Antiretroviral Genotypic Resistance Mutations in HIV-1 Infected Korean Patients with Virologic Failure

Resistance assays are useful in guiding decisions for patients experiencing virologic failure (VF) during highly-active antiretroviral therapy (HAART). We investigated antiretroviral resistance mutations in 41 Korean human immunodeficiency virus type 1 (HIV-1) infected patients with VF and observed immunologic/virologic response 6 months after HAART regimen change. Mean HAART duration prior to resistance assay was 45.3±27.5 months and commonly prescribed HAART regimens were zidovudine/lamivudine/nelfinavir (22.0%) and zidovudine/lamivudine/efavirenz (19.5%). Forty patients (97.6%) revealed intermediate to high-level resistance to equal or more than 2 antiretroviral drugs among prescribed HAART regimen. M184V/I mutation was observed in 36 patients (87.7%) followed by T215Y/F (41.5%) and M46I/L (34%). Six months after resistance assay and HAART regimen change, median CD4+ T cell count increased from 168 cells/µL (interquartile range [IQR], 62-253) to 276 cells/µL (IQR, 153-381) and log viral load decreased from 4.65 copies/mL (IQR, 4.18-5.00) to 1.91 copies/mL (IQR, 1.10-3.60) (P<0.001 for both values). The number of patients who accomplished viral load <400 copies/mL was 26 (63.4%) at 6 months follow-up. In conclusion, many Korean HIV-1 infected patients with VF are harboring strains with multiple resistance mutations and immunologic/virologic parameters are improved significantly after genotypic resistance assay and HAART regimen change

Clinical Review of Endogenous Endophthalmitis in Korea: A 14-Year Review of Culture Positive Cases of Two Large Hospitals

PURPOSE: To identify the clinical features and outcomes of endogenous endophthalmitis in Korea. MATERIALS AND METHODS: We reviewed 18 patients with endogenous endophthalmitis at 2 Korean hospitals, treated over a 14 year period between January 1993 and December 2006. RESULTS: The comorbidities observed in these cases were diabetes mellitus and liver cirrhosis. The most common pathogens, which were found in 7 patients each (38.9%), were Klebsiella pneumonia and Pseudomonas aeruginosa. All patients were treated with systemic antibiotics and fortified topical antibiotics. A surgical approach including vitrectomy was performed in 9 cases (50.0%). The prognosis was generally poor, and visual acuity improved slightly in 6 patients (33.3%). CONCLUSION: In this study, diabetes mellitus and Klebsiella pneumonia showed a close relationship with endogenous endophthalmitis, respectively. Endogenous endophthalmitis is a serious risk to sight and careful attention to establishing the diagnosis and management may decrease the ocular morbidity.ope

The Characteristics of Metallo-β-Lactamase-Producing Gram-Negative Bacilli Isolated from Sputum and Urine: A Single Center Experience in Korea

Metallo-β-lactamase (MBL) production usually results in high-level resistance to most β-lactams, and a rapid spread of MBL producing major gram-negative pathogens is a matter of particular concern worldwide. However, clinical data are scarce and most studies compared MBL producer (MP) with MBL non-producer (MNP) strains which included carbapenem susceptible isolates. Therefore, we collected clinical data of patients in whom imipenem-nonsusceptible Pseudomonas aeruginosa (PA) and Acinetobacter baumannii (AB) were isolated from sputum or urine, and investigated MBL production and the risk factors related with MBL acquisition. The antimicrobial susceptibility patterns were also compared between MPs and imipenem-nonsusceptible MNPs (INMNP). Among the 176 imipenem-nonsusceptible isolates, 12 MPs (6.8%) were identified. There was no identifiable risk factor that contributed to the acquisition of MPs when compared to INMNPs, and case-fatalities were not different between the two groups. The percentage of susceptible isolates was higher among MPs for piperacilin/tazobactam and fluoroquinolones while that of ceftazidime was higher in INMNPs (p < 0.05). As regards to aztreonam, which has been known to be a uniquely stable β-lactam against MBLs, susceptibility was preserved in only two isolates (16.7%) among MPs, and was not higher than that of INMNPs (23.2%). In conclusion, the contribution of MBLs to imipenem non-susceptibility in PA/ABs isolated from sputum and urine was relatively limited, and there was no significant risk factor associated with acquisition of MPs compared with INMNPs. However, limited susceptibility to aztreonam implies that MPs may hold additional resistance mechanisms, such as extended spectrum β-lactamases, AmpC β-lactamases, or other non-enzymatic mechanisms

