Seungok Lee

Wide dissemination of OXA-type carbapenemases in clinical Acinetobacter spp. isolates from South Korea

Carbapenem-resistant Acinetobacter spp. are being increasingly reported worldwide, including in South Korea, where we examined 144 representative isolates collected in a nationwide hospital survey in 2005. Metallo-beta-lactamases were detected in only 19.4% of isolates, none of which were Acinetobacter baumannii, whereas 74.3% of isolates (mostly A. baumannii) expressed bla(OXA) carbapenemase genes. Among the latter, 47 had bla(OXA-23)-like genes and 56 had upregulated bla(OXA-51)-like variants, including bla(OXA-66), (-83), (-109) and (-115); bla(OXA-115) was a novel variant, detected in two isolates. bla(OXA-72) (bla(OXA-40)-like) was detected in only a single Acinetobacter baylyi isolate, whilst three Acinetobacter calcoaceticus isolates had both bla(VIM-2)-like and bla(OXA-58) genes. Pulsed-field gel electrophoresis (PFGE) suggested the spread of A. baumannii clones with OXA carbapenemases within and between hospitals. In conclusion, the recent increase in imipenem-resistant Acinetobacter spp. from South Korea is mostly due to OXA-type carbapenemases.

Prevalence of metallo-β-lactamase among Pseudomonas aeruginosa and Acinetobacter baumannii in a Korean University hospital and comparison of screening methods for detecting metallo-β-lactamase

To identify the metallo-β-lactamases (MBLs) prevalent in Korea, a total of 130 clinical isolates of Pseudomonas aeruginosa and Acinetobacter baumannii (99 P. aeruginosa and 31 A. baumannii) with a reduced susceptibility to imipenem (IPM) and/or ceftazidime (CAZ) was subjected to PCR analyses with primers specific to blaIMP-1, blaVIM-1, and blaVIM-2. In addition, inhibitor-potentiated disk diffusion methods (IPD) using two kinds of substrate–inhibitor combinations (ceftazidime–2-mercaptopropionic acid (2MPA) and imipenem–EDTA) were investigated. Thirty-three isolates (29 P. aeruginosa and 4 A. baumannii) carried blaVIM-2 and two P. aeruginosa isolates harbored blaIMP-1. The enterobacterial repetitive intergenic consensus PCR (ERIC-PCR) pattern revealed that many of the VIM-2-producing P. aeruginosa isolates were clonally related, whereas the A. baumannii isolates were diverse. The inhibitor-potentiated disk diffusion test using imipenem–EDTA was highly sensitive and specific for detecting the VIM-2 producer. These results suggest that VIM-2 is an important MBL in P. aeruginosa and A. baumannii in the Korean hospital of this study and that the IMP-1-producing P. aeruginosa has also emerged. Screening for MBLs and strict infection control for these isolates will contribute to prevent further spread of resistance.

Emergence of Community‐Associated Methicillin‐Resistant Staphylococcus aureus Strains as a Cause of Healthcare‐Associated Bloodstream Infections in Korea

BACKGROUND The prevalence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strains causing bloodstream infection (BSI) has not been studied in Korea. OBJECTIVE We sought to determine the prevalence of CA-MRSA strains among isolates recovered from patients with MRSA BSIs and to explore epidemiological changes in Korea. We also sought to evaluate clinical characteristics relevant to the development of healthcare-associated BSIs. METHODS We prospectively collected consecutive MRSA isolates from patients with BSI at 4 hospitals from July 1 through November 30, 2007, and we also included MRSA isolates recovered from culture of blood samples collected during a previous year (October 1, 2004 through September 30, 2005) at a different hospital. Molecular typing studies were performed, including pulsed-field gel electrophoresis (PFGE), multilocus sequence typing, Staphylococcus protein A (spa) typing, and staphylococcal cassette chromosome mec (SCCmec) typing. We compared the clinical characteristics and outcomes of patients with healthcare-associated BSI due to CA-MRSA strains with those of patients with healthcare-associated BSI due to healthcare-associated MRSA (HA-MRSA) strains. RESULTS There were 76 cases of MRSA BSI, of which 4 (5.3%) were community-associated and 72 (94.7%) were healthcare-associated. Among the 72 HA-MRSA BSIs, 18 (25%) were community onset, and 54 (75%) were hospital onset. PFGE type D-ST72-spa B-SCCmec type IVA MRSA, the predominant genotype of CA-MRSA in Korea, accounted for 19 (25%) of all 76 MRSA BSIs, including 17 (23.6%) of 72 HA-MRSA BSIs and 11 (20.8%) of 53 hospital-onset HA-MRSA BSIs. Patients with healthcare-associated BSIs due to CA-MRSA strains carrying SCCmec type IVA tended to have fewer healthcare-associated risk factors, compared with patients with healthcare-associated BSIs due to HA-MRSA strains carrying other SCCmec types. The presence of a central venous catheter or other invasive device was the only independent factor differentiating patients infected with hospital-associated genotype strains from patients infected with other strains. Clinical outcomes were similar between both groups. CONCLUSIONS CA-MRSA strains are emerging as a major cause of BSI in healthcare settings in Korea. This changing epidemiology of MRSA poses a challenge to public health and infection control in hospital settings.

