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Background: Carbapenem-resistant Pseudomonas aeruginosa (CrPA) is a leading cause of healthcare-associated urinary tract infections (UTIs). Carbapenemase production is an important mechanism that significantly alters the efficacy of frequently used anti-pseudomonal agents. Reporting the current genotypic distribution of carbapenemase-producing P. aeruginosa (CPPA) isolates in relation to antimicrobial susceptibility, UTI risk factors, and mortality is necessary to increase the awareness and control of these strains., Methods: In total, 1,652 non-duplicated P. aeruginosa strains were isolated from hospitalized patients between 2015 and 2020. Antimicrobial susceptibility, carbapenemase genotypes, risk factors for UTI, and associated mortality were analyzed., Results: The prevalence of carbapenem-non-susceptible P. aeruginosa isolates showed a decreasing trend from 2015 to 2018 and then increased in the background of the emergence of New Delhi metallo-β-lactamase (NDM)-type isolates since 2019. The CPPA strains showed 100.0% non-susceptibility to all tested antibiotics, except aztreonam (94.5%) and colistin (5.9%). Carbapenems were identified as a risk and common predisposing factor for UTI (odds ratio [OR]=1.943) and mortality (OR=2.766). Intensive care unit (ICU) stay (OR=2.677) and white blood cell (WBC) count (OR=1.070) were independently associated with mortality., Conclusions: The changing trend and genetic distribution of CPPA isolates emphasize the need for relentless monitoring to control further dissemination. The use of carbapenems, ICU stay, and WBC count should be considered risk factors, and aggressive antibiotic stewardship programs and monitoring may serve to prevent worse outcomes.

Background: The emergence of carbapenemase-producing Enterobacteriaceae (CPE) represents a major clinical problem. Recently, the occurrence of CPE has increased globally, but epidemiological patterns vary across region. We report the trends in the genotypic distribution and antimicrobial susceptibility of CPE isolated from rectal and clinical samples during a four-year period., Methods: Between January 2016 and December 2019, 1,254 nonduplicated CPE isolates were obtained from four university hospitals in Korea. Carbapenemase genotypes were determined by multiplex real-time PCR. Antimicrobial susceptibility was profiled using the Vitek 2 system (bioMérieux, Hazelwood, MO, USA) or MicroScan Walkaway-96 system (Siemens West Sacramento, CA, USA). The proportions of carbapenemase genotypes and nonsusceptibility were analyzed using Pearson's chi-square test., Results: Among the 1,254 CPE isolates, 486 (38.8%), 371 (29.6%), 357 (28.5%), 8 (0.6%), 8 (0.6%), and 24 (1.9%) were Klebsiella pneumoniae carbapenemase (KPC), oxacillinase (OXA)-48-like, New Delhi metallo-β-lactamase (NDM), imipenemase (IMP), Verona integron-encoded metallo-β-lactamase (VIM), and multiple producers, respectively. The predominant species was K. pneumoniae (72.6%), followed by Escherichia coli (6.5%). More than 90% of the isolates harboring KPC , NDM , and OXA-48 -like were nonsusceptible to cephalosporins, aztreonam, and carbapenems., Conclusions: The impact of CPE is primarily due to KPC-, NDM-, and OXA-48-like-producing K. pneumoniae isolates. Isolates carrying these carbapenemase are mostly multidrug-resistant. Control strategies based on these genotypic distributions and antimicrobial susceptibilities of CPE isolates are required.

Background: Reference intervals defined for adults or children of other ethnicities cannot be applied in the evaluation of Korean pediatric patients. Pediatric reference intervals are difficult to establish because children are in their growing stage and their physiology changes continuously. We aimed to establish reference intervals for routine laboratory tests for Korean pediatric patients through retrospective multicenter data analysis., Methods: Preoperative laboratory test results from 1,031 pediatric patients aged 0 month-18 years who underwent minor surgeries in four university hospitals were collected. Age- and sex-specific reference intervals for routine laboratory tests were defined based on the Clinical and Laboratory Standards Institute (CLSI) EP28-A3c guidelines., Results: The pediatric reference intervals determined in this study were different from existing adult reference intervals and pediatric reference intervals for other ethnicities. Most tests required age-specific partitioning, and some of those required sex-specific partitioning for at least one age-partitioned subgroup. Erythrocyte sedimentation rate, monocyte percentage, basophil percentage, activated partial thromboplastin time, glucose, cholesterol, albumin, bilirubin, chloride, and C-reactive protein did not show any difference between age- or sex-partitioned subgroups., Conclusions: We determined Korean pediatric reference intervals for hematology, coagulation, and chemistry tests by indirect sampling based on medical record data from multiple institutions. These reference intervals would be valuable for clinical evaluations in the Korean pediatric population.

