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The Journal of International Medical... Sep 2022This study aimed to investigate vancomycin therapeutic drug monitoring (TDM) in patients on continuous renal replacement therapy (CRRT) and explore the risk factors for...
OBJECTIVES
This study aimed to investigate vancomycin therapeutic drug monitoring (TDM) in patients on continuous renal replacement therapy (CRRT) and explore the risk factors for exceeding the target concentration.
METHODS
This retrospective study enrolled patients aged ≥18 years who were admitted to the intensive care unit and treated with ≥3 intravenous vancomycin doses during CRRT, and who underwent vancomycin TDM. Demographic and other information were collected. Multivariate logistic regression was used assess the risk factors for exceeding the target concentration.
RESULTS
Sixty-nine patients were included, and 40.6% patients underwent TDM. Additionally, 14.5% of patients reached the optimal concentration, and 87.5% of patients who exceeded the target received a daily dose adjustment. The cumulative dose of vancomycin and serum albumin were risk factors for exceeding the target concentration in patients on CRRT.
CONCLUSIONS
Patients on CRRT did not meet the optimal vancomycin management; <50% of the patients routinely received vancomycin TDM, and <15% achieved the optimal concentration. Fewer patients in the subtherapeutic group received a daily dose adjustment than those who exceeded the target concentration. Cumulative vancomycin and serum albumin doses before TDM were the risk factors for exceeding the target concentration in CRRT patients.
Topics: Adolescent; Adult; Anti-Bacterial Agents; Continuous Renal Replacement Therapy; Drug Monitoring; Humans; Renal Replacement Therapy; Retrospective Studies; Serum Albumin; Vancomycin
PubMed: 36177821
DOI: 10.1177/03000605221126871 -
Orthopaedic Surgery Nov 2017Intra-site prophylactic vancomycin in spine surgery is an effective method of decreasing the incidence of postsurgical wound infection. However, there are differences in... (Meta-Analysis)
Meta-Analysis Review
Intra-site prophylactic vancomycin in spine surgery is an effective method of decreasing the incidence of postsurgical wound infection. However, there are differences in the prophylactic programs used for various spinal surgeries. Thus, this systematic review and meta-analysis aimed to evaluate the effectiveness of using intra-wound vancomycin during spinal surgery and to explore the effects of dose-dependence and the method of administration in a subgroup analysis. A total of 628 citations or studies were searched in PubMed, Ovid, Web of Science, and Google Scholar that were published before August 2016 with the terms "local vancomycin", "intra-wound vancomycin", "intraoperative vancomycin", "intra-site vancomycin", "topical vancomycin", "spine surgery", and "spinal surgery". Finally, 19 retrospective cohort studies and one prospective case study were eligible for inclusion in the systematic review and meta-analysis. The odds of developing postsurgical wound infection without prophylactic local vancomycin use were 2.83-fold higher than the odds of experiencing wound infection with the use of intra-wound vancomycin (95% confidence interval, 2.03-3.95; P = 0.083; I = 32.2%). The subgroup analysis including the dosage and the method of administration, revealed different results compared to previous research. The value of I in the 1-g group was 27.2%, which was much lower than in the 2-g group (I = 57.6%). At the same time, the value of I was 0.0% (P = 0.792, OR = 2.70) when vancomycin powder was directly sprinkled into all layers of the wound. However, there is high heterogenicity (I = 60.0%, P = 0.007, OR = 2.83) when vancomycin powder is not exposed to the bone graft and instrumentation. There are differences found with the method of local application of vancomycin for reducing postoperative wounds and further studies are necessary, including investigations focusing on the dose-dependent effects during spinal or the topical pharmacokinetic and other orthopaedic surgeries.
Topics: Administration, Topical; Anti-Bacterial Agents; Dose-Response Relationship, Drug; Humans; Models, Statistical; Orthopedic Procedures; Spine; Surgical Wound Infection; Treatment Outcome; Vancomycin
PubMed: 29178308
DOI: 10.1111/os.12356 -
PloS One 2023Vancomycin prescription and monitoring guidelines have been reported to be poorly followed by various centers.
BACKGROUND
Vancomycin prescription and monitoring guidelines have been reported to be poorly followed by various centers.
AIMS
Identifying barriers to compliance with vancomycin dosing and therapeutic drug monitoring guidelines (TDM) and possible ways to enhance compliance based on the healthcare providers' (HCPs) perspective.
