Duck Jin Hong

Diagnostic performances of HE4 and CA125 for the detection of ovarian cancer from patients with various gynecologic and non-gynecologic diseases.

OBJECTIVES We compared diagnostic performance of CA125 and HE4 in various gynecologic and non-gynecologic diseases. DESIGN AND METHODS Sera from 176 patients with various diseases were collected, and CA125 and HE4 levels were compared. ROC curves were constructed to estimate the diagnostic performance. RESULTS Levels of both markers were elevated in ovarian cancer. CA125 was also high in benign gynecologic diseases, but HE4 was not. CA125 levels of pregnant women were higher than those of control group, and HE4 was increased in chronic renal diseases. The sensitivity for discriminating ovarian cancer from healthy or benign conditions was 44.8% for HE4 and 55.2% for CA125 at 95% specificity. The ROC-AUC values for HE4 and CA125 were 0.85 and 0.87 respectively. CONCLUSIONS HE4 demonstrated comparable diagnostic performances to CA125, though each marker had its own strengths and weaknesses. Combining CA125 and HE4 might be more advantageous than either one alone.

Epidemiology and Characteristics of Metallo-β-Lactamase-Producing Pseudomonas aeruginosa

Metallo-β-lactamase-producing Pseudomonas aeruginosa (MPPA) is an important nosocomial pathogen that shows resistance to all β-lactam antibiotics except monobactams. There are various types of metallo-β-lactamases (MBLs) in carbapenem-resistant P. aeruginosa including Imipenemase (IMP), Verona integron-encoded metallo-β-lactamase (VIM), Sao Paulo metallo-β-lactamase (SPM), Germany imipenemase (GIM), New Delhi metallo-β-lactamase (NDM), Florence imipenemase (FIM). Each MBL gene is located on specific genetic elements including integrons, transposons, plasmids, or on the chromosome, in which they carry genes encoding determinants of resistance to carbapenems and other antibiotics, conferring multidrug resistance to P. aeruginosa. In addition, these genetic elements are transferable to other Gram-negative species, increasing the antimicrobial resistance rate and complicating the treatment of infected patients. Therefore, it is essential to understand the epidemiology, resistance mechanism, and molecular characteristics of MPPA for infection control and prevention of a possible global health crisis. Here, we highlight the characteristics of MPPA.

Soluble human leukocyte antigen-G expression in hepatitis B virus infection and hepatocellular carcinoma

We investigated soluble human leukocyte antigen-G (sHLA-G) expression according to the phases of hepatitis B virus (HBV) infections and hepatocellular carcinoma (HCC). A total of 267 sera from anti-HBs positive healthy individuals (n = 50), chronic HBV carriers (n = 45), as well as patients with active hepatitis B (n = 46), liver cirrhosis (LC, n = 46) and early stage HCC (n = 80) were collected and assayed for sHLA-G. Relationships between sHLA-G levels and clinicopathologic parameters including HCC stages, differentiation grades, and levels of aminotransferases, HBV DNA and alpha-fetoprotein (AFP) were assessed. Concentrations of sHLA-G were higher in the active hepatitis B and HCC groups (median sHLA-G 53.7 and 178.8 U/ml, respectively) in comparison to other groups (P < 0.05), and there were no significant differences among sHLA-G levels of the anti-HBs positive, chronic HBV carrier and LC groups. Serum sHLA-G concentrations were not shown to be associated with clinicopathologic indices including the levels of aminotransferases, AFP, anti-HBs titer, HBV DNA, as well as HCC stages, numbers of tumor nodules, pathologic grades and presence of vessel invasion. The receiver-operating characteristic area under the curve (AUC) value of sHLA-G for differentiating HCC from LC was 0.98, which was greater than that of AFP (0.78) (P < 0.0001), and sensitivity and specificity of sHLA-G were, respectively, 90.0% and 95.7% for HCC when applying a cutoff level of 97.3 U/ml. Serum sHLA-G levels could be used as a diagnostic marker for HCC. Although sHLA-G levels did not reflect the severity of HBV infections and HCC, they were related with phases of the disease.

