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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 -
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 -
The Turkish Journal of Pediatrics 2022All drugs may cause hypersensitivity reactions. Anaphylaxis is a medical emergency that rarely occurs in newborns due to immature immunity. Early diagnosis and treatment...
BACKGROUND
All drugs may cause hypersensitivity reactions. Anaphylaxis is a medical emergency that rarely occurs in newborns due to immature immunity. Early diagnosis and treatment are life-saving. Vancomycin, a glycopeptide antibiotic with bactericidal action against Gram-positive bacteria, is commonly used for neonatal nosocomial sepsis.
CASE
We hereby present a premature infant (born at the 33rd week of gestation, birth weight: 1745 grams) who was started on vancomycin on postnatal day 7. He had severe circulatory failure and stridor during infusion on day 7 of vancomycin treatment and his tryptase level was elevated to 64.60 micrograms/L Conclusions. To the best of our knowledge, there is no neonatal case of anaphylaxis due to vancomycin in the literature. Neonatologists should keep in mind that an anaphylactic reaction with a fatal course may develop during vancomycin infusion.
Topics: Male; Infant, Newborn; Humans; Vancomycin; Anaphylaxis; Anti-Bacterial Agents; Infant, Premature; Birth Weight
PubMed: 36583898
DOI: 10.24953/turkjped.2021.1941 -
Annals of Clinical Microbiology and... Mar 2020The influence of liver disease on the pharmacokinetic profile, the risk of acute kidney injury, and excessive drug exposure in patients treated with vancomycin was...
BACKGROUND
The influence of liver disease on the pharmacokinetic profile, the risk of acute kidney injury, and excessive drug exposure in patients treated with vancomycin was examined.
METHODS
A retrospective cohort study was performed with patients discharged from a medical center between January 2011 and June 2018 who received vancomycin therapy. Patients were stratified according to liver dysfunction (no to mild liver dysfunction (NMLD) and moderate to severe liver dysfunction (MSLD) based on the Child-Pugh score. The risk of acute kidney injury was compared between patients who were stratified by the attainment of a target serum trough concentration (10 mg/dL to 20 mg/dL) and the vancomycin ratio formed between the area under the curve and minimum inhibitory concentration. The impact of liver dysfunction and a daily dose of vancomycin on the risk of acute kidney injury and vancomycin AUC:MIC > 600 were tested using logistic regression with and without adjusting for the study variables.
RESULTS
A total of 408 patients empirically treated with vancomycin were included in this study (237 with NMLD and 171 with MSLD). Mean vancomycin trough concentrations (17.5 ± 8.4 mg/dL versus 15.3 ± 5.2 mg/dL, p = 0.0049) and AUC:MIC ratios (549.4 ± 217.2 versus 497.5 ± 117.3, 0.0065) were significantly higher in the MSLD group when compared to the NMLD group, respectively. Vancomycin clearance was also lower in the MSLD group and corresponded to a longer half-life. The proportion of patients who developed acute kidney injury was greater in patients with MSLD when compared to NMLD (7.6% versus 3.8%, respectively; p = 0.0932); however, the difference was statistically insignificant. Furthermore, supratherapeutic serum trough concentrations and AUC:MIC ratios were more common in the MSLD group versus the NMLD group (27.5% versus 13.9%, p = 0.0007 and 28.7% versus 17.3%, respectively; p = 0.0063).
CONCLUSIONS
MSLD correlates with an increased risk of supratherapeutic vancomycin exposure. Although patients with MSLD had a higher risk of acute kidney injury, the difference was not significant.
Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Anti-Bacterial Agents; Female; Humans; Liver Diseases; Logistic Models; Male; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Serum; Staphylococcal Infections; Vancomycin; Young Adult
PubMed: 32234065
DOI: 10.1186/s12941-020-00354-2 -
The American Journal of Sports Medicine Feb 2021The use of the vancomycin wrap to pretreat the hamstring graft in anterior cruciate ligament reconstruction (ACLR) has grown in popularity since it was first described...
BACKGROUND
The use of the vancomycin wrap to pretreat the hamstring graft in anterior cruciate ligament reconstruction (ACLR) has grown in popularity since it was first described in 2012 and has significantly reduced rates of postoperative infection. However, it remains unknown if this antibiotic treatment affects the molecular composition of the graft.
PURPOSE
To establish whether treatment with vancomycin at 5 mg/mL, the most commonly used concentration, alters the molecular function of the hamstring graft in ACLR.
STUDY DESIGN
Controlled laboratory study.
METHODS
Surplus hamstring tendon collected after routine ACLR surgery was used for in vitro cell culture and ex vivo tissue experiments. Vancomycin was used at 5 mg/mL in RPMI or saline diluent to treat cells and tendon tissue, respectively, with diluent control conditions. Cell viability at 30, 60, and 120 minutes was assessed via colorimetric viability assay. Tendon cells treated with control and experimental conditions for 1 hour was evaluated using semiquantitative reverse transcription analysis, immunohistochemistry staining, and protein quantitation via enzyme-linked immunosorbent assay for changes in apoptotic, matrix, and inflammatory gene and protein expression.
