Colistin, a polymyxin antibiotic reintroduced as a last-resort therapy against multidrug-resistant Gram-negative bacteria, is increasingly being compromised by the emergence of plasmid-mediated colistin resistance genes (mcr-1 to mcr-10). The human gut microbiota serves as a major reservoir and transmission hub for these resistance determinants, even among individuals without prior colistin exposure. This review explores the mechanisms, dissemination, and clinical implications of mcr-mediated colistin resistance within the gut microbiota, highlighting its role in horizontal gene transfer, colonization, and environmental persistence. A comprehensive synthesis of the recent literature was conducted, focusing on epidemiological studies, molecular mechanisms, neonatal implications and decolonization strategies. The intestinal tract supports the enrichment and exchange of mcr genes among commensal and pathogenic bacteria, especially under antibiotic pressure. Colistin use in agriculture has amplified gut colonization with resistant strains in both animals and humans. Surveillance gaps remain, particularly in neonatal populations, where colonization may occur early and persist silently. Promising interventions, such as fecal microbiota transplantation and phage therapies, are under investigation but lack large-scale clinical validation. The gut microbiome plays a central role in the global spread of colistin resistance. Mitigating this threat requires integrated One Health responses, improved diagnostics for gut colonization, and investment in microbiome-based therapies. A proactive, multisectoral approach is essential to safeguard colistin efficacy and address the expanding threat of mcr-mediated resistance.

Background/Objectives: Vancomycin is a reserve antibiotic that is frequently prescribed for central venous catheter (CVC)-associated infections in hemodialysis patients. Hemodialysis patients are very fragile patients and the presence of CVCs increases the risk of sepsis. We conducted a prospective study, evaluating the needs of changes in vancomycin dosing for treatment based on the use of the new 2020 vancomycin dosing guidelines, to increase drug safety (preventing subtherapeutic or supratherapeutic doses and offering therapeutic concentrations of the drug) in a particular group of patients with sepsis caused by catheter infections and being on intermittent hemodialysis. Methods: This prospective study included patients with sepsis caused by catheter infections and being on intermittent hemodialysis, treated with vancomycin, admitted in the nephrology department and intensive care unit (ICU). Vancomycin levels were adjusted according to the 2020 vancomycin guidelines. Results: In our study, nine (45%) patients had a vancomycin AUC between 400 and 600 mcg × h/mL, five (25%) patients had a subtherapeutic AUC, and six (30%) patients had a supratherapeutic AUC. It is important to mention that in 10 (50%) of the patients included in the study, the loading and maintenance doses mentioned in the protocol were respected, but 50% of them had a supratherapeutic AUC. We observed that a supratherapeutic AUC occurred when the loading dose was 1500 mg or 2000 mg, and in one case at 1000 mg with a low BMI. Conclusions: a therapeutic level of vancomycin can often be difficult to achieve because of different reasons, mainly in hemodialysis patients.

Autosomal dominant polycystic kidney disease (ADPKD, OMIM # 601313, # 173900) and tuberous sclerosis complex (TSC2, OMIM # 191092, #613254) are inherited multisystemic diseases that rarely associate. Large deletion on chromosome 16 can result in TSC2/PKD1 contiguous gene (deletion) syndrome (PKDTS, OMIM # 600273) presenting significant diagnostic and management challenges. A 50-year-old male presented clinical features consistent with autosomal dominant polycystic kidney disease (ADPKD) and signs of tuberous sclerosis complex (TSC), such as multiple facial angiofibroma, cortical tubers, cerebral hamartomas, and renal and hepatic angiomyolipomas, was investigated for the multisystemic disease pattern. Genetic testing confirmed the diagnosis of TSC2/PKD1 contiguous gene deletion syndrome (PKDTS), leading to the initiation of tolvaptan treatment to reduce the progression of ADPKD and considering everolimus as a potential therapeutic solution to decrease the size of angiomyolipomas, thereby minimizing the risk of spontaneous bleeding. Our report underlines for the first time, up to our knowledge, that the proposed therapy protocol for PKD1/TSC2 contiguous gene deletion syndrome could have potential. This case illustrates the importance of recognizing overlapping genetic disorders, and providing insights into an innovative therapeutic approach. By integrating detailed clinical assessment with genetic testing, the diagnosis was clarified, and targeted therapies can be selected to address the dual impact of ADPKD and TSC; however, further studies are needed to evaluate the efficacy and safety of this approach. We also emphasize the need to recognize other cases of renal polycystic disease associated with angiomyolipomas and cutaneous manifestations.