There is an urgent need for accurate and rapid diagnostic assays capable of identifying carbapenemase-producing Enterobacteriaceae (CPE). We assessed the performance of the RESIST-4 O.K.N.V. (OKNV) assay (Coris BioConcept, Gembloux, Belgium) for the identification of oxacillinase (OXA)-48-like-, Klebsiella pneumoniae carbapenemase (KPC)-, New Delhi metallo-β-lactamase (NDM)-, and Verona integron-encoded metallo-β-lactamase (VIM)-producing Enterobacteriaceae grown on sheep blood agar (SBA) and the CHROMagar KPC medium. Sixty-five carbapenem-resistant Enterobacteriaceae (CRE) isolates with characterized carbapenemase content were used to evaluate the OKNV assay. The assay correctly identified all 30 isolates that produced one of the four targeted carbapenemase families. Additionally, it correctly identified 15 isolates that co-produced KPC and NDM, VIM and NDM or OXA-48-like and NDM, but failed to identify an NDM-1 and OXA-232 co-producing Klebsiella pneumoniae isolate. All 16 non-carbapenemase-producing CRE and four CPE isolates exhibited negative results, and no cross-reaction was observed. Overall, the sensitivity and specificity of the assay were 97.8% and 100%, respectively. The OKNV assay is an accurate and rapid assay for identifying OXA-48-like, KPC, NDM, and VIM carbapenemases produced by Enterobacteriaceae isolates cultured on both SBA and the CHROMagar KPC media in the clinical microbiology laboratory., Competing Interests: No potential conflicts of interest relevant to this paper were reported., (© The Korean Society for Laboratory Medicine.)

Background: The urinary albumin/creatinine ratio (ACR) is an important indicator of albuminuria. We aimed to estimate ACR uncertainty and its impact on test results and proposed imprecision quality goals based on the estimated uncertainty., Methods: The combined ACR uncertainty was calculated using the individual uncertainties of urinary albumin and creatinine. ACR confidence intervals (CIs) were estimated based on the expanded uncertainty. When the CI contained the ACR category boundary (30 or 300 mg/g), the cases were considered ambiguous. Quality goals for ACR were suggested using the number of ambiguous cases among actual patient results., Results: The number of ambiguous cases resulting from the combined ACR uncertainty was higher than expected based on biological variation (BV) quality goals. When the ACR met BV quality specifications, we estimated that 4.8-15.5% of the results may have been misclassified. To minimize the number of ambiguous results, the minimum, desirable, and optimum quality goals were set at 34.0%, 18.0%, and 4.5%, respectively., Conclusions: We expressed ACR uncertainty using the uncertainties of urinary albumin and creatinine and assessed the impact of this combined uncertainty on the test results. Subsequently, we proposed imprecision quality goals for ACR based on ambiguous results., Competing Interests: No potential conflicts of interest relevant to this article were reported., (© The Korean Society for Laboratory Medicine.)

Hemolysis frequently causes preanalytical errors in laboratory measurements. We aimed to develop a quality improvement indicator for evaluating the extent of inappropriate procedures causing hemolysis in clinical samples collected in medical care units. We defined the threshold value of the hemolysis index (H index) causing significant interference with analyte measurement and analyzed the H index values of clinical samples in relation to the threshold. The H index threshold value causing a 10% bias in the measurement of lactate dehydrogenase was found to be 25. The monthly mean H index and monthly frequency of samples with an H index >25 were significantly different among the types of ward (P=0.001, respectively), and significantly decreased after replacement of a laboratory centrifuge lacking temperature control (20.6±0.58 vs 23.30±1.08, P=0.01; 23.4±1.69% vs 32.6±1.78%, P=0.01). The monthly mean H index and the monthly frequency of samples with an H index above a threshold value may be useful quality improvement indicators for detection of inappropriate procedures in the acquisition and handling of blood samples in medical care units., Competing Interests: Authors' Disclosures of Potential Conflicts of Interest: No potential conflicts of interest relevant to this article were reported.