METHODS
A qualitative study based on semi-structured interviews with HCP (physicians, pharmacists, and nurses) was conducted at two Jordanian Teaching Hospitals. Interviews were audio-recorded and analyzed through thematic analysis. The COREQ criteria for qualitative research were utilized to report the study findings.
RESULTS
A total of 34 HCPs were interviewed. HCP perceived several factors as barriers to guideline recommendation compliance. Such factors included negative perception towards prescription guidelines, lack of knowledge regarding TDM guidelines, the hierarchy of medication management, work pressure, and ineffective communication among healthcare providers. Potential strategies to optimize guidelines adaptation included providing HCPs with more training and decision support tools in addition to activating the role of clinical pharmacists.
CONCLUSIONS
The main barriers to guideline recommendations uptake were identified. Interventions should address those barriers related to the clinical environment, including enhancing interprofessional communication related to vancomycin prescription and TDM, reducing workload and providing support systems, promoting educational and training programs, in addition to adopting guidelines suitable for the local environment.
Topics: Humans; Vancomycin; Drug Monitoring; Health Personnel; Physicians; Pharmacists; Qualitative Research
PubMed: 37195936
DOI: 10.1371/journal.pone.0285717 -
International Journal of Environmental... Feb 2022Under the Japanese health insurance system, medicines undergoing therapeutic drug monitoring (TDM) can be billed for medical fees if they meet the specified... (Review)
Review
Under the Japanese health insurance system, medicines undergoing therapeutic drug monitoring (TDM) can be billed for medical fees if they meet the specified requirements. In Japan, TDM of vancomycin, teicoplanin, aminoglycosides, and voriconazole, which are used for the treatment of infectious diseases, is common practice. This means the levels of antibiotics are measured in-house using chromatography or other methods. In some facilities, the blood and/or tissue concentrations of other non-TDM drugs are measured by HPLC and are applied to treatment, which is necessary for personalized medicine. This review describes personalized medicine based on the use of chromatography as a result of the current situation in Japan.
Topics: Anti-Bacterial Agents; Drug Monitoring; Insurance; Japan; Vancomycin
PubMed: 35270215
DOI: 10.3390/ijerph19052516 -
Antimicrobial Agents and Chemotherapy Jun 2023Biofilm-forming bacterial infections result in clinical failure, recurring infections, and high health care costs. The antibiotic concentrations needed to eradicate...
Biofilm-forming bacterial infections result in clinical failure, recurring infections, and high health care costs. The antibiotic concentrations needed to eradicate biofilm require further research. We aimed to model an prosthetic joint infection (PJI) to elucidate the activity of traditional systemic concentrations versus supratherapeutic concentrations to eradicate a Staphylococcus epidermidis biofilm PJI. We evaluated S. epidermidis high-biofilm-forming (ATCC 35984) and low-biofilm-forming (ATCC 12228) isolates in an pharmacodynamic biofilm reactor model with chromium cobalt coupons to simulate prosthetic joint infection. Vancomycin, daptomycin, levofloxacin, and minocycline were used alone and combined with rifampin to evaluate the effect of biofilm eradication. We simulated three exposures: (i) humanized systemic dosing alone, (ii) supratherapeutic doses (1,000× MIC), and (iii) and dosing in combination with rifampin. Resistance development was monitored throughout the study. Simulated humanized systemic doses of a lipoglycopeptide (daptomycin), a fluoroquinolone (levofloxacin), a tetracycline (minocycline), and a glycopeptide (vancomycin) alone failed to eradicate a formed S. epidermidis biofilm. Supratherapeutic doses of vancomycin (2,000 μg/mL) and minocycline (15 μg/mL) with or without rifampin (15 μg/mL) failed to eradicate biofilms. However, a levofloxacin supratherapeutic dose (125 μg/mL) with rifampin eradicated the high-biofilm-producing isolate by 48 h. Interestingly, supratherapeutic-dose exposures of daptomycin (500 μg/mL) alone eradicated high- and low-biofilm-forming isolates in established biofilms. The concentrations needed to eradicate biofilms on foreign materials are not obtained with systemic dosing regimens. The failure of systemic dosing regimens to eradicate biofilms validates clinical findings with recurring infections. The addition of rifampin to supratherapeutic dosing regimens does not result in synergy. Supratherapeutic daptomycin dosing may be effective at the site of action to eradicate biofilms. Further studies are needed.
