BACKGROUND: This study investigates the distribution and characteristics of linezolid and vancomycin susceptibilities among Enterococcus faecalis (E. faecalis) and Enterococcus faecium (E. faecium) and explores the underlying resistance mechanisms.
METHODS: A total of 2842 Enterococcus clinical isolates from patients were retrospectively collected, and their clinical data were further analyzed. The minimum inhibitory concentrations (MICs) of vancomycin and linezolid were validated by broth dilution method. The resistance genes optrA, cfr, vanA, vanB and vanM were investigated using polymerase chain reaction (PCR). Housekeeping genes and resistance genes were obtianed through whole-genome sequencing (WGS).
RESULTS: Of the 2842 Enterococcus isolates, 88.5% (2516) originated from urine, with E. faecium accounted for 60.1% of these. The vanA gene was identified in 27/28 vancomycin resistant Enterococcus (VRE) isolates, 4 of which carried both vanA and vanM genes. The remaining strain was vanM positive. The optrA gene was identified in all E. faecalis isolates among linezolid resistant Enterococcus (LRE). E. faecium showed a higher multiple antibiotic resistance index (MAR index) compared to E. faecalis. The multi-locus sequence typing (MLST) showed the sequence type of E. faecium mainly belongs to clonal complex (CC) 17, nearly E. faecalis isolates analyzed were differentiated into 7 characteristics of sequence types (STs), among which ST16 of CC16 were the major lineage.
CONCLUSIONS: Urine was the primary source of VRE and LRE isolates in this study. E. faecium showed higher levels of resistance compared to E. faecalis. OptrA gene was detected in 91.6% of LRE, which could explain linezolid resistance, and van genes were detected in all vancomycin resistant Enterococcus strains, while vanA was a key resistance mechanism in VRE identified in this study.

A dual-recognition strategy is reported to construct a one-step washing and highly efficient signal-transduction tag system for high-sensitivity colorimetric detection of Staphylococcus aureus (S. aureus). The porous (gold core)@(platinum shell) nanozymes (Au@PtNEs) as the signal labels show highly efficient peroxidase mimetic activity and are robust. For the sake of simplicity the detection involved the use of a vancomycin-immobilized magnetic bead (MB) and aptamer-functionalized Au@PtNEs for dual-recognition detection in the presence of S. aureus. In addition, we designed a magnetic plate to fit the 96-well microplate to ensure consistent magnetic properties of each well, which can quickly remove unreacted Au@PtNEs and sample matrix while avoiding tedious washing steps. Subsequently, Au@PtNEs catalyze hydrogen peroxide (H2O2) to oxidize 3,3\',5,5\'-tetramethylbenzidine (TMB) generating a color signal. Finally, the developed Au@PtNEs-based dual-recognition washing-free colorimetric assay displayed a response in the range of S. aureus of 5 × 101-5 × 105 CFU/mL, and the detection limit was 40 CFU/mL within 1.5 h. In addition, S. aureus-fortified samples were analyzed to further evaluate the performance of the proposed method, which yielded average recoveries ranging from 93.66 to 112.44% and coefficients of variation (CVs) within the range 2.72-9.01%. These results furnish a novel horizon for the exploitation of a different mode of recognition and inexpensive enzyme-free assay platforms as an alternative to traditional enzyme-based immunoassays for the detection of other Gram-positive pathogenic bacteria.

Keratinicyclins and keratinimicins are recently discovered glycopeptide antibiotics. Keratinimicins show broad-spectrum activity against Gram-positive bacteria, while keratinicyclins form a new chemotype by virtue of an unusual oxazolidinone moiety and exhibit specific antibiosis against Clostridioides difficile. Here we report the mechanism of action of keratinicyclin B (KCB). We find that steric constraints preclude KCB from binding peptidoglycan termini. Instead, KCB inhibits C. difficile growth by binding wall teichoic acids (WTAs) and interfering with cell wall remodeling. A computational model, guided by biochemical studies, provides an image of the interaction of KCB with C. difficile WTAs and shows that the same H-bonding framework used by glycopeptide antibiotics to bind peptidoglycan termini is used by KCB for interacting with WTAs. Analysis of KCB in combination with vancomycin (VAN) shows highly synergistic and specific antimicrobial activity, and that nanomolar combinations of the two drugs are sufficient for complete growth inhibition of C. difficile, while leaving common commensal strains unaffected.

