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Colistin resistance in the era of antimicrobial resistance: challenges and strategic countermeasures.
Authors:RoyChowdhury D et al
Abstract
Colistin resistance represents a mounting global health concern, particularly alarming in the face of multidrug-resistant (MDR) and extensively drug-resistant (XDR) bacterial infections. As a polymyxin-class antibiotic, colistin has long served as a critical last-line defence against severe Gram-negative infections caused by pathogens such as Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. However, its increasing and, at times, indiscriminate use has driven the emergence of resistant strains, thereby compromising its clinical utility.Mechanistically, colistin resistance arises from diverse genetic adaptations that alter the bacterial outer membrane, diminishing the drug’s binding affinity. Prominent among these are modifications to lipopolysaccharides (LPS), including the incorporation of cationic groups that neutralise the membrane’s negative charge, effectively impeding colistin interaction. In addition to chromosomal mutations, resistance is often mediated through horizontal gene transfer-most notably via mobile colistin resistance (mcr) genes-which facilitates rapid dissemination among bacterial populations.To counter this growing threat, innovative therapeutic strategies are urgently needed. These include the development of novel antibiotics with distinct mechanisms of action, synergistic combination regimens (e.g., colistin paired with potentiating agents), and the exploration of alternative modalities such as bacteriophage therapy. Gene-editing technologies like CRISPR-Cas9 also offer a promising frontier for targeting resistance determinants directly at the genetic level.Equally important are robust antimicrobial stewardship programmes and comprehensive surveillance systems to monitor resistance trends and guide rational antibiotic use. Ultimately, overcoming colistin resistance demands a multifaceted and integrative approach-one that merges scientific innovation with global public health initiatives.
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Mortality Risk of Colistin vs. Non-Colistin Use in Cancer Patients with Multidrug-Resistant Gram-Negative Bacterial Infections: Stratified by Resistance Profile and Concomitant Medications.
Authors: Lee SH et al
Abstract
Background and Objectives: Cancer patients are particularly susceptible to infections caused by multidrug-resistant Gram-negative bacteria (MDR GNB) due to chemotherapy- or radiation therapy-induced immunosuppression. Colistin is often prescribed as a last-resort agent for MDR GNB infection, but its clinical benefit in oncology patients remains unclear. This study aims to evaluate the mortality risk associated with colistin versus non-colistin regimens in cancer patient with MDR GNB infections, stratified by resistance profiles, infection sites, and concomitant medication use.
Materials and Methods: A retrospective cohort study was conducted in adult cancer patients with MDR GNB infections that are resistant to at least three antibiotic classes and identified from at least two anatomical sites at a tertiary care hospital in Korea. Propensity score-matched in a 1:3 ratio either to the colistin group or non-colistin group and multivariate Cox hazard regression analyses were used to evaluate mortality in cancer patients with MDR GNB infections, primarily Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa.
Results: A total of 85 patients (29 patients in the colistin and 56 patients in the non-colistin group) were included in the analysis. Overall, colistin use did not show a statistically significant mortality benefit compared to non-colistin regimens (hazard ratio (HR) 0.93, 95% CI 0.47-1.87). However, the subgroup analysis revealed that colistin had a potential association with significantly lower mortality in pneumonia patients with aminoglycoside-resistant infections (HR 0.04, 95% CI 0.002-0.69). Concomitant use of antipsychotics and benzodiazepines in selected resistance profiles also correlated with improved outcomes. In contrast, a potential association was found between concomitant macrolide use and increased mortality in patients with fluoroquinolone- or penicillin-resistant profiles.
Conclusions: Colistin may offer survival benefits in selected high-risk cancer patients with MDR GNB pneumonia. Treatment outcomes are influenced by resistance profiles, infection sites, and concomitant medications, indicating the significant importance of individualized antimicrobial therapy and antimicrobial stewardship in oncology patients.