Topics: Anti-Bacterial Agents; Daptomycin; Staphylococcus epidermidis; Vancomycin; Minocycline; Rifampin; Levofloxacin; Biofilms; Microbial Sensitivity Tests
PubMed: 37154699
DOI: 10.1128/aac.00108-23 -
Frontiers in Bioscience (Scholar... Mar 2018We aimed to assess the anti-biofilm activity of vancomycin, maltodextrin, and their combination against vancomycin resistant (VRSA) and vancomycin-susceptible (VSSA)...
We aimed to assess the anti-biofilm activity of vancomycin, maltodextrin, and their combination against vancomycin resistant (VRSA) and vancomycin-susceptible (VSSA) strains based on an static model. Biofilms of 4 VSSA and 2 VRSA strains were grown in a 96-well static model. Vancomycin 2 mM, maltodextrin 10 mM, and both in combination were tested using tetrazolium salt (XTT), resazurin, and cfu/well counts. The efficacy of the antimicrobial solutions was expressed as the percentage reduction in metabolic activity with each method. Overall percentage reduction in the metabolic activity of VSSA was 79.3%, 34%, and 75.7% for vancomycin, maltodextrin, and their combination (p<0.001). Overall percentage reduction in metabolic activity of VRSA was 46.7%, 27.8%, and 34.6% for vancomycin, maltodextrin, and their combination (p>0.05). Maltodextrin did not improve the anti-biofilm efficacy of vancomycin in VSSA or in VRSA biofilms. XTT cannot replace cfu counts as a means of quantifying cell viability. Futures studies are needed to assess the synergistic effects of other non-antimicrobial molecules combined with vancomycin.
Topics: Anti-Bacterial Agents; Biofilms; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Polysaccharides; Staphylococcal Infections; Staphylococcus aureus; Vancomycin
PubMed: 29293434
DOI: 10.2741/s517 -
Orthopaedic Surgery Jul 2021A bone defect rat model was established to investigate the osteogenic effect of local delivery two antibiotics (vancomycin and tobramycin powder) on bone regeneration.
OBJECTIVE
A bone defect rat model was established to investigate the osteogenic effect of local delivery two antibiotics (vancomycin and tobramycin powder) on bone regeneration.
METHODS
Twenty-four Sprague-Dawley (SD) male rats (6 to 8 weeks, 200 to 250 g) were used in this study. All these rats were randomly divided into four groups. Based on dose conversion between rat and human via body surface area, the rat dose of two antibiotics was 88μg/g and 176 μg/g for vancomycin and tobramycin, respectively. Con group (no antibiotic), Van group (vancomycin, 88 μg/g), Tob group (tobramycin 176 μg/g), and Van+Tob group (vancomycin 88μg/g combined with tobramycin 176 μg/g). A 5.0-mm full-thickness standardized mandibular bone defect was performed with a drill in each rat and different antibiotic powders were placed over the bone defect space, respectively. All these animals were sacrificed after 12 weeks post-operation. The mandible bones were harvested for further radiographic and histologic analysis. The bone volume/total volume (BV/TV) ratio, bone volume (BV), and bone fractional area (BFA) in the defect area via micro-computed tomography (μCT scanning) were further analyzed. Then, we performed a histological assessment via hematoxylin and eosin (H&E) and Masson's trichrome staining to analyze bone regeneration and also analyze the number of osteoblasts per filed.
RESULTS
There were no postoperative deaths, signs of vancomycin-related or tobramycin-related toxicity, or signs of systemic illness in any of the four groups. All wounds healed well, and no complications or surgical site infection were observed in all rats. From the μCT scans analyses, there was less bone regeneration in the Van group than in the Con group (BV/TV: F = 64.29, R = 0.9602; P = 0.0052; BFA: F = 76.17, R = 0.9662, P = 0.0007; BV: F = 194.4, R = 0.9865, P = 0.0022). However, when the tobramycin and vancomycin were combined, an increase in bone defect re-ossification was found in the Van+Tob group than in the Van group (BV/TV: F = 64.29, R = 0.9602, P = 0.0033; BFA: F = 76.17, R = 0.9662, P = 0.0006; BV: F = 194.4, R = 0.9865, P = 0.0033). Routine H&E and Masson staining supported the finding of μCT scanning. Quantitative indices confirmed that both the bone regeneration and the number of osteoblasts per filed in the defect area was higher in the Van+Tob group than in the Van group (percentage of bone tissue: F = 145.7, R = 0.9562, P = 0.0008; number of osteoblasts per file; F = 67.3, R = 0.9098, P < 0.0001). There was no significant difference between the Con group and the Van+Tob group on the number of osteoblasts each field (F = 145.7, R = 0.9562, P > 0.9999).
