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Comparative Immunology, Microbiology... Jul 2022The objective of this study was to evaluate local antimicrobial delivery from temperature-responsive hydrogels for preventing infection in a rat model of intra-abdominal...
The objective of this study was to evaluate local antimicrobial delivery from temperature-responsive hydrogels for preventing infection in a rat model of intra-abdominal infection (IAI), and to determine whether delivery of tobramycin and vancomycin in combination is effective against IAI pathogens. Rats received intraperitoneal inoculation of E. coli, rat cecal contents, or cecal contents supplemented with E. coli, and received either no treatment, subcutaneous cefoxitin, or local delivery from hydrogels containing vancomycin, tobramycin, or both antimicrobials. Only the hydrogel with tobramycin and vancomycin significantly increased the infection free-rate compared to no treatment for all inocula (E. coli: 13/17, p < 0.0001; cecal contents: 11/17, p = 0.0013; cecal contents + E. coli: 15/19, p < 0.0001). Additionally, tobramycin and vancomycin displayed no synergy or antagonism against clinical isolates in vitro. Local delivery of tobramycin and vancomycin from temperature-responsive hydrogels provides broad coverage and high antimicrobial concentrations for several hours that may be effective for preventing IAIs.
Topics: Animals; Anti-Bacterial Agents; Escherichia coli; Hydrogels; Incidence; Intraabdominal Infections; Rats; Temperature; Tobramycin; Vancomycin
PubMed: 35636372
DOI: 10.1016/j.cimid.2022.101823 -
American Family Physician Mar 2011Surgical site infections are the most common nosocomial infections in surgical patients, accounting for approximately 500,000 infections annually. Surgical site... (Review)
Review
Surgical site infections are the most common nosocomial infections in surgical patients, accounting for approximately 500,000 infections annually. Surgical site infections also account for nearly 4 million excess hospital days annually, and nearly $2 billion in increased health care costs. To reduce the burden of these infections, a partnership of national organizations, including the Centers for Medicare and Medicaid Services and the Centers for Disease Control and Prevention, created the Surgical Care Improvement Project and developed six infection prevention measures. Of these, three core measures contain recommendations regarding selection of prophylactic antibiotic, timing of administration, and duration of therapy. For most patients undergoing clean-contaminated surgeries (e.g., cardiothoracic, gastrointestinal, orthopedic, vascular, gynecologic), a cephalosporin is the recommended prophylactic antibiotic. Hospital compliance with infection prevention measures is publicly reported. Because primary care physicians participate in the pre- and postoperative care of patients, they should be familiar with the Surgical Care Improvement Project recommendations.
Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Humans; Surgical Wound Infection; Vancomycin
PubMed: 21391526
DOI: No ID Found -
ACS Infectious Diseases Sep 2021Vancomycin functions by binding to lipid II, the penultimate bacterial cell wall building block used by both Gram-positive and Gram-negative species. However, vancomycin...
Vancomycin functions by binding to lipid II, the penultimate bacterial cell wall building block used by both Gram-positive and Gram-negative species. However, vancomycin is generally only able to exert its antimicrobial effect against Gram-positive strains as it cannot pass the outer membrane (OM) of Gram-negative bacteria. To address this challenge, we here describe efforts to conjugate vancomycin to the OM disrupting polymyxin E nonapeptide (PMEN) to yield the hybrid "vancomyxins". In designing these hybrid antibiotics, different spacers and conjugation sites were explored for connecting vancomycin and PMEN. The vancomyxins show improved activity against Gram-negative strains compared with the activity of vancomycin or vancomycin supplemented with PMEN separately. In addition, the vancomyxins maintain the antimicrobial effect of vancomycin against Gram-positive strains and, in some cases, show enhanced activity against vancomycin-resistant strains. The hybrid antibiotics described here have reduced nephrotoxicity when compared with clinically used polymyxin antibiotics. This study demonstrates that covalent conjugation to an OM disruptor contributes to sensitizing Gram-negative strains to vancomycin while retaining anti-Gram-positive activity.
Topics: Anti-Bacterial Agents; Gram-Negative Bacteria; Microbial Sensitivity Tests; Polymyxins; Vancomycin
PubMed: 34387988
DOI: 10.1021/acsinfecdis.1c00318 -
Clinical Pharmacokinetics Dec 2020Extracorporeal membrane oxygenation (ECMO) is a form of cardiopulmonary life support frequently utilized in catastrophic lung and or cardiac failure. Patients on ECMO... (Observational Study)
Observational Study
BACKGROUND
Extracorporeal membrane oxygenation (ECMO) is a form of cardiopulmonary life support frequently utilized in catastrophic lung and or cardiac failure. Patients on ECMO often receive vancomycin therapy for treatment or prophylaxis against Gram-positive organisms. It is unclear if ECMO affects vancomycin pharmacokinetics, thus we modeled the pharmacokinetic behavior of vancomycin according to ECMO-specific variables.
