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Surgical Infections Dec 2015Current recommendations suggest that vancomycin dosing utilize actual rather than ideal body weight in obese patients. Thus, obese patients may be at greater risk for...
BACKGROUND
Current recommendations suggest that vancomycin dosing utilize actual rather than ideal body weight in obese patients. Thus, obese patients may be at greater risk for nephrotoxicity. The purpose of this study was to compare the incidence of nephrotoxicity in vancomycin-treated obese and lean patients at our institution, where unadjusted, actual body weight-based dosing (capped at 2 g per dose twice daily) is used. We expected obese patients to experience a greater incidence of nephrotoxicity than lean patients.
METHODS
This study examined a retrospective cohort of patients treated with vancomycin for gram-positive or mixed infections in our facility from 2005-2009 who were not receiving hemodialysis at the time of admission. Patients were stratified by body mass index (BMI; obese ≥30 kg/m(2) vs. lean <30 kg/m(2)). Relative risk (RR), 95% confidence intervals (CIs), and p values were computed using a generalized estimating equation to accommodate a correlated data structure corresponding to multiple episodes of infection per individual. Multivariable analysis was performed.
RESULTS
A total of 530 patients (207 obese; 323 lean) with 1,007 episodes of infection were treated with vancomycin. Patient demographics, co-morbidities, sites of infection, and infecting organisms were similar in the two groups. Female gender (p=0.042), diabetes mellitus (DM) (p=0.018), and hypertension (HTN) (p=0.0009) were more often associated with obesity, whereas allografts (p=0.022) and peripheral vascular disease (p=0.036) were more often present in lean patients. The Acute Physiology and Chronic Health Evaluation II score >21 was the only variable associated with nephrotoxicity (p=0.039). After adjusting for statistically significant variables, obesity was found not to be associated with a greater risk of nephrotoxicity (RR=0.98; 95% CI=0.93-1.04; p=0.59).
CONCLUSION
No difference in nephrotoxicity was observed between lean and obese patients treated with vancomycin at our institution.
Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Female; Humans; Incidence; Male; Middle Aged; Obesity; Retrospective Studies; Vancomycin
PubMed: 26324996
DOI: 10.1089/sur.2014.198 -
European Journal of Hospital Pharmacy :... Mar 2020This study aimed to characterise vancomycin pharmacokinetics in critically ill neonates undergoing extracorporeal membrane oxygenation.
OBJECTIVE
This study aimed to characterise vancomycin pharmacokinetics in critically ill neonates undergoing extracorporeal membrane oxygenation.
METHODS
In a retrospective analysis, the pharmacokinetics of vancomycin were determined in 25 full-term neonates receiving extracorporeal membrane oxygenation and compared with those of matched controls (n = 25) not receiving extracorporeal membrane oxygenation.
RESULTS
The half-life of vancomycin in the neonates undergoing extracorporeal membrane oxygenation was significantly prolonged compared with that in the controls (17.45 ± 11.01 hour vs 5.92 ± 2.70 hour, P<0.001). Clearance decreased significantly in the extracorporeal membrane oxygenation group relative to the control group (0.03 ± 0.02 L/kg/hr vs 0.08 ± 0.05 L/kg/hr, P<0.001). No significant difference was found in the volume of distribution between the two groups (0.63 ± 0.30 L/kg in the extracorporeal membrane oxygenation group vs 0.57 ± 0.14 L/kg/hr in control, P=0.596). Clearance values were significantly correlated with serum creatinine (r = - 0.528, P<0.001). In the subgroup analysis using patients with serum creatinine < 0.5 mg/dL, similar results were obtained including significantly prolonged half-life (11.52 ± 6.31 hour vs 5.44 ± 2.36 hour, P<0.001) and decreased clearance (0.05 ± 0.02 L/kg/hr vs 0.09 ± 0.05 L/kg/hr, P<0.001) in the extracorporeal membrane oxygenation group relative to the control group.
CONCLUSIONS
Vancomycin clearance decreased significantly in the neonates undergoing extracorporeal membrane oxygenation compared with the controls. Dosing adjustments of vancomycin and close therapeutic drug monitoring are required for the safe and effective management of neonates during extracorporeal membrane oxygenation.
