Kyeong Seob Shin

Analysis of a novel class 1 integron containing metallo-β-lactamase gene VIM-2 in Pseudomonas aeruginosa

Carbapenems such as imipenem are stable to most β-lactamases. Recently, increased numbers of carbapenemase producing Gram-negative bacterial strains have been isolated because of the increased use of cabapenems. In this respect, control of these infectious carbapenemase producing Gram-negative bacteria and understanding their resistance mechanism are becoming more important. These carbapenem-hydrolyzing β-lactamase genes have been reported to exist mostly as gene cassettes in an integron. This implies that antibiotic resistance genes may be transferred to other bacteria via the integron. In the present study, we identified and analyzed an integron containing VIM-2 type metallo-β-lactamase gene in a carbapenemase producing Pseudomonas aeruginosa. In addition, the possibility of resistance spread by integron located in a plasmid was tested. Among glucose non-fermenting Gram-negative bacilli with reduced imipenem susceptibility (MIC≥8 μg/ml) isolated from Korean patients, P. aeruginosa 1082 showed resistance to most β-lactams, cephalosporin, and aminoglycoside. We found that P. aeruginosa 1082 was inhibited by EDTA in EDTA double disk synergy test which means that this strain produces metallo-β-lactamase. Class 1 integron containing blaVIM-2 (carbapenem resistance gene), qacF (quaternary ammonium compound resistance gene), aacA4 (aminoglycoside resistance gene), catB3 (chloramphenicol resistance gene), blaoxa-30 (extended-spectrum β-lactam resistance gene), and aadAl (aminoglycoside resistance gene) gene cassettes was detected in P. aeruginosa 1082. The size of the integron was 5,246 bp and the structure and arrangement of the integron was a novel one in comparison with other integrons found in other P. aeruginosa. The integron could be transferred to Escherichia coli JM109 from P. aeruginosa 1082 possibly via self-transferable plasmid DNA. The integron and a blaVIM-2 gene were detected in the plasmid DNA of the transconjugants whose imipenem resistance was slightly increased as a result of accepting the integron from the donor strain.

[Dissemination of IMP-1 and OXA type beta-lactamase in carbapenem-resistant Acinetobacter baumannii].

BACKGROUND Acinetobacter baumannii is an aerobic, gram-negative, glucose-nonfermenting bacterium, which has emerged as a serious opportunistic pathogen. In recent years, the increasing instance of carbapenem-resistant A. baumannii producing metallo-beta-lactamases (MBLs) or OXAtype beta-lactamases is causing a serious clinical problem. In this study, we investigated the prevalence of Ambler class A, B, and D beta-lactamases and their extended-spectrum derivatives in carbapenem-resistant A. baumannii isolates. METHODS A total of 31 consecutive, non-duplicate, carbapenem-resistant A. baumannii were isolated from three university hospitals in the Chungcheong province of Korea. The modified Hodge and inhibitor-potentiated disk diffusion tests were conducted for the screening of carbapenemase and MBL production, respectively. PCR and DNA sequencing were performed for the detection of beta-lactamase genes. We also employed the enterobacterial repetitive intergenic consensus (ERIC)-PCR method for the epidemiologic study. RESULTS Twenty-three of 31 isolates harbored bla(OXA-2)(51.6%), bla(OXA-23)(22.6%), bla(IMP-1)(48.4%),and bla(VIM-2)(3.2%). All of the OXA-2-producing strains also evidenced MBLs. The strains that harbored bla(OXA-23)were isolated only in hospital C, and only in a limited fashion. The ERIC-PCR pattern of the five OXA-23 strains indicated that the isolates were closely related in terms of clonality. The six strains producing IMP-1 isolated from hospital A were confirmed to be identical strains. CONCLUSIONS A. baumannii strains harboring IMP-1 or OXA-type beta-lactamases are currently widely distributed throughout the Chungcheong province of Korea. The most notable finding in this study was that a bla(OXA-2)-producing A. baumannii harboring MBL, which has not been previously reported, can also lead to outbreaks.

Dipicolinic acid-based disk methods for detection of metallo-β-lactamase-producing Pseudomonas spp. and Acinetobacter spp.

We evaluated novel and simple dipicolinic acid (DPA)-based phenotypic screening methods to detect metallo-beta-lactamase (MBL)-producing isolates: DPA disk synergy tests and DPA-based disk tests (DPA-imipenem, DPA-meropenem, or DPA-ceftazidime disk tests). Upon testing these methods on 79 MBL-producing and 95 MBL-nonproducing isolates of Pseudomonas spp. and Acinetobacter spp., their specificity and sensitivity were superior or comparable with those of the EDTA-based phenotypic screening methods.

