Molecular and Clinical Features of Fluconazole Non-susceptible Candida albicans Bloodstream Isolates Recovered in Korean Multicenter Surveillance Studies.

Acquired fluconazole resistance (FR) in bloodstream infection (BSI) isolates of Candida albicans is rare. We investigated the FR mechanisms and clinical features of 14 fluconazole non-susceptible (FNS; FR and fluconazole-susceptible dose-dependent) BSI isolates of C. albicans recovered from Korean multicenter surveillance studies during 2006-2021. Mutations causing amino acid substitutions (AASs) in the drug-target gene ERG11 and the FR-associated transcription factor genes TAC1, MRR1, and UPC2 of the 14 FNS isolates were compared with those of 12 fluconazole-susceptible isolates. Of the 14 FNS isolates, eight and seven had Erg11p (K143R, F145L, or G464S) and Tac1p (T225A, R673L, A736T, or A736V) AASs, respectively, which were previously described in FR isolates. Novel Erg11p, Tac1p, and Mrr1p AASs were observed in two, four, and one FNS isolates, respectively. Combined Erg11p and Tac1p AASs were observed in seven FNS isolates. None of the FR-associated Upc2p AASs were detected. Of the 14 patients, only one had previous azole exposure, and the 30-day mortality rate was 57.1% (8/14). Our data show that Erg11p and Tac1p AASs are likely to contribute to FR in C. albicans BSI isolates in Korea and that most FNS C. albicans BSIs develop without azole exposure.

Whole-Genome Sequence Analysis of Candida glabrata Isolates from a Patient with Persistent Fungemia and Determination of the Molecular Mechanisms of Multidrug Resistance.

Whole-genome sequencing (WGS) was used to determine the molecular mechanisms of multidrug resistance for 10 serial Candida glabrata bloodstream isolates obtained from a neutropenic patient during 82 days of amphotericin B (AMB) or echinocandin therapy. For WGS, a library was prepared and sequenced using a Nextera DNA Flex Kit (Illumina) and the MiseqDx (Illumina) instrument. All isolates harbored the same Msh2p substitution, V239L, associated with multilocus sequence type 7 and a Pdr1p substitution, L825P, that caused azole resistance. Of six isolates with increased AMB MICs (≥2 mg/L), three harboring the Erg6p A158fs mutation had AMB MICs ≥ 8 mg/L, and three harboring the Erg6p R314K, Erg3p G236D, or Erg3p F226fs mutation had AMB MICs of 2-3 mg/L. Four isolates harboring the Erg6p A158fs or R314K mutation had fluconazole MICs of 4-8 mg/L while the remaining six had fluconazole MICs ≥ 256 mg/L. Two isolates with micafungin MICs > 8 mg/L harbored Fks2p (I661_L662insF) and Fks1p (C499fs) mutations, while six isolates with micafungin MICs of 0.25-2 mg/L harbored an Fks2p K1357E substitution. Using WGS, we detected novel mechanisms of AMB and echinocandin resistance; we explored mechanisms that may explain the complex relationship between AMB and azole resistance.

Accuracy Validation of the Elecsys HBsAg II Quant Assay and Its Utility in Resolving Equivocal Qualitative HBsAg Results.

Background and Objectives: There are reports of false qualitative HBsAg results, because of various causes, such as samples with low HBsAg concentrations that may produce false positives. The main aims of this study were to validate the analytical accuracy and to assess the utility of the Elecsys assay compared to that of the qualitative HbsAg assay as a screening test in resolving equivocal qualitative HbsAg results. Materials and Methods: The limit of blank (LoB), the limit of detection (LoD), the limit of quantification (LoQ), and linearity were estimated to validate the analytical accuracy of the Elecsys HBsAg II Quant assay. A total of 449 serum samples showing initial equivocal results (1-50 index) were evaluated by Elecsys HBsAg II Quant and ADVIA Centaur HBsAg II assays. Results: The LoQ of the assay was determined to be 0.050 IU/mL, as provided by the manufacturer. The Kappa agreement between the two assays was almost perfect, at 0.9669, despite seven discordant results. With a specificity of 100% at new cut-off index value ≥5.42, about 78 samples (17%, 78/449) with index value ≥5.42 were interpreted as positives without further duplicate tests, however the remaining 371 samples with index value <5.42 need to be confirmed with additional HBV marker assays. Conclusions: We confirm that the Elecsys HBsAg II Quant assay is accurate and sensitive for HBV infection and recommend it as an alternative confirmatory HBsAg assay for resolving equivocal qualitative HBsAg results.