Factors Associated with HIV-1 Proviral DNA Loads in Patients with Undetectable Plasma RNA Load

To evaluate factors associated with human immunodeficiency virus type 1 (HIV-1) proviral DNA load, we conducted a cross-sectional study of 36 chronically HIV-1-infected individuals with undetectable plasma viral RNA. We used real-time polymerase chain reaction to determine the number of HIV-1 proviral DNA copies per 106 peripheral blood mononuclear cells. The mean level of plasma viral RNA when the CD4+ T cell count was above 500 cells/µL without highly active antiretroviral therapy (HAART) was significantly associated with proviral DNA load at the time of undetectable plasma HIV RNA with HAART. Strategies to reduce the level of plasma viral RNA when patients' CD4+ T cell counts are above 500 cells/µL without HAART could help reduce HIV-1 proviral DNA load

Lack of Effect of Dexamethasone on Growth of Orientia Tsutsugamushi Gilliam in Mouse L929 Cells

PURPOSE: Previous studies and our own clinical experience suggest that concurrent corticosteroid treatment for severe rickettsial disease with multiorgan failure may improve the clinical course or reduce mortality. However, the use of corticosteroids as adjunctive treatment for rickettsial diseases is controversial. We attempted to determine the influences of corticosteroid on the growth of Orientia tsutsugamushi in vitro to justify and evaluate the clinical applicability of corticosteroid in rickettsial disease. MATERIALS AND METHODS: L929 cells were infected with Orientia tsutsugamushi Gilliam. Dexamethasone was added to the cells at final concentrations of 10¹ and 10⁷ pg/mL. Cultures were incubated at 35°C and processed for flow cytometry on the 6th day after addition of dexamethasone. RESULTS: Observation on the 6th day after treatment with dexamethasone in infected cultures revealed that there was no difference in fluorescence intensity among the treatment wells. Treatment of the cells with dexamethasone at concentrations of 10¹ and 10⁷ pg/mL showed no influence on the growth of Orientia tsutsugamushi. CONCLUSION: Our results to show that isolated corticosteroid does not enhance the replication of Orientia tsutsugamushi in vitro. Concurrent use of anti-inflammatory or immunosuppressive doses of corticosteroids in conjunction with antibiotics may not have detrimental effects on the course of scrub typhus.ope

Disseminated Mycobacterium kansasii Infection Associated with Skin Lesions: A Case Report and Comprehensive Review of the Literature

Mycobacteruim kansasii occasionally causes disseminated infection with poor outcome in immunocompromised patients. We report the first case of disseminated M. kansasii infection associated with multiple skin lesions in a 48-yr-old male with myelodysplastic syndrome. The patient continuously had taken glucocorticoid during 21 months and had multiple skin lesions developed before 9 months without complete resolution until admission. Skin and mediastinoscopic paratracheal lymph node (LN) biopsies showed necrotizing granuloma with many acid-fast bacilli. M. kansasii was cultured from skin, sputum, and paratracheal LNs. The patient had been treated successfully with isoniazid, rifampin, ethmabutol, and clarithromycin, but died due to small bowel obstruction. Our case emphasizes that chronic skin lesions can lead to severe, disseminated M. kansasii infection in an immunocompromised patient. All available cases of disseminated M. kansasii infection in non HIV-infected patients reported since 1953 are comprehensively reviewed

Clinical Features of Re-Emerging Hepatitis A: An Analysis of Patients Hospitalized during an Urban Epidemic in Korea

From April 2008 to November 2008, many cases of hepatitis A were reported in Seoul and Gyeonggi Province in Korea. Furthermore, the rate of severe or fulminant hepatitis have significantly increased during the latest epidemic (13.4% vs. 5.2%, p=0.044). Therefore, widespread use of vaccine is warranted to reduce the burden of hepatitis A in Korea

Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance:an individual-patient- and sequence-level meta-analysis

Regional and subtype-specific mutational patterns of HIV-1 transmitted drug resistance (TDR) are essential for informing first-line antiretroviral (ARV) therapy guidelines and designing diagnostic assays for use in regions where standard genotypic resistance testing is not affordable. We sought to understand the molecular epidemiology of TDR and to identify the HIV-1 drug-resistance mutations responsible for TDR in different regions and virus subtypes.status: publishe