Drug utilization review of mupirocin ointment in a Korean university-affiliated hospital.

BACKGROUND/AIMS: Intranasal mupirocin and chlorhexidine bathing are candidate strategies to prevent healthcare-associated infections caused by methicillin-resistant Staphylococcus aureus (MRSA). In Korea, intranasal mupirocin is not available, and mupirocin ointment, an over-the-counter drug, has been used indiscriminately. Furthermore, because it is covered by health insurance, mupirocin is easy to prescribe within hospitals. METHODS: We performed a mupirocin drug utilization review (DUR) within Hallym University Sacred Heart Hospital. Annual use of mupirocin was investigated between 2003 and 2013, and monthly consumption of mupirocin was assessed during the final 2-year period. The DUR focused on August 2012, the period of highest use of mupirocin. Also, we investigated trends in mupirocin resistance in MRSA between 2011 and 2013. RESULTS: Annual consumption of mupirocin increased from 3,529 tubes in 2003 to 6,475 tubes in 2013. During August 2012, 817 tubes were prescribed to 598 patients; of these, 84.9% were prescribed to outpatients, and 77.6% at the dermatology department. The most common indication was prevention of skin infections (84.9%), and the ointment was combined with systemic antibiotics in 62.9% of cases. The average duration of systemic antibiotic administration was about 7.8 days. The rate of low-level mupirocin resistance in MRSA increased from 8.0% to 22.0%, and that of high-level mupirocin resistance increased from about 4.0% to about 7.5%. CONCLUSIONS: Inappropriate use of mupirocin is prevalent. Considering the increase in resistance and the future application of intranasal mupirocin, prophylactic use of mupirocin in dermatology departments should be reconsidered.

A pharmacokinetic comparison of two voriconazole formulations and the effect of CYP2C19 polymorphism on their pharmacokinetic profiles.

PURPOSE: SYP-1018 is a lyophilized polymeric nanoparticle formulation of voriconazole that is under development for intravenous dosing. This study compared the pharmacokinetic and tolerability profiles of SYP-1018 with those of Vfend(®), the marketed formulation of voriconazole. The effect of CYP2C19 polymorphism on the voriconazole pharmacokinetics was also evaluated. METHODS: An open-label, two-treatment, two-period, two-sequence crossover study was conducted in 52 healthy male volunteers, who randomly received a single intravenous infusion of either of the two voriconazole formulations at 200 mg. Blood samples were collected up to 24 hours after drug administration for pharmacokinetic analysis. The plasma concentrations of voriconazole were determined using liquid chromatography with tandem mass spectrometry, and the pharmacokinetic parameters were estimated using a noncompartmental method. CYP2C19 genotype was identified in 51 subjects. RESULTS: The geometric mean ratio (90% confidence interval) of SYP-1018 to Vfend(®) was 0.99 (0.93-1.04) for the maximum plasma concentrations (Cmax) and 0.97 (0.92-1.01) for the area under the concentration-time curve (AUC) from dosing to the last quantifiable concentration (AUClast). Nineteen homozygous extensive metabolizers (EMs, *1/*1), 19 intermediate metabolizers (IMs, *1/*2 or *1/*3), and ten poor metabolizers (PMs, *2/*2, *2/*3, or *3/*3) were identified, and the pharmacokinetic comparability between SYP-1018 and Vfend(®) was also noted when analyzed separately by genotype. The systemic exposure to voriconazole was greatest in the PM group, followed by the IM, and then the EM groups. Furthermore, the intrasubject variability for Cmax and AUClast was greater in IMs and PMs than in EMs. No serious adverse event occurred, and both treatments were well tolerated. CONCLUSION: SYP-1018 had comparable pharmacokinetic and tolerability profiles to Vfend(®) after a single intravenous infusion. CYP2C19 genotype affected not only the pharmacokinetics of voriconazole, but its intrasubject variability. SYP-1018 can be further developed as a clinically effective alternative to Vfend(®).

Trough concentration over 12.1 mg/L is a major risk factor of vancomycin-related nephrotoxicity in patients with therapeutic drug monitoring.