Evaluation of the Accuracy of Cr and BUN Using the ABL90 FLEX PLUS Blood Gas Analyzer and the Equivalence of Candidate Specimens for Assessment of Renal Function.

BACKGROUND: The ABL90 FLEX PLUS (Radiometer) is a blood gas analyzer that also provides creatinine (Cr) and blood urea nitrogen (BUN) results. We assessed the accuracy of the ABL90 FLEX PLUS to measure Cr and BUN and find suitable candidate specimens against primary specimens (heparinized whole-blood (H-WB)). METHODS: Paired H-WB, serum, and sodium-citrated whole-blood (C-WB) samples (105) were collected. The Cr and BUN levels in the H-WB using the ABL90 FLEX PLUS were compared with those of the serum using four automated chemistry analyzers. The suitability of the candidate specimens was assessed at each medical decision level according to the CLSI guideline EP35-ED1. RESULTS: The respective mean differences of the ABL90 FLEX PLUS for the Cr and BUN were below -0.10 and -3.51 mg/dL compared to the other analyzers. The systematic differences between the serum and the H-WB at the low, medium, and high medical decision levels were all 0% for Cr, but those of the C-WB were -12.96%, -11.81%, and -11.30%, respectively. Regarding imprecision, the SDserum/SDH-WB ratios at each level were 0.14, 1.41, and 0.68, whereas the SDC-WB/SDH-WB ratios were 0.35, 2.00, and 0.73, respectively. CONCLUSIONS: The ABL90 FLEX PLUS provided Cr and BUN results comparable with the four widely used analyzers. Among the candidates, the serum was suitable for Cr testing using the ABL90 FLEX PLUS, while the C-WB did not satisfy the acceptance criteria.

Validation and application of new NGS-based HLA genotyping to clinical diagnostic practice.

Next-generation sequencing (NGS) has revolutionized clinical genotyping, providing high-resolution HLA genotyping with a low ambiguity rate. This study aimed to develop new NGS-based HLA genotyping (HLAaccuTest, NGeneBio, Seoul, KOREA) on the Illumina MiSeq platform and validate the clinical performance. The analytical performance of HLAaccuTest was validated for 11 loci comprising HLA-A, -B, -C, -DRB1/3/4/5, -DQA1, -DQB1, -DPA1, and -DPB1 using 157 reference samples. Among the 345 clinical samples, 180 were tested for performance evaluation and protocol optimization, and 165 were used in clinical trials in the validation phase for five loci, including HLA-A, -B, -C, -DRB1, and -DQB1. In addition, the improvement in the resolution of ambiguous alleles was also evaluated and compared with other NGS-based HLA genotyping for 18 reference samples, including five overlapping samples in analytical performance validation. All reference materials produced 100% concordant results for 11 HLA loci, 96.9% (2092 of 2160 HLA alleles) of the clinical samples were matched with the SBT results in the pre-validation phase. After the optimization phase, the clinical trials in the validation phase showed 99.7% (1645/1650 alleles) concordance with the complete resolution for 34 ambiguity results. The retesting of five discordant cases resolved all issues and yielded 100% concordant results with the SBT method. Additionally, for ambiguity using 18 reference materials with ambiguous alleles, about 30% of ambiguous alleles were more resolved than Trusight HLA v2. HLAaccuTest was successfully validated using a large volume of clinical samples and is fully applicable to the clinical laboratory.

