Eun Jin Kim, Yee Gyung Kwak, Sun Hee Kwak, Su Hui Ko, Oh Mee Kweon, Eu Suk Kim, Jin Hwa Kim, Tae Hyong Kim, Taek Soo Kim, Hee-Won Moon, Sun Hee Park, Jin Young Ahn, So-Yeon Yoo, Hyeon Mi Yoo, Sang-Oh Lee, Yu-Mi Lee, Nan-Hyoung Cho, Young Hwa Choi, Pyoeng Gyun Choe, Ki Ho Hong, Mi Suk Lee, Korean National Healthcare-associated Infections Surveillance System (KONIS) ICU module. Korean J healthc assoc Infect Control Prev 2023;28:64-77. https://doi.org/10.14192/kjicp.2023.28.1.64

The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is the most commonly used equation for estimated glomerular filtration rate (eGFR). Recently, the European Kidney Function Consortium (EKFC) announced a full-age spectrum equation, and the CKD-EPI announced the CKD-EPI refit equations (CKD-EPI-R). We compared CKD-EPI, EKFC, and CKD-EPI-R equations in a large-scale Korean population and investigated their potential implications for CKD prevalence. In a total of 106,021 individuals who received annual check-ups from 2018 to 2020, we compared the eGFR equations according to the Clinical and Laboratory Standards Institute guidelines. Weighted kappa (κ) agreement was used to compare the potential implications for CKD prevalence across the equations. The median value of eGFR tended to increase in the order of EKFC, CKD-EPI, and CKD-EPI-R equations (92.4 mL/min/1.73 m2, 96.0 mL/min/1.73 m2, and 100.0 mL/min/1.73 m2, respectively). The EKFC and CKD-EPI-R equations showed a very high correlation of eGFR and good agreement for CKD prevalence with CKD-EPI equation (r = 0.98 and 1.00; κ = 0.80 and 0.82, respectively). Compared with the CKD-EPI equation, the EFKC equation overestimated CKD prevalence (3.5%), and the CKD-EPI-R equation underestimated it (1.5%). This is the first study comparing CKD-EPI, EKFC, and CKD-EPI-R equations simultaneously. The EKFC and CKD-EPI-R equations were statistically interchangeable with CKD-EPI equations in this large-scale Korean population. The transition of eGFR equations, however, would lead to sizable changes in the CKD prevalence. To improve kidney health, in-depth discussion considering various clinical aspects is imperative for the transition of eGFR equations.

Presepsin is a highly specific biomarker for diagnosing bacterial infections, but its clinical usefulness is not well validated. A retrospective cross-sectional study was conducted. Among the patients suspected bacterial infection or fulfilled the criteria of systemic inflammatory response syndrome (SIRS) and patients who underwent blood culture, presepsin, procalcitonin (PCT), and C-reactive protein (CRP) at the same time were included. Receiver operating characteristic (ROC) curve analysis and logistic regression were used to compare performance of three biomarkers. A total of 757 patients were enrolled, including 256 patients (33.8%) with culture-proven bacterial infection and 109 patients (14.4%) with bacteremia. The 28-day mortality rate was 8.6%. ROC curve analysis revealed that the area under the curve (AUC) of PCT was higher than that of presepsin for both culture-proven bacterial infection (0.665 and 0.596, respectively; p = 0.003) and bacteremia (0.791 and 0.685; p < 0.001). In contrast, AUC of PCT for 28-day mortality was slower than presepsin (0.593 and 0.720; p = 0.002). In multivariable logistic regression analysis, PCT showed the highest ORs for culture-proven bacterial infection (OR 2.23, 95% CI 1.55-3.19; p < 0.001) and for bacteremia (OR 5.18, 95% CI 3.13-8.56; p < 0.001), while presepsin showed the highest OR for 28-day mortality (OR 3.31, 95% CI 1.67-6.54; p < 0.001). CRP did not show better performance than PCT or presepsin in any of the analyses. PCT showed the best performance predicting culture-proven bacterial infection and bacteremia, while presepsin would rather be useful as a prognostic marker.