METHODS
Adult patients receiving vancomycin and Veno-Arterial-ECMO between 12/1/2016 and 10/1/2017 were prospectively enrolled. Extracorporeal membrane oxygenation settings and four sets of pre- and post-oxygenator vancomycin concentrations were collected for each patient. Compartmental models were built and assessed ECMO flow rates on vancomycin clearance and potential circuit sequestration. Bayesian posterior concentrations of the pre- and post-oxygenator concentrations were obtained for each patient, and summary pharmacokinetic parameters were calculated. Simulations were performed from the final model for efficacy and toxicity predictions.
RESULTS
Eight patients contributed 64 serum concentrations. Patients were a median (interquartile range) age of 58.5 years (50.8-62.3) with a calculated creatinine clearance of 39 mL/min (29.5-62.5) and ECMO flow rates of 3980 mL/min (interquartile range = 3493.75-4132.5). A three-compartment model best fit the data (Bayesian: plasma pre-oxygenation R = 0.99, post-oxygenation R = 0.99). Vancomycin clearance was not impacted by ECMO flow rate (p = 0.7). Simulations demonstrated that vancomycin 1 g twice daily was rarely sufficient for minimum inhibitory concentrations > 0.5 mg/L. Doses ≥ 1.5 g twice daily often exceeded toxicity thresholds for exposure.
CONCLUSIONS
Extracorporeal membrane oxygenation flow rates did not influence vancomycin clearance between flow rates of 3500 and 5000 mL/min and vancomycin was not sequestered in ECMO. Common vancomycin regimens resulted in suboptimal efficacy and/or excessive toxicity. Individual therapeutic drug monitoring is recommended for patients on ECMO.
Topics: Anti-Bacterial Agents; Bayes Theorem; Extracorporeal Membrane Oxygenation; Female; Humans; Male; Middle Aged; Oxygenators; Vancomycin
PubMed: 32468446
DOI: 10.1007/s40262-020-00902-1 -
Journal of Pharmacy & Pharmaceutical... 2018The antibacterial activity of some antibiotics is specific to either Gram-positive or Gram-negative bacteria. There are different mechanisms behind such...
PURPOSE
The antibacterial activity of some antibiotics is specific to either Gram-positive or Gram-negative bacteria. There are different mechanisms behind such insensitivities like inability of antibiotics to permeate through some bacterial membranes, as is the case for vancomycin in Gram-negative bacteria. The present investigation tries to overcome this problem by dendrimers, in order to make Gram-negative bacteria responsive to vancomycin.
METHODS
The effects of generations 3 (G3) and 5 (G5) polyamidoamine amine-terminated dendrimers (NH2-PAMAM), on the antibacterial activity of vancomycin, were evaluated. Vancomycin-PAMAM dendrimers complexes were prepared and their antibacterial activities were evaluated by determination of their "minimum inhibitory concentration (MIC)", "minimum bactericidal concentration" and "fractional inhibitory concentration index" values against two Gram-positive and four Gram-negative bacteria, using broth micro-dilution method. The complexation of vancomycin and dendrimers was also assessed by in vitro release studies across dialysis tubing using a developed HPLC method.
RESULTS
Results showed that vancomycin solution was effective against Gram-positive bacteria, but, was not effective in Gram-negative ones. Vancomycin-PAMAM dendrimers exhibited significant antibacterial efficacy against Gram-negative bacteria resulting in a decline of vancomycin MIC values by about 2, 2, 4 and 64 times in E. coli, K. pneumonia, S. typhimurium and P. aeruginosa, respectively. Results also showed that enhanced effect by G5 is more than G3. Dendrimers did not affect antibacterial activity of vancomycin in Gram-positive bacteria, as no permeation problem exists here.
CONCLUSIONS
The present study revealed that both G3 and G5 cationic PAMAM dendrimers are able to make Gram-negative bacteria sensitive to vancomycin, resulting in decline of MIC values up to 64 times, possibly by increasing its permeation through bacterial membrane. These results look promising for broadening the antibacterial spectrum of vancomycin and such a strategy might be used for increasing the overall life of antibiotics.
Topics: Anti-Bacterial Agents; Dendrimers; Dose-Response Relationship, Drug; Gram-Negative Bacteria; Microbial Sensitivity Tests; Polyamines; Vancomycin
PubMed: 30589641
DOI: 10.18433/jpps29659 -
Journal of Materials Science. Materials... Apr 2021Usage of implants containing antibiotic agents has been a common strategy to prevent implant related infections in orthopedic surgery. Unfortunately, most implants with...
