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Abstract Background Age-dependent immune responses to coronavirus disease 2019 (COVID-19) vaccinations and breakthrough infections (BIs) in young and middle-aged individuals are unclear. Methods This nationwide multicenter prospective cohort study analyzed immune responses in participants of the ChAdOx1 (ChAd)-ChAd-mRNA vaccine group using cytometry by time-of-flight, anti-spike protein antibody (Sab) and anti-nucleocapsid antibody (Nab) titers, plaque reduction neutralization tests (PRNTs), and interferon-gamma (IFN-γ) release assays at various time points. Results We evaluated 347 participants with an average age of 38.9 ± 9.4 years (range: 21–63). There was a significant inverse correlation between age and Sab levels after the second dose (slope − 14.96, P = 0.032), and this was more pronounced after the third dose (slope − 208.9, P

Abstract This study evaluated the determinants of mortality and the T cell immune response in patients with persistent Staphylococcus aureus bacteremia (SAB). This was a prospective cohort study and patients with confirmed SAB were enrolled from 2008 to 2020. We compared clinical, microbiological, and genotypic features between surviving and deceased patients with persistent SAB. The concentrations of cytokines and the proportions of IFN-γ secreting CD4+ T cells were measured serially during the bacteremia period. Of the 1760 patients, 242 had persistent bacteremia (PB), and 49 PB patients died within 30 days. In the multivariate analysis, the APACHE II score and female sex were independently associated with 30 days mortality. The level of IL-10 was significantly increased in the plasma of patients with a high Pitt bacteremia score and those who died within 12 weeks from the index day. The proportion of IFN-γ-secreting CD4+ T cells were the highest just before the positive-to-negative conversion of blood cultures in patients with a low Pitt bacteremia score and those who survived for 12 weeks. The level of IL-10 is correlated with clinical outcomes in PB patients. IFN-γ secreting CD4+ T cells might play a pivotal role in SAB PB.

ABSTRACT The incidence of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) infection is increasing and is associated with vancomycin treatment failures. However, studies investigating the risk factors for treatment failure in hVISA infection are limited. Patients with hVISA bacteremia treated with vancomycin over 7 days between August 2008 and June 2020 were enrolled in this study. Clinical and microbiological characteristics were compared between vancomycin treatment failure and success groups to identify the risk factors for vancomycin treatment failure. Among the 180 patients with hVISA bacteremia, 102 patients treated with vancomycin over 7 days were included. Vancomycin treatment failed in 80 (78%) patients. Patients in the vancomycin treatment failure group were older (P < 0.001) and more frequently had solid cancer (P = 0.04) than those in the vancomycin treatment success group. Solid organ transplantation (SOT) was more frequent (P < 0.001) in the vancomycin treatment success group. The Charlson comorbidity index (P = 0.01) and Acute Physiology and Chronic Health Evaluation II scores (P < 0.001) were higher in the vancomycin treatment failure group. In multivariate analysis, independent risk factors for vancomycin treatment failure were old age and severity of bacteremia. SOT and vancomycin minimal inhibitory concentration (MIC) ≤ 1.0 mg/L using the broth microdilution (BMD) method were associated with successful vancomycin treatment. Old age and infection severity were independent risk factors for vancomycin treatment failure. Vancomycin MIC using the BMD method is an important risk factor for vancomycin treatment failure, and its use should be considered in hVISA bacteremia.IMPORTANCEIn this study, we assessed the clinical and microbiological characteristics of heterogeneous vancomycin-intermediated Staphylococcus aureus (hVISA) bacteremia and identified risk factors for vancomycin treatment failure. We found that advanced age and severity of infection were independent risk factors for vancomycin treatment failure. On the other hand, solid organ transplantation and a low vancomycin minimal inhibitory concentration were associated with successful vancomycin treatment. This study highlights the importance of vancomycin minimal inhibitory concentration in hVISA bacteremia.