The performance of platelet (PLT) counting in thrombocytopenic samples is crucial for transfusion decisions. We compared PLT counting and its reproducibility between Mindray BC-6800Plus (BC-6800P, Mindray, Shenzhen, China) and Sysmex XN-9000 (XN, Sysmex, Kobe, Japan), especially focused on thrombocytopenic samples. We analyzed the correlation and agreement of PLT-I channels in both analyzers and BC-6800P PLT-O mode and XN PLT-F channel in 516 samples regarding PLT counts. Ten thrombocytopenic samples (≤2.0 × 109/L by XN PLT-F) were measured 10 times to investigate the reproducibility with the desirable precision criterion, 7.6%. The correlation of BC-6800P PLT-I and XN PLT-I was arranged moderate to very high; but the correlation of BC-6800P PLT-O and XN PLT-F was arranged high to very high. Both BC-6800P PLT-I vs. XN PLT-I and BC-6800P PLT-O vs. XN PLT-F showed very good agreement (κ = 0.93 and κ = 0.94). In 41 discordant samples between BC-6800P PLT-O and XN PLT-F at transfusion thresholds, BC-6800P PLT-O showed higher PLT counts than XN-PLT-F, except the one case. BC-6800P PLT-O exceeded the precision criterion in one of 10 samples; but XN PLT-F exceeded it in six of 10 samples. BC-6800P would be a reliable option for PLT counting in thrombocytopenic samples with good reproducibility.

For the clinical application of semi-quantitative anti-SARS-CoV-2 antibody tests, the analytical performance and titer correlation of the plaque reduction neutralization test (PRNT) need to be investigated. We evaluated the analytical performance and PRNT titer-correlation of one surrogate virus neutralization test (sVNT) kit and three chemiluminescent assays. We measured the total antibodies for the receptor-binding domain (RBD) of the spike protein, total antibodies for the nucleocapsid protein (NP), and IgG antibodies for the RBD. All three chemiluminescent assays showed high analytical performance for the detection of SARS-CoV-2 infection, with a sensitivity ≥ 98% and specificity ≥ 99%; those of the sVNT were slightly lower. The representativeness of the neutralizing activity of PRNT ND50 ≥ 20 was comparable among the four immunoassays (Cohen’s kappa ≈ 0.80). Quantitative titer correlation for high PRNT titers of ND50 ≥ 50, 200, and 1,000 was investigated with new cut-off values; the anti-RBD IgG antibody kit showed the best performance. It also showed the best linear correlation with PRNT titer in both the acute and convalescent phases (Pearson’s R 0.81 and 0.72, respectively). Due to the slowly waning titer of anti-NP antibodies, the correlation with PRNT titer at the convalescent phase was poor. In conclusion, semi-quantitative immunoassay kits targeting the RBD showed neutralizing activity that was correlated by titer; measurement of anti-NP antibodies would be useful for determining past infections.

Background: Neutrophil gelatinase-associated lipocalin (NGAL) is a useful biomarker for acute kidney injury (AKI) prediction. However, studies on whether using both plasma NGAL (PNGAL) and urine NGAL (UNGAL) can improve AKI prediction are limited. We investigated the best approach to predict AKI in high-risk patients when using PNGAL and UNGAL together. Methods: We enrolled 151 AKI suspected patients with one or more AKI risk factors. We assessed the diagnostic performance of PNGAL and UNGAL for predicting AKI according to chronic kidney disease (CKD) status by determining the areas under the receiver operating curve (AuROC). Independent predictors of AKI were assessed using univariate and multivariate logistic regression analyses. Results: In the multivariate logistic regression analysis for all patients (N=151), Model 2 and 3, including PNGAL (P=0.012) with initial serum creatinine (S-Cr), showed a better AKI prediction power (R-2 =0.435, both) than Model 0, including S-Cr only (R-2 =0.390). In the non-CKD group (N=135), the AuROC of PNGAL for AKI prediction was larger than that of UNGAL (0.79 vs 0.66, P=0.010), whereas in the CKD group (N=16), the opposite was true (0.94 vs 0.76, P=0.049). Conclusions: PNGAL may serve as a useful biomarker for AKI prediction in high-risk patients. However, UNGAL predicted AKI better than PNGAL in CKD patients. Our findings provide guidance for selecting appropriate specimens for NGAL testing according to the presence of CKD in AKI high-risk patients.

Eun Jin Kim, Yee Gyung Kwak, Sun Hee Kwak, Su Hui Ko, Oh Mee Kweon, Eu Suk Kim, Jin Hwa Kim, Tae Hyong Kim, Taek Soo Kim, Hee-Won Moon, Sun Hee Park, Jin Young Ahn, So-Yeon Yoo, Hyeon Mi Yoo, Sang-Oh Lee, Nan-Hyoung Cho, Pyoeng Gyun Choe, Ki Ho Hong, Yu-Mi Lee, Mi Suk Lee. Korean J healthc assoc Infect Control Prev 2021;26:115-28. https://doi.org/10.14192/kjicp.2021.26.2.115