Usage of implants containing antibiotic agents has been a common strategy to prevent implant related infections in orthopedic surgery. Unfortunately, most implants with microbial repellent properties are characterized by accessibility limitations during daily clinical practice. Aim of this in vitro study was to investigate whether suture tapes and cerclage wires, which were treated with vancomycin, show a sustainable antibacterial activity. For this purpose, we used 24 stainless steel wire cerclages and 24 ultra-high molecular weight polyethylene and polyester suture tape test bodies. The test bodies were incubated for 30 min. in 100 mg/ml vancomycin solution or equivalent volumes of 0.9% NaCl. After measuring the initial solution uptake of the test bodies, antibacterial efficacy via agar diffusion test with Staphylococcus aureus and vancomycin elution tests were performed 1, 2, 3, and 6 days after incubation. Vancomycin-loaded tapes as well as vancomycin-loaded cerclage wires demonstrated increased bacterial growth inhibition when compared to NaCl-treated controls. Vancomycin-loaded tapes showed an additional twofold and eightfold increase of bacterial growth inhibition compared to vancomycin-loaded wires at day 1 and 2, respectively. Elution tests at day 1 revealed high levels of vancomycin concentration in vancomycin loaded tapes and wires. Additionally, the concentration in vancomycin loaded tapes was 14-fold higher when compared to vancomycin loaded wires. Incubating suture tapes and cerclage wires in vancomycin solution showed a good short-term antibacterial activity compared to controls. Considering the ease of vancomycin application on suture tapes or wires, our method could represent an attractive therapeutic strategy in biofilm prevention in orthopedic surgery.
Topics: Anti-Bacterial Agents; Biocompatible Materials; Bone Wires; Drug Liberation; Materials Testing; Prostheses and Implants; Staphylococcus aureus; Sutures; Vancomycin
PubMed: 33825078
DOI: 10.1007/s10856-021-06513-x -
Microbial Genomics Jul 2023Linezolid is used as first-line treatment of infections caused by vancomycin-resistant . However, resistance to linezolid is increasingly detected. The aim of the...
Linezolid is used as first-line treatment of infections caused by vancomycin-resistant . However, resistance to linezolid is increasingly detected. The aim of the present study was to elucidate the causes and mechanisms for the increase in linezolid-resistant at Copenhagen University Hospital - Rigshospitalet. We therefore combined patient information on linezolid treatment with whole-genome sequencing data for vancomycin- or linezolid-resistant isolates that had been systematically collected since 2014 (=458). Whole-genome sequencing was performed for multilocus sequence typing (MLST), identification of linezolid resistance-conferring genes/mutations and determination of phylogenetically closely related strains. The collection of isolates belonged to prevalent vancomycin-resistant MLST types. Among these, we identified clusters of closely related linezolid-resistant strains compatible with nosocomial transmission. We also identified linezolid-resistant enterococcus isolates not genetically closely related to other isolates compatible with generation of linezolid resistance. Patients with the latter isolates were significantly more frequently exposed to linezolid treatment than patients with related linezolid-resistant enterococcus isolates. We also identified six patients who initially carried a vancomycin-resistant, linezolid-sensitive enterococcus, but from whom vancomycin-resistant, linezolid-resistant enterococci (LVRE) closely related to their initial isolate were recovered after linezolid treatment. Our data illustrate that linezolid resistance may develop in the individual patient subsequent to linezolid exposure and can be transmitted between patients in a hospital setting.
Topics: Humans; Linezolid; Anti-Bacterial Agents; Enterococcus faecium; Vancomycin; Tertiary Care Centers; Multilocus Sequence Typing; Vancomycin-Resistant Enterococci
PubMed: 37410656
DOI: 10.1099/mgen.0.001055 -
European Journal of Clinical... Apr 2024To investigate the occurrence of vancomycin-variable enterococci (VVE) in a hospital in central Italy.
PURPOSE
To investigate the occurrence of vancomycin-variable enterococci (VVE) in a hospital in central Italy.
METHODS
vanA positive but vancomycin-susceptible Enterococcus faecium isolates (VVE-S) were characterized by antibiotic susceptibility tests, molecular typing (PFGE and MLST), and WGS approach. The reversion of VVE-S to a resistant phenotype was assessed by exposure to increasing vancomycin concentrations, and the revertant isolates were used in filter mating experiments. qPCR was used to analyze the plasmid copy number.