Topics: Anti-Bacterial Agents; Critical Illness; Drug Monitoring; Extracorporeal Membrane Oxygenation; Female; Half-Life; Humans; Infant, Newborn; Infusions, Intravenous; Male; Retrospective Studies; Vancomycin
PubMed: 32296501
DOI: 10.1136/ejhpharm-2018-001720 -
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 -
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 -
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 -
European Journal of Hospital Pharmacy :... Sep 2020To analyse the influence of factors on the steady-state trough concentration (C) of vancomycin, especially in patients with augmented renal clearance, and to provide a...
OBJECTIVE
To analyse the influence of factors on the steady-state trough concentration (C) of vancomycin, especially in patients with augmented renal clearance, and to provide a reference for clinical application.
METHODS
Data on patient demographics, routine blood examination, hepatic function and kidney function were collected from May 2013 to October 2016. A total of 292 patients were enrolled and correlations between Cof vancomycin and other test indices were analysed by SPSS software.
RESULTS
The patients with augmented renal clearance were significantly younger with relatively lower C values and higher weight, ALB and PLT compared to others. And age was the most important factor of Camong subgroups of ARC.
CONCLUSIONS
Inpatients with augmented renal clearance,vancomycin C was mainly affected by age. Clinicians and pharmacists should adjust the dosage regimen in a timely manner based on therapeutic drug monitoring and these influencing factors.
Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Anti-Bacterial Agents; Child; Creatinine; Drug Monitoring; Female; Humans; Kidney; Male; Metabolic Clearance Rate; Middle Aged; Vancomycin; Young Adult
PubMed: 32839259
DOI: 10.1136/ejhpharm-2018-001781 -
Pediatrics and Neonatology May 2022The currently advocated ratio of area under the curve (AUC) over 24 h to minimum inhibitory concentration (AUC/MIC) > 400 and AUC < 600 mg h/L as the therapeutic...
Optimal exposure targets for vancomycin in the treatment of neonatal coagulase-negative Staphylococcus infection: A retrospective study based on electronic medical records.
BACKGROUND
The currently advocated ratio of area under the curve (AUC) over 24 h to minimum inhibitory concentration (AUC/MIC) > 400 and AUC < 600 mg h/L as the therapeutic drug monitoring (TDM) target of vancomycin is based on data from multiple observational studies in adult patients with methicillin-resistant Staphylococcus aureus (MRSA) infection. It may not be applicable to newborns with coagulase-negative Staphylococcus (CoNS) infection. We conducted a retrospective study to identify the optimal exposure targets for vancomycin in the treatment of neonatal CoNS infection.
METHODS
Based on the inclusion and exclusion criteria, serum vancomycin concentration, demographics, clinical data, and related laboratory data of newborns who received vancomycin intravenous infusion from June 1, 2016 to February 1, 2021 were collected retrospectively. The AUC was calculated using the maximum a posteriori Bayesian (MAPB) method. The vancomycin exposure threshold of AUC/MIC for efficacy and AUC for toxicity (acute kidney injury, AKI) were determined based on receiver operating characteristic (ROC) curve analysis. The correlation between vancomycin exposure and both clinical effect and nephrotoxicity was analyzed using logistic multivariate regression.
RESULTS
In total, 153 patients and 245 vancomycin concentrations (160 trough and 85 peak concentrations) were included. The ROC curve analysis showed that the exposure thresholds of AUC/MIC for clinical efficacy and AUC for nephrotoxicity were 281 and 602 mg h/L, respectively. The multivariate regression analysis showed that AUC/MIC > 280 was a predictor of efficacy (OR: 13.960, 95% CI: 1.891-103.078, P < 0.05) and AUC > 600 mg h/L was associated with AKI (OR: 9.008, 95% CI: 2.706-29.983, P < 0.05). The vancomycin AUC/MIC threshold for treating neonatal CoNS infection with vancomycin is lower than the currently advocated AUC/MIC >400.
CONCLUSION
The optimal exposure targets for vancomycin in neonatal CoNS infection were AUC/MIC > 280 and AUC < 600 mg h/L.
Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Bayes Theorem; Coagulase; Electronic Health Records; Female; Humans; Infant, Newborn; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Retrospective Studies; Staphylococcal Infections; Vancomycin
PubMed: 35190273
DOI: 10.1016/j.pedneo.2021.11.010 -
Drug Design, Development and Therapy 2021To date, outcome data with a large sample size and data regarding the clinical outcomes of pharmacokinetic-guided (PK) dosing of vancomycin are limited. (Observational Study)
Observational Study
BACKGROUND
To date, outcome data with a large sample size and data regarding the clinical outcomes of pharmacokinetic-guided (PK) dosing of vancomycin are limited.