In this study, we aimed to evaluate the composition of the intestinal microbiota and level of fecal calprotectin in Clostridioides difficile-colonized patients. We included 102 C. difficile non-colonized (group I), 93 C. difficile colonized subjects (group II), and 89 diarrhea patients with C. difficile (group III). Chao1 index for alpha diversity and principal coordinate analysis was performed for beta diversity using QIIME. The mean relative abundance in each group was compared at the phylum and genus levels. Fecal calprotectin was measured using EliA calprotectin (Thermo Fisher Scientific). Group II showed significantly lower levels of Sutterella, Blautia, Ruminococcus, Faecalibacterium, Bilophila, and Ruminococcaceae and higher levels of Enterobacteriaceae compared to group I (p = 0.012, 0.003, 0.002, 0.001, 0.027, 0.022, and 0.036, respectively). Toxigenic C. difficile colonized subjects showed significantly lower levels of Prevotella, Phascolarctobacterium, Succinivibrio, Blautia, and higher levels of Bacteroides. The level of fecal calprotectin in group III was significantly higher than those in group I and group II (p < 0.001 for both). These data could be valuable in understanding C. difficile colonization process and the microbiota and inflammatory markers could be further studied to differentiate colonization from CDI.

Clostridioides difficile, previously known as Clostridium difficile, is a anaerobic gram-positive spore-forming bacterium that is prevalent in soil [1]. Active C. difficile infections (CDIs) are a leading cause of antibiotic-associated nosocomial diarrhea and colitis in hospitals in the industrialized world [2]. Current diagnostic methods [3, 4] for CDI recommend a combination of a toxin enzyme immunoassay (EIA), nucleic acid ampli cation test, and glutamate dehydrogenase assay, but these tests do not provide direct information on intestinal in ammation status [5-7]. As fecal biomarkers are more re ective of intestinal in ammation status than serumbased biomarkers, there is a need for easily measurable fecal bioClostridioides (Clostridium) difficile 감염에서 대변 Neutrophil Gelatinase-Associated Lipocalin과 Calprotectin의 생물학적 표지자로서의 임상적 유용성 Clinical Utility of Fecal Neutrophil Gelatinase-Associated Lipocalin and Calprotectin as Biomarkers of Clostridioides (Clostridium) difficile Infection

Objectives: In South Korea, automated T. pallidum Latex Agglutination (TPLA) based on turbidoimmunoassays and immunochromatographic assay (ICA) are widely used for syphilis diagnosis. However, there is sparse data on the validation of these assays in the reverse-sequence algorithm setting. Methods: We assessed 551 specimens submitted for syphilis testing. We compared varying reverse-sequence algorithms using combinations of the Cobas Syphilis EIA (Roche Diagnostics, Mannheim, Germany), Mediace TPLA (Sekisui Medical Co., Tokyo, Japan), TPPA (Fujirebio Inc., Tokyo, Japan), and SD Bioline ICA (Standard Diagnostic, Yongin, Korea). We also evaluated modified algorithms incorporating a cut off of high specificity for EIA and TPLA using receiver operating characteristic curves. Results: The agreement was almost perfect between EIA and TPLA (Kappa, 0.953) and strong between TPPA and ICA (Kappa, 0.887). Among TPPA positive and ICA negative specimens, 67% of the specimens were from individuals with syphilis histories. Compared to EIA/RPR/TPPA, the agreement with EIA/RPR/ICA, TPLA/RPR/ TPPA and TPLA/RPR/ICA were almost perfect (Kappa, 0.930, 0.995 and 0.914, respectively). When a cut off of 95% specificity was applied, the number of TPPA tests could be reduced by 44% and 40% in EIA and TPLA, respectively. Conclusions: TPLA showed almost perfect agreement with EIA and that it could be used in the site of EIA in a reverse sequence algorithm. ICA showed a lower detection rate than TPPA as a 2nd treponemal test and should be used with caution. With cut offs of higher specificity, more efficient reverse-sequence algorithms can be made possible.

Objectives The aim of this study was to investigate the diagnostic accuracy of rheumatoid factor (RF) isotype for the detection of primary Sjogren’s syndrome (pSS) and evaluate the clinical and serological associations of immunoglobulin (Ig) A RF in patients with pSS. Materials and methods RF levels were measured in 77 and 37 patients with pSS and idiopathic sicca symptoms, respectively, using ELISA and analysed with respect to clinical and laboratory disease characteristics. Receiver operating characteristic curves were used to determine and compare the diagnostic accuracy of IgA RF with other diagnostic tests. Results Serum levels of IgA RF were significantly higher in patients with pSS than in those with idiopathic sicca symptoms. IgA RF showed sensitivity, specificity, positive, and negative predictive values of 83.1, 78.4, 88.9, and 69.0%, respectively, for pSS diagnosis. IgA RF was associated with xerostomia, severe sialoscintigraphic grade, low unstimulated salivary flow rate (USFR), antinuclear antibody, high IgG and IgM/G RF levels, and low C3 levels in patients with pSS. IgA RF titres had positive correlations with sialoscintigraphic grade and IgG and IgG/M RF levels and had negative correlations with USFR and C3 levels. Conclusion Our findings confirmed the potential of IgA RF to distinguish pSS from idiopathic sicca symptoms. The presence of IgA RF in patients with pSS was associated with significantly worse exocrine function and active serologic profile. No association between IgA RF and extra-glandular manifestations was noted. Clinical relevance IgA RF should be the predictive and diagnostic marker in patients with pSS.