Background: The emergence of carbapenemase-producing Enterobacteriaceae (CPE) represents a major clinical problem because these bacteria are resistant to most antibiotics. CPE remain relatively uncommon in Korea. We report the prevalence, clinical characteristics, and molecular epidemiology of CPE isolates collected from five university hospitals in Korea., Methods: Between January and December 2015, 393 non-duplicated isolates that were nonsusceptible to ertapenem were analyzed. Production of carbapenemase, extended-spectrum β-lactamase, and AmpC β-lactamase was determined by genotypic tests. Antimicrobial susceptibility profiles were determined by using an Etest. Clonality of Klebsiella pneumoniae carbapenemase (KPC)-2-producing and oxacillinase (OXA)-232-producing Klebsiella pneumoniae isolates was determined by pulsed-field gel electrophoresis (PFGE)., Results: Of the 393 isolates tested, 79 (20.1%) were CPE. Of these 79 isolates, 47 (59.5%) harbored the bla(OXA-232) gene while the remaining isolates carried genes bla(KPC-2) (n=27), bla(IMP-1) (n=4), and bla(NDM-1) (n=1). Among the 24 KPC-2 K. pneumoniae isolates from hospital B, 100% were resistant to carbapenems, 8% to colistin, and 0% to tigecycline. Among the 45 OXA-232 K. pneumoniae at hospital C, 95% were resistant to ertapenem, 68% to imipenem, 95% to meropenem, 10% to colistin, and 24% to tigecycline. PFGE analysis revealed a unique pattern for KPC-2 K. pneumoniae and identified 30 isolates belonging to the dominant pulsotypes (PT)1 and PT2 among 41 OXA-232 K. pneumoniae isolates., Conclusions: CPE strains are present in Korea, with the majority of K. pneumoniae isolates producing OXA-232 and KPC-2. The prevalence and predominant genotypes of CPE show hospital-specific differences., Competing Interests: Authors' Disclosures of Potential Conflicts of Interest: No potential conflicts of interest relevant to this article were reported.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia with a vancomycin minimum inhibitory concentration (MIC) of 2 µg/mL presents a high rate of therapeutic failure in response to vancomycin. In addition, polymorphism in accessory gene regulator (agr) is associated with vancomycin therapeutic effects. The association between agr polymorphism and vancomycin MICs was investigated in MRSA isolates., Methods: Agr group-specific PCR was conducted on 118 MRSA bloodstream isolates. Vancomycin susceptibility tests were conducted, while E-test GRD (bioMérieux SA, France) was used to detect heterogeneous vancomycin-intermediate S. aureus (hVISA)., Results: Of the 118 MRSA isolates, 59 (50.0%), 43 (36.4%), and 10 (8.5%) isolates belonged to agr group I, II, and III, respectively. Six isolates could not be classified. Twenty-six, 73, and 19 isolates presented a vancomycin MIC of 2, 1, and 0.5 µg/mL, respectively. Nine (34.6%), 14 (53.8%), and 2 (7.7%) isolates with MICs of 2 µg/mL belonged to agr group I, II, and III, respectively. Thirty-seven (50.6%), 26 (35.6%), and 6 (8.2%) isolates with MICs of 1 µg/mL belonged to agr group I, II, and III, respectively. Thirteen (68.4%), 3 (15.8%), and 2 (10.5%) isolates with MICs of 0.5 µg/mL belonged to agr group I, II, and III, respectively. The agr group II presented more isolates with MIC of 2 µg/mL (32.6%) than the agr non-group II (16%). Four isolates tested positive for hVISA. Three of them belonged to agr group II., Conclusions: MRSA isolates with vancomycin MIC of 2 µg/mL were more common in agr group II than in agr non-group II.