Prognostic value of C-reactive protein and neutrophil-to-lymphocyte ratio in patients with hepatocellular carcinoma

BackgroundAccumulating evidence indicates that components of the systemic inflammatory response, such as C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR), have been associated with prognosis of various cancers. We aimed to elucidate whether CRP and NLR could serve as potential surrogate markers for response and survival in patients with hepatocellular carcinoma (HCC).MethodsThe study population consisted of 318 consecutive patients with HCC. CRP and NLR were measured at baseline with follow-up measurements.ResultsWith the mean follow-up of 13.9 months, the median survival time was 13.8 months. Child-Pugh class, tumor size > 5 cm, tumor multiplicity, presence of portal vein thrombosis, α-fetoprotein > 200 ng/mL, CRP > 6.3 mg/L and NLR > 2.3 were identified as independent factors for worse survival of HCC (all p < 0.05). Patients with elevated CRP (> 6.3 mg/L) and elevated NLR (> 2.3) had a significantly shorter overall survival than those with low CRP and low NLR (all p < 0.001). The combined use of CRP and NLR provided incremental prognostic information. With significant inter-correlations, levels of CRP and NLR escalated with aggravating Child-Pugh class from A to C or progressing tumor stage from I to IV. CRP and NLR on baseline and serial measurements were well predictive of treatment response (p < 0.001).ConclusionsCRP and NLR are independent indicators for survival in HCC patients, reflecting tumor burden and hepatic reserve. Their role in predicting tumor response and survival is more enhanced when used in combination. This study suggests that CRP and NLR are important prognostic biomarkers for HCC.

Photocatalytic Synthesis of Pure and Water‐Dispersible Graphene Monosheets

Several research groups are actively investigating graphene, which consists of a one-atom thick planar sheet of sp bonded carbon, in attempts to understand its unusual characteristics, such as outstanding electronic properties, optical properties, thermal conductivity (5000 Wm 1 K ), high mechanical strength (200 times stronger than steel), and large surface area per unit mass (2,630 mg 1 calculated,) Novoselov et al. first obtained high quality monosheet graphene detached from natural graphite by the so-called Scotch tape method in 2004. Chemical vapor deposition (CVD) is frequently used to synthesize graphene in a practical scale, and it is suitable for producing a large area (on the inches scale) of high-quality graphene as good as that obtained from natural graphite. However, the CVD process requires high processing temperatures and etching processes, which remove Ni or Cu catalyst nanoparticle layers to yield mono layers or a few layers of graphene on the substrate. Thus, the process remains expensive. Its applications have focused on replacing indium tin oxide (ITO) or fluorinedoped tin oxide (FTO) in transparent conducting electrodes. If an efficient solution-based chemical reduction method were available, we could produce graphene by reducing graphene oxide (GO) on a large scale at low cost. Unfortunately, these types of graphene intrinsically contain many defects that cannot be removed by reduction or thermal treatment. Still, because reduced graphene oxide (RGO) can be obtained easily as powder or solution forms, its utility in, for example, photocatalysts, fuel cells, batteries, ultracapacitors, and hydrogen storage is highly valuable. And solution forms of RGO can be easily applied for inkjetprinting, spray or spin-coating on various substrates. In the solution phase synthesis of graphene, aggregation is a serious problem. Graphene layers tend to aggregate due to high van der Waals interactions. Li et al. solved this problem by reducing GO by hydrazine (RGOH2N NH2) in a basic solution, where RGOH2N NH2 remained dissolved by electrostatic repulsion between the negatively charged carboxylic groups on the graphene sheets. The advantage of this method is that water-dispersible graphene could be made without the use of surfactants or stabilizers. However, one of the problems is that hydrazine is harmful, explosive, and expensive. Furthermore, nitrogen impurities derived from hydrazine impose limits on the conductivity, and residual hydrazine in graphene solutions make its handling and further processing dangerous. Williams et al. introduced the use of ultraviolet (UV) photocatalysis to produce a composite of TiO2 and graphene. [16]

Population pharmacokinetics of intravenous valproic acid in Korean patients

Objective:  To determine population‐based pharmacokinetic parameters for intravenous valproic acid, and the factors influencing these parameters, in Korean adults.

Effects of zonisamide on isolated head tremor

Background and purpose:  The medical treatment available for patients with essential tremor (ET) is often inadequate. Furthermore, the efficacy of the medical treatments currently available for patients with ET of cranial nerve areas is less satisfactory than that of the medical treatments available for patients with ET involving the upper extremities. This pilot study was performed to evaluate whether zonisamide (ZNS) is effective in the treatment of patients with isolated head tremor.