Surgical site infection (SSI) after posterior open lumbar fusion (POLF) is a major concern for both surgeons and patients. We sought to explore whether local application of vancomycin could decrease the rate of SSI. We reviewed the clinical data of patients who underwent POLF between June 2015 and June 2022 at 3 spinal centers. Patients were divided into those who received local vancomycin (vancomycin group) and those who did not (non-vancomycin group). The SSI rates at 12 months postoperatively were compared between the 2 groups. Although a trend toward a lower infection rate was observed in the vancomycin group than in the non-vancomycin group; the difference was not statistically significant (3.6% vs 5.5%, P = .121). However, we found that the postoperative SSI rate was significantly lower in the vancomycin group than in the non-vancomycin group (4.9% vs 11.4%, P = .041) in patients ≥ 2 fused segments, while there was no significant difference in postoperative SSI rate in patients with single fusion segment (3.1% vs 3.6%, P = .706). The logistic regression analysis indicated that the SSI rate in the non-vancomycin group was approximately 2.498 times higher than that in the vancomycin group (P = .048, odds ratio: 2.498, 95% confidence interval: 1.011-6.617) in patients with ≥2 fused segments. In SSI patients with confirmed pathogens, the SSI rate of Gram-negative bacteria in the vancomycin group was significantly higher than that in the non-vancomycin group (10/14 [71.4%] vs 5/22 [31.8%]), whereas the SSI rate of Gram-positive bacteria in the vancomycin group was significantly lower than that in the non-vancomycin group (4/14 [28.6%] vs 15/22 [68.2%]). Local administration of vancomycin is recommended in patients with ≥2 fused segments as it may facilitate to reduce the postoperative rate of SSI after POLF. Additionally, the local use of vancomycin can decrease the Gram-positive bacterial infections but is not effective against Gram-negative infections, which indirectly leads to an increase in the proportion of Gram-negative infections in SSI patients with confirmed pathogens.

This study conducted a quantitative meta-analysis to investigate the association of vancomycin indicators, particularly area under the curve over 24 h (AUC24) and trough concentrations (Ctrough), and their relationship with both nephrotoxicity and efficacy. Literature research was performed in PubMed and Web of Science on vancomycin nephrotoxicity and efficacy in adult inpatients. Vancomycin Ctrough, AUC24, AUC24/minimum inhibitory concentration (MIC), nephrotoxicity evaluation and treatment outcomes were extracted. Logistic regression and Emax models were conducted, stratified by evaluation criterion for nephrotoxicity and primary outcomes for efficacy. Among 100 publications on nephrotoxicity, 29 focused on AUC24 and 97 on Ctrough, while of 74 publications on efficacy, 27 reported AUC24/MIC and 68 reported Ctrough. The logistic regression analysis indicated a significant association between nephrotoxicity and vancomycin Ctrough (odds ratio = 2.193; 95% CI 1.582-3.442, p < 0.001). The receiver operating characteristic curve had an area of 0.90, with a cut-off point of 14.55 mg/L. Additionally, 92.3% of the groups with a mean AUC24 within 400-600 mg·h/L showed a mean Ctrough of 10-20 mg/L. However, a subtle, non-statistically significant association was observed between the AUC24 and nephrotoxicity, as well as between AUC24/MIC and Ctrough concerning treatment outcomes. Our findings suggest that monitoring vancomycin Ctrough remains a beneficial and valuable approach to proactively identifying patients at risk of nephrotoxicity, particularly when Ctrough exceeds 15 mg/L. Ctrough can serve as a surrogate for AUC24 to some extent. However, no definitive cut-off values were identified for AUC24 concerning nephrotoxicity or for Ctrough and AUC24/MIC regarding efficacy.