Background: The heme oxygenase-1 gene (HMOX1) promoter polymorphisms modulate its transcription in response to oxidative stress. This study screened for HMOX1 polymorphisms and investigated the association between HMOX1 polymorphisms and coronary artery disease (CAD) in the Korean population., Methods: The study population consisted of patients with CAD with obstructive lesions (n=110), CAD with minimal or no lesions (n=40), and controls (n=107). Thirty-nine patients with CAD with obstructive lesions underwent follow-up coronary angiography after six months for the presence of restenosis. The 5'-flanking region containing (GT)n repeats of the HMOX1 gene was analyzed by PCR., Results: The numbers of (GT)n repeats in the HMOX1 promoter showed a bimodal distribution. The alleles were divided into two subclasses, S25 and L25, depending on whether there were less than or equal to and more than 25 (GT)n repeats, respectively. The allele and genotype frequencies among groups were statistically not different. More subjects in the S25-carrier group had the low risk levels of high sensitivity C-reactive protein (hsCRP) for the CAD than those in the non-S25 carrier group (P=0.034). Multivariate logistic regression analysis revealed that the genotypes of (GT)n repeats were not related to CAD status. The restenosis group in the coronary angiography follow-up did not show any significant difference in HMOX1 genotype frequency., Conclusions: The HMOX1 genotypes were not found to be associated with CAD, but the short allele carrier group contained more individuals with hsCRP values reflecting low risk of cardiovascular disease in the Korean population.

We investigated the occurrence and genetic basis of AmpC β-lactamase (AmpC)-mediated antibiotic resistance, by examining Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis isolates at a university hospital, from 2007 to 2010. The ampC genes were detected by multiplex AmpC PCR, and AmpC-positive strains were subjected to DNA sequencing. Extended-spectrum β-lactamase (ESBL) production was assessed using the ESBL disk test based on the utilization of boronic acid. Carbapenem-resistant isolates were further investigated by the modified Hodge test, a carbapenemase inhibition test and SDS-PAGE experiments. AmpC expression was detected in 1.6% of E. coli (39 DHA-1, 45 CMY-2, and 1 CMY-1) isolates, 7.2% of K. pneumoniae (39 DHA-1, 45 CMY-2, and 1 CMY-1) isolates, and 2.5% of P. mirabilis (8 CMY-2 and 1 CMY-1) isolates. Of the 198 acquired AmpC producers, 58 isolates (29.3%) also produced an ESBL enzyme. Among the acquired AmpC-producing K. pneumoniae isolates, the minimum inhibitory concentration (MIC) MIC50/MIC90 values for cefoxitin, cefotaxime, cefepime, imipenem, and meropenem were >32/>32, 16/>32, 1/16, 0.25/0.5, and <0.125/0.125 µg/mL, respectively. The MIC values for carbapenem were ≥2 µg/mL for 2 K. pneumoniae isolates, both of which carried the bla DHA-1 gene with a loss of OmpK36 expression, but were negative for carbapenemase production. The acquisition of AmpC-mediated resistance in K. pneumoniae isolates increased, as did the proportion of AmpC and ESBL co-producers among the hospital isolates. The accurate identification of isolates producing AmpCs and ESBLs may aid in infection control and will assist physicians in selecting an appropriate antibiotic regimen.

Background: N-ras mutations are one of the most commonly detected abnormalities of myeloid origin. N-ras mutations result in a constitutively active N-ras protein that induces uncontrolled cell proliferation and inhibits apoptosis. We analyzed N-ras mutations in adult patients with AML at a particular institution and compared pyrosequencing analysis with a direct sequencing method for the detection of N-ras mutations., Methods: We analyzed 90 bone marrow samples from 83 AML patients. We detected N-ras mutations in codons 12, 13, and 61 using the pyrosequencing method and subsequently confirmed all data by direct sequencing. Using these methods, we screened the N-ras mutation quantitatively and determined the incidence and characteristic of N-ras mutation., Results: The incidence of N-ras mutation was 7.2% in adult AML patients. The patients with N-ras mutations showed significant higher hemoglobin levels (P=0.022) and an increased incidence of FLT3 mutations (P=0.003). We observed 3 cases with N-ras mutations in codon 12 (3.6%), 2 cases in codon 13 (2.4%), and 1 case in codon 61 (1.2%). All the mutations disappeared during chemotherapy., Conclusions: There is a low incidence (7.2%) of N-ras mutations in AML patients compared with other populations. Similar data is obtained by both pyrosequencing and direct sequencing. This study showed the correlation between the N-ras mutation and the therapeutic response. However, pyrosequencing provides quantitative data and is useful for monitoring therapeutic responses.