Genetic and epigenetic alterations of bone marrow stromal cells in myelodysplastic syndrome and acute myeloid leukemia patients

We evaluated the characteristics of bone marrow stromal cells (BMSCs) and hematopoietic cells (HCs) from patients of myelodysplastic syndrome (MDS, n=21) and acute myeloid leukemia (AML, n=58), and compared the results with control BMSCs derived from healthy donors (n=8). The patient BMSCs had lower proliferative activity than that of the controls due to increased senescence. This retarded proliferation induced failure to obtain enough metaphase cells for karyotyping in patient BMSCs (10%). Patient BMSCs were genetically altered which was demonstrated by chromosome abnormalities in 5% of the patients (one MDS and three AML), whereas no clonal abnormalities were detected in the controls. The most common abnormality of the BMSCs was an extra chromosome 5, followed by an extra chromosome 7 and balanced translocations. The proportion of the abnormal metaphase cells was low (17.8%). We also analyzed the epigenetic changes of long interspersed nucleotide element 1 (LINE-1) repetitive element and CDKN2B using pyrosequencing. The quantitative measurement of global LINE-1 methylation demonstrated that patient BMSCs revealed global hypomethylation (68.2±3.8) compared with controls (72.9±3.4, P<0.001) and that the global hypomethylation of BMSCs were more significant in AML than in MDS patients (67.9±3.8, 69.4±4.2, respectively). These findings seem worthy of further evaluation of their association with ineffective hematopoiesis and leukemogenesis.

Change in inflammatory cytokine profiles after transarterial chemotherapy in patients with hepatocellular carcinoma.

BACKGROUND Alterations in cytokine profiles after chemotherapy can affect the outcomes of cancer patients. This study evaluated the clinical implications of cytokine changes after transarterial chemo-embolization (TACE) in patients with hepatocellular carcinoma (HCC). METHODS Cytometric bead immunoassays were used to simultaneously measure 13 cytokines (interleukin [IL]-12p70, interferon-γ, IL-17A, IL-2, IL-10, IL-9, IL-22, IL-6, IL-13, IL-4, IL-5, IL-1β, and tumor necrosis factor-α) in the sera of 83 patients with HCC and 33 healthy controls. Cytokines were serially monitored at baseline, on days 3 and 7, and 2months after TACE in 63 evaluable patients. RESULTS Serum levels of IL-5, IL-6, and IL-17A were higher in patients with HCC than in healthy controls, whereas IL-1β and IL-22 levels were lower in patients with HCC. Of the cytokines measured, only the IL-6 level showed a significant positive correlation with both tumor size and Child-Pugh score. The Child-Pugh B/C group had higher IL-6 and lower IL-22 levels at baseline and exhibited relatively minor changes in cytokine levels compared with the Child-Pugh A group. We observed diverse changing patterns of individual cytokines on each date tested, with IL-6 and IL-22 increasing early after TACE. Particularly, IL-6 reached a peak on day 3 and finally decreasing on and after day 7. IL-4, IL-5, and IL-10, on the other hand, increased during the late phase, 2months after TACE. Patients with larger tumors (>5cm) showed a transient but significant early-phase increase in IL-6 levels coupled with severe post-TACE hepatitis, as well as late-phase increases in IL-4, IL-5, and IL-10 levels after TACE. CONCLUSIONS TACE induces changes in levels of multiple cytokines. Distinct panels of cytokine changes are not uniform, and are influenced by treatment-induced inflammation, underlying liver function, and HCC stage. Early-phase increases in IL-6 after TACE reflect acute-phase responses and are partly associated with post-treatment hepatitis, while late-phase increases in Th2 cytokine profiles suggest immune suppression in patients with large tumors.

Comparative evaluation of three chromogenic media combined with broth enrichment and the real-time PCR-based Xpert MRSA assay for screening of methicillin-resistant Staphylococcus aureus in nasal swabs.

Background We evaluated the performance of three chromogenic media (Brilliance agar I [Oxoid, UK], Brilliance agar II [Oxoid], and ChromID MRSA [Biomérieux, France]) combined with broth enrichment and the Xpert MRSA assay for screening of methicillin-resistant Staphylococcus aureus (MRSA). Methods We obtained 401 pairs of duplicate nasal swabs from 321 patients. One swab was suspended overnight in tryptic soy broth; 50-µL aliquots of suspension were inoculated on the three chromogenic media. Brilliance agar I and II were examined after 24 hr, and ChromID MRSA, after 24 and 48 hr. The paired swab was processed directly using real-time PCR-based Xpert MRSA assay. Results True positives, designated as MRSA growth in any of the culture media, were detected with the prevalence of 17% in our institution. We report the sensitivity, specificity, positive predictive value, and negative predictive value of MRSA growth as follows: 92.3%, 94.0%, 75.9%, and 98.4% in Brilliance agar I (24 hr); 92.7%, 97.9%, 90.0%, and 98.5% in Brilliance agar II (24 hr); 95.6%, 95.8%, 82.3%, and 99.1% in ChromID MRSA (24 hr); 100%, 92.5%, 73.1%, and 100% in ChromID MRSA (48 hr); 92.6%, 96.7%, 85.1%, and 98.5% in Xpert MRSA assay. The agreement between the enriched culture and Xpert MRSA assay was 96.0%. Conclusions Three chromogenic culture media combined with enrichment and Xpert MRSA assay demonstrated similar capabilities in MRSA detection. The Xpert MRSA assay yielded results comparable to those of culture methods, saving 48-72 hr, thus facilitating earlier detection of MRSA in healthcare settings.