ABSTRACT This study aimed to identify which streptococcal species are closely associated with infective endocarditis (IE) and to evaluate risk factors for mortality in patients with streptococcal IE. We performed a retrospective cohort study of all patients with streptococcal bloodstream infection (BSI) from January 2010 to June 2020 in a tertiary hospital in South Korea. We compared clinical and microbiological characteristics of streptococcal BSIs according to the diagnosis of IE. We performed multivariate analysis to evaluate the risk of IE according to streptococcal species and risk factors for mortality in streptococcal IE. A total of 2,737 patients were identified during the study period, and 174 (6.4%) were diagnosed with IE. The highest IE prevalence was in patients with Streptococcus mutans BSI (33% [9/27]) followed by S. sanguinis (31% [20/64]), S. gordonii (23% [5/22]), S. gallolyticus (16% [12/77]), and S. oralis (12% [14/115]). In multivariate analysis, previous IE, high-grade BSI, native valve disease, prosthetic valve, congenital heart disease, and community-onset BSI were independent risk factors for IE. After adjusting for these factors, S. sanguinis (adjusted OR [aOR], 7.75), S. mutans (aOR, 5.50), and S. gallolyticus (aOR, 2.57) were significantly associated with higher risk of IE, whereas S. pneumoniae (aOR, 0.23) and S. constellatus (aOR, 0.37) were associated with lower risk of IE. Age, hospital-acquired BSI, ischemic heart disease, and chronic kidney disease were independent risk factors for mortality in streptococcal IE. Our study points to significant differences in the prevalence of IE in streptococcal BSI according to species. IMPORTANCE Our study of risk of infective endocarditis in patients with streptococcal bloodstream infection demonstrated that Streptococcus sanguinis, S. mutans, and S. gallolyticus were significantly associated with higher risk of infective endocarditis. However, when we evaluated the performance of echocardiography in patients with streptococcal bloodstream infection, patients with S. mutans and S. gordonii bloodstream infection had a tendency of low performance in echocardiography. There are significant differences in the prevalence of infective endocarditis in streptococcal bloodstream infection according to species. Therefore, performing echocardiography in streptococcal bloodstream infection with a high prevalence of, and significant association with, infective endocarditis is desirable.

Background/Aims The rapidity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific memory B or T cell response in vaccinated individuals is important for our understanding of immunopathogenesis of coronavirus disease 2019 (COVID-19). We therefore compared the timing of adequate immune responses between the first and booster doses of COVID-19 vaccines in infection-naïve healthcare workers. Methods We enrolled healthcare workers who received two doses of either the BNT162b2 vaccine or the ChAdOx1 vaccine, all of whom received the BNT162b2 vaccine as the booster (the third) dose. Spike 1 (S1)-immunoglobulin G (IgG) antibodies and interferon gamma producing T cell responses were measured at 0, 7, 14, and 21 days after the first dose, and at 0 and between 2 to 7 days after the booster dose. Results After the first-dose vaccination, the S1-IgG antibody responses were elicited within 14 days in the BNT162b2 group and within 21 days in the ChAdOx1 group. After the booster dose, the S1-IgG antibody responses were elicited within 5 days in both groups. The SARS-CoV-2-specific T cell responses appeared at 7 days after the first dose and at 4 days after the booster dose. Conclusions SARS-CoV-2-specific immune responses by memory B cells and T cells may be expected to appear around 4 to 5 days after the booster dose.

Abstract Concern about resistance to chlorhexidine has increased due to the wide use of the latter. The impact of the qacA/B and smr chlorhexidine tolerance genes on the outcome of methicillin-resistant Staphylococcus aureus (MRSA) infections is unclear. We evaluated the prevalence and clinical impact of, and microbiological risk factors for, qacA/B tolerance in MRSA bacteremia. MRSA bacteremia that occurred more than two days after intensive care unit admission between January 2009 and December 2018 was identified from a prospective cohort of S. aureus bacteremia in a tertiary-care hospital from South Korea. A total of 183 MRSA blood isolates was identified, and the major genotype found was ST5-MRSA-II (87.4%). The prevalences of qacA/B and smr were 67.2% and 3.8%, respectively. qacA/B-positive isolates were predominantly ST5-MRSA-II (96.7% [119/123]), the dominant hospital clone. In a homogenous ST5-MRSA-II background, qacA/B positivity was independently associated with septic shock (aOR, 4.85), gentamicin resistance (aOR, 74.43), and non-t002 spa type (aOR, 74.12). qacA/B positivity was found to have decreased significantly in ST5-MRSA-II in association with a decline in qacA/B-positive t2460, despite the increasing use of chlorhexidine since 2010 (P

Background/Aims Data comparing the antibody responses of different coronavirus disease 2019 (COVID-19) vaccine platforms according to dose with natural severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection-induced antibody responses are limited. Methods Blood samples from adult patients with mild and severe COVID-19 and healthcare workers who received ChAdOx1 nCoV-19 vaccine (2nd dose at 12-week intervals) and BNT162b2 vaccine (2nd dose at 3-week intervals) were collected and compared by immunoglobulin G immune responses to SARS-CoV-2 specific spike protein using an in-house-developed enzyme-linked immunosorbent assay. Results A total of 53 patients, including 12 and 41 with mild and severe COVID-19, respectively, were analyzed. In addition, a total of 73 healthcare workers, including 37 who received ChAdOx1 nCoV-19 and 36 who received BNT162b2, were enrolled. Antibody responses after the first and second doses of the ChAdOx1 nCoV-19 vaccine or the first dose of the BNT162b2 vaccine were similar to those in convalescent patients with mild COVID-19, but lower than those in convalescent patients with severe COVID-19, respectively. However, after the second dose of the BNT162b2 vaccine, the antibody response was comparable to that in convalescent patients with severe COVID-19. Conclusions Our data suggest that the second dose of mRNA vaccination may be more beneficial in terms of long-term immunity and prevention of SARS-CoV-2 variant infection than a single dose of COVID-19 vaccination or homologous second challenge ChAdOx1 nCoV-19.