CONCLUSION
For bone defect, local application of vancomycin combined with tobramycin was recommended over vancomycin alone. This animal study presents data suggesting that the use of local delivery of vancomycin and tobramycin should be investigated further in clinical studies.
Topics: Animals; Anti-Bacterial Agents; Bone Regeneration; Disease Models, Animal; Drug Therapy, Combination; Male; Mandible; Powders; Rats; Rats, Sprague-Dawley; Surgical Wound Infection; Tobramycin; Vancomycin; Wound Healing
PubMed: 34124847
DOI: 10.1111/os.13020 -
The Lancet. Child & Adolescent Health Jan 2022Vancomycin is the most widely used antibiotic for neonatal Gram-positive sepsis, but clinical outcome data of dosing strategies are scarce. The NeoVanc programme... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Vancomycin is the most widely used antibiotic for neonatal Gram-positive sepsis, but clinical outcome data of dosing strategies are scarce. The NeoVanc programme comprised extensive preclinical studies to inform a randomised controlled trial to assess optimised vancomycin dosing. We compared the efficacy of an optimised regimen to a standard regimen in infants with late onset sepsis that was known or suspected to be caused by Gram-positive microorganisms.
METHODS
NeoVanc was an open-label, multicentre, phase 2b, parallel-group, randomised, non-inferiority trial comparing the efficacy and toxicity of an optimised regimen of vancomycin to a standard regimen in infants aged 90 days or younger. Infants with at least three clinical or laboratory sepsis criteria or confirmed Gram-positive sepsis with at least one clinical or laboratory criterion were enrolled from 22 neonatal intensive care units in Greece, Italy, Estonia, Spain, and the UK. Infants were randomly assigned (1:1) to either the optimised regimen (25 mg/kg loading dose, followed by 15 mg/kg every 12 h or 8 h dependent on postmenstrual age, for 5 ± 1 days) or the standard regimen (no loading dose; 15 mg/kg every 24 h, 12 h, or 8 h dependent on postmenstrual age for 10 ± 2 days). Vancomycin was administered intravenously via 60 min infusion. Group allocation was not masked to local investigators or parents. The primary endpoint was success at the test of cure visit (10 ± 1 days after the end of actual vancomycin therapy) in the per-protocol population, where success was defined as the participant being alive at the test of cure visit, having a successful outcome at the end of actual vancomycin therapy, and not having a clinically or microbiologically significant relapse or new infection requiring antistaphylococcal antibiotics for more than 24 h within 10 days of the end of actual vancomycin therapy. The non-inferiority margin was -10%. Safety was assessed in the intention-to-treat population. This trial is registered at ClinicalTrials.gov (NCT02790996).
FINDINGS
Between March 3, 2017, and July 29, 2019, 242 infants were randomly assigned to the standard regimen group (n=122) or the optimised regimen group (n=120). Primary outcome data in the per-protocol population were available for 90 infants in the optimised group and 92 in the standard group. 64 (71%) of 90 infants in the optimised group and 73 (79%) of 92 in the standard group had success at test of cure visit; non-inferiority was not confirmed (adjusted risk difference -7% [95% CI -15 to 2]). Incomplete resolution of clinical or laboratory signs after 5 ± 1 days of vancomycin therapy was the main factor contributing to clinical failure in the optimised group. Abnormal hearing test results were recorded in 25 (30%) of 84 infants in the optimised group and 12 (15%) of 79 in the standard group (adjusted risk ratio 1·96 [95% CI 1·07 to 3·59], p=0·030). There were six vancomycin-related adverse events in the optimised group (one serious adverse event) and four in the standard group (two serious adverse events). 11 infants in the intention-to-treat population died (six [6%] of 102 infants in the optimised group and five [5%] of 98 in the standard group).
INTERPRETATION
In the largest neonatal vancomycin efficacy trial yet conducted, no clear clinical impact of a shorter duration of treatment with a loading dose was demonstrated. The use of the optimised regimen cannot be recommended because a potential hearing safety signal was identified; long-term follow-up is being done. These results emphasise the importance of robust clinical safety assessments of novel antibiotic dosing regimens in infants.
FUNDING
EU Seventh Framework Programme for research, technological development and demonstration.