RESULTS
Vancomycin treatment at 5 mg/mL significantly reduced tenocyte viability in vitro after 60 minutes of treatment ( < .05); however, this was not sustained at 120 minutes. Vancomycin-treated tendon tissue showed no significant increase in apoptotic gene expression, or apoptotic protein levels in tissue or supernatant, ex vivo. Vancomycin was associated with a reduction in inflammatory proteins from treated tendon supernatants (IL-6; < .05).
CONCLUSION
Vancomycin did not significantly alter the molecular structure of the hamstring graft. Reductions in matrix protein and inflammatory cytokine release point to a potential beneficial effect of vancomycin in generating a homeostatic environment.
CLINICAL RELEVANCE
Vancomycin ACL wrap does not alter the molecular structure of the ACL hamstring graft and may improve graft integrity.
Topics: Anterior Cruciate Ligament Injuries; Anterior Cruciate Ligament Reconstruction; Apoptosis; Hamstring Tendons; Humans; Tissue Culture Techniques; Transplantation, Autologous; Vancomycin
PubMed: 33406371
DOI: 10.1177/0363546520981570 -
BMC Pediatrics May 2023Methicillin-resistant Staphylococcus aureus (MRSA) can cause invasive infections with significant mortality in neonates. This study aimed to analyze the clinical...
BACKGROUND
Methicillin-resistant Staphylococcus aureus (MRSA) can cause invasive infections with significant mortality in neonates. This study aimed to analyze the clinical characteristics and antibiotic resistance profiles of invasive MRSA infections and determine risk factors associated with invasive MRSA infections in newborn inpatients.
METHODS
This multicenter retrospective study of inpatients from eleven hospitals in the Infectious Diseases Surveillance of Pediatrics (ISPED) group of China was performed over a two-year period (2018-2019). Statistical significance was calculated by applying the χ2 test or by Fisher's exact test in the case of small sample sizes.
RESULTS
A total 220 patients were included. Among included cases, 67 (30.45%) were invasive MRSA infections, including two deaths (2.99%), while 153 (69.55%) were noninvasive infections. The invasive infections of MRSA occurred at a median age of 8 days on admission, which was significantly younger compared to 19 days in noninvasive cases. Sepsis (86.6%) was the most common invasive infection, followed by pneumonia (7.4%), bone and joint infections (3.0%), central nervous system infection (1.5%), and peritonitis (1.5%). Congenital heart disease, low birth weight infant (<2500 g), but not preterm neonates, and bronchopulmonary dysplasia, were more commonly found in invasive MRSA infections. All these isolates were susceptible to vancomycin and linezolid and were resistant to penicillin. Additionally, 69.37% were resistant to erythromycin, 57.66% to clindamycin, 7.04% to levofloxacin, 4.62% to sulfamethoxazole-trimethoprim, 4.29% to minocycline, 1.33% to gentamicin, and 3.13% were intermediate to rifampin.
CONCLUSION
Low age at admission (≤8 days), congenital heart disease, and low birth weight were associated with invasive MRSA infections in neonates, and no isolates resistant to vancomycin and linezolid were found. Determining these risks in suspected neonates may help identify patients with imminent invasive infections who may require intensive monitoring and therapy.
Topics: Infant; Infant, Newborn; Humans; Child; Methicillin-Resistant Staphylococcus aureus; Anti-Bacterial Agents; Vancomycin; Retrospective Studies; Linezolid; Staphylococcal Infections; Inpatients; Microbial Sensitivity Tests; Drug Resistance, Microbial
PubMed: 37231456
DOI: 10.1186/s12887-023-04084-0 -
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 -
Pharmacology Research & Perspectives Dec 2022The most recent consensus guidelines for dosing and monitoring vancomycin recommended the use of area-under-the-curve with Bayesian estimation for therapeutic... (Review)
Review
The most recent consensus guidelines for dosing and monitoring vancomycin recommended the use of area-under-the-curve with Bayesian estimation for therapeutic monitoring. As this is a modern concept in the practice of clinical pharmacy, the main objective of this review is to introduce the fundamentals of Bayesian estimation and its mathematical application as it relates to vancomycin therapeutic drug monitoring. In addition, we aim to identify pharmacokinetic (PK) software programs that incorporate Bayesian estimation for vancomycin dosing and to describe the PK models utilized in those software programs for the adult population. Twelve software programs that utilize Bayesian estimation were identified, which included: Adult and Pediatric Kinetics, Best Dose, ClinCalc, DoseMeRx, ID-ODS, InsightRx, MwPharm++, NextDose, PrecisePK, TDMx, Tucuxi, and VancoCalc. The software programs varied in the population PK models used as the Bayesian a priori. With the presence of various vancomycin Bayesian software programs, it is important to choose those that utilize PK models reflective of the specific patient population.
