In 2009, American Journal of Health-System Pharmacy (AJHP) recommended that targeting vancomycin trough concentrations of 10 mg/L or more because of therapeutic failure and potential risk of developing vancomycin resistance. Therefore, new dosage guidelines that could achieve to these higher target were needed. The aims of this study were to develop dosage guidelines targeting new vancomycin trough concentration and to evaluate the performance of these new guidelines. All data analysis were performed using NONMEM(R). Population pharmacokinetic model was first developed from vancomycin dosage and concentration data collected retrospectively during routine therapeutic drug monitoring in 441 patients, then new vancomycin dosage guidelines were developed by using the model to predict vancomycin trough and peak concentrations in a simulated dataset. The estimates, such as, vancomycin concentration trough level, time to achieve target level, mean error were performed to evaluate and compare difference between conventional dosage and new dosage guidelines. The proposed dosage guidelines were predicted to achieve 43.5% of vancomycin trough level within 10~20 mg/L, which is significantly higher than current guidelines (26.3%). Time to achieve target trough level was 19.4 hours in new guidelines comparing to 93.1 hours in the conventional dosage. Thus, new vancomycin dosage guidelines have been developed to achieve new target trough concentrations earlier and more consistently than conventional guidelines.
This research developed an intravenous (IV) vancomycin dosing nomogram based on the clinical pharmacokinetic data of Korean adult patients. Total 99 pairs of steady-state peak and trough serum concentrations of vancomycin were obtained from 73 adult patients in a tertiary general hospital. Serum vancomycin concentrations were determined to assess the appropriateness of initial vancomycin dosing. Only 47.2% of the cases were within therapeutic range. To characterize the clinical pharmacokinetics (PK) of vancomycin, PK parameters including elimination rate constant ( $K_{e}$) half-life( $T_{1}$2/), clearance (C $l_{van}$), volume of distribution ( $V_{d}$) were calculated by using one-compartment, first order pharmacokinetic equations. PK parameters were evaluated based on the differences of patients'renal function and age. Regression analysis showed a significant correlation between C $l_{van}$ and $C_{cr}$ (C $l_{van}$ = -1.89+0.914 $C_{cr}$ , r=0.763) and between $K_{e}$ and $C_{cr}$ , ( $K_{e}$=-0.0037+0.00139 $C_{cr}$ =0.724). The relationship between $K_{e}$ and $C_{cr}$ , and the mean $V_{d}$ were utilized for developing the nomogram to individualize the initial dosing regimen of vancomycin for the patients with various degrees of renal functions. The nomogram may be used as an efficient tool to determine safe and effective doses of vancomycin for the Korean adult patients.nts.nts.nts.s.nts.
Background: Clostridium difficile associated diarrhea (CDAD) is a leading cause of hospital-associated gastrointestinal illness. Risk factors for CDAD include advanced age, long-term admission, antibiotics, proton-pump inhibitor or $H_2$ blocker use and immunosuppression. The practice guideline of American Journal of Gastroenterology (2013) suggests metronidazole for the first-line therapy of mild-moderate CDAD as well as vancomycin for severe CDAD. MICU inpatients receiving stress ulcer prophylaxis and antibiotics are susceptible to nosocomial CDAD. Therefore, this study aimed to evaluate occurrence and treatment of CDAD in MICU. Methods: Patients who were admitted to the MICU and had CDAD from August 2012 to August 2015 were analyzed retrospectively. Results: Of the 90 patients with CDAD, 20 patients (2.22%) had mild-moderate CDAD (16 received metronidazole and 4 received vancomycin therapy) and 70 patients (77.8%) had severe CDAD(54 received metronidazole and 16 received vancomycin therapy). Among the patients with mild- moderate CDAD, treatment with metronidazole or vancomycin resulted in same clinical cure in 50% of the patients (p=1.00). Among the patients with severe CDAD, treatment with metronidazole or vancomycin resulted in clinical cure in 40.7% and 50.0% of the patients, respectively (p=0.511). Clinical symptoms recurred in 7.4% of the severe CDAD patients treated with metronidazole and 6.3% of those treated with vancomycin(p=0.875). Conclusion: Our findings suggest that metronidazole and vancomycin are equally effective for the treatment of mild-moderate CDAD; however, vancomycin demonstrated higher clinical cure rate and lower recurrence rate for severe CDAD, although the difference was not statistically significant. For better clinical outcomes, appropriate medication use by disease severity is needed.
Emeka, Promise M.;Rasool, Sahibzada T.;Morsy, Mohamed A.;Islam, Mohamed I. Hairul;Chohan, Muhammad S.