Topics: Anti-Bacterial Agents; Equivalence Trials as Topic; Europe; Humans; Infant; Infant, Newborn; Infusions, Intravenous; Intensive Care Units, Neonatal; Sepsis; Spain; Time Factors; Treatment Outcome; United Kingdom; Vancomycin
PubMed: 34843669
DOI: 10.1016/S2352-4642(21)00305-9 -
PloS One 2016A target AUC0-24/MIC ratio of 400 has been associated with its clinical success when treating Staphylococcus aureus infections but is not currently supported by... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A target AUC0-24/MIC ratio of 400 has been associated with its clinical success when treating Staphylococcus aureus infections but is not currently supported by state-of-the-art evidence-based research.
OBJECTIVE
This current systematic review aimed to evaluate the available evidence for the association between the AUC0-24/MIC ratio of vancomycin and its clinical effectiveness on hospitalized patients and to confirm the existing target value of 400.
METHODS
PubMed, Embase, Web of Sciences, the Cochrane Library and two Chinese literature databases (CNKI, CBM) were systematically searched. Manual searching was also applied. Both RCTs and observational studies comparing the clinical outcomes of high AUC0-24/MIC groups versus low AUC0-24/MIC groups were eligible. Two reviewers independently extracted the data. The primary outcomes were mortality and infection treatment failure. Risk ratios (RRs) with 95% confidence intervals (95%CIs) were calculated.
RESULTS
No RCTs were retrieved. Nine cohort studies were included in the meta-analysis. Mortality rates were significantly lower in high AUC0-24/MIC groups (RR = 0.47, 95%CI = 0.31-0.70, p<0.001). The rates of infection treatment failure were also significantly lower in high AUC/MIC groups and were consistent after correcting for heterogeneity (RR = 0.39, 95%CI = 0.28-0.55, p = 0.001). Subgroup analyses showed that results were consistent whether MIC values were determined by broth microdilution (BMD) method or Etest method. In studies using the BMD method, breakpoints of AUC0-24/MIC all fell within 85% to 115% of 400.
CONCLUSIONS
This meta-analysis demonstrated that achieving a high AUC0-24/MIC of vancomycin could significantly decrease mortality rates by 53% and rates of infection treatment failure by 61%, with 400 being a reasonable target.
Topics: Anti-Bacterial Agents; Humans; Microbial Sensitivity Tests; Staphylococcal Infections; Treatment Outcome; Vancomycin
PubMed: 26731739
DOI: 10.1371/journal.pone.0146224 -
Journal of Orthopaedic Research :... Feb 2019Revisions TKAs are being completed with uncemented constructs more frequently. We hypothesized that tantalum cones could be an efficient carrier of antibiotics in... (Comparative Study)
Comparative Study
Revisions TKAs are being completed with uncemented constructs more frequently. We hypothesized that tantalum cones could be an efficient carrier of antibiotics in uncemented procedures. We aimed to compare the release of vancomycin between (i) tantalum and smooth stainless cylinders; (ii) different concentrations of vancomycin; and (iii) different durations of bathing. Specifically designed tantalum cylinders were bathed in a vancomycin solution with various durations of baths. We investigated rinses between each interval as well as the dose of vancomycin. Vancomycin concentrations were determined in each group by fluorescence polarization immunoassay at different intervals (1 h, days 1, 2, 3, 5). At 1 h, the mean vancomycin concentration for the 1-hour soaking group was 3,172 μg/ml, whereas mean concentration for the smooth stainless steel group was 39.37 μg/ml (p < 0.001). The rinsing group showed a significantly lower concentration at 1 h and 1 day (p < 0.05). The 2-gram vancomycin group showed no difference at days 1, 2, and 3 compared to the 1-hour group. The 5, 15, and 30-minute bathing groups showed significantly lower vancomycin concentrations at all-time points. All vancomycin concentrations at day 3 were superior to the minimal inhibitory concentration of Staphyloccocus aureus. The mean concentration of vancomycin depends on the material, duration of bathing, the rinsing effect, and the drug dose. Our in-vitro study is the first to show that porous tantalum cylinders allow antibiotic carriage and progressive release. If appearing in vivo, in a similar extent, this intrinsic property might be useful to prevent and/or treat peri-prosthetic joint infection. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:308-312, 2019.
Topics: Anti-Bacterial Agents; Arthroplasty, Replacement; Humans; Kinetics; Prosthesis-Related Infections; Reoperation; Tantalum; Vancomycin
PubMed: 30325073
DOI: 10.1002/jor.24160