Moon Hyun Chung

Apoptosis of Endothelial Cell Line ECV304 Persistently Infected with Orientia tsutsugamushi

Endothelial cells are major targets of Orientia tsutsugamushi. To examine the consequences of the infection of endothelial cells with O. tsutsugamushi, we used human endothelial cell line ECV304. Persistent infection was established and infected cultures could be maintained for over seven months without the addition of normal cells. The heavily infected cells became round and floated in the culture medium, harboring large numbers of organisms inside them. Some of the infected ECV304 cells showed features of apoptotic cells, as determined by the terminal deoxytransferase‐mediated dUTP nick end‐labeling reaction and DNA fragmentation. We also found that O. tsutsugamushi increased transcription of the mRNAs of proinflammatory cytokines such as IL‐6 and IL‐8. These results show the first evidence of in vitro‐persistent infection by O. tsutsugamushi, which may be related to in vivo persistence reported previously.

Susceptibility of Escherichia coli from Community-Acquired Urinary Tract Infection to Fosfomycin, Nitrofurantoin, and Temocillin in Korea

With increase of multi-drug resistant Escherichia coli in community-acquired urinary tract infections (CA-UTI), other treatment option with a therapeutic efficacy and a low antibiotic selective pressure is necessary. In this study, we evaluated in vitro susceptibility of E. coli isolates from CA-UTI to fosfomycin (FM), nitrofurantoin (NI), temocillin (TMO) as well as trimethoprim-sulfamethoxazole (SMX), ciprofloxacin (CIP) and cefepime (FEP). The minimal inhibitory concentrations were determined by E-test or agar dilution method according to the Clinical and Laboratory Standards Institute guidelines, using 346 E. coli collected in 12 Korean hospitals from March 2010 to February 2011. FM, NI and TMO showed an excellent susceptibility profile; FM 100% (346/346), TMO 96.8% (335/346), and NI 99.4% (344/346). Conversely, resistance rates of CIP and SMX were 22% (76/346) and 29.2% (101/349), respectively. FEP still retained an activity of 98.5%. In Korea, NI and TMO in addition to FM are a good therapeutic option for uncomplicated CA-UTI, especially for lower UTI. Graphical Abstract

Immunogenicity and safety of a novel quadrivalent meningococcal conjugate vaccine (MenACWY-CRM) in healthy Korean adolescents and adults.

OBJECTIVESnThis phase III placebo-controlled study evaluated the immunogenicity and safety of MenACWY-CRM vaccination in healthy Korean adolescents and adults.nnnMETHODSnSerum bactericidal activity with human complement (hSBA) was measured before and 1 month after vaccination against all four meningococcal serogroups. The IgG concentration specific for serogroup W capsular polysaccharide was measured in a subset of subjects in a post-hoc analysis. Adverse reactions were monitored throughout the study.nnnRESULTSnFour hundred and fifty subjects were randomized 2:1 to receive MenACWY-CRM (N=297) or a saline placebo (N=153). MenACWY-CRM induced a good immune response against all four serogroups, with seroprotection rates (hSBA titers ≥8) of 79%, 99%, 98%, and 94% for serogroups A, C, W, and Y, respectively. Seroresponse rates were high for serogroups A, C, and Y, i.e. 76%, 86%, and 69%, respectively; the rate for serogroup W was 28%. MenACWY-CRM vaccine induced serum bactericidal antibodies against all four serogroups in a majority of subjects regardless of their baseline hSBA titers. MenACWY-CRM was generally well tolerated with most reactions being transient and mild to moderate in severity.nnnCONCLUSIONSnFindings of this first study of a quadrivalent meningococcal polysaccharide conjugate vaccine in Korean adults and adolescents demonstrated that a single dose of MenACWY-CRM was well tolerated and immunogenic, as indicated by the percentages of subjects with hSBA titers ≥8 (79%, 99%, 98%, and 94% of subjects) and geometric mean titers (48, 231, 147, and 107) against serogroups A, C, W, and Y, respectively, at 1 month post-vaccination.

In vitro bacteriostatic effects of rifampin on Orientia tsutsugamushi.

We performed an in vitro cell culture experiment to ascertain whether rifampin exhibits bactericidal effects against Orientia tsutsugamushi, the causative agent of scrub typhus. ECV304 cells were infected with the Boryong or AFSC-4 strain of O. tsutsugamushi and then, the cultures were maintained in media with increasing concentrations of rifampin, azithromycin, doxycycline, or chloramphenicol for 4 days. On day 5, the media were replaced with fresh antibiotic-free medium and the cultures were maintained until day 28. On days 5, 13, and 28, immunofluorescence (IF) staining of O. tsutsugamushi was performed. IF staining on days 13 and 28 revealed increasing numbers of IF-positive foci in all cultures, even in cultures initially exposed to the highest concentration of rifampin (80 µg/mL), azithromycin (80 µg/mL), doxycycline (20 µg/mL), or chloramphenicol (100 µg/mL). The present study reveals that rifampin has no bactericidal effect against O. tsutsugamushi as observed for azithromycin, doxycycline, and chloramphenicol. A subpopulation of the bacteria that are not killed by high concentrations of the antibiotics may explain the persistence of O. tsutsugamushi in humans even after complete recovery from scrub typhus with antibiotic therapy. Graphical Abstract

Comparison of Ertapenem and Ceftriaxone Therapy for Acute Pyelonephritis and Other Complicated Urinary Tract Infections in Korean Adults: A Randomized, Double-Blind, Multicenter Trial