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Integrated Multimodal Strategy to Reduce Healthcare-Associated Infections in a Trauma ICU: Impact of a Quality Improvement Project.
DOI: 10.3390/jcm14165826
Authors: Toma D et al
Abstract
Background: Healthcare-associated infections (HAIs) remain a significant challenge in intensive care units (ICUs), especially in trauma settings where invasive interventions are frequent. This study aimed to assess the impact of a structured quality improvement project (QIP) on nosocomial infection rates and patient outcomes in a polytrauma ICU.
Methods: We conducted a retrospective observational study at the “Pius Brînzeu” County Emergency Clinical Hospital, Timișoara. A total of 78 ICU trauma patients were included: 35 in the Pre-QIP group and 43 in the Post-QIP group. The QIP integrated evidence-based interventions, including hand hygiene reinforcement, individualized protective equipment, improved nurse staffing, and antimicrobial stewardship. Outcomes analyzed included nosocomial infection rate, ICU length of stay, antibiotic use, mechanical ventilation days, and mortality. Multivariable logistic, linear, and Poisson regression models were applied to control for confounding variables. Results: The Post-QIP group showed a significantly lower number of infections per patient (0.60 ± 0.95 vs. 1.41 ± 1.97, p = 0.03) and a trend toward lower mortality (0.19 vs. 0.34, p = 0.18). While ICU stay, antibiotic use, and ventilation days decreased post-QIP, these changes were not statistically significant. ISS and Charlson scores were consistent predictors of worse outcomes. Conclusions: Implementation of a targeted, multidisciplinary QIP was associated with improved infection control and patient outcomes. These results support the feasibility and value of structured infection prevention strategies in resource-constrained ICU settings.
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Pseudomonas aeruginosa-driven airway dysbiosis and machine learning prediction of acute exacerbations in non-cystic fibrosis bronchiectasis: a microbial-inflammatory signature approach.
Authors: Wang WW et al
Abstract
Background: While Pseudomonas aeruginosa (PA) colonization is linked to poor outcomes in bronchiectasis, emerging evidence suggests that microbial community collapse-marked by diversity loss and depletion of commensal taxa-may better reflect disease progression than pathogen load alone. This study investigates whether airway microbiota dysbiosis driven by PA colonization induces ecological fragility and evaluates the predictive utility of integrating microbial diversity indices with systemic inflammation markers to forecast 1-year acute exacerbation risk using interpretable machine learning.
Methods: Bronchoalveolar lavage fluid (BALF) samples from 23 patients (8 PA-colonized, 15 non-colonized) underwent 16 S rRNA gene sequencing. Microbial diversity and taxonomic composition were analyzed. An eXtreme Gradient Boosting (XGBoost) model with SHapley Additive exPlanations (SHAP) analysis was constructed to assess exacerbation risk, focusing on microbial and inflammatory markers. Results: PA-colonized patients (P1) exhibited significantly worse clinical severity than non-colonized patients (P2), with higher Bronchiectasis Severity Index scores (8.38 vs. 4.33, P < 0.01), poorer quality-of-life (SGRQ: 35.75 vs. 22.79; CAT: 24.00 vs. 16.26, P < 0.01), and elevated dyspnea (mMRC: 1.62 vs. 0.95, P < 0.05). P1 also had more acute exacerbations annually (retrospective: 3.00 vs. 1.20; prospective: 3.75 vs. 0.80, P < 0.05-0.001). Notably, P1 exhibited significantly reduced alpha diversity compared to P2 (Shannon index: 1.96 vs. 3.47; Simpson index: 0.46 vs. 0.77, P < 0.05). Weighted UniFrac PCoA revealed distinct clustering between groups (R²=0.162, P < 0.05). The XGBoost model, integrating microbial taxa relative abundances, alpha diversity indices, and inflammatory markers demonstrated robust performance in predicting 1-year acute exacerbation risk (AUC = 0.85). SHAP analysis identified the microbial diversity, rather than Pseudomona abundance was the most influential predictor of exacerbation risk.
