-
The Journal of Hospital Infection Nov 2023Vancomycin-resistant enterococci (VRE) cause many infections in the healthcare context. Knowledge regarding the epidemiology and burden of VRE infections, however,... (Meta-Analysis)
Meta-Analysis Review
Vancomycin-resistant enterococci (VRE) cause many infections in the healthcare context. Knowledge regarding the epidemiology and burden of VRE infections, however, remains fragmented. We aimed to summarize recent studies on VRE epidemiology and outcomes in hospitals, long-term-care facilities (LTCFs) and nursing homes worldwide based on current epidemiological reports. We searched MEDLINE/PubMed, the Cochrane Library, and Web of Science for observational studies, which reported on VRE faecium and faecalis infections in in-patients published between January 2014 and December 2020. Outcomes were incidence, infection rate, mortality, length of stay (LOS), and healthcare costs. We conducted a meta-analysis on mortality (PROSPERO registration number: CRD42020146389). Of 681 identified publications, 57 studies were included in the analysis. Overall quality of evidence was moderate to low. VRE incidence was rarely and heterogeneously reported. VRE infection rate differed highly (1-55%). The meta-analysis showed a higher mortality for VRE faecium bloodstream infections (BSIs) compared with VSE faecium BSIs (risk ratio, RR 1.46; 95% confidence interval (CI) 1.17-1.82). No difference was observed when comparing VRE faecium vs VRE faecalis BSI (RR 1.00, 95% CI 0.52-1.93). LOS was higher in BSIs caused by E. faecium vs E. faecalis. Only three studies reported healthcare costs. In contrast to previous findings, our meta-analysis of included studies indicates that vancomycin resistance independent of VRE species may be associated with a higher mortality. We identified a lack of standardization in reporting outcomes, information regarding healthcare costs, and state-of-the-art microbiological species identification methodology, which may inform the set-up and reporting of future studies.
Topics: Humans; Vancomycin; Anti-Bacterial Agents; Enterococcus faecalis; Enterococcus faecium; Gram-Positive Bacterial Infections; Vancomycin-Resistant Enterococci; Sepsis
PubMed: 37734679
DOI: 10.1016/j.jhin.2023.09.008 -
Journal of Advanced Research Dec 2023Treating orthopedic implant-associated infections, especially those caused by Staphylococcus aureus (S. aureus), remains a significant challenge. S. aureus has the...
INTRODUCTION
Treating orthopedic implant-associated infections, especially those caused by Staphylococcus aureus (S. aureus), remains a significant challenge. S. aureus has the ability to invade host cells, enabling it to evade both antibiotics and immune responses during infection, which may result in clinical treatment failures. Therefore, it is critical to identify the host cell type of implant-associated intracellular S. aureus infections and to develop a strategy for highly targeted delivery of antibiotics to the host cells.
OBJECTIVES
Introduced an antibody-antibiotic conjugate (AAC) for the targeted elimination of intracellular S. aureus.
METHODS
The AAC comprises of a human monoclonal antibody (M0662) directly recognizes the surface antigen of S. aureus, Staphylococcus protein A, which is conjugated with vancomycin through cathepsin-sensitive linkers that are cleavable in the proteolytic environment of the intracellular phagolysosome. AAC, vancomycin and vancomycin combined with AAC were used in vitro intracellular infection and mice implant infection models. We then tested the effect of AAC in vivo and in vivo by fluorescence imaging, in vivo imaging, bacterial quantitative analysis and bacterial biofilm imaging.
RESULTS
In vitro, it was observed that AAC captured extracellular S. aureus and co-entered the cells, and subsequently released vancomycin to induce rapid elimination of intracellular S. aureus. In the implant infection model, AAC significantly improved the bactericidal effect of vancomycin. Scanning electron microscopy showed that the application of AAC effectively blocked the formation of bacterial biofilm. Further histochemical and micro-CT analysis showed AAC significantly reduced the level of bone marrow density (BMD) and bone volume fraction (BV/TV) reduction caused by bacterial infection in the distal femur of mice compared to vancomycin treatment alone.
CONCLUSIONS
The application of AAC in an implant infection model showed that it significantly improved the bactericidal effects of vancomycin and effectively blocked the formation of bacterial biofilms, without apparent toxicity to the host.
PubMed: 38048846
DOI: 10.1016/j.jare.2023.12.001 -
Biomaterials Advances Aug 2023Hydrogel-forming microneedle arrays as a technique for transdermal drug delivery show promise as an alternative to traditional drug delivery methods. In this work,...
Hydrogel-forming microneedle arrays as a technique for transdermal drug delivery show promise as an alternative to traditional drug delivery methods. In this work, hydrogel-forming microneedles have been created with effective, controlled delivery of amoxicillin and vancomycin within comparable therapeutic ranges to that of oral delivered antibiotics. Fabrication using reusable 3D printed master templates enabled quick and low-cost hydrogel microneedle manufacturing through micro-molding. By 3D printing at a tilt angle of 45° the resolution of the microneedle tip was improved by double (from ca. 64 μm down to 23 μm). Amoxicillin and vancomycin were encapsulated within the hydrogel's polymeric network through a unique room temperature swell/deswell drug loading method within minutes, eliminating the need for an external drug reservoir. The hydrogel-forming microneedle mechanical strength was maintained, and successful penetration of porcine skin grafts observed with negligible damage to the needles or surrounding skin morphology. Hydrogel swell rate was tailored by altering the crosslinking density, resulting in controlled antimicrobial release for an applicable delivered dosage. The potent antimicrobial properties of the antibiotic-loaded hydrogel-forming microneedles against both Escherichia coli and Staphylococcus aureus, highlights the beneficial use of hydrogel-forming microneedles towards the minimally invasive transdermal drug delivery of antibiotics.
