Jacob Lee

Efficacy of monotherapy and combined antibiotic therapy for carbapenem-resistant Acinetobacter baumannii pneumonia in an immunosuppressed mouse model

Acinetobacter baumannii is an important cause of nosocomial infection with increasing carbapenem resistance. The aim of this study was to compare the efficacy of colistin+rifampicin and imipenem+rifampicin combinations with that of several other antibiotic regimens against carbapenem-resistant A. baumannii pneumonia using an immunosuppressed mouse model. Three different A. baumannii strains with diverse resistance mechanisms (OXA-51-, IMP-1- and VIM-2-type beta-lactamases) were used. Among the monotherapy regimens, only rifampicin significantly reduced the bacterial load in lungs 24 h after infection with the OXA-51-producing strain. Addition of rifampicin to either imipenem or colistin yielded synergistic results after 48 h. Rifampicin was bactericidal against the IMP-1-producing strain, and only the imipenem+rifampicin combination yielded synergistic effects. In contrast, rifampicin alone was not effective against the VIM-2-producing strain, but the imipenem+rifampicin combination was bacteriostatic even at 24 h post-infection. Tigecycline and amikacin were not effective against any of the three strains. Rifampicin-based combinations were effective against A. baumannii bacteraemia and improved survival regardless of the strain type. Contrary to the similar minimum inhibitory concentration results, the antibacterial effects of rifampicin were quite different according to the strains; a tailored antibiotic strategy must be considered in treatment. Addition of rifampicin to either imipenem or colistin would be effective.

Clinical outcome and predictive factors of recurrence among patients with Kikuchi's disease.

OBJECTIVES To evaluate the clinical outcome and predictive factors of recurrence among patients with Kikuchis disease. METHODS Between January 2001 and December 2006, all patients with Kikuchis disease were included in the study. Data were collected on co-morbidities, clinical manifestations, and ultrasound/laboratory findings, and the differences were compared between recurrent disease and non-recurrent disease groups. RESULTS The study included 102 patients with a mean age of 26.7 years. Among these patients, three developed systemic lupus erythematosus during the follow-up period, while two cases were later associated with tuberculosis. Eight patients (7.8%) experienced early relapse and 13 (12.7%) showed late recurrence. Patients with recurrent episodes were more likely to have fever and fatigue with extranodal involvement. Compared to the non-recurrent cases, recurrent cases remained symptomatic for a rather longer duration. The positive rate of the fluorescence anti-nuclear antibody (FANA) test was significantly higher in the recurrent disease group compared to the non-recurrent disease group. CONCLUSIONS Kikuchis disease took a self-limiting clinical course in most cases, but the recurrence rate found in the present study was higher than that of previous reports. Kikuchis disease might be a phenotype of diverse disease entities. The prognosis is different according to the underlying cause. The FANA test would be useful in predicting recurrence.

Colistin and rifampicin combination in the treatment of ventilator-associated pneumonia caused by carbapenem-resistant Acinetobacter baumannii

f VRE. A quantitative drug usage evaluation performed ndependently in our hospital from 2004 to 2006 revealed 104% increase in vancomycin usage. The qualitative rug usage evaluation results indicated that only 40% of he patients were prescribed vancomycin for one of the pproved indications according to the Hospital Infection ontrol Practices Advisory Committee (HICPAC) guidelines 7]. Having a malignant disease remained protective for RE in the multivariate model (OR 0.26, 95% CI 0.07– .97). The crude associated mortality rate was higher in atients with VRE infections (VRE 53.1% vs. VSE 32.3%; = 0.047). The total hospital stay (VRE 51.5 ± 27.8 days vs. SE 37.6 ± 29.6 days) was longer in VRE-infected patients han in those with VSE infections (P = 0.028).