Conclusions: PA colonization disrupts airway microbial diversity and outcompetes commensal species in bronchiectasis, yet our XGBoost model reveals that ecological resilience-not pathogen load-best predicts exacerbation risk when integrated with inflammatory markers. This paradigm shift from pathogen-centric to ecosystem-driven risk assessment provides an actionable framework for personalized management and antibiotic stewardship in chronic airway diseases.”
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Impact of surgical field disinfection on vaginal microbiome in transvaginal urogynecological surgery: a prospective cohort study
Authors: Yingan Zhang
Abstract
Background: The study aimed to assess the effects of vaginal disinfection and sterile draping on the composition and dynamics of the vaginal microbiota during vaginal surgery.
Methods: A prospective cohort study was conducted involving post-menopausal patients undergoing vaginal urogynecological surgery. The vaginal microbiota was assessed by partial 16 S rRNA gene sequencing at three time points: before disinfection (V1); immediately after disinfection and sterile draping (V2); and one-hour post-disinfection (V3).
Findings:In a cohort of 54 postmenopausal women (median age: 69.2 ± 7.6 years), with a mean operative time of 92.89 ± 45.92 min, native tissue prolapse repair was the most common urogynecological vaginal procedure performed (n = 47, 87%). The vaginal microbiota diversity was significantly increased after disinfection associated with reduced abundance of Lactobacillus and Bifidobacterium and increased Pseudomonas (p < 0.0001). Community state type (CST) I prevalence decreased notably from 20% at V1 to 6% at V3, primarily due to the disappearance of CST I-A, while CST IV prevalence rose from 31 to 44%, which was mainly secondary to an increase in CST IV-C (from 20 to 33%).
Conclusions: These findings highlight the impact of povidone-iodine on vaginal microbiota composition during vaginal urogynecological surgery. Disinfection significantly increased vaginal bacterial diversity and reducing Lactobacillus abundance. This observation requires further exploration in the context of development of optimized disinfection protocols aimed at preserving vaginal health during and after surgery.”
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Secular trends of bloodstream infections in hemodialysis patients: insights from a longitudinal Swiss study
Authors: Nasreen Hassoun-Kheir
Abstract
Background: Hemodialysis-associated bloodstream infections (BSIs) represent a significant burden for patients. Understanding the trends in BSIs among hemodialysis patients is crucial for informing strategies to reduce their incidence and improve patient outcomes. This study aimed to evaluate secular trends, identify causative organisms, assess resistance patterns, and determine the sources of hemodialysis-associated BSIs at Geneva University Hospitals, where Staphylococcus aureus screening and decolonization of hemodialysis patients have been implemented since the year 2000.
Methods: A longitudinal cohort study was conducted using data from 2006 to 23. We included all patients receiving maintenance hemodialysis treatment at our institution. A hemodialysis-associated BSI was defined as BSI occurring during active hemodialysis treatment and diagnosed either during hospital admission or in outpatient hemodialysis unit. Outcomes included incidence rates of hemodialysis-associated BSIs, trends in causative pathogens, sources, and resistant organisms. Poisson regression was used to model trends over time of incidence rate ratios (IRR).
Results: A total of 313 true BSI episodes were identified in 218 hemodialysis patients over 11,413 patient-hemodialysis months. The overall BSI incidence rate was 2.7 episodes per 100 patient-hemodialysis-months, with a consistent decrease over time. Compared to 2006-08, hemodialysis-associated BSI rates decreased by 16% in 2009-11 (IRR 0.84, 95% confidence interval [CI] 0.60–1.18), and by a maximum of 44% in 2021-23 (IRR 0.56, 95% CI 0.36–0.83). The decreasing trend was mainly due to reduced S. aureus BSIs, while Enterobacterales BSIs rates remained stable. Catheter-related BSIs accounted for 41.5% of infections (130/313), with marked reduction following 2014. BSIs caused by resistant bacteria were rare, with decreasing trends of methicillin-resistant S. aureus.
