). Similarly, no significant difference was observed for voriconazole susceptibility (p = 0.116). High in vitro susceptibility rates were observed for caspofungin, amphotericin B, and micafungin in both groups. Multivariable Firth logistic regression analysis demonstrated that smoking (OR = 3.83; 95% CI: 1.81–8.81; p < 0.001), intrauterine device use (OR = 16.77; 95% CI: 4.13–153.53; p < 0.001), and antibiotic use (OR = 7.81; 95% CI: 3.90–17.30; p < 0.001) were significantly associated with recurrence, whereas pregnancy was not significantly associated with recurrence (OR = 2.05; 95% CI: 0.78–5.66; p = 0.147).

Background/Objectives: The clinical utility of polymyxin B (PB), a critical last–line antibiotic for multidrug–resistant Gram–negative infections, is severely compromised by acute kidney injury (AKI). However, the lack of specific diagnostic biomarkers and the incomplete understanding of pathogenic mechanisms pose substantial challenges to clinical management of PB–associated AKI. Methods: We enrolled 83 patients receiving PB regimens (23 AKI, 60 non–AKI) and quantified the plasma concentrations of five PB components to identify the optimal therapeutic drug monitoring (TDM) metric for nephrotoxicity. A rat model of PB–induced AKI was established to map renal PB distribution via mass spectrometry imaging and screen targets for tubular accumulation virtually. Untargeted metabolomics was performed on clinical and rat samples to identify metabolic dysregulation, with key pathways validated by reverse transcription quantitative real–time PCR (RT–qPCR). Diagnostic models were constructed using the eXtreme Gradient Boosting (XGBoost) algorithm and evaluated using Area Under the Curve (AUC). Shapley Additive exPlanations (SHAP) analysis was applied to interpret the models, and decision curve analysis (DCA) was used to assess clinical utility. Results: A novel PB–component model outperformed the conventional TDM index (AUC 0.703 vs. 0.561), and a 6–metabolite exploratory classifier achieved 0.95 accuracy and AUC 1.000 for PB–AKI discrimination on an independent test set. Mechanistically, high PB concentrations might saturate P–glycoprotein (P–gp), leading to PB accumulation in renal tubules and subsequent metabolic dysregulation, manifested as upregulation of fatty acid pathways and downregulation of the TCA cycle. Conclusions: These findings advance our understanding of metabolic dysregulation in PB–induced AKI and support the potential utility of responsive metabolic features in the clinical diagnosis of PB-induced AKI.

Crohn’s disease (CD) is a chronic inflammatory disorder characterized by complex interactions among genetic susceptibility, environmental factors, dysregulated immune responses, and alterations of the intestinal microbiota. Although corticosteroids, immunomodulators, biologics, and advanced small-molecule therapies remain central to disease management, a substantial proportion of patients experience primary non-response, loss of response, or treatment-related adverse effects. This has stimulated interest in complementary therapeutic strategies targeting host–microbe interactions and intestinal microbial homeostasis. This review critically examines emerging microbiome-directed approaches for CD, with particular emphasis on pathobionts such as adherent-invasive Escherichia coli (AIEC). We discuss the available evidence for antibiotics, antimicrobial peptides (AMP), gut bacteriophages, fecal microbiota transplantation (FMT), and selected nutraceutical and dietary interventions. While some approaches show promising biological or clinical signals, the strength of evidence varies considerably, ranging from in vitro and animal studies to randomized clinical trials and meta-analyses. Antibiotic therapies targeting intestinal pathogens have shown heterogeneous results, suggesting the need for pathogen-guided and intracellularly active antimicrobial strategies. Novel approaches, including AIEC-specific phages and AMP-based interventions, represent promising microbiome-sparing alternatives capable of selectively modulating disease-associated microorganisms. Furthermore, FMT and nutraceuticals may contribute to restoring microbial balance and strengthening intestinal homeostasis, although their efficacy requires further validation in controlled clinical trials. Overall, these strategies support a transition toward precision medicine approaches integrating microbial profiling, host immune characterization, and targeted antimicrobial interventions to improve therapeutic outcomes in CD.