The Korean Journal of Physiology and Pharmacology
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제25권4호
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pp.321-331
/
2021
Vancomycin, an antibiotic used occasionally as a last line of treatment for methicillin-resistant Staphylococcus aureus, is reportedly associated with nephrotoxicity. This study aimed at evaluating the protective effects of lutein against vancomycin-induced acute renal injury. Peroxisome proliferator-activated receptor gamma (PPARγ) and its associated role in renoprotection by lutein was also examined. Male BALB/c mice were divided into six treatment groups: control with normal saline, lutein (200 mg/kg), vancomycin (250 mg/kg), vancomycin (500 mg/kg), vancomycin (250 mg/kg) with lutein, and vancomycin (500 mg/kg) with lutein groups; they were euthanized after 7 days of treatment. Thereafter, samples of blood, urine, and kidney tissue of the mice were analyzed, followed by the determination of levels of N-acetyl-β-D-glucosaminidase (NAG) in the urine, renal creatine kinase; protein carbonyl, malondialdehyde, and caspase-3 in the kidney; and the expression of PPARγ, nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear factor-kappaB (NF-κB) in renal tissue. Results showed that the levels of protein carbonyl and malondialdehyde, and the activity of NAG, creatine kinase and caspase-3, were significantly increased in the vancomycin-treatment groups. Moreover, the levels of Nrf2 significantly decreased, while NF-κB expression increased. Lutein ameliorated these effects, and significantly increased PPARγ expression. Furthermore, it attenuated vancomycin-induced histological alterations such as, tissue necrosis and hypertrophy. Therefore, we conclude that lutein protects against vancomycin-induced renal injury by potentially upregulating PPARγ/Nrf2 expression in the renal tissues, and consequently downregulating the pathways: inflammation by NF-κB and apoptosis by caspase-3.
Purpose: The purpose of this study was to identify factors influencing Vancomycin-resistant enterococcus infection control among nurses in intensive care units. Method: Data were collected from August 15 to October 14, 2007 from 188 nurses working in intensive care units. The nurses answered a 26 item-questionnaire, which included management of the cohort (14 items), hand washing (6 items) and management of the environment (6 items). Descriptive statistics, t or F test, ANOVA, and multiple regression analysis were used with SPSS PC+ 14.0 to analyze the data. Results: The participant's level of awareness of Vancomycin-resistant enterococcus infection control was 3.87; that of compliance was 3.74. Significant factors influencing the level of compliance with Vancomycin-resistant enterococcus infection control were'the level of the awareness' and 'the type of intensive care unit'. These two variables accounted for 21.0% of variance for compliance with the Vancomycin-resistant enterococcus infection control among the participants. Conclusion: In order to develop a strategy to increase the compliance with Vancomycin-resistant enterococcus infection control, it is necessary to be concerned about 'the level of the awareness', 'the type of intensive care unit;', and 'experiences of caring for patients with Vancomycin-resistant enterococcus'.
The 'Pharmacy and Therapeutic Committee' decided to restrict the use of vancomycin which was categorized into restricted antimicrobials, among general, reserved and restricted antimicrobials. The committee also established prescribing guidelines of vancomycin in Seoul National University Hospital, May, 1991. Especially, the restricted antimicrobials should be used after approval by infectious disease specialist physician. A retrospective drug use evaluation (DUE) on vancomycin has been conducted to compare with the previous vancomycin DUE study in 1990. 'Criteria for DUE on vancomycin' was modified from Am J Hosp Pharm. Total 65 charts of patients were retrospectively reviewed from July 1991 to June 1992 in Seoul National University Children's Hospital. The justification of use was improved from 56% to 75% comparing with the previous study. In analyzing process indicators, several criteria including body temperature monitoring, WBC monitoring and use of concomitant antibiotics were well documented, but serum creatinine monitoring, culture and sensitivity test and level monitoring were infrequently performed, while the accepted level has been improved. Accepted level for appropriate initial dosage and duration of therapy were decreased. In outcome analysis, blood culture after discontinuing the drug was relatively well documented compared with the previous study. As the results, the approval vancomycin use was shown to be effective and rational in antibiotic therapy. And it is suggested that the above findings should be communicated to the medical staff, and a active intervention, such as feedback control, also be necessary for rational drug use.
Kim, Dae-Il;Im, Mi-Sun;Choi, Jin-Hyoung;Lee, Jin-A;Choi, Eun Hwa;Lee, Hoan-Jong
Clinical and Experimental Pediatrics
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제53권12호
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pp.1000-1005
/
2010
Purpose: This study aimed to determine the optimal initial vancomycin dose to achieve appropriate trough levels in pediatric patients. Methods: We analyzed clinical data for 309 children treated with intravenous vancomycin between 2004 and 2009 at 2 different hospitals in South Korea. The patients were 1-16 years old and exhibited normal renal function. Patient data, including reason for treatment and initial dosing regimen, were reviewed. Two subgroups were identified and compared according to initial vancomycin dose: 40 (35-45) mg/kg/day and 60 (55-65) mg/kg/day. Trough levels were obtained at steady state after at least 4 doses of vancomycin. Results: Patients who received vancomycin had post-operation or wound-related infections (37.2%), localized infection (12.9%), catheter-related infections (9.4%), meningitis (8.7%), or endocarditis (6.8%). Pathogens were confirmed in 79 cases: 28 cases of methicillin-resistant $Staphylococcus$$epidermidis$ (35.4%) and 25 of methicillin-resistant $Staphylococcus$$aureus$ (31.6%). Out of the 309 patients, 201 (65%) received vancomycin at 40 mg/kg/day and 108 (35%) at 60 mg/kg/day. Average trough concentrations were significantly different between the groups ($P$<0.001). Trough levels over 10 mg/L were less likely to be achieved in the 40 mg/kg/day group (14%) than in the 60 mg/kg/day group (49%) ($P$<0.001). There were no differences in renal function deterioration between the groups. Conclusion: A common vancomycin dosing regimen, 40 mg/kg/day, was not high enough to achieve trough levels of over 10 mg/L in pediatric patients. Careful drug monitoring must be performed, and increasing initial dose of vancomycin should be considered in pediatric patients.