Conclusions : Hemodialysis-associated BSI rates significantly declined, driven largely by reductions in S. aureus BSIs and catheter-related infections. No replacement by Gram-negative BSI was observed. Prevention of hemodialysis-associated BSI is key for reducing infection burden among hemodialysis patients.”
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Hidden transmissions of Pseudomonas aeruginosa ST111 –the importance of continuous molecular surveillance
Authors: Jasmin Kaur Jasuja
Abstract
Background: A series of transmission of Pseudomonas aeruginosa ST111 blaVIM−2, previously undetected by standard surveillance, was discovered in a tertiary care hospital in Northern Germany through molecular genetic monitoring. Hence, environmental sampling was initiated to find the source of infection.
Methods: First, routine epidemiological data ruled out patient-to-patient transmission and two initial diagnoses were assessed as externally acquired. After the discovery of the highly related cluster by whole genome sequencing, a more detailed epidemiological analysis was carried out, including previous hospitalizations. An environmental investigation was initiated due to a possible connection of transmissions with an intensive care unit.
Results: Between 2018 and 2023 16 clinical isolates of Pseudomonas aeruginosa ST111 blaVIM−2 were identified of which 12 isolates belonged to ST111 carrying an In59-like integron. Routine whole-genome sequencing of carbapenem resistant P. aeruginosa identified a highly related cluster (maximum of three allelic differences) of high-risk ST111 isolates in ICU patients over five years, confirming sink-to-patient transmission associated to sink drains in two ICU rooms. In initial routine epidemiological categorization of these highly related isolates four isolates were categorized as possible nosocomial acquisition without direct epidemiological link to other patients, whereas two isolates were categorized as ‘externally acquired’.
Conclusions:
This finding highlights the ability of high-risk clone ST111 to persist in hospital environments and emphasizes the importance of integrating molecular surveillance with routine epidemiology to uncover hidden transmissions. In this case, the frequent detection of the ST111 high-risk clone led to targeted environmental sampling, uncovering a prolonged outbreak that had gone unnoticed by conventional surveillance. The clone was eliminated from the ward during a reconstruction project.”
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Investigation of colistin heteroresistance in multidrug-resistant Acinetobacter baumannii clinical isolates
Authors:Ali Hematian
Abstract
Background : Colistin is considered a last-resort antibiotic against Acinetobacter baumannii strains with advanced drug resistance. Various mechanisms, such as those affecting the bacterial outer membrane and efflux pumps, mediate colistin resistance.
Methods: One hundred clinical A. baumannii isolates were collected from various infections and identified using standard tests. The minimum inhibitory concentrations (MICs) of nine antibiotics, as well as colistin, against the isolates were determined using the broth microdilution method. The population analysis profile (PAP) was conducted to determine colistin heteroresistance, and a time-kill assay was also performed. Using polymerase chain reaction (PCR) and sequencing, the presence of mcr1-3 genes, as well as mutations in the pmrCAB and lpx genes, were investigated.
Results : All isolates were multidrug-resistant, and more than 85% of the isolates were resistant to all antibiotics tested except colistin (colistin MIC ≤ 1 mg/L). Eleven colistin-heteroresistant isolates were found. All heteroresistant isolates were also resistant to imipenem. The time-kill assay indicated at 1 × MIC and 2 × MIC concentrations, the three heteroresistant isolates showed noteworthy regrowth at 6 and 12 hours, respectively. All of the isolates were negative for mcr genes. Among 11 heteroresistant isolates, mutations in the pmrB, lpxC, and lpxD genes were found in four isolates, with one isolate having double mutations in the pmrB and lpxD genes.
Conclusion: Our research indicates that resistant subpopulations may develop during colistin monotherapy. These findings highlight the importance of continuous surveillance, the use of combination therapy, and the development of new strategies to combat A. baumannii infections.”