Antimicrobial Susceptibility of Stenotrophomonas maltophilia Isolates from Korea, and the Activity of Antimicrobial Combinations against the Isolates

The aim of this study was to determine antimicrobial susceptibility of recent clinical Stenotrophomonas maltophilia isolates from Korea, and to compare the activity levels of several combinations of antimicrobials. A total of 206 non-duplicate clinical isolates of S. maltophilia was collected in 2010 from 11 university hospitals. Antimicrobial susceptibility testing was performed using the Clinical Laboratory Standards Institute agar dilution method. In vitro activity of antimicrobial combinations was tested using the checkerboard method. The susceptibility rates to trimethoprim-sulfamethoxazole and minocycline were 96% and 99%, respectively. The susceptibility rate to levofloxacin was 64%. All of four antimicrobial combinations showed synergy against many S. maltophilia isolates. A combination of trimethoprim-sulfamethoxazole plus ticarcillin-clavulanate was most synergistic among the combinations. None of the combinations showed antagonistic activity. Therefore, some of the combinations may be more useful than individual drugs in the treatment of S. maltophilia infection. Further clinical studies are warranted to validate our in vitro test results.

Bowel infarction due to intestinal mucormycosis in an immunocompetent patient

Mucormycosis is a fatal opportunistic fungal infection that typically occurs in immunocompromised patients. The classical manifestation of mucormycosis is a rhinocerebral infection, and although primary gastrointestinal infection is uncommon, it has an extremely high mortality rate in immunocompromised patients. Furthermore, cases of gastrointestinal mucormycosis in an immunocompetent host are rarely reported. Here, we describe our experience of a male patient, with no underlying disease, who succumbed to a bowel infarction caused by intestinal mucormycosis during mechanical ventilatory care for severe pneumonia and septic shock.

Co-existence of blaOXA-23 and armA in multidrug-resistant Acinetobacter baumannii isolated from a hospital in South Korea

The co-existence of carbapenemase, 16S rRNA methylase and mutated quinolone resistance-determining regions (QRDRs) can cause serious difficulty in treating infections with multidrug-resistant Acinetobacter baumannii. In this study, we aimed to determine the mechanisms of imipenem, amikacin and ciprofloxacin resistance in A. baumannii isolates with resistance to these antibiotics. A total of 31 non-duplicate isolates of amikacin- and ciprofloxacin-resistant Acinetobacter isolates were identified from April to August 2010 from a single hospital in South Korea. To assess the clonal relatedness of the 31 Acinetobacter isolates, multilocus sequence typing, network phylogenetic analysis and enterobacterial repetitive intergenic consensus-PCR were utilized. Detection of OXA-type carbapenemase and 16S rRNA methylase was conducted using a multiplex PCR assay. The QRDRs of the gyrA and parC genes were amplified and sequenced. The result showed that 30/31 isolates harboured the blaOXA-23-like carbapenemase, which made them resistant to imipenem (MICs ≥16 µg ml(-1)). Twenty-eight of the 31 isolates were found to possess armA, a 16S rRNA methylase gene, and showed resistance to amikacin, arbekacin, gentamicin and tobramycin (MICs >256 µg ml(-1)). All of the isolates were determined to carry QRDR mutations in both gyrA and parC: a Ser83Leu substitution in gyrA and a Ser80Leu substitution in parC, causing a ciprofloxacin MIC ≥64 µg ml(-1). In conclusion, A. baumannii with co-existence of carbapenemase, 16S rRNA methylase and mutated QRDRs are extremely prevalent in South Korea, which may cause serious problems in the treatment of A. baumannii infections using carbapenem, amikacin and ciprofloxacin.

Comparison of Outcomes of Unilateral Lateral Rectus Recession for Exotropia between First and Second Operations

Purpose To compare the outcomes of unilateral lateral rectus recession between the first operation and second operation for exotropia. Methods Thirty-two patients who underwent unilateral lateral rectus recession for exotropia of 15 to 20 prism diopters (PD) were investigated. The follow-up period was at least 6 months. We classified 17 patients without a surgical history for exotropia (first operation group) and 15 patients with a previous procedure (second operation group). Surgical success was defined as an exodeviation or esodeviation of less than 10 PD at the primary position. Postoperative deviation angles and success rates were compared between the two groups. Results There were no significant differences in the age, gender, visual acuity (logarithm of the minimal angle of resolution), preoperative deviation, and amount of recession between the two groups. Postoperative deviations were -1.7 ± 5.5:1.3 ± 5.1 PD at one day, 4.3 ± 3.8:5.6 ± 5.1 PD at 1 month, 4.3 ± 4.3:3.0 ± 8.1 PD at 3 months, and 5.0 ± 4.3:4.5 ± 7.2 PD at 6 months post-operation, and there was no statistically significant difference between the two study groups. Surgical success rate were 95.2:100% at one day, 95.2:92.9% at 1 month, 90.5:85.7% at 3 months, and 90.0:92.9% a 6 months post-operation. Conclusions In patients with exotropia of 15 to 20 PD, no significant difference was found in terms of the postoperative deviation angle and the surgical success rate between the first operation and the second operation groups. Unilateral lateral rectus recession can lead to similar results in 15 to 20 PD exotropia for the first operation or recurrent exotropia.