AIM
We evaluated the pharmacokinetic and clinical outcomes of a PK-guided dosing advisory program, pharmacokinetic consultation service (PKCS), in vancomycin treatment.
METHODS
We investigated vancomycin therapeutic drug monitoring (TDM) and PKCS use through a retrospective review of patients who had serum vancomycin trough concentration data from October 2017 to November 2018. Among these patients, we selected non-critically ill adult patients satisfying our selection criteria to evaluate the effect of PKCS. Target trough attainment rate, time to target attainment, vancomycin-induced nephrotoxicity (VIN), vancomycin treatment failure rate, and duration of vancomycin therapy were compared between patients whose dosing was adjusted according to PKCS (PKCS group), and those whose dose was adjusted at the discretion of the attending physician (non-PKCS group).
RESULTS
A total of 280 patients met the selection criteria for the VIN analysis (PKCS, n=134; non-PKCS, n=146). The incidence of VIN was similar between the two groups (PKCS, n=5; non-PKCS, n=5); however, the target attainment rate was higher in the PKCS group (75% vs 60%, = 0.012). The time to target attainment was similar between the two groups. Further exclusions yielded 112 patients for the clinical outcome evaluation (PKCS, n=51; non-PKCS, n=61). The treatment failure rate was similar, and the duration of vancomycin therapy was longer in the PKCS group (12 vs 8 days, = 0.008).
CONCLUSION
In non-critically ill patients, an increase in target trough achieved by PKCS did not lead to decreased vancomycin treatment failures, shorter vancomycin treatment, or decreased nephrotoxicity in vancomycin treatment. Considering the excessive amount of effort currently put into vancomycin dosing and monitoring, more selective criteria for individualized pharmacokinetic-guided dosing needs to be applied.
Topics: Aged; Anti-Bacterial Agents; Dose-Response Relationship, Drug; Drug Monitoring; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Referral and Consultation; Retrospective Studies; Staphylococcus aureus; Treatment Outcome; Vancomycin
PubMed: 33692613
DOI: 10.2147/DDDT.S285488 -
Kidney360 Feb 2022
Topics: Fantasy; Humans; Kidney; Kidney Diseases; Vancomycin
PubMed: 35373135
DOI: 10.34067/KID.0007282021 -
Journal of Mass Spectrometry : JMS Mar 2021Suboptimal antibiotic dosing has been identified as one of the key drivers in the development of multidrug-resistant (MDR) bacteria that have become a global health...
Suboptimal antibiotic dosing has been identified as one of the key drivers in the development of multidrug-resistant (MDR) bacteria that have become a global health concern. Aminoglycosides and vancomycin are broad-spectrum antibiotics used to treat critically ill patients infected by a variety of MDR bacterial species. Resistance to these antibiotics is becoming more prevalent. In order to design proper antibiotic regimens that maximize efficacy and minimize the development of resistance, it is pivotal to obtain the in situ pharmacokinetic-pharmacodynamic profiles at the sites of infection. Mass spectrometry imaging (MSI) is the ideal technique to achieve this. Aminoglycosides, due to their structure, suffer from poor ionization efficiency. Additionally, ion suppression effects by endogenous molecules greatly inhibit the detection of aminoglycosides and vancomycin at therapeutic levels. In the current study, an optimized method was developed that enabled the detection of these antibiotics by MSI. Tissue spotting experiments demonstrated a 5-, 15-, 35-, and 54-fold increase in detection sensitivity in the washed samples for kanamycin, amikacin, streptomycin, and vancomycin, respectively. Tissue mimetic models were utilized to optimize the washing time and matrix additive concentration. These studies determined the improved limit of detection was 40 to 5 μg/g of tissue for vancomycin and streptomycin, and 40 to 10 μg/g of tissue for kanamycin and amikacin. The optimized protocol was applied to lung sections from mice dosed with therapeutic levels of kanamycin and vancomycin. The washing protocol enabled the first drug distribution investigations of aminoglycosides and vancomycin by MSI, paving the way for site-of-disease antibiotic penetration studies.
Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Female; Mice; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Tissue Distribution; Vancomycin
PubMed: 33586279
DOI: 10.1002/jms.4708