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We report an unusual case of lupus flare induced by intravenous vancomycin in a patient with systemic lupus erythematosus. Due to methicillin resistant staphylococcus aureus in wound culture, intravenous vancomycin was administered to the patient. The patient had been on vancomycin for several days then she experienced fever, malar rash, and vomiting. Based on laboratory results, it was confirmed as lupus flare. Oral prednisolone was given to the patient for symptom control. However, when vancomycin was readministered, the patient had similar symptom to the previous one more intensively. Vancomycin was stopped then the patient became stable. This case report demonstrates that intravenous vancomycin may manifest as lupus flare in patients with systemic lupus erythematosus.

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®. 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.

The objective of this study was to analyze and to improve therapeutic drug monitoring(TDM) service of vancomycin in a local hospital. Patients with TDM service between September 2005 and December 2008 were included and the data were collected for vancomycin use and components of TDM. During that period, 421 cases of TDM service of vancomycin in 236 patients were retrospectively reviewed. The first dosages of vancomycin were appropriate in 135(57.2%) patients and administration of vancomycin was discontinued in 126(53.4%) patients due to therapeutic failure or adverse drug reaction. MRSA was identified in 191(80.9%) patients and 135(70.7%) samples for the identification were sputum. According to the TDM reports, 232(55.1%) serum samples were obtained at the steady-state conditions and 55.5% of the samples that were drawn before the steady-state was due to the physician's inappropriate knowledge about the steady-state. Based on the time of vancomycin administration, 35.8% of the samples were not obtained at the recommended sampling time. For the patients in general wards, the most common reason for the incorrect samples was routine serum sampling by the laboratory medicine phlebotomists between 6 and 8 a.m. except sunday. In contrast, samples drawn by nurses or physicians at inappropriate time were the most common reason for the incorrect samples with patients in the intensive care units. Physicians accepted 68.5% of the recommendations for vancomycin dosage and administration. In conclusion, TDM service of vancomycin needs to be improved in inappropriate sampling time and vancomycin dosage. For solving these problems, current team made of TDM pharmacists and physicians of laboratory medicine can be expanded to include a physician of infectious diseases, nurses and laboratory medicine phlebotomists as new members. Through the TDM service of vancomycin by the new team, we can settle the problems and make the guideline for the scientific controversies associated with therapeutic monitoring of vancomycin.

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.

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 H2 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.

Background : A recently published review on the therapeutic monitoring of the vancomycin has recommended maintaining the vancomycin trough concentration at 15-20 mg/L for severe infections caused by methicillin-resistant Staphylococcus aureus. Additionally, in Seoul St. Mary’s Hospital, the vancomycin trough concentrations above 15 mg/L are increasingly recommended for therapeutic outcome. The purpose of the study was to analyze the efficacy and safety according to the vancomycin trough concentration and to apply the trough concentration in clinical trials. Methods : A retrospective analysis was conducted among patients age 18 and older detected Gram-positive cocci at Seoul St. Mary’s Hospital and received vancomycin for three days or more October 2018-May 2019. The patients were stratified by the mean vancomycin trough concentration [T1 (<15 mg/L), T2 (≥15 mg/L)]. To evaluate the efficacy, we assessed the rate of the two consecutive growth-negative blood cultures and the mean of the c-reactive protein (CRP) change. The safety was evaluated through the percentage of the serum creatinine (SCr) and blood urea nitrogen (BUN) levels exceeding normal range after administration. Results : Of the 89 patients, 72 patients were in T1. The mean trough concentration of the vancomycin was 9.0±3.0 mg/L in T1 and 19.5±7.2 mg/L in the T2 (p<0.001). The T2 showed significantly higher rates of the two consecutive growth-negative blood cultures which were 58.8% of T2 and 26.4% in the T1 (p=0.014). The CRP change was not significantly higher in the T2 (p=0.577). The proportion of the SCr and BUN beyond the normal range after the vancomycin administration was not statistically significant different (p=0.251, p=0.154). Conclusion : The patients with the mean trough concentration of the vancomycin higher than 15 mg/L had significantly higher rates of the two consecutive growth-negative blood cultures, and there was no significant difference in the incidence of renal toxicity. Thus, increasing the vancomycin trough concentration to 15 mg/L or higher could enhance the therapeutic effect without significant increase in the nephrotoxicity.