Protic Ionic Liquids for Intrinsically Stretchable Conductive Polymers.

Inspired by the classic hard-soft acid-base theory and intrigued by a theoretical prediction of spontaneous ion exchange between poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) and hard-cation-soft-anion ionic liquid (IL), we treat PEDOT:PSS with a new IL composed of a protic (i.e., extremely hard) cation (3-methylimidazolium, p-MIM+) and an extremely soft anion (tetracyanoborate, TCB-). In fact, this protic IL (p-MIM:TCB) accomplishes the same levels of ion-exchange-mediated PEDOT-PSS separation, PEDOT-rich nanofibril formation, and electrical conductivity enhancement (∼2500 S/cm) as its aprotic counterpart (EMIM:TCB with 1-ethyl-3-methylimidazolium), the best IL used for this purpose so far. Furthermore, p-MIM:TCB significantly outperforms EMIM:TCB in terms of improving the stretchability (i.e., the highest tensile strain) of the PEDOT:PSS thin film. This enhancement is a result of the aromatic and protic cation p-MIM+, which acts as a molecular adhesive holding the exchanged ion pairs (PEDOT+:TCB----p-MIM+:PSS-) via ionic intercalation (at the surface of TCB--decorated PEDOT+ clusters) and hydrogen bonding (to PSS-), in which washing p-MIM+ out of the film degrades the stretchability while keeping the morphology. Our results offer molecular-level insight into the morphological, electrical, and mechanical properties of PEDOT:PSS and a molecular-interaction-based enhancement strategy that can be used for intrinsically stretchable conductive polymers.

Case report: Compound heterozygosity in PKLR gene with a large exon deletion and a novel rare p.Gly536Asp variant as a cause of severe pyruvate kinase deficiency.

Red cell pyruvate kinase (PK) deficiency is the most common cause of hereditary nonspherocytic hemolytic anemia and the most frequent enzyme abnormality of the glycolytic pathway. To the best of our knowledge, this is the first Korean PK deficiency study that analyzes copy number variation (CNV) using next-generation sequencing (NGS). A 7-year-old girl with jaundice was admitted for evaluation of a persistent hemolytic anemia. The proband appeared chronically ill, showing a yellowish skin color, icteric sclera, hepatomegaly, and splenomegaly on physical examination. Sequence variants and CNV generated from NGS data were estimated to determine if there was a potential genetic cause. As a result, compound heterozygosity in the PKLR gene for a large exon deletion between exon 3 and exon 9 accompanied with a novel rare p.Gly536Asp variant located on exon 10 was identified as a cause of severe PK deficiency in the proband. The PK activity of the proband had been measured at the time of day 1, 21, and 28 after receiving transfusion to indirectly assume the effect of the transfused blood, and the results were 100.9%, 73.0%, and 48.5%, compared with average of normal controls, respectively. Our report emphasizes the need to perform complete CNV analysis of NGS data and gene dosage assays such as multiplex ligation-dependent probe amplification to evaluate large deletions or duplications/insertions of the PKLR gene in patients with suspected PK deficiency.

Gene Panel Sequencing Identifies a Novel RYR1 p.Ser2300Pro Variant as Candidate for Malignant Hyperthermia with Multi-Minicore Myopathy.