The alarming rise in antibiotic resistance necessitates urgent action, particularly against the backdrop of resistant bacteria evolving to render conventional antibiotics less effective, leading to an increase in morbidity, mortality, and healthcare costs. Vancomycin-loaded Metal-Organic Framework (MOF) nanocomposites have emerged as a promising strategy in enhancing the eradication of pathogenic bacteria. This study introduces lignin as a novel synergistic agent in Vancomycin-loaded MOF (Lig-Van-MOF), which substantially enhances the antibacterial activity against drug-resistant bacteria. Lig-Van-MOF exhibits six-fold lower minimum inhibitory concentration (MICs) than free vancomycin and Van-MOF with a much higher antibacterial potential against sensitive and resistant strains of Staphylococcus aureus and Escherichia coli. Remarkably, it reduces biofilms of these strains by over 85 % in minimal biofilm inhibitory concentration (MBIC). Utilization of lignin to modify surface properties of MOFs improves their adhesion to bacterial membranes and boosts the local concentration of Reactive Oxygen Species (ROS) via unique synergistic mechanism. Additionally, lignin induces substantial cell deformation in treated bacterial cells. It confirms the superior bactericidal properties of Lig-Van-MOF against Staphylococcus species, underlining its significant potential as a bionanomaterial designed to combat antibiotic resistance effectively. This research paves the way for novel antibacterial platforms that optimize cost-efficiency and broaden microbial resistance management applications.

BACKGROUND: Periprosthetic joint infection after total joint arthroplasty has a large incidence, and it may often require two or more stages of revision, placing an additional burden on clinicians and patients. The purpose of this network meta-analysis is to evaluate the effect of four different preventive strategies during total joint arthroplasty on the prevention of periprosthetic joint infection.
METHODS: The study protocol was registered at PROSPERO (CRD: 42,023,448,868), and the literature search databases included Web of Science, PubMed, OVID Cochrane Central Register of Controlled Trials, OVID EMBASE, and OVID MEDLINE (R) ALL that met the requirements. The network meta-analysis included randomized controlled trials, retrospective cohort studies and prospective cohort studies with the outcome of periprosthetic joint infection. The gemtc R package was applied to perform the network meta-analysis to evaluate the relative results of different preventive strategies.
RESULTS: This network meta-analysis study included a total of 38 articles with 4 preventive strategies and negative controls. No improvement was observed in antibiotic-loaded bone cement compared with negative controls. Chlorhexidine showed the highest probability of delivering the best preventive effect, and povidone iodine had the second highest probability. Although vancomycin ranked after chlorhexidine and povidone iodine, it still showed a significant difference compared with negative controls. In addition, the incidence after applying chlorhexidine was significantly lower than that after applying negative controls and vancomycin. In the heterogeneity test between direct and indirect evidence, there was no apparent heterogeneity between them.
CONCLUSIONS: The study indicated that chlorhexidine, povidone iodine and vancomycin showed significant efficacy in preventing periprosthetic joint infection after total joint arthroplasty, while antibiotic-loaded bone cement did not. Therefore, more high-quality randomized controlled trials are needed to verify the results above.