Effectiveness of the pandemic influenza A/H1N1 2009 monovalent vaccine in Korea

The 2009 influenza pandemic was caused by a novel triple-reassortant influenza A/H1N1 virus that was further recombined with a Eurasian pig flu virus. Vaccination is a key countermeasure for disease; however, little data assessing vaccine effectiveness (VE) against the pandemic H1N1 virus are available. We conducted a matched case-control study to assess effectiveness of the 2009 influenza A/H1N1 monovalent vaccine against laboratory-confirmed, medically attended influenza patients. Subjects included in the study were ≥ 10 years of age and were treated at five university hospitals in the Republic of Korea (ROK) from December 2009 through March 2010. For subjects visiting outpatient clinics with influenza-like illness (ILI), real time reverse transcription polymerase chain reaction (rRT-PCR) was used to diagnose 2009 H1N1 influenza virus infection. Subjects with positive rRT-PCR were classified as cases, while those testing negative were controls. A valid vaccination corresponded to ≥ 14 days between receiving a dose of vaccine and symptom onset. Overall, 416 ILI subjects were analyzed, and 60 (14.4%) were vaccinated with the 2009 influenza A/H1N1 monovalent vaccine. The overall VE against pandemic 2009 A/H1N1 virus illness after adjustment for age group and presence of chronic medical conditions was 73.4% (95% confidence interval [CI]=49.1-86.1%). Both vaccine formulations (unadjuvanted and MF-59 adjuvanted) showed a statistically significant VE. In conclusion, the 2009 influenza A/H1N1 monovalent vaccine was substantially protective against pandemic influenza in the ROK during the 2009-2010 season.

Protein phosphatase 1 nuclear targeting subunit is a hypoxia inducible gene: its role in post-translational modification of p53 and MDM2.

p53, the most commonly mutated tumor suppressor gene in human cancers, is a master regulator of apoptosis in many types of cells. Recently, protein phosphatase-1 (PP1) has emerged as a key phosphatase of p53, which modulates the interaction of p53 with its regulatory protein mouse double minute 2 (MDM2) and transcriptional activity. In the present study, we demonstrate the potential role of PP1 nuclear targeting subunit (PNUTS) in regulating the phosphorylation and apoptotic activities of p53. Hypoxia significantly increased mRNA and protein expression of PNUTS in various cell lines concomitantly with increases in p53. Promoter analysis confirmed the presence of hypoxia response elements in the promoter region of the PNUTS gene, which respond to hypoxia and forced expression of hypoxia-inducible factor 1 α. Overexpression of PNUTS markedly increased cell death in response to hypoxia, with increased expression of Bax, an apoptosis-related gene induced by p53. Consistently, PNUTS increased the nuclear localization, phosphorylation, and transcriptional activity of p53 as well as the ubiquitin-dependent proteosomal degradation of MDM2. However, the W401A mutant form of PNUTS, which is incapable of binding to PP1, failed to induce these events. Taken together, our findings suggest that PNUTS may play an important role in controlling cell death in response to cellular stresses such as hypoxia through the post-translational modification of p53 and MDM2.

Environmental Contamination and Viral Shedding in MERS Patients During MERS-CoV Outbreak in South Korea

Viable Middle East Respiratory Syndrome coronavirus (MERS-CoV) could be isolated from the environment surfaces and respiratory specimens from clinically recovered patients. Our results suggested that MERS-CoV can be transmitted through contaminated fomites, hence strict environmental hygiene, and sufficient isolation period are essential for MERS-CoV control.

A Comparison of the Clinical and Epidemiological Characteristics of Adult Patients with Laboratory-Confirmed Influenza A or B during the 2011–2012 Influenza Season in Korea: A Multi-Center Study