Malignant hyperthermia (MH), a rare autosomal dominant pharmacogenetic disorder of skeletal muscle calcium regulation, is triggered by sevoflurane in susceptible individuals. We report a Korean having MH with multi-minicore myopathy functionally supported by RYR1-mediated intracellular Ca2+ release testing in B lymphocytes. A 14-year-old boy was admitted for the evaluation of progressive torticollis accompanied by cervicothoracic scoliosis. During the preoperative drape of the patient for the release of the sternocleidomastoid muscle under general anesthesia, his wrist and ankle were observed to have severe flexion contracture. The body temperature was 37.1 °C. To treat MH, the patient was administered a bolus of dantrolene intravenously (1.5 mg/kg) and sodium bicarbonate. After a few minutes, muscle rigidity, tachycardia, and EtCO2 all resolved. Next-generation panel sequencing for hereditary myopathy identified a novel RYR1 heterozygous missense variant (NM_000540.2: c.6898T > C; p.Ser2300Pro), which mapped to the MH2 domain of the protein, a hot spot for MH mutations. Ex vivo RYR1-mediated intracellular Ca2+ release testing in B lymphocytes showed hypersensitive Ca2+ responses to isoflurane and caffeine, resulting in an abnormal Ca2+ release only in the proband, not in his family members. Our findings expand the clinical and pathological spectra of information associated with MH with multi-minicore myopathy.

Pyogenic spondylitis caused by Klebsiella pneumoniae: should the possibility of hypervirulent Klebsiella pneumoniae be considered?

BACKGROUND: Klebsiella pneumoniae is rare but the second most common causative agent among gram-negative bacteria that cause pyogenic spondylitis. However, there are no available studies on the serotype, virulence factors, and clinical characteristics associated with K. pneumoniae-caused pyogenic spondylitis. Accordingly, we investigated the clinical characteristics of pyogenic spondylitis, K1 and K2 serotypes, and virulence factors of K. pneumoniae. METHODS: We reviewed the microbiological reports of specimens collected between January 2014 and December 2019 as well as the medical records of patients with pyogenic spondylitis caused by K. pneumoniae. We also evaluated K1 and K2 serotypes and the virulent genes rmpA, iutA, mrkD, ybtS, entB, and kfu. Strains that possessed rmpA and iutA were defined as hypervirulent K. pneumoniae. RESULTS: Six patients with pyogenic spondylitis caused by K. pneumoniae were enrolled in the study. The capsular serotypes K1 and K2 were present in 66.7% (4/6) of cases, and the hypervirulent strains were present in 88.3% (5/6) of cases. All patients had community-acquired infections, and all strains isolated were susceptible to antimicrobial agents. Intravenous antibiotic treatment continued for 2-7 weeks, and no patient underwent decompressive operation or surgical debridement. There was no recurrence. One patient died from pneumonia with a septic lung. CONCLUSION: Hypervirulent K. pneumoniae is a rare but possible causative agent associated with pyogenic spondylitis.

Efficient Imidazolium-Biomolecule Interaction-Assisted Amplified Quenching for Ultrasensitive Detection of Heparin.

Detection of heparin (HP) under physiological conditions is difficult due to the presence of biological obstructions including proteins and lipids. Thus, it is highly challenging to selectively detect HP and to increase its sensitivity in complex systems. Here, we report the detection of HP at nanomolar levels via efficient imidazolium-HP interaction-assisted fluorescence quenching amplification. The self-assembled pyrenyl aggregates are devised as a conduit for efficient exciton transport, which induces amplified fluorescence quenching for HP detection. This amplified quenching is enhanced by introducing an imidazolium receptor designed to have a high affinity to HP via electrostatic and/or additional interactions with C2 protons, resulting in a very high Stern-Volmer quenching constant of approximately 1.17×108  M-1 .

Prostatic Abscess Caused by Klebsiella pneumoniae: A 6-Year Single-Center Study.