Topics: Adult; Humans; Child; Vancomycin; Bayes Theorem; Anti-Bacterial Agents; Drug Monitoring; Pharmacy
PubMed: 36398492
DOI: 10.1002/prp2.1026 -
Microbiology Spectrum Aug 2022Vancomycin and β-lactams are clinically important antibiotics that inhibit the formation of peptidoglycan cross-links, but their binding targets are different. The...
Vancomycin and β-lactams are clinically important antibiotics that inhibit the formation of peptidoglycan cross-links, but their binding targets are different. The binding target of vancomycin is d-alanine-d-alanine (d-Ala-d-Ala), whereas that of β-lactam is penicillin-binding proteins (PBPs). In this study, we revealed the divergent effects of peptidoglycan (PG) carboxypeptidase DacA on vancomycin and β-lactam resistance in Escherichia coli and Bacillus subtilis. The deletion of DacA induced sensitivity to most β-lactams, whereas it induced strong resistance toward vancomycin. Notably, both phenotypes did not have a strong association with ld-transpeptidases, which are necessary for the formation of PG 3-3 cross-links and covalent bonds between PG and an Lpp outer membrane (OM) lipoprotein. Vancomycin resistance was induced by an increased amount of decoy d-Ala-d-Ala residues within PG, whereas β-lactam sensitivity was associated with physical interactions between DacA and PBPs. The presence of an OM permeability barrier strongly strengthened vancomycin resistance, but it significantly weakened β-lactam sensitivity. Collectively, our results revealed two distinct functions of DacA, which involved inverse modulation of bacterial resistance to clinically important antibiotics, β-lactams and vancomycin, and presented evidence for a link between DacA and PBPs. Bacterial PG hydrolases play important roles in various aspects of bacterial physiology, including cytokinesis, PG synthesis, quality control of PG, PG recycling, and stress adaptation. Of all the PG hydrolases, the role of PG carboxypeptidases is poorly understood, especially regarding their impacts on antibiotic resistance. We have revealed two distinct functions of PG carboxypeptidase DacA with respect to antibiotic resistance. The deletion of DacA led to sensitivity to most β-lactams, while it caused strong resistance to vancomycin. Our study provides novel insights into the roles of PG carboxypeptidases in the regulation of antibiotic resistance and a potential clue for the development of a drug to improve the clinical efficacy of β-lactam antibiotics.
Topics: Alanine; Anti-Bacterial Agents; Bacterial Proteins; Carboxypeptidases; Escherichia coli; Peptidoglycan; Vancomycin; Vancomycin Resistance; beta-Lactams
PubMed: 35758683
DOI: 10.1128/spectrum.01734-22 -
Biomedical and Environmental Sciences :... May 2023This study aimed to evaluate the clinical benefits of a vancomycin dosage strategy based on a serum trough concentration model in elderly patients. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
This study aimed to evaluate the clinical benefits of a vancomycin dosage strategy based on a serum trough concentration model in elderly patients.
METHODS
This prospective single-center, open-label, randomized controlled trial categorized 66 elderly patients with severe pneumonia into study and control groups. The control group received vancomycin using a regimen decided by the attending physician. Meanwhile, the study group received individualized vancomycin therapy with a dosing strategy based on a serum trough concentration model. The primary endpoint was the proportion of patients with serum trough concentrations reaching the target values. The secondary endpoints were clinical response, vancomycin treatment duration, and vancomycin-associated acute kidney injury (VA-AKI) occurrence.
RESULTS
All patients were at least 60 years old (median age = 81 years). The proportion of patients with target trough concentration achievement (≥ 15 mg/L) with the initial vancomycin regimen was significantly higher in the study group compared to the control group (75.8% . 42.4%, = 0.006). Forty-five patients (68.2%) achieved clinical success, the median duration of vancomycin therapy was 10.0 days, and VA-AKI occurred in eight patients (12.1%). However, there were no significant differences in these parameters between the two groups. The model for predicting vancomycin trough concentrations was upgraded to: serum trough concentration (mg/L) = 17.194 - 0.104 × creatinine clearance rate (mL/min) + 0.313 × vancomycin daily dose [(mg/(kg∙d)].
CONCLUSION
A vancomycin dosage strategy based on a serum trough concentration model can improve the proportion of patients achieving target trough concentrations in elderly patients with severe pneumonia.
Topics: Humans; Aged; Aged, 80 and over; Middle Aged; Vancomycin; Anti-Bacterial Agents; Prospective Studies; Retrospective Studies; Acute Kidney Injury; Pneumonia
PubMed: 37253666
DOI: 10.3967/bes2023.049