Purpose : This study was undertaken to find an appropriate vancomycin dosage for patients who had undergone hemodialysis. Methods : We retrospectively reviewed the medical records of patients who had undergone hemodialysis and were administered i.v vancomycin between 1st Jan, 2014 to 30th Jun, 2016. The association between vancomycin dosage, serum trough concentrations and hemodialysis were further evaluated. Results : Only 18(26.9%) serum samples achieved the therapeutic range; 16(23.9%) were complicated infections, and 2(3.0%) were simple infections. Most patients’serum concentrations were under the therapeutic range. Frequency of hemodialysis and vancomycin dosage had an effect on the serum concentrations. Totally, 32 patients with complicated infections had undergone hemodialysis three times per week. Serum concentration of 14(43.8%) patients achieved the therapeutic range, of which 10(42.8%) patients were administered i.v vancomycin 15~20 mg/kg, every 3 or 4 days. Of the 49 patients who had undergone hemodialysis three times per week, the serum concentration of only 9(18.4%) patients was under 10 mg/L. Conclusion : We recommend an i.v vancomycin dosage of 15~20 mg/kg, every 3 or 4 days, to treat patients undergoing regular hemodialysis, who present with complicated infections. However, further evaluation of the vancomycin dosage in hemodialysis patents should be performed, to confirm the appropriacy of the recommendation.

Vancomycin-associated nephrotoxicity(VAN) is a well-known adverse effect of vancomycin. The risk further increases in patients who are on concomitant nephrotoxic agents and/orwith higher vancomycin dose, longer duration of use, undergoing prolonged duration of therapy, etc. Although the 2009 consensus statements from American Society of Health-System Pharmacistsrecommended the target trough concentration of above 10 mg/L, the higher trough concentrationshave been associated with increased VAN. The purpose of this study is to determine the incidenceand risk factors for VAN. In retrospective analysis of adult patients who received vancomycin at Samsung Medical Center, wecollected data on patient characteristics as follows; treatment, including daily doses; duration ofvancomycin therapy and concomitant nephrotoxic agents; and serum creatinine and vancomycintrough levels. We excluded the patients with the baseline serum creatinine of >2 mg/dL or those witha known history of end-stage renal disease or dialysis at baseline. Clinical characteristics were compared between the patients with and without nephrotoxicity to identify the risk factors associatedwith VAN. The relationship was observed between the risk factors and the occurrence of nephrotoxicityby using multivariate logistic regression analysis. Of 191 vancomycin-treated patients, nephrotoxicity occurred in 17.8%. In multivariate analysis,higher vancomycin trough concentrations and the use of concomitant nephrotoxic agents were independentlyassociated with nephrotoxicity. Vancomycin trough concentrations of >20 mg/L appearedto be associated with a 6 to 8-fold increased risk of nephrotoxicity, compared to the trough concentrationsof <15 mg/L. Our findings suggest the need for additional studies to assess the relationship between the highervancomycin target trough concentrations and VAN.

Background : Recent guidelines recommend that vancomycin trough concentrations should be maintained above 10mg/L and 15-20mg/L for complicated infections. Several studies have suggested that higher trough values are associated with higher risk of nephrotoxicity. The aim of this study was to determine the incidence and risk factors for vancomycin associated nephrotoxicity, among patients managed through therapeutic drug monitoring (TDM). Method : A retrospective study was conducted among adult patients who received vancomycin TDM service more than twice, at Seoul National University Hospital between July, 2009 and December, 2009. Patients were excluded, if they had a baseline serum creatinine level of 〉1.4mg/dl, were in ICU when they initiated vancomycin therapy, or received vancomycin with nephrotoxic agents during therapy. Vancomycin associated nephrotoxicity was defined as an increase in serum creatinine of 0.5mg/dl from the baseline, on at least two consecutive days. Risk factors for nephrotoxicity are classified into patient-related factors, underlying disease-related factors, drug-related factors, and TDM-related factors. Univariate and multivariate analyses were performed for comparison of the patients. Results : The incidence of vancomycin associated nephrotoxicity is 21/173 (12.1%) in patients managed through vancomycin therapeutic monitoring. Patients with nephrotoxicity had higher average and 1st trough concentration (19.9mg/L vs. 12.2mg/L, p=0.005; 20.6mg/L vs. 19.9mg/L, p=0.015), than patients without nephrotoxicity. Vancomycin duration therapy of ≥14days (76.2% vs. 50%, p=0.024) were associated with increasing nephrotoxicity. Presence of underlying diseases (diabetes, heart failure, hepatic disease) was likely to be associated with development of nephrotoxicity, though this was not statistically significant. Conclusions : Vancomycin trough concentration (≥15mg/L) and duration of therapy (≥14days) are identified to be significant predictors of nephrotoxicity. It is necessary to carry out more studies, focusing in particular on the association between vancomycin nephrotoxicity and underlying disease.