Hypervirulent Klebsiella pneumoniae (hvKp) is an important strain that can cause multiple organ infections. Although hvKp infection cases are increasing, there is limited information on the prostatic abscesses caused by K. pneumoniae. Furthermore, the clinical significance of hvKp associated with K1 or K2 capsular types or virulence genes in prostatic abscesses remains unclear. Therefore, we aimed to elucidate the clinical and microbiological characteristics of prostatic abscesses caused by K. pneumoniae in relation to various virulence genes. A retrospective study was performed at a 1200-bed tertiary hospital between January 2014 and December 2019. Patients diagnosed with prostatic abscesses with K. pneumoniae isolated from blood, urine, pus, or tissue cultures were enrolled in this study. Our results demonstrate that 30.3% (10/33) of the prostatic abscesses were caused by K. pneumoniae. All strains isolated from patients with prostatic abscesses due to K. pneumoniae were the K1 capsular type, and eight patients (80.0%) carried rmpA and iutA genes that identified hvKp. These findings suggest that hvKp is an important pathogen in prostatic abscesses. Therefore, when treating patients with K. pneumoniae prostatic abscesses, attention should be paid to the characteristics of hvKp, such as bacteremia, multiorgan abscess formation, and metastatic spread.

Comparative Evaluation of Three Immunoassays for the Simultaneous Detection of Clostridioides difficile Glutamate Dehydrogenase and Toxin A/B.

BACKGROUND: In the medical laboratory, a step-by-step workflow for Clostridioides difficile infection (CDI) detection using glutamate dehydrogenase (GDH) and toxin A/B assays for initial screening, along with a nucleic acid amplification test (NAAT), has been recommended recently. In this study, we evaluated these three immunoassays for the simultaneous detection of GDH and Clostridioides difficile (CD) toxin A/B. METHODS: A total of 304 stool samples were tested for the presence of GDH antigen and CD toxin A/B using VIDAS C. difficile GDH and toxin A/B (CDAB), RIDASCREEN C. difficile GDH and toxin A/B (RIDA), and C. DIFF QUIK CHEK COMPLETE according to the manufacturers' recommendations. As complementary reference methods for GDH and toxin A/B detection in the three immunoassays, CD cultures using ChromID C. difficile agar and the Xpert C. difficile assay, respectively, were tested. RESULTS: All three GDH assays showed overall substantial agreement with the CD culture. All three toxin A/B assays showed overall moderate agreement with the Xpert C. difficile assay. In comparison with consensus results, VIDAS GDH and QCC GDH showed almost perfect agreement, whereas RIDA GDH showed inferior but substantial agreement. All three toxin A/B assays showed almost perfect agreement. CONCLUSIONS: Since the QCC GDH and toxin A/B assay is relatively more sensitive and specific than the other two immunoassays for discriminating toxigenic or non-toxigenic CDI, QCC is very helpful for the simultaneous identification of GDH and CD toxin A/B in the initial step of the two-round workflow for diagnosing CDI.

Performance of Severe Acute Respiratory Syndrome Coronavirus 2 Serological Diagnostic Tests and Antibody Kinetics in Coronavirus Disease 2019 Patients.

Serological testing is recommended to support the detection of undiagnosed coronavirus disease 2019 (COVID-19) cases. However, the performance of serological assays has not been sufficiently evaluated. Hence, the performance of six severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binding antibody assays [three chemiluminescence (CLIAs) and three lateral flow immunoassays (LFIAs)] and a surrogate virus neutralization test (sVNT) was analyzed in a total of 988 serum samples comprising 389 COVID-19-positives and 599 COVID-19-negatives. The overall diagnostic sensitivities of CLIAs and LFIAs ranged from 54.2 to 56.6% and from 56.3 to 64.3%, respectively. The overall diagnostic specificities of CLIAs and LFIAs ranged from 98.2 to 99.8% and from 97.3 to 99.0%, respectively. In the symptomatic group (n = 321), the positivity rate increased by over 80% in all assays > 14 days after symptom onset. In the asymptomatic group (n = 68), the positivity rate increased by over 80% in all assays > 21 days after initial RT-PCR detection. In LFIAs, negatively interpreted trace bands accounted for the changes in test performance. Most false-positive results were weak or trace reactions and showed negative results in additional sVNT. For six binding antibody assays, the overall agreement percentages ranged from 91.0 to 97.8%. The median inhibition activity of sVNT was significantly higher in the symptomatic group than in the asymptomatic group (50.0% vs. 29.2%; p < 0.0001). The median times to seropositivity in the symptomatic group were 9.7 days for CLIA-IgG, 9.2 and 9.8 days for two CLIAs-Total (IgM + IgG), 7.7 days for LFIA-IgM, 9.2 days for LFIA-IgG, and 8.8 days for sVNT-IgG, respectively. There was a strong positive correlation between the quantitative results of the four binding antibody assays and sVNT with Spearman ρ-values ranging from 0.746 to 0.854. In particular, when using LFIAs, we recommend using more objective interpretable assays or establishing a band interpretation system for each laboratory, accompanied by observer training. We also anticipate that sVNT will play an essential role in SARS-CoV-2 antibody testing and become the practical routine neutralizing antibody assay.