OBJECTIVE: Necrotizing tracheobronchitis is a rare clinical entity presented as a necrotic inflammation involving the mainstem trachea and distal bronchi. We reported a case of severe necrotizing tracheobronchitis caused by influenza B and methicillin-resistant Staphylococcus aureus (MRSA) co-infection in an immunocompetent patient.
METHODS: We described a 36-year-old man with initial symptoms of cough, rigors, muscle soreness and fever. His status rapidly deteriorated two days later and he was intubated. Bronchoscopy demonstrated severe necrotizing tracheobronchitis, and CT imaging demonstrated multiple patchy and cavitation formation in both lungs. Next-generation sequencing (NGS) and bronchoalveolar lavage fluid (BALF) culture supported the co-infection of influenza B and MRSA. We also found T lymphocyte and NK lymphocyte functions were extremely suppressed during illness exacerbation. The patient was treated with antivirals and antibiotics including vancomycin. Subsequent bronchoscopy and CT scans revealed significant improvement of the airway and pulmonary lesions, and the lymphocyte functions were restored. Finally, this patient was discharged successfully.
CONCLUSIONS: Necrotizing tracheobronchitis should be suspected in patients with rapid deterioration after influenza B infection. The timely diagnosis of co-infection and accurate antibiotics are important to effective treatment.

BACKGROUND: Vancomycin trough concentration is closely associated with clinical efficacy and toxicity. Predicting vancomycin trough concentrations in pediatric patients is challenging due to significant inter-individual variability and rapid physiological changes during maturation.
OBJECTIVE: This study aimed to develop a machine learning model to predict vancomycin trough concentrations and determine optimal dosing regimens for pediatric patients < 4 years of age using ML algorithms.
METHODS: A single-center retrospective observational study was conducted from January 2017 to March 2020. Pediatric patients who received intravenous vancomycin and underwent therapeutic drug monitoring were enrolled. Seven ML models [linear regression, gradient boosted decision trees, support vector machine, decision tree, random forest, Bagging, and extreme gradient boosting (XGBoost)] were developed using 31 variables. Performance metrics including R-squared (R2), mean square error (MSE), root mean square error (RMSE), and mean absolute error (MAE) were compared, and important features were ranked.
RESULTS: The study included 120 eligible trough concentration measurements from 112 patients. Of these, 84 measurements were used for training and 36 for testing. Among the seven algorithms tested, XGBoost showed the best performance, with a low prediction error and high goodness of fit (MAE = 2.55, RMSE = 4.13, MSE = 17.12, and R2 = 0.59). Blood urea nitrogen, serum creatinine, and creatinine clearance rate were identified as the most important predictors of vancomycin trough concentration.
CONCLUSIONS: An XGBoost ML model was developed to predict vancomycin trough concentrations and aid in drug treatment predictions as a decision-support technology.

Staphylococcus aureus is a notorious pathogen responsible for various severe diseases. Due to the emergence of drug-resistant strains, the prevention and treatment of S. aureus infections have become increasingly challenging. Vancomycin is considered to be one of the last-resort drugs for treating most methicillin-resistant S. aureus (MRSA), so it is of great significance to further reveal the mechanism of vancomycin resistance. VraFG is one of the few important ABC (ATP-binding cassette) transporters in S. aureus that can form TCS (two-component systems)/ABC transporter modules. ABC transporters can couple the energy released from ATP hydrolysis to translocate solutes across the cell membrane. In this study, we obtained a strain with decreased vancomycin susceptibility after serial passaging and selection. Subsequently, whole-genome sequencing was performed on this laboratory-derived strain MWA2 and a novel single point mutation was discovered in vraF gene, leading to decreased sensitivity to vancomycin and daptomycin. Furthermore, the mutation reduces autolysis of S. aureus and downregulates the expression of lytM, isaA, and atlA. Additionally, we observed that the mutant has a less net negative surface charge than wild-type strain. We also noted an increase in the expression of the dlt operon and mprF gene, which are associated with cell surface charge and serve to hinder the binding of cationic peptides by promoting electrostatic repulsion. Moreover, this mutation has been shown to enhance hemolytic activity, expand subcutaneous abscesses, reflecting an increased virulence. This study confirms the impact of a point mutation of VraF on S. aureus antibiotic resistance and virulence, contributing to a broader understanding of ABC transporter function and providing new targets for treating S. aureus infections.