The therapeutic concentration maintenance of vancomycin has become an important concern due to emergence of vancomycin-intermediate and vancomycin-resistant Staphylococcus aureus, and it can be achieved through therapeutic drug monitoring (TDM) service. This study was designed to evaluate the usefulness of TDM service in Korean patients. Patients received TDM service between December 2002 and February 2005 in Korea University Anam Hospital were categorized into four groups. Three of these groups were based on modified doses of vancomycin after TDM service: group A, B and C had ＞ 2 g/day, 2 g/day and ＜ 2 g/day, respectively, and patients on dialysis belong to the fourth group D. Each group was evaluated in accordance with the guidelines suggested by Korean Society of Infectious Diseases and Korean Society for Chemotherapy. These guidelines that encourage TDM service include concomitant therapy with nephrotoxic agents, high dose vancomycin therapy, unstable renal function, dialysis, central nervous system infection, serious disease and neonate. Total 702 patients (412 males, 290 females, average 55.96 ± 16.97 years in age, 60.37 ± 11.37 kg in weight and 12.56 ± 11.23 days in vancomycin use) were retrospectively reviewed. The rate of group A who satisfied the guidelines was 58.7%(74/126): group B, 53.8%(120/223); group C, 76.0%(219/288); group D, 100%(65/65). 68.1%(478/702) of all patients satisfied the guidelines, and 68.2%(479/702) of patients were r ecommended to modify vancomycin dose. The number of patients who met the guidelines or were recommended to modify vancomycin dose reached 85.3%(599/702) and, it can be concluded that TDM service is useful in majority of patients receiving vancomycin therapy.

Vancomycin is the drug of choice for treatment of methicillin-resistant coagulase-negative Staphylococcus aureus (MRSA) infection in neonatal intensive care units (NICUs). Although the Infectious Disease Society of America (IDSA) and American Society of Hospital Pharmacists (ASHP) recommended that vancomycin trough concentrations remain above 10 mcg/ml in order to prevent resistance, the Neofax?? guidelines have not recommended a new dosing guideline to achieve the therapeutic dosing goal; this has consequently raised concerns in relation to reaching the therapeutic range. The purpose of this study was to evaluate the rate of achieving serum trough concentrations ranged 10~20 mcg/ml in NICU patients when initial vancomycin dosing was carried out as recommended by the Neofax?? guidelines. A retrospective chart review was conducted of 63 NICU patients at Seoul National University Bundang Hospital, for whom there was at least one piece of data relating to trough level serum concentrations between June 25, 2003 and July 31, 2015. The duration of therapy, total length of stay, dose adjustments to attain therapeutic range, total daily dose and adverse effects were evaluated. For the primary outcome, 3 patients were excluded because of renal dysfunction, 13 patients were excluded because the initial trough was drawn inappropriately, and 14 patients were excluded because vancomycin was not administrated according to the Neofax?? guidelines. Only 6 of 38 (15.8%) patients achieved the therapeutic range with empiric dosing following the Neofax?? guidelines. Postmenstrual age and weight at the beginning of vancomycin treatment were significantly associated with the achievement of the vancomycin therapeutic range. Two out of 60 (3.3%) patients experienced nephrotoxicity. In conclusion, the status of attaining therapeutic range by following the Neofax?? dosing guideline was suboptimal. Further studies are urgently needed to assist the development of appropriate dosing guidelines for the treatment of MRSA infections in neonates.