Anti-cyclic citrullinated peptide antibodies (anti-CCPs) are important diagnostic markers for rheumatoid arthritis (RA). We evaluated the analytical and clinical performance of the QUANTA Flash CCP3 (INOVA Diagnostics, USA), a fully automated third-generation anti-CCP assay, in comparison with three second-generation anti-CCP (CCP2) assays. A total of 300 sera (67 from RA patients, 64 from other rheumatic diseases, 43 from osteoarthritis [OA], and 126 from other conditions) were tested with QUANTA Flash CCP3, Kallestad Anti-CCP II (Bio-Rad, USA), Elecsys Anti-CCP (Roche Diagnostics GmbH, Germany), and ARCHITECT Anti-CCP (Abbott Diagnostics, USA). Within-run and total imprecision (% coefficient of variation) of the QUANTA Flash CCP3 were <6%, and its linearity was acceptable over the claimed range (4.0-2,749.7 chemiluminescent units). The frequency of anti-CCP was similar between QUANTA Flash CCP3 and the other CCP2 assays in the RA (67.2% vs. 62.7-70.1%), other rheumatic diseases (7.8% vs. 6.3%), and OA (2.3% vs. 0-2.3%) groups. The concordance rate between QUANTA Flash CCP3 and the other assays ranged from 96.3% to 97.7% (kappa from 0.87 to 0.92). For the diagnosis of RA, the sensitivity/specificity was 67.2%/95.7%, 62.7%/98.3%, 70.2%/96.6%, and 67.2%/97.9%, and the areas under the receiver operating characteristic curves were 0.851, 0.791, 0.853, and 0.867 for QUANTA Flash CCP3, Kallestad, Elecsys, and ARCHITECT assays, respectively. The performance of the QUANTA Flash CCP3 was satisfactory and comparable to that of the three CCP2 assays. This fully automated assay would be a practical and reasonable option in clinical laboratories.

ABSTRACT Although launched in 2015, little is known about the accuracy of QuantiFERON-TB Gold-Plus (QFT-Plus) for diagnosis of latent M. tuberculosis infection (LTBI). Unlike its predecessor, QFT-Plus utilizes two antigen tubes to elicit an immune response from CD4+ and CD8+ T lymphocytes. We conducted a cross-sectional study in low-risk health care workers (HCWs) at a single U.S. center to compare QFT-Plus to QuantiFERON-TB Gold in-tube (QFT). A total of 989 HCWs were tested with both QFT and QFT-Plus. Risk factors for LTBI were obtained from a questionnaire. QFT-Plus was considered positive if either antigen tube 1 (TB1) or TB2 tested positive, per the manufacturer's recommendations, or if both TB1 and TB2 tested positive, using a conservative definition. Results were compared using Cohen's kappa and linear regression, respectively. Agreement of QFT with QFT-Plus was high, at 95.6% (95% confidence interval [CI], 94.3 to 96.9; kappa, 0.57). The majority of discordant results between QFT and QFT-Plus TB1 (84.8%) and QFT and QFT-Plus TB2 (88.6%) fell within the range of 0.2 to 0.7 IU/ml. The positivity rate in 626 HCWs with no identifiable risk factors and no self-reported history of positive LTBI tests was 2.1% (CI, 1.0 to 3.2) and 3.0% (CI, 1.7 to 4.3) with QFT and QFT-Plus, respectively. A conservative definition of a QFT-Plus-positive result yielded a positivity rate of 1.0% (CI, 0.2 to 1.7; P value of 0.0002 versus QFT-Plus and 0.07 versus QFT). On follow-up testing, of 11 HCWs with discordant QFT-Plus results, 90.9% (10/11) had a negative QFT result. The QFT-Plus assay showed a high degree of agreement with QFT in U.S. HCWs. A conservative interpretation of QFT-Plus eliminated nearly all nonreproducible positive results in low-risk HCWs. Larger studies are needed to validate the latter finding and to more clearly define conditions under which a conservative interpretation can be used to minimize nonreproducible positive results in low-risk populations.