Identification of the novel HLA-C*04:440 allele using next-generation sequencing.

The HLA-C*04:440 allele differs from HLA-C*04:82:01 by a single non-synonymous change, c.14C > A.

The novel HLA-DRB1*04:05:19 allele identified by sequencing-based typing.

The HLA-DRB1*04:05:19 allele differs from DRB1*04:05:01:01 by a synonymous nucleotide polymorphism at cDNA position 102.

Sensitive electrochemical immunosensor to detect prohibitin 2, a potential blood cancer biomarker.

Blood cancers are difficult to cure completely and frequently show a poor prognosis. Recently, prohibitin 2 (PHB2) has been shown to be a potential biomarker for blood cancers. Sandwich ELISA can be used as a reference method for quantitative analysis of PHB2; however, ELISA can be challenging for early diagnosis and continuous monitoring method due to the need for large sample volumes (25 µL <), technical expertise, complex procedure, relative high cost, and non-portability. Thus, this study developed a sensitive and time efficient electrochemical immunosensor for detecting PHB2 from a blood cancer patient. It is a simple and portable platform consisting of a disposable electrode and blood sample volume of 4 µL. The sensor uses a gold nanostructured electrode and square wave voltammetry (SWV) measurement of a horseradish peroxidase (HRP) label to amplify the electrochemical signal. The immunosensor could quantitatively detect PHB2 with high sensitivity (limit of detection [LoD] = 0.04 ng/mL) and satisfactory reproducibility (relative standard deviation [RSD] <5.2%). The sensor achieved an LoD of 0.63 ng/mL with satisfactory recovery (89.1-104.7%) and reproducibility (RSD <6.4%) with PHB2 spiked into white blood cell (WBC) lysates. When the sensor was compared to a reference ELISA to determine the PHB2 concentrations in WBC lysate samples from healthy patients and those with blood cancer, the correlation coefficient (R2) was 0.996. A 3.3-fold difference was detected in the measured PHB2 concentration between blood cancer patients and healthy individuals. Accordingly, this study suggests a sensitive and accurate analytical method for quantitatively detecting the PHB2 in blood samples.

Effects of osmolality and solutes on the morphology of red blood cells according to three-dimensional refractive index tomography.

Phosphate-buffered saline (PBS) and Alsever's solution (AS) are frequently used as media in blood-related studies, while 0.9% normal saline (NS) is frequently used in transfusion medicine. Despite the frequent use, the effects of these solutions on the shape and volume of red blood cells (RBCs) have not been reported. We collected blood samples from five healthy adults and used three-dimensional refractive index tomography to investigate the changes in the morphology of RBCs caused by changes in osmolality and solutes at the single-cell level. After diluting 2 µL of RBCs 200-fold with each solution (PBS, AS, and 0.9% NS), 40 randomly selected RBCs were microscopically observed. RBC shape was measured considering sphericity, which is a dimensionless quantity ranging from 0 (flat) to 1 (spherical). RBCs in plasma or AS showed a biconcave shape with a small sphericity, whereas those in 0.9% NS or PBS showed a spherical shape with a large sphericity. Moreover, we confirmed that sodium chloride alone could not elicit the biconcave shape of RBCs, which could be maintained only in the presence of an osmotic pressure-maintaining substance, such as glucose or mannitol. Although 0.9% NS solution is one of the most commonly used fluids in hematology and transfusion medicine, RBCs in 0.9% NS or PBS are not biconcave. Therefore, as the debate on the use of NS continues, future clinical studies or applications should consider the effect of glucose or mannitol on the shape of RBCs.