As interest in patients’safety has been increasing, the timely administration ofscheduled medication is being more and more emphasized. In 2013, the research hospital establishedthe guideline for‘ time-critical medications (TCM)’based on the‘30-minute rule’from theInstitute for Safe Medication Practices (ISMP) and the ‘medication management and use (MMU)standard’of the Joint Commission International. According to this guideline, if the maintenancedoses of these medications are administrated early or delayed for more than 30 minutes before orafter the scheduled dose, such effect may cause harm or result in substantial sub-optimal therapyor pharmacological effect. The research hospital has a total 125 TCMs, including those medications that need therapeutic drug monitoring. At the pharmacy, before prepared TCMs aredelivered to each ward, warning labels are attached to each TCM during the inspection procedureby charging pharmacists. If delayed or early administration of TCM occurs, it should be reportedas a near miss to the internal patient safety management program. Among these time-criticalmedications, this research was conducted on vancomycin of which dosing time could significantlyaffect the maintenance of therapeutic plasma concentration. From April to August 2013, vancomycinadministration status (administration time adherence, and the reason of early or delayedadministration, where applicable) was inspected at the wards of pulmonary medicine, internalmedicine intensive care unit, and emergency center. Overall, vancomycin was administrated a total 1,638 times in 167 patients in 3 investigateddepartments. Except for the 563 first doses, the administration time of 997 cases was adhered(administration time adherence rate = 92.74%, 997/1,075). The reason for early or delayed administrationwas omitted in most cases (61.54%, 48/78). The most frequently marked reason for suchaction was the‘ change of the administration time based on the TDM result or change the ward’(26.92%, 21/78) and‘ other medical care procedures(operation, lab test , etc)’(11.54%, 9/78). The adherence rate of vancomycin timely administration was high and well maintained in theresearch hospital. Pharmacists also played an important role in this favorable result. Furthersustained education of healthcare professionals will be needed for a more detail management ofsome early of delayed administration.

Our study aims to analyze the effect of the initial dose of vancomycin in 146 criticallyill patients, including those with impaired kidney function, in order to determine a clinically relevantloading dose (25~30 mg/kg). From January 1, 2010 ~ May 31, 2013, vancomycin dosageschedules and plasma concentrations in ICU patients in our hospital were collected. The plasmaconcentration was predicted prior to the next dose after the initial dose of vancomycin. The concentrationat which vancomycin treatment failed was defined to be under 10 mg/l. The averageconcentration after the initial dose of vancomycin was 7.5±3.2 mg/l, which meant that only 20.5% of them reached the target concentration. Compared to the other groups, the one thatreceived over 25 mg per kg, the initial concentration was 10.4±3.1 mg/l, which translated into62.5% of them reaching the target concentration without differences in kidney function and alower mortality rate 28 days after the vancomycin dose. In conclusion, a dose greater than 25 mgvancomycin per kg of body weight is required, regardless of kidney function, in order to reachtherapeutic concentrations with only one dose prior to reaching the steady state.

It is now well established that the bactericidal activity of vancomycin is not temporally stationary. As a result, clinical pharmacokinetics consultation service (CPCS) become necessary for the maintenance of the trough concentration of vancomycin to minimize adverse effect while maximizing therapeutic effect. In particular, CPCS was essential in geriatric, pediatric patients or patients over moderate stage kidney disease patients with creatinine clearance (CLcr) < 60ml/min (by National Kidney Foundation standards) for successful vancomycin therapy. However, in previous studies, CPSS was claimed to be not clinically relevant in adult patients with CLcr ≥ 60ml/min. Therefore, the objective of the present study was to evaluate the merit of CPCS and the factor(s) influencing the results of CPCS in adult patients with CLcr ≥ 60ml/min. Accordingly, the patients, from 18 to 65 years of age, with calculated CLcr values above of 60ml/min by Cockroft-Gault equation received vancomycin CPCS between January and June 2008 in Seoul National University Bundang Hospital; The electronic medical records (EMRs) of the patients were retrospectively reviewed. The patients were first classified into the maintenance dose group, the increased dose group or the reduced dose group according to CPCS results. A number of factors, such as gender, age, body weight, CLcr, duration of therapy, indication, dosage, combination of nephrotoxic drugs and occurrence of adverse effects, were studied for the potential impact on the results of CPCS. Among 132 cases, 83 cases were categorized as the maintenance dose group, 30 cases as the increased dose group, and 19 cases as the reduced dose group; The rate of patients having the dose adjustment was 37.1%. A significant (44.7%) number of patients received medications that potentially affected renal function (e.g., diuretics, aminoglycosides, amphotericin B). Approximately 6.1% of the patients experienced adverse effects (e.g., renal failure and thrombocytopenia) related to vancomycin administration. Statistical analysis indicate that age and CLcr show statistical significance between the three groups, suggesting vancomycin dose adjustment is necessary in the younger patients and/or patients having higher CLcr. When vancomycin was empirically administered in adult patients under 65 years of age with CLcr ≥ 60ml/min, the therapeutic trough range was not achieved depending on the age and the renal function, suggesting that CPCS is vital in the dose adjustment for the drug in the patient group.