Background/Objectives: KDIGO supports molecular testing in selected autosomal dominant polycystic kidney disease (ADPKD) scenarios and targeted next-generation sequencing panels when broader evaluation is warranted; however, gene inclusion alone establishes neither analytical completeness nor clinical reportability. Methods: We designed and evaluated a 28-gene ADPKD-spectrum hybrid-capture panel in a 16-sample, two-configuration pilot using 694 analytical target intervals per sample. Multiplex ligation-dependent probe amplification assessed dosage in suspected PKD1-related disease or TSC2/PKD1 contiguous-gene deletion, and whole-exome sequencing selectively supported short-read reidentification. Results: In the primary eight-sample dataset, 4592/5552 observations (82.7%) had interval mean depth ≥20×, 4256/5552 (76.7%) had interval minimum depth ≥20×, and 89.6% of interval-record bases reached ≥10×. Nine genes (FLCN, GANAB, HNF1B, PRKCSH, REN, SEC61A1, TSC2, UMOD and VHL) met mean depth ≥20× throughout; six also met the minimum-depth criterion. For PKD1, 45/46 intervals met both criteria in all samples, but exon 1 remained undercovered, and nominal depth in duplicated sequence did not establish authentic-locus callability. Signals were observed at all four positive-comparator loci, although two lacked sufficient support for independent reporting. Seven of nine panel-first cases yielded observations: one HNF1B and one unique-locus PKD1 finding were supported, whereas four duplicated-sequence PKD1 findings remained confirmation-dependent. Conclusions: Responsible implementation requires explicit analytical boundaries and staged complementary testing.

Background/Objectives: Colistin is a last-resort agent against multidrug-resistant Gram-negative infections and is administered predominantly to complex, comorbid inpatients in whom mortality is high. We aimed to identify independent baseline predictors of in-hospital mortality in colistin-treated patients and to characterize temporal changes in mortality over 15 years. Methods: We conducted a retrospective cohort study of 1225 consecutive patients receiving systemic colistin between November 2009 and November 2024 at Parhon Hospital, a tertiary urology–nephrology center in Iași, Romania; independent predictors of death were identified using multivariable logistic regression restricted to variables fixed at the time of colistin initiation, reported as adjusted odds ratios (aOR) with 95% confidence intervals (CI). Results: Patients were predominantly male (60.2%), with a mean age of 65.1 ± 14.4 years; 85.6% were admitted to urology or nephrology. In-hospital mortality was 27.6%. Mortality was independently associated with acute kidney injury (aOR 3.72, 95% CI 2.76–5.01), sepsis (aOR 2.79, 95% CI 2.11–3.70), emergency admission (aOR 1.91, 95% CI 1.40–2.61), Charlson comorbidity index (aOR 1.13 per point, 95% CI 1.05–1.22), and older age (aOR 1.03 per year, 95% CI 1.02–1.04); sex was not associated. Crude mortality increased across the study period (odds ratio 1.16 per year, 95% CI 1.13–1.20) and remained elevated after adjustment for case-mix (adjusted odds ratio 1.13 per year, 95% CI 1.09–1.17). Conclusions: Acute kidney injury, sepsis, emergency admission, comorbidity burden, and age were independently associated with in-hospital death. Mortality rose progressively over 15 years, only partly explained by an increasingly severe case-mix, supporting early risk stratification of colistin recipients.