The efficacy and safety of ertapenem, 1 g once daily, were compared with that of ceftriaxone, 2 g once daily, for the treatment of adults with acute pyelonephritis (APN) and complicated urinary tract infections (cUTIs) in a prospective, multicenter, double-blinded, randomized study. After ≥ 3 days of parenteral study therapy, patients could be switched to an oral agent. Of 271 patients who were initially stratified by APN (n = 210) or other cUTIs (n = 61), 66 (48.9%) in the ertapenem group and 71 (52.2%) in the ceftriaxone group were microbiologically evaluable. The mean duration of parenteral and total therapy, respectively, was 5.6 and 13.8 days for ertapenem and 5.8 and 13.8 days for ceftriaxone. The most common pathogen was Escherichia coli. At the primary efficacy endpoint 5-9 days after treatment, 58 (87.9%) patients in the ertapenem group and 63 (88.7%) in the ceftriaxone had a favorable microbiological response. When compared by stratum and severity, the outcomes in the two groups were equivalent. The frequency and severity of drug-related adverse events were generally similar in both treatment groups. The results indicate that ertapenem is highly effective and safe for the treatment of APN and cUTIs.

Usefulness of Blood Cultures and Radiologic Imaging Studies in the Management of Patients with Community-Acquired Acute Pyelonephritis

Background The objective of this study was to examine the usefulness of blood cultures and radiologic imaging studies for developing therapeutic strategies in community-acquired acute pyelonephritis (CA-APN) patients. Materials and Methods We prospectively collected the clinical data of CA-APN patients who visited 11 hospitals from March 2010 to February 2011. Results Positive urine and blood cultures were obtained in 69.3% (568/820) and 42.7% (277/648), respectively, of a total of 827 CA-APN patients. Blood culture identified the urinary pathogen in 60 of 645 (9.3%) patients for whom both urine and blood cultures were performed; the organisms isolated from urine were inconsistent with those from blood in 11 and only blood cultures were positive in 49 patients. Final clinical failure was more common in the bacteremic patients than the non-bacteremic ones (8.0% vs. 2.7%, P = 0.003), as was hospital mortality (3.6% vs. 0.3%, P = 0.003). Likewise, durations of hospitalization and fever were significantly longer. Bacteremia was independent risk factor for mortality (OR 9.290, 1.145-75.392, P = 0.037). With regard to radiologic studies, the detection rate of APN was 84.4% (445/527) by abdominal computed tomography and 40% (72/180) by abdominal ultrasonography. Eighty-one of 683 patients (11.9%) were found to have renal abscess, perinephric abscess, urolithiasis, hydronephorosis/hydroureter or emphysematous cystitis, which could potentially impact on clinical management. Patients with Pitt score ≥ 1, flank pain or azotemia were significantly more likely to have such structural abnormalities. Conclusion Blood cultures are clinically useful for diagnosis of CA-APN, and bacteremia is predictive factor for hospital mortality. Early radiologic imaging studies should be considered for CA-APN patients with Pitt scores ≥1, flank pain or azotemia.

Extensive Thrombosis in a Patient with Familial Mediterranean Fever, Despite Hyperimmunoglobulin D State in Serum - First Adult Case in Korea

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent episodes of fever accompanied by peritonitis, pleuritis, arthritis, or erysipelas-like erythema. It is known to occur mainly among Mediterranean and Middle Eastern populations such as non-Ashkenazi Jews, Arabs, Turks, and Armenians. FMF is not familiar to clinicians beyond this area and diagnosing FMF can be challenging. We report a 22-yr old boy who presented with fever, arthalgia and abdominal pain. He had a history of recurrent episodes of fever associated with arthalgia which would subside spontaneously or by antipyretics. Autosomal recessive periodic fever syndromes were suspected. Immunoglobulin D (IgD) level in the serum was elevated and DNA analysis showed complex mutations (p.Glu148Gln, p.Pro369Ser, p.Arg408Gln) in the MEFV gene. 3D angio computed tomography showed total thrombosis of splenic vein with partial thrombosis of proximal superior mesenteric vein, main portal vein and intrahepatic both portal vein. This is a case of FMF associated with multiple venous thrombosis and elevated IgD level. When thrombosis is associated with elevated IgD, FMF should be suspected. This is the first adult case reported in Korea.

In Vitro Activity of Tigecycline Against Orientia tsutsugamushi

Scrub typhus is a zoonosis caused by Orientia tsutsugamushi (O. tsutsugamushi) occurring mainly in autumn in Korea. The need of new antibiotics has arisen with a report on strains resistant to antibiotics and chronic infection. This study aims to identify susceptibility of tigecycline in-vitro as a new therapeutic option for O. tsutsugamushi. Antibacterial activity of tigecycline against the O. tsutsugamushi was compared with doxycycline using flow cytometry assay. The inhibitory concentration 50 (IC50) was 3.59×10-3 µg/mL in doxycycline-treated group. Whereas in 0.71×10-3 µg/mL tigecycline-treated group. These findings indicate that tigecycline may be a therapeutic option for the treatment of scrub typhus.

A Case of Disseminated Nocardiosis Secondary to the Skin Nodules in an Elderly Woman.

Nocardiosis refers to a locally invasive or disseminated infection associated with the Nocardia species. Most infections enter through the respiratory tract and then disseminate systemically. Rarely can a primary nocardial infection of the skin spread to contiguous structures or disseminate to other internal organs in immunocompromised hosts. We describe a 70-year-old woman who suffered from recurrent nodular skin lesions on her right hand, forearm and elbow following inoculation of a traumatic injury. Analysis of the purulent exudates obtained from the nodule revealed Nocardia species. After 20 days, a chest X-ray showed newly developed multiple nodules in both lungs. The diagnosis of systemic nocardiosis was established, and we treated this case with trimethoprim-sulfamethoxazole.

Comparison of HIV-infected patients' characteristics and clinical outcomes between cohort-dependent and independent patients: Korean HIV cohort study.

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