Disk Diffusion Susceptibility Testing for the Rapid Detection of Fluconazole Resistance in Candida Isolates.

BACKGROUND: Given the increased fluconazole resistance (FR) among Candida isolates, we assessed the suitability of disk diffusion susceptibility testing (DDT) for the early detection of FR using well-characterized Candida isolates. METHODS: In total, 188 Candida isolates, including 66 C. albicans (seven Erg11 mutants), 69 C. glabrata (33 Pdr1 mutants), 29 C. parapsilosis (15 Erg11 mutants), and 24 C. tropicalis (eight Erg11 mutants) isolates, were tested in this study. FR was assessed using DDT according to the standard CLSI M44-ED3 method, except that two cell suspensions, McFarland 0.5 (standard inoculum) and 2.5 (large inoculum), were used, and the inhibition zones were read at 2-hour intervals from 10 hours to 24 hours. RESULTS: DDT results for the standard inoculum were readable after 14 hours (C. albicans, C. glabrata, and C. tropicalis) and 20 hours (C. parapsilosis) for >95% of the isolates, whereas the results for the large inoculum were readable after 12 hours (C. glabrata and C. tropicalis), 14 hours (C. albicans), and 16 hours (C. parapsilosis) for >95% of the isolates. Compared with the results produced using the CLSI M27-ED4 broth microdilution method, the first readable results from the DDT method for each isolate exhibited an agreement of 97.0%, 98.6%, 72.4%, and 91.7% for the standard inoculum and 100%, 98.6%, 96.6%, and 95.8% for the large inoculum for C. albicans, C. glabrata, C. parapsilosis, and C. tropicalis, respectively. CONCLUSIONS: DDT using large inoculum may detect FR rapidly and reliably in the four most common Candida species.

Source Analysis and Effective Control of a COVID-19 Outbreak in a University Teaching Hospital during a Period of Increasing Community Prevalence of COVID-19.

BACKGROUND: South Korea has been experiencing a third wave of coronavirus disease 2019 (COVID-19) since mid-November 2020. Our hospital in Gwangju metropolitan city experienced a healthcare-associated COVID-19 outbreak early in the third wave. The first confirmed COVID-19 patient was a symptomatic neurosurgery resident with high mobility throughout the hospital. We analyzed the transmission routes of nosocomial COVID-19 and discussed infection control strategies. METHODS: We retrospectively analyzed the severe acute respiratory syndrome coronavirus 2 reverse transcription-polymerase chain reaction (RT-PCR) testing results according to time point and evaluated transmission routes. RESULTS: Since COVID-19 was first confirmed in a healthcare worker (HCW) on 11/13/2020, we performed RT-PCR tests for all patients and caregivers and four complete enumeration surveys for all HCWs. We detected three clusters of nosocomial spread and several sporadic cases. The first cluster originated from the community outbreak spot, where an asymptomatic HCW visited, which led to a total of 22 cases. The second cluster, which included patient-to-patient transmission, originated from a COVID-19 positive caregiver before diagnosis and the third cluster involved a radiologist and a banker. We took measures to isolate Building 1 of the hospital for 17 days and controlled the outbreak during a period of increasing community COVID-19 prevalence. Universal screening of all inpatients upon admission and resident caregivers was made mandatory and hospital-related employees are now screened monthly. CONCLUSION: Infection control strategies to prevent the nosocomial transmission of emerging infectious diseases must correspond with community disease prevalence. Our data reinforce the importance of multi-time point surveillance of asymptomatic HCWs and routine surveillance of patients and caregivers during an epidemic.