Background During the 2011/2012 winter influenza season in the Republic of Korea, influenza A (H3N2) was the predominant virus in the first peak period of influenza activity during the second half of January 2012. On the other hand, influenza B was the predominant virus in the second peak period of influenza activity during the second half of March 2012. The objectives of this study were to compare the clinical and epidemiological characteristics of patients with laboratory-confirmed influenza A or influenza B. Methodology/Principal Findings We analyzed data from 2,129 adult patients with influenza-like illnesses who visited the emergency rooms of seven university hospitals in Korea from October 2011 to May 2012. Of 850 patients with laboratory-confirmed influenza, 656 (77.2%) had influenza A (H3N2), and 194 (22.8%) influenza B. Age, and the frequencies of cardiovascular disorders, diabetes, hypertension were significantly higher in patients with influenza A (H3N2) (P<0.05). The frequencies of leukopenia or thrombocytopenia in patients with influenza B at initial presentation were statistically higher than those in patients with influenza A (H3N2) (P<0.05). The rate of hospitalization, and length of hospital stay were statistically higher in patients with influenza A (H3N2) (P<0.05), and of the 79 hospitalized patients, the frequency of diabetes, hypertension, cases having at least one of the comorbid conditions, and the proportion of elderly were significantly higher in patients with influenza A (H3N2) (P<0.05). Conclusions The proportion of males to females and elderly population were significantly higher for influenza A (H3N2) patients group compared with influenza B group. Hypertension, diabetes, chronic lung diseases, cardiovascular disorders, and neuromuscular diseases were independently associated with hospitalization due to influenza. Physicians should assess and treat the underlying comorbid conditions as well as influenza viral infections for the appropriate management of patients with influenza.

Disease burden of herpes zoster in Korea

BACKGROUND The occurrence of herpes zoster can deteriorate the quality of life considerably, resulting in high disease burden. While Korea is assumed to have high disease burden of herpes zoster, there has been no researches analyzing this. OBJECTIVES We performed this study to investigate the disease burden of herpes zoster in the Korean population as a whole. STUDY DESIGN We used the database of the Health Insurance Review & Assessment Service of Korea and analyzed the data of patients who had herpes zoster as a principal diagnosis during the period from 2003 to 2007. We investigated the annual prevalence, rate of clinical visits, rate of hospitalization, and the pattern of medical services use. The socioeconomic burden of herpes zoster was calculated by a conversion into cost. RESULTS Rates of clinic visits and hospitalizations due to herpes zoster during the 5-year period from 2003 to 2007 were 7.93-12.54 per 1000 population and 0.22-0.32 per 1000 population, respectively. Prevalence rates according to age increased sharply after 50 years and reached a peak at 70 years. The total socioeconomic cost of herpes zoster was

Ischemia-related changes of adrenocorticotropic hormone immunoreactivity and its protective effect in the gerbil hippocampus after transient forebrain ischemia

75.9-143.8 million per year, increasing every year by 14-20%. CONCLUSIONS There is a heavy socioeconomic burden due to herpes zoster in Korea and indicate that appropriate policies need to be established to reduce this burden. Additional researches are also necessary to assess the safety, efficacy and cost-effectiveness of a herpes zoster vaccine in the Korean population.

The Clinical Usefulness of the SD Bioline Influenza Antigen Test® for Detecting the 2009 Influenza A (H1N1) Virus

In the present study, the temporal and spatial alterations of adrenocorticotropic hormone (ACTH) immunoreactivity in the gerbil hippocampus after 5 min transient forebrain ischemia were investigated as followed up 7 days after ischemic insult, and the effects of ACTH after ischemic insult were also investigated 4 days after ischemic insult. The ectopic expression of ACTH (1-24 fragments) immunoreactive neurons in the cornus ammonis 1 (CA1) region of hippocampus and hilar region of the dentate gyrus 1 day after the ischemic insult was observed. Judging from the double immunofluorescence study, these neurons contain GABA. Four days after ischemic insult, the ACTH immunoreactivity was localized in CA1 pyramidal cells and glia near the stratum pyramidale, which normally do not express ACTH. In addition, in the saline-treated groups, the percentage of the detected Cresyl Violet positive neurons was 11.2% compared with the sham-operated group 4 and 7 days after ischemic insult. In these groups, the OX-42 immunoreactive microglia were detected in the strata pyramidale, oriens and radiatum. However, in the Org2766 (analog of ACTH)-treated group, 57.8% neurons compared with the sham-operated group were stained with Cresyl Violet 4 and 7 days after ischemic insult. In these groups, the OX-42 immunoreactive microglia were significantly reduced in the stratum pyramidale. These results suggest that transient forebrain ischemia may provoke selective ectopic and enhanced expression of ACTH in the hippocampus, and further suggest that ACTH plays an important role in reducing the ischemic damage.