The number of Clostridium difficile-associated disease(CDAD) event and mortality of CDAD have been increasing due to the emergence of mutant BI/NAP1/027 which can produce C.difficile toxin about 10~20 times more than the existing C.difficile. According to the clinical practice guideline from Society for Healthcare Epidemiology of America (SHEA) and the Society for Healthcare Epidemiology of America (SHEA), prescribing oral metron-idazole or oral vancomycin for 10~14 days depending on clinical status is recommended for adult Clostridium difficile infection. This study aimed to evaluate oral vancomycin use for the treatment of CDAD and analyze the risk factor for treatment failure. Clinical data of CDAD patient who treated with oral vancomycin from April 2008 to August 2010 were retrospectively reviewed. We classified patients into two groups, depending on the clinical outcome on the 10th day and identified risk factor of treatment failure. Seventy two patients were included in this analysis. Forty eight patients (66.7%) and sixty one patients (84.7%) recovered from CDAD on the 10th day of treatment and by 28th days from the start of oral vancomycin. Patients with high disease severity score and patients who defecate more than six times a day at the time of treatment start are more likely to experience treatment failure.

American Journal of Health-System Pharmacy (AJHP) recommended 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 these higher targets were needed. However, these higher trough levels have potential risk, such as renal toxicity. The purpose of this study is to compare the antimicrobial effect of the trough vancomycin level and vancomycin area under the concentration-time curve from 0 to 24 h (AUC24)/minimum inhibitory concentration(MIC). A retrospective, observational study set within pharmacist-managed clinical pharmacokinetic service in a teaching hospital was performed. Patients with MRSA pneumonia and vancomycin therapy between November 2009 and July 2010 were included (n=45). No difference between the MRSA positive group (n=17) and the MRSA negative group (n=28) were showed in the demo-graphic data and vancomycin trough level (p=0.925). However significant difference between the MRSA positive group (n=17) and MRSA negative group (n=28) were showed in AUC24/MIC 666.97 (95% CI, 419.18-1,295.51) and 1272.21 (95% CI, 1,011.6-1,389.46) respectively. (p=0.025)In conclusion, targeted exposure using AUC24/MIC compared trough concentrations is a more realistic target in patients with MRSA pneumonia.

Purpose: This study was to examine whether VRE infection control strategies have an effect on the decrease in incidence rates for VRE acquisition and VRE nosocomial infection in ICU. Methods: All the patients were examined for VRE carriers on ICU admission. Among them, patients hospitalized for over 48 hours were investigated for VRE acquisition rates and VRE nosocomial infection rate using VRE infection control strategies in ICU for the experimental group from September 2007 to April 2008. Before that, incidence of VRE acquisition and VRE nosocomial infection for the control group without Intervention were investigated from May to August 2007 retrospectively. Results: VRE acquisition rate in clinical specimens was 0.6% in the experimental group, that was significantly lower when compared to the control group. VRE carrier rate at admission to ICU was 15.4%. Out of 182 VRE carriers, 180 patients were identified by the active surveillance culture. Conclusion: These results suggested that active surveillance culture at admission was considered to be an essential measure for detection of VRE carrier. But without strict isolation and adherence rating after each intervention, hand washing and contact isolation alone did not significantly decrease VRE nosocomial infection, although it did significantly decrease incidence of VRE acquired from clinical specimen.