Rifampin resistance (RIF-R) in Staphylococcus aureus (S. aureus) with rpoB mutations as one of its resistance mechanisms has raised concern about clinical treatment and infection prevention strategies. Data on the prevalence and molecular epidemiology of RIF-R S. aureus blood isolates in South Korea are scarce. We used broth microdilution to investigate RIF-R prevalence and analyzed the rpoB gene mutation in 1615 S. aureus blood isolates (772 methicillin-susceptible and 843 methicillin-resistant S. aureus (MRSA)) from patients with bacteremia, between 2008 and 2017. RIF-R prevalence and antimicrobial susceptibility were determined. Multilocus sequence typing was used to characterize the isolate’s molecular epidemiology; Staphylococcus protein A (spa), staphylococcal cassette chromosome mec (SCCmec), and rpoB gene mutations were detected by PCR. Among 52 RIF-R MRSA isolates out of 57 RIF-R S. aureus blood isolates (57/1615, 0.4%; 5 methicillin-susceptible and 52 MRSA), ST5 (44/52, 84.6%), SCCmec IIb (40/52, 76.9%), and spa t2460 (27/52, 51.9%) were predominant. rpoB gene mutations with amino acid substitutions showed that A477D (17/48, 35.4%) frequently conferred high-level RIF resistance (MIC > 128 mg/L), followed by H481Y (4/48, 8.3%). RIF-R S. aureus blood isolates in South Korea have unique molecular characteristics and are closely associated with rpoB gene mutations. RIF-R surveillance through S. aureus–blood isolate epidemiology could enable effective therapeutic management.

The impact of the coronavirus disease 2019 (COVID-19) vaccination on humoral and cellular immunity in transplant recipients remains unknown. We report the case of a 78-year-old kidney transplant recipient who experienced acute T cell-mediated rejection after receiving the second dose of the BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioN-Tech). She had no history of acute rejection throughout the 13 years after deceased donor kidney transplantation. Fifteen days after receiving the second dose of the BNT162b2 vaccine, the recipient visited our center with a mild headache and fever. Her serum creatinine level had increased from 0.61 to 4.95 mg/dL. Kidney allograft biopsy indicated acute T cell-mediated rejection (grade IB) with no pathologic evidence of antibody-mediated rejection. Anti-severe acute respiratory syndrome coronavirus 2 spike-immunoglobulin G and -immunoglobulin M measurements were weak positive and negative, respectively. Careful monitoring of kidney allograft function is vital for transplant recipients undergoing COVID-19 vaccination.

ABSTRACT Estimating neutralizing activity in vaccinees is crucial for predicting the protective effect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As the plaque reduction neutralization test (PRNT) requires a biosafety level 3 facility, it would be advantageous if surrogate virus neutralization test (sVNT) assays and binding assays could predict neutralizing activity. Here, five different assays were evaluated with respect to the PRNT in vaccinees: three sVNT assays from GenScript, Boditech Med, and SD Biosensor and two semiquantitative binding assays from Roche and Abbott. The vaccinees were subjected to three vaccination protocols: homologous ChAdOx1, homologous BNT162b2, and heterologous administration. The ability to predict a 50% neutralizing dose (ND50) of ≥20 largely varied among the assays, with the binding assays showing substantial agreement (kappa, ~0.90) and the sVNT assays showing relatively poor performance, especially in the ChAdOx1 group (kappa, 0.33 to 0.97). The ability to predict an ND50 value of ≥118.25, indicating a protective effect, was comparable among different assays. Applying optimal cutoffs based on Youden’s index, the kappa agreements were greater than 0.60 for all assays in the total group. Overall, relatively poor performance was demonstrated in the ChAdOx1 group, owing to low antibody titers. Although there were intra-assay differences related to the vaccination protocols, as well as interassay differences, all assays demonstrated fair performance in predicting the protective effect using the new cutoffs. This study demonstrates the need for a different cutoff for each assay to appropriately determine a higher neutralizing titer and suggests the clinical feasibility of using various assays for estimation of the protective effect. IMPORTANCE The coronavirus disease 2019 (COVID-19) pandemic continues to last, despite high COVID-19 vaccination rates. As many people experience breakthrough infection after prior infection and/or vaccination, estimating the neutralization activity and predicting the protective effect are major issues of concern. However, since standard neutralization tests are not available in most clinical laboratories, it would be beneficial if commercial assays could predict these aspects. In this study, we evaluated the performance of three sVNT assays and two semiquantitative binding assays targeting the receptor-binding domain with respect to the PRNT. Our results suggest that these assays could be used for predicting the protective effect by adjusting the cutoffs.

Background/Aims Multi-drug resistant pathogens are increasing among healthcare-associated infections. It is well known that copper and copper alloys have antimicrobial activity. We evaluated the activity of copper against bacteria in a hospital setting in Korea. Methods This study was conducted in a laboratory and medical intensive care unit (ICU). Methicillin resistant