Reversible Splenium Lesion of the Corpus Callosum in Hemorrhagic Fever with Renal Failure Syndrome

This is the first case of virus-associated encephalitis/encephalopathy in which the pathogen was Hantaan virus. A 53-yr-old man presented fever, renal failure and a hemorrhagic tendency and he was diagnosed with hemorrhagic fever with renal failure syndrome (HFRS). In the course of his illness, mild neurologic symptoms such as dizziness and confusion developed and magnetic resonance images revealed a reversible lesion in the splenium of the corpus callosum. This case suggests that HFRS patients with neurologic symptoms like dizziness and mental slowing should be considered to have structural brain lesions and to require brain imaging studies.

Extended Spectrum-β-Lactamase or Carbapenemase Producing Bacteria Isolated from Patients with Acute Cholangitis

Background/Aims This study assessed the antibiotic resistance organisms isolated from the blood and bile of acute cholangitis and evaluated risk factors associated with them and their impact on clinical outcomes. Methods The identities and antibiotic resistance profiles of bacteria isolated from 433 cases of acute cholangitis from 346 patients were analyzed. Risk factors and the outcomes of patients infected with them were assessed. Results Microorganisms were isolated from 266 of 419 blood cultures and 256 of 260 bile cultures. Isolates from bile and blood were identical in 71% of the cases. A total of 20 extended spectrum-β-lactamase (ESBL)-producers and 4 carbapenemase-producing organisms were isolated from blood, and 34 ESBL-producers and 13 carbapenemase-producers were isolated from bile. Sixty-four (14.8%) cases were infected with any one of these bacteria isolated from blood or bile. Risk factors associated with them in blood were nosocomial infection and prior biliary intervention. In bile, indwelling biliary device was a risk factor associated with them. Antibiotic-resistant bacteria were associated with mortality, independent of other prognostic factors. Conclusions ESBL or carbapenemase-producing bacteria were frequently isolated in acute cholangitis patients especially with prior biliary intervention and nosocomial infection. Isolation of antibiotic-resistant bacteria was an independent risk factor of mortality.

Effects Of (-)-Sesamin On Motor And Memory Deficits In An Mptp-Lesioned Mouse Model Of Parkinson's Disease Treated With L-Dopa.

The present study investigated the effects of (-)-sesamin on motor and memory deficits in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model of Parkinsons disease (PD) with l-3,4-dihydroxyphenylalanine (l-DOPA). MPTP-lesioned (30mg/kg/day, 5days) mice showed deficits in memory including habit learning memory and spatial memory, which were further aggravated by daily treatment with 25mg/kg l-DOPA for 21days. However, daily treatment with (-)-sesamin (25 and 50mg/kg) for 21days ameliorated memory deficits in an MPTP-lesioned mouse model of PD treated with l-DOPA (25mg/kg). Both (-)-sesamin doses reduced decreases in the retention latency time in the passive avoidance test, latency to fall of rotarod test and distance traveled in the open field test, and attenuated decreases in tyrosine hydroxylase (TH)-immunopositive cells, dopamine, and its metabolites in the substantia nigra-striatum. (-)-Sesamin reduced increases in the retention transfer latency time in the elevated plus-maze test and N-methyl-d-aspartate receptor (NMDAR) expression and reduced decreases in the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and cyclic AMP-response element binding protein (CREB) in the hippocampus. In contrast, daily treatment with 10mg/kg l-DOPA for 21days ameliorated memory deficits in MPTP-lesioned mice, and this effect was further improved by treatment with (-)-sesamin (25 and 50mg/kg). These results suggest that (-)-sesamin protects against habit learning memory deficits by activating the dopamine neuronal system, while spatial memory deficits are decreased by its modulatory effects on the NMDAR-ERK1/2-CREB system. Accordingly, (-)-sesamin may act as an adjuvant phytonutrient for motor and memory deficits in patients with PD receiving l-DOPA.