Background : Vancomycin is a mainstay of treatment of serious methicillin-resistant Staphylococcus aureus (MRSA) infections. The recently published guideline on vancomycin monitoring recommends that a vancomycin loading dose can be considered and an individualized target AUC/MIC ratio of 400-600 and should be advocated to achieve clinical efficacy while improving safety in patients with the suspected or definitive MRSA infections. Methods : To evaluate the correlation between the vancomycin trough concentration and the area under the curve over 24 hours to the MIC (AUC/MIC) ratio according to the guideline recently published. A retrospective cohort study was conducted on adult patients treated for MRSA proven pneumonia with the vancomycin. We enrolled patients administered with the vancomycin loading dose before the maintenance dose and the monitored vancomycin trough concentrations at the steady state in medical intensive care units April 2017-March 2020. We calculated the vancomycin AUC/MIC ratio based on the trough concentration measured for each patient using the Bayesian software. The difference between the microbiological cure, all-cause mortality, and nephrotoxicity for each group was studied. Results : There was low correlation between the vancomycin AUC/MIC and trough concentration in MRSA pneumonia. A total of 35 patients were included. Thirty-one patients (88.6%) were above the AUC/MIC ratio 400, while 19 patients (54.3%) were in the trough range above 15 mcg/ ml. Although there was a weak correlation between the vancomycin trough concentration and the AUC/MIC ratio (r=0.427, p=0.010), the vancomycin through concentrations at the steady state within the therapeutic ranges did not mean the vancomycin AUC/MIC ratio within the therapeutic ranges (p=0.580). No significant difference was observed in the microbiological cure, all-cause mortality, and incidence of acute kidney injury in each group. Conclusion : The trough level-guided monitoring of the vancomycin should be replaced by the AUC/MIC ratio-guided monitoring in the clinical practice in Korea.

Background : Vancomycin is commonly used in neonatal intensive care units (NICU) for the treatment of gram-positive bacterial infections. The aims of this study were to determine the pharmacokinetic parameters of vancomycin in Korean neonates and to assess the percentage of neonates who reached a therapeutic level (trough concentrations of 10 to 20 mg/L) with empirical vancomycin dosing according to the Neofax??. Methods : This retrospective study reviewed data from 81 neonates admitted to the NICU. The elimination rate constant (Ke), half-life (T1/2), clearance (CL), and the extrapolated trough and peak levels were calculated using first-order pharmacokinetics and a one-compartment model. Results : Only 21% of the patients achieved therapeutic trough levels (10 to 20 mg/L) with initial dosing according to the Neofax??. Vancomycin clearance was significantly correlated with postmenstrual age (PMA), postnatal age (PNA), weight, and serum creatinine (SCr) level. The recommended dosing regimen in neonates 27 weeks PMA was 10~15 mg/kg q12hr. For neonates in the 27 to 30 week PMA range, the recommended regimen was 15 mg/kg q12hr or 10 mg/kg q8hr for PNA 0~14 days, 10~13 mg/kg q8hr for PNA 14 days with SCr 0.6 mg/dL, and 10~15 mg/kg q12hr for PNA 14 days with SCr 0.6 to 1.5 mg/dL. For neonates in the 30 to 37 week PMA range, the recommended regimen was 10~13 mg/kg q8hr for PNA 0~14 days, 13 mg/kg q8hr or 10 mg/kg q6hr for PNA 14 days with SCr 0.6 mg/dL, and 15 mg/kg q12hr or 10 mg/kg q8hr for PNA 14 days with SCr 0.6 to 1.5 mg/dL. For neonates in the 37 to 44 week PMA range, the recommended regimen was 10~13 mg/kg q8hr for PNA 0~7 days, 13~15 mg/kg q6hr for PNA 7 days with SCr 0.6 mg/dL, and 13 mg/kg q8hr or 10 mg/kg q6hr for PNA 7 days with SCr 0.6 to 1.5 mg/dL. Sixty-three percent (51/81) of the neonates reached a therapeutic level with the new dosing regimen. Conclusions : The Neofax?? vancomycin initial dosing regimen is insufficient for Korean neonates. Further studies are needed to validate the new dosing regimen suitable for achieving target therapeutic levels in Korean neonates.