RESULTS
Eleven putative VVE-S were selected. WGS revealed two categories of vanA cluster plasmid located: the first type showed the lack of vanR, the deletion of vanS, and an intact vanH/vanA/vanX cluster; the second type was devoid of both vanR and vanS and showed a deletion of 544-bp at the 5'-end of the vanH. Strains (n = 7) carrying the first type of vanA cluster were considered VVE-S and were able to regain a resistance phenotype (VVE-R) in the presence of vancomycin, due to a 44-bp deletion in the promoter region of vanH/vanA/vanX, causing its constitutive expression. VVE-R strains were not able to transfer resistance by conjugation, and the resistance phenotype was unstable: after 11 days of growth without selective pressure, the revertants were still resistant but showed a lower vancomycin MIC. A higher plasmid copy number in the revertant strains was probably related to the resistance phenotype.
CONCLUSION
We highlight the importance of VVE transition to VRE under vancomycin therapy resulting in a potential failure treatment. We also report the first-time identification of VVE-S isolates pstS-null belonging to ST1478.
Topics: Humans; Vancomycin; Enterococcus faecium; Anti-Bacterial Agents; Multilocus Sequence Typing; Vancomycin Resistance; Microbial Sensitivity Tests; Enterococcus; Bacterial Proteins; Gram-Positive Bacterial Infections
PubMed: 38296911
DOI: 10.1007/s10096-024-04768-0 -
Expert Review of Anti-infective Therapy Jan 2010Vancomycin is a commonly used antimicrobial in patients with methicillin-resistant Staphylococcus aureus (MRSA) infections. Increasing vancomycin MIC values in MRSA... (Review)
Review
Vancomycin is a commonly used antimicrobial in patients with methicillin-resistant Staphylococcus aureus (MRSA) infections. Increasing vancomycin MIC values in MRSA clinical isolates makes the optimization of vancomycin dosing pivotal to its continued use. Unfortunately, limited data exist regarding the optimal pharmacokinetic-pharmacodynamic (PK-PD) goal to improve bacterial killing and clinical outcomes with vancomycin. The hallmark study in this area suggests that achieving an AUC to MIC ratio of over 400 improves the likelihood of achieving these outcomes. Challenges in the implementation of PK-PD-based dosing for vancomycin include current methodologies utilized in microbiology laboratories, as well as intra- and interpatient pharmacokinetic variability. Individualized dosing based on MIC and specific patient factors is important to achieve optimal outcomes from vancomycin therapy.
Topics: Anti-Bacterial Agents; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Staphylococcal Infections; Vancomycin
PubMed: 20014904
DOI: 10.1586/eri.09.123 -
Acta Orthopaedica Feb 2018Background and purpose - The incidence of orthopedic methicillin-resistant Staphylococcus aureus (MRSA) infections is increasing. Vancomycin may therefore play an...
Background and purpose - The incidence of orthopedic methicillin-resistant Staphylococcus aureus (MRSA) infections is increasing. Vancomycin may therefore play an increasingly important role in orthopedic perioperative antimicrobial prophylaxis. Studies investigating perioperative bone and soft tissue concentrations of vancomycin are sparse and challenged by a lack of appropriate methods. We assessed single-dose plasma, subcutaneous adipose tissue (SCT) and bone concentrations of vancomycin using microdialysis in male patients undergoing total knee replacement. Methods - 1,000 mg of vancomycin was administered postoperatively intravenously over 100 minutes to 10 male patients undergoing primary total knee replacement. Vancomycin concentrations in plasma, SCT, cancellous, and cortical bone were measured over the following 8 hours. Microdialysis was applied for sampling in solid tissues. Results - For all solid tissues, tissue penetration of vancomycin was significantly impaired. The time to a mean clinically relevant minimal inhibitory concentration (MIC) of 2 mg/L was 3, 36, 27, and 110 min for plasma, SCT, cancellous, and cortical bone, respectively. As opposed to the other compartments, a mean MIC of 4 mg/L could not be reached in cortical bone. The area under the concentration-time curve from 0 to the last measured value and peak drug concentrations (C) for SCT, cancellous, and cortical bone was lower than that of free plasma. The time to C was higher for all tissues compared with free plasma. Interpretation - Postoperative penetration of vancomycin to bone and SCT was impaired and delayed in male patients undergoing total knee replacement surgery. Adequate perioperative vancomycin concentrations may not be reached using standard prophylactic dosage.
Topics: Anti-Bacterial Agents; Arthroplasty, Replacement, Knee; Cancellous Bone; Humans; Male; Microdialysis; Subcutaneous Fat; Surgical Wound Infection; Vancomycin
PubMed: 28914105
DOI: 10.1080/17453674.2017.1373497