BACKGROUND: High doses of vancomycin increase the risk of nephrotoxicity, but the quantitative relationship between vancomycin exposure and nephrotoxicity is still controversial. This study evaluated the relationship between vancomycin trough concentration and nephrotoxicity, and risk factors for nephrotoxicity in patients undergoing therapeutic drug monitoring. METHODS: A total of 1269 cases from patients who underwent therapeutic drug monitoring were collected from 2006 to 2010. Receiver operating characteristic curve analysis was used to evaluate the relationship between trough concentration and the incidence of nephrotoxicity. Logistic regression using the generalized Least Absolute Shrinkage and Selection Operator (lasso) method was used to evaluate possible risk factors for nephrotoxicity. The data were divided into high/low-concentration groups by the cutoff value obtained from the receiver operating characteristic curve, and additional logistic regression using the generalized lasso method was performed for each group. RESULTS: The cutoff value of the vancomycin trough concentration was 12.1 mg/L. Patients with high concentrations (>12.1 mg/L) were more likely to develop nephrotoxicity (odds ratio = 16.0, 95% confidence interval, 8.2-31.1). The vancomycin trough concentration was the only significant risk factor for nephrotoxicity identified using the generalized lasso (P < 0.001). In contrast, no factor was associated with nephrotoxicity in the low-concentration group. CONCLUSIONS: Vancomycin trough concentrations over 12.1 mg/L were associated with an increased risk of nephrotoxicity. This is lower than the known threshold. Trough vancomycin concentration over the threshold was the only risk factor of nephrotoxicity among demographic factors, dosing regimen, and other clinical conditions in this study. It is suggested that vancomycin trough concentrations greater than 12.1 mg/L require close monitoring for nephrotoxicity.

Reduced valproic acid serum concentrations due to drug interactions with carbapenem antibiotics: overview of 6 cases.

BACKGROUND: The plasma concentrations of valproic acid (VPA) are known to decrease during the concomitant administration of carbapenem antibiotics, such as meropenem, imipenem, and ertapenem. This study summarizes 6 cases of drug-drug interactions between VPA and carbapenem antibiotics. METHODS: To investigate the onset and severity of the reductions in the concentration of VPA in patients with or without the coadministration of carbapenem antibiotics, the authors performed a retrospective evaluation of therapeutic drug monitoring (TDM) reports that described a decrease in the serum concentrations of VPA during the concomitant use of carbapenem antibiotics from January 2008 to December 2010 in the Seoul National University Hospital. The evaluated TDM reports included 6 cases. The decrement ratio of the VPA serum concentration was calculated from the TDM reports, and the change in the half-life of the VPA was also estimated. RESULTS: Six cases presented with changes in the VPA serum concentration before and after the administration of carbapenem antibiotics. (Three cases were treated with meropenem, 2 were treated with ertapenem, and 1 was treated with imipenem.) The VPA concentrations reduced by (mean ± SD) 88.7 ± 5.3% (3 cases of meropenem), 74.0 ± 9.8% (2 cases of ertapenem), and 73.3% (1 case of imipenem), respectively, and the half-life of VPA reduced by 80.1 ± 9.0%, 64.4 ± 24.2%, and 50.6%, respectively. CONCLUSION: The interaction between VPA and carbapenem antibiotics caused decreases in the VPA serum concentrations; the extent of this decrease was greater in the meropenem-treated patients than in the imipenem-treated or ertapenem-treated cases. Because the therapeutic effect of VPA depends on its serum concentration, it should be recognized that there may be a loss of seizure control in patients using VPA with carbapenem antibiotics.

Cultural and ethical issues in Korea's recent elder abuse reporting system.

The primary purpose of this article is to examine the relevance of cultural values, such as familism and individualism, that influence public policy implementation processes for protecting older adults in Korea and the United States. The secondary purpose is to identify ethical dilemmas and policy implications for effectively implementing the recently developed public law designed to protect vulnerable older adults in Korea. This article discusses both similarities and differences found in the two countries' elder abuse reporting systems and the service delivery systems for protecting older adults at risk of abuse and neglect.