Topics: Swine; Animals; Hydrogels; Vancomycin; Anti-Infective Agents; Anti-Bacterial Agents; Amoxicillin
PubMed: 37236117
DOI: 10.1016/j.bioadv.2023.213467 -
European Respiratory Review : An... Dec 2023Methicillin-resistant (MRSA) is responsible for an array of problematic community- and healthcare-acquired infections, including pneumonia, and is frequently associated... (Review)
Review
Methicillin-resistant (MRSA) is responsible for an array of problematic community- and healthcare-acquired infections, including pneumonia, and is frequently associated with severe disease and high mortality rates. Standard recommended treatments for empiric and targeted coverage of suspected MRSA in patients with community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP), are vancomycin and linezolid. However, adverse events such as acute kidney injury and infection have been associated with these antibiotics. Ceftaroline fosamil is a β-lactam/extended-spectrum cephalosporin approved for the treatment of adults and children with CAP and complicated skin and soft tissue infections. Ceftaroline has activity against a range of common Gram-positive bacteria and is distinct among the β-lactams in retaining activity against MRSA. Due to the design of the pivotal randomised controlled trials of ceftaroline fosamil, outcomes in patients with MRSA CAP were not evaluated. However, various reports of real-world outcomes with ceftaroline fosamil for pneumonia caused by MRSA, including CAP and HAP/VAP, been published since its approval. A systematic literature review and qualitative analysis of relevant publications was undertaken to collate and summarise relevant published data on the efficacy and safety of ceftaroline fosamil in patients with MRSA pneumonia. While relatively few real-world outcomes studies are available, the available data suggest that ceftaroline fosamil is a possible alternative to linezolid and vancomycin for MRSA pneumonia. Specific scenarios in which ceftaroline fosamil might be considered include bacteraemia and complicating factors such as empyema.
Topics: Adult; Child; Humans; Methicillin-Resistant Staphylococcus aureus; Linezolid; Vancomycin; Cephalosporins; Anti-Bacterial Agents; Community-Acquired Infections; Pneumonia, Ventilator-Associated; Ceftaroline
PubMed: 37852658
DOI: 10.1183/16000617.0117-2023 -
BMC Health Services Research Jul 2023Currently, the detection rates of methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci (MRCoNS) in the blood cultures of...
BACKGROUND AND OBJECTIVE
Currently, the detection rates of methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci (MRCoNS) in the blood cultures of neonates with sepsis exceed the national average drug resistance level, and vancomycin and linezolid are the primary antibacterial drugs used for these resistant bacteria according to the results of etiological examinations. However, a comprehensive evaluation of their costs and benefits in late-onset neonatal sepsis in a neonatal intensive care unit (NICU) has not been conducted. This study aimed to compare the cost and effectiveness of vancomycin and linezolid in treating neonatal sepsis in the NICU.
METHODS
A cost-effectiveness analysis of real-world data was carried out by retrospective study in our hospital, and the cost and effectiveness of vancomycin and linezolid were compared by establishing a decision tree model. The drug doses in the model were 0.6 g for linezolid and 0.5 g for vancomycin. The cost break down included cost of medical ward, NICU stay, intravenous infusion of vancomycin or linezolid, all monitoring tests, culture tests and drugs. The unit costs were sourced from hospital information systems. The effectiveness rates were obtained by cumulative probability analysis. One-way sensitivity analysis was used to analyze uncertain influencing factors.
RESULTS
The effectiveness rates of vancomycin and linezolid in treating neonatal sepsis in the NICU were 89.74% and 90.14%, respectively, with no significant difference. The average cost in the vancomycin group was ¥12261.43, and the average cost in the linezolid group was ¥17227.96. The incremental cost effectiveness was ¥12416.33 cost per additional neonate with treatment success in the linezolid group compared to vancomycin group at discharge. Factors that had the greatest influence on the sensitivity of the incremental cost-effectiveness ratio were the price of linezolid and the effectiveness rates.
CONCLUSIONS
The cost for treatment success of one neonate in linezolid group was ¥5449.17 more than that in vancomycin group, indicating that vancomycin was more cost-effective. Therefore, these results can provide a reference for a cost effectiveness treatment scheme for neonatal sepsis in the NICU.
Topics: Vancomycin; Linezolid; Anti-Bacterial Agents; Neonatal Sepsis; Cost-Effectiveness Analysis; Humans; Methicillin-Resistant Staphylococcus aureus; Male; Female; Infant; Coagulase; Retrospective Studies; Drug Costs; Treatment Outcome; China
PubMed: 37468855
DOI: 10.1186/s12913-023-09628-9