This study aimed to investigate whether CHROMagar Acinetobacter medium (CHROMagar, France) in combination with an antimicrobial supplement (modified CHROMagar Acinetobacter; CHROMagar, France) can be used for detecting and isolating multidrug-resistant Acinetobacter species (MRA) in nasal and rectal surveillance cultures. Nasal and rectal swab samples were collected from patients in an intensive care unit at a teaching hospital. The samples were used to inoculate modified CHROMagar Acinetobacter plates, which were examined after 24 and 48 hr of incubation at 37℃. Their susceptibility against the antimicrobial agents meropenem, imipenem, ciprofloxacin, and amikacin was analyzed using the Etest (bioMerieux, France). A total of 406 paired samples (406 nasal swabs and 406 rectal swabs) were obtained from 226 patients, and 120 samples (28 nasal and 28 rectal cultures, 47 nasal cultures only, and 17 rectal cultures only) yielded MRA. Seventy-five MRA isolates (18.5%) were recovered from the 406 nasal samples, and 45 MRA isolates (11.1%) were recovered from the 406 rectal samples. Of the 120 MRA isolates, 3 (2.5%) were detected only after 48 hr of incubation. The use of modified CHROMagar Acinetobacter together with nasal and rectal swabs and 1-day incubation is an effective surveillance tool for detecting MRA colonization.

Brachydactyly type C (BDC) is characterized by shortening of the middle phalanges of the index, middle, and little fingers. Hyperphalangy of the index and middle finger and shortening of the first metacarpal can also be observed. BDC is a rare genetic condition associated with the GDF5 gene, and this condition has not been confirmed by genetic analysis so far in the Korean population. Herein, we present a case of a 6-yr-old girl diagnosed with BDC confirmed by molecular genetic analysis. The patient presented with shortening of the second and third digits of both hands. Sequence analysis of the GDF5 gene was performed and the pathogenic mutation, c.1312C>T (p.Arg438Cys), was identified. Interestingly, this mutation was previously described in a patient who presented with the absence of the middle phalanges in the second through fifth toes. However, our patient showed no involvement of the feet. Considering intrafamilial and interfamilial variability, molecular analysis of isolated brachydactyly is warranted to elucidate the genetic origin and establish a diagnosis.

B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL) (intermediate DLBCL/BL), is a heterogeneous group with some features resembling DLBCL and others resembling BL. Here, we report a case of intermediate DLBCL/BL in a Korean child. A 2-yr-old male was admitted for evaluation and management of left hip pain. Immunohistochemistry of a biopsy of the femur neck revealed tumor cells positive for CD20, CD10, BCL2, BCL6, and Ki67. A bone marrow (BM) aspirate smear revealed that 49.3% of all nucleated cells were abnormal lymphoid cells, composed of large- and medium-sized cells. Immunophenotyping of the neoplastic cells revealed positivity for CD19, CD10, CD20, and sIg lambda and negativity for CD34, Tdt, and myeloperoxidase (MPO). Cytogenetic and FISH analyses showed a complex karyotype, including t(8;14)(q24.1;q32) and IGH-MYC fusion. Intensive chemotherapy was initiated, including prednisone, vincristine, L-asparaginase, daunorubicin, and central nervous system prophylaxis with intrathecal methotrexate (MTX) and cytarabine. One month after the initial diagnosis, BM examination revealed the persistent of abnormal lymphoid cells; cerebrospinal fluid cytology, including cytospin, showed atypical lymphoid cells. The patient was treated again with cyclophosphamide, vincristine, prednisone, adriamycin, MTX, and intrathecal MTX and cytarabine. The patient died of sepsis 5 months after the second round of chemotherapy.