Urinary iodine and sodium status of urban Korean subjects: a pilot study.

OBJECTIVES We estimated iodine status of Korean population by determining the concentration of spot urinary iodine (UI) with a reliable method based on the Sandell-Kolthoff reaction. MATERIALS AND METHODS A total of 540 urine samples from apparently healthy subjects were collected, and UI, urinary sodium (UNa), and urinary creatinine (UCr) were determined from those samples and analyzed with age. RESULTS There were significant decreases in either UI (P<0.0001), UI/UCr ratio (P=0.0001), UNa (P<0.0001), or UNa/Cr ratio (P=0.0001) in younger subjects than older ones. The median value of UI was 267.6 μg/L, but the median UI of the younger group (191.8 μg/L) was significantly decreased compared to that of the older group (383.9 μg/L). CONCLUSIONS This study showed that the median of UI in Korean urban population was in a more than adequate iodine nutritional state, but UI was significantly different between the younger age group and the older age group.

Performance Evaluation of New Automated Hepatitis B Viral Markers in the Clinical Laboratory Two Quantitative Hepatitis B Surface Antigen Assays and an HBV Core-Related Antigen Assay

We evaluated quantitative hepatitis B surface antigen (qHBsAg) assays and a hepatitis B virus (HBV) core-related antigen (HBcrAg) assay. A total of 529 serum samples from patients with hepatitis B were tested. HBsAg levels were determined by using the Elecsys (Roche Diagnostics, Indianapolis, IN) and Architect (Abbott Laboratories, Abbott Park, IL) qHBsAg assays. HBcrAg was measured by using Lumipulse HBcrAg assay (Fujirebio, Tokyo, Japan). Serum aminotransferases and HBV DNA were respectively quantified by using the Hitachi 7600 analyzer (Hitachi High-Technologies, Tokyo, Japan) and the Cobas AmpliPrep/Cobas TaqMan test (Roche). Precision of the qHBsAg and HBcrAg assays was assessed, and linearity of the qHBsAg assays was verified. All assays showed good precision performance with coefficients of variation between 4.5% and 5.3% except for some levels. Both qHBsAg assays showed linearity from 0.1 to 12,000.0 IU/mL and correlated well (r = 0.9934). HBsAg levels correlated with HBV DNA (r = 0.3373) and with HBcrAg (r = 0.5164), and HBcrAg also correlated with HBV DNA (r = 0.5198; P < .0001). This observation could provide impetus for further research to elucidate the clinical usefulness of the qHBsAg and HBcrAg assays.

In vitro antimicrobial synergy of colistin with rifampicin and carbapenems against colistin-resistant Acinetobacter baumannii clinical isolates

Increased use of colistin in a clinical setting had resulted in the emergence of colistin-resistant (CoR) Acinetobacter baumannii. Combination therapy has been studied as a new approach to treat infections caused by A. baumannii. Here, we investigated the in vitro antimicrobial synergistic activities of several antimicrobial agent combinations against CoR A. baumannii. A total of 41 non-duplicate clinical isolates of CoR A. baumannii from a tertiary care hospital in Korea were prospectively collected from April 2012 to December 2014. As a control group, 41 carbapenem-resistant but colistin-susceptible (CoS) A. baumannii strains were also evaluated. Minimum inhibitory concentrations (MICs) of antimicrobial agents were determined by Etest in triplicate, and in vitro synergy tests were performed by the Etest MIC:MIC ratio method. Synergistic activity was determined as the sum of each antimicrobial agents fractional inhibitory concentration evaluated (ΣFIC): synergy, ≤0.5; indifference, >0.5-4; and antagonism, >4. Synergistic activities were more frequently observed in the CoR group than the CoS group for combinations of colistin-rifampicin (80.5% vs. 14.6%, P< 0.0001), colistin-meropenem (85.4% vs. 4.9%, P< 0.0001), and colistin-imipenem (46.3% vs. 2.4%, P< 0.0001). Combination with rifampicin or meropenem lowered colistin MICs against CoR A. baumannii clinical isolates to the susceptible range (≤ 2 μg/mL) more frequently (61.0%, 25/41, both) than combination with imipenem (29.3%, 12/41). Clinical trials are needed to prove the in vivo efficacy of those antimicrobial combinations that exhibited significant in vitro antimicrobial synergistic effects against CoR A. baumannii.

Febrile Respiratory Illness Associated with Human Adenovirus Type 55 in South Korea Military, 2014–20161

An outbreak of febrile respiratory illness associated with human adenovirus (HAdV) occurred in the South Korea military during the 2014–15 influenza season and thereafter. Molecular typing and phylogenetic analysis of patient samples identified HAdV type 55 as the causative agent. Emergence of this novel HAdV necessitates continued surveillance in military and civilian populations.

First Case Report of Human Infection With Ochrobactrum tritici Causing Bacteremia and Cholecystitis.

Dear Editor, Herein, we report the first case of human infection with Ochrobactrum tritici, primarily isolated from environmental sources and not previously known to infect humans. A 70-yr-old male patient was admitted to a tertiary-care hospital for jaundice. He had a medical history of cholangiocellular carcinoma (CCC). On the first day of hospitalization, he presented a 38.1℃ body temperature, 98/81 mmHg blood pressure, 87 beats per minute heart rate, and abdominal distention. Laboratory findings indicated a white blood cell count of 5.63×109/L with a differential of 71% neutrophils, a hemoglobin level of 10 g/dL, a platelet count of 25×109/L, and a C-reactive protein level of 48.5 mg/L (reference range, 0.1–6.0 mg/L). Two sets of blood cultures were performed at the time of high fever on admission. Among these four cultures, only one aerobic culture was positive for gram-negative short rods after 4 days of incubation. Intravenous antibiotics with metronidazole (500 mg every 8 hr) and cefoperazone/ sulbactam (2,000 mg every 12 hr) were started on the first day of hospitalization. His condition improved after antibiotic therapy and he was discharged from the hospital on day five. The isolate (named GNOT01) was identified as Ochrobactrum anthropi by matrix-assisted laser desorption ionization–time of flight mass spectrometer (MALDI-TOF MS; MicroFlex LT, Bruker Daltonics, Bremen, Germany). Two weeks later, the patient presented with exacerbated jaundice and abdominal pain. Physical examination revealed abdominal distention and ascites. Laboratory analysis indicated a leukocyte count of 6.5×109/L with a differential of 71% neutrophils, a platelet count of 83×109/L, a C-reactive protein level of 77.4 mg/L, and a total bilirubin of 6.7 mg/dL (reference range, 0.3–1.8 mg/dL). He received intravenous cefoperazone/sulbactam (2,000 mg every 12 hr) from the first day of hospitalization. Culture of the bile specimen collected during percutaneous transhepatic biliary drainage procedure yielded gram-negative rods (isolate GNOT02) and gram-positive cocci, identified as Ochrobactrum species and Enterococcus faecalis, respectively, by MALDI-TOF MS. The patient fully recovered from cholecystitis without any evidence of infection and was discharged on day 28 without specific complications. The clinical isolates, GNOT01 and GNOT02, were biochemically identified as O. anthropi with >99% probability. However, PCR and sequencing indicated that the 16S rRNA partial sequences of both isolates were 100% identical to those of strain CCUG 47104T, the O. tritici type strain. Scanning electron microscopy (SEM) images of the isolates revealed that they had a single polar flagellum, which was not observed in the type strain CCUG 47104T (Fig. 1). On bacterial motility test using motility indole ornithine (MIO) agar, GNOT01 and GNOT02 showed upper stab lines that diffused out just beneath the surface of the MIO agar creating an umbrella-shape, which suggests that they are strictly aerobic and motile. No finding related to motility was obtained with CCUG 47104T. Fig. 1 Scanning electron micrographs of Ochrobactrum tritici clinical isolate GNOT01 (A) and the type strain CCUG 47104T (B). GNOT01 isolate presented a single polar flagellum, while CCUG 47104T strain did not (Magnification, ×20,000). Pulsed-field gel electrophoresis (PFGE) presented identical XbaI macro-restriction banding patterns between the two isolates, which were different from that of CCUG 47104T (similarity, 84.2%) indicating that the bacteremia of the patient originated from cholecystitis. Antimicrobial susceptibility testing showed that CCUG 47104T was susceptible to ticarcillin, ceftriaxone, and cefepime, while GNOT01 and GNOT02 were resistant to these antimicrobials. Extended-spectrum β-lactamase (ESBL) genes and plasmid-encoded AmpC β-lactamase genes were not detected in GNOT01 and GNOT02 isolates by double disk synergy test and PCR, suggesting that they acquired resistance to β-lactams not by production of plasmid-mediated ESBLs or AmpC β-lactamases, but by overexpression of species-specific intrinsic AmpC β-lactamases. To date, only four species, O. anthropi, O. intermedium, O. haematophilum, and O. pseudogrignonense, have been reported to cause human infections [1,2,3,4]. Among these, O. anthropi is the most frequently reported human pathogen, especially in immunocompromised patients. Phylogenetic analysis of 16S rRNA gene sequences revealed a high similarity between O. tritici and O. anthropi with 98% identity [5]. However, O. tritici strains exhibit low DNA-DNA re-association values (< 60%) with O. anthropi probes and showed different phenotypic characteristics. These genotypic and phenotypic differences resulted in the classification of O. tritici as a distinct species. In summary, we reported the first case of human infection with an O. tritici motile strain isolated from the blood and bile. O. tritici should be considered as a potential pathogen that can cause bloodstream and biliary tract infections in humans. In addition, both commercial bacterial identification kits and MALDI-TOF MS misidentified O. tritici clinical isolates as O. anthropic. Thus, 16S rRNA sequencing should be performed when a clinical isolate is identified as O. anthropi by routine bacterial identification processes.

Evaluation of an automated urinary iodine measurement using AU5800 analyzer with AutoLab Iodine reagent.

*Corresponding author: Duck Jin Hong, Department of Laboratory Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea, Fax: +82-2-2057-8926, E-mail: dududuck@hanmail.net Soon Sung Kwon, Byungkwang Kim, Sung Won Hwang, Kwangwoo Kim and Seok Hoon Jeong: Department of Laboratory Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea Jeong-Ho Kim: Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea Letter to the Editor

Differences in Colistin-resistant Acinetobacter baumannii Clinical Isolates Between Patients With and Without Prior Colistin Treatment

Background The increasing morbidity and mortality rates associated with Acinetobacter baumannii are due to the emergence of drug resistance and the limited treatment options. We compared characteristics of colistin-resistant Acinetobacter baumannii (CR-AB) clinical isolates recovered from patients with and without prior colistin treatment. We assessed whether prior colistin treatment affects the resistance mechanism of CR-AB isolates, mortality rates, and clinical characteristics. Additionally, a proper method for identifying CR-AB was determined. Methods We collected 36 non-duplicate CR-AB clinical isolates resistant to colistin. Antimicrobial susceptibility testing, Sanger sequencing analysis, molecular typing, lipid A structure analysis, and in vitro synergy testing were performed. Eleven colistin-susceptible AB isolates were used as controls. Results Despite no differences in clinical characteristics between patients with and without prior colistin treatment, resistance-causing genetic mutations were more frequent in isolates from colistin-treated patients. Distinct mutations were overlooked via the Sanger sequencing method, perhaps because of a masking effect by the colistin-susceptible AB subpopulation of CR-AB isolates lacking genetic mutations. However, modified lipid A analysis revealed colistin resistance peaks, despite the population heterogeneity, and peak levels were significantly different between the groups. Conclusions Although prior colistin use did not induce clinical or susceptibility differences, we demonstrated that identification of CR-AB by sequencing is insufficient. We propose that population heterogeneity has a masking effect, especially in colistin non-treated patients; therefore, accurate testing methods reflecting physiological alterations of the bacteria, such as phosphoethanolamine-modified lipid A identification by matrix-assisted laser desorption ionization-time of flight, should be employed.