Objective: Infection is very common in the elderly, so there is a high prevalence of antibiotics use among this population. Especially, due to the emergence of resistant bacteria, the use of vancomycin is growing. The purpose of this study was to evaluate risk factors associated with vancomycin-induced nephrotoxicity in elderly patients. Methods: The subjects of this study were patients over 18 years old who received intravenous vancomycin in a general hospital located in Gangneung-si, Korea between August 1, 2013 and July 31, 2015. Data collection regarding vancomycin use and baseline characteristics was conducted using computerized hospital database. Logistic regression analysis was used to identify risk factors associated with vancomycin-induced nephrotoxicity. Results: A total of 290 patients were finally included, and 191(66%) out of these patients were age 65 or older. The incidence of vancomycin-induced nephrotoxicity was 11.0%, 12.6%, and 7.0% in the all adult patients, the elderly patients, and the non-elderly patients, respectively. There were significant differences in comorbidities between patients with nephrotoxicity and patients without nephrotoxicity in the all adult patients, and there were significant differences in vancomycin duration, comorbidities, and number of nephrotoxic agents between patients with nephrotoxicity and patients without nephrotoxicity in the elderly patients. However, according to the logistic regression analysis, there was no significant risk factor that increases the incidence of vancomycin-induced nephrotoxicity in all three age groups. Conclusion: There were no differences in risk factors that increase the incidence of vancomycin-induced nephrotoxicity between all adult patients, elderly patients, and non-elderly patients. Further studies with larger sample sizes to identify risk factors associated with vancomycin-induced nephrotoxicity in the elderly to improve the outcome of pharmacotherapy are required.
Leuconostoc spp. is intrinsically resistant against vancomycin and rarely causes the infection in immunocompromised patients. In this report, we describe a fatal case of Leuconostoc lactis bacteremia in a patient with biliary tract stent insertion to resolve the biliary tract obstruction by multiple pseudocysts in the pancreatic head region. Leuconostic lactis isolated from the blood of the patients was confirmed by 16S rRNA sequencing and this isolate was susceptible against most antibiotics, including levofloxacin, penicillin, erythromycin and cefotaxime except vancomycin. The septic shock and multi-organ failure was abruptly progressed due to delayed use of adequate antibiotic. Using vancomycin as the empirical antibiotics in a bacteremic patient by Gram positive cocci, the treatment failures by the isolates with intrinsic resistance against vancomycin have to be considered. In addition, the prompt and accurate identification of Leuconostoc spp. are very important to select the adequate antibiotics.
This research is conducted to evaluate the clinical and economic benefits from therapeutic drug monitoring(TDM) service on vancomycin in a tertiary general hospital. Total 99 pairs of steady state peak and trough concentrations of vancomycin were obtained from 73 patients. To see the clinical benefits, the appropriateness of vancomycin dosing before TDM was evaluated. In 72 pairs of vancomycin blood concentrations obtained prior to TDM consultation, $47.2\%$ of the cases had reached within therapeutic range. Serum vancomycin levels in patients with $40{\leq}CLcr<60$ (ml/min) were higher and than the levels in patients with 40>CLcr and $60{\leq}CLcr$ (ml/min). Dose reduction rate in patients with creatinine clearance $40{\leq}CLcr<60$ (ml/min) were also significantly higher than those of compared groups ($61.5\%$, p=0.0138). Serum vancomycin concentrations were re-obtained from 21 patients who received modified dose through TDM service. Ninety percent (19/21cases) of them were within the target therapeutic range. For the evaluation of economic benefits from TDM consultation, estimated cost savings were calculated in those patients. The total drug saving were 586 vials in 21 patients. The calculated mean cost saving from the drugs was 314,570 won (range: $11,273\sim473,466)$ per patient. The study revealed that TDM service for vancomycin is necessary because empirical dosing is not effective for obtaining therapeutic drug level, especially patients with mild renal insufficiencies. The cost saving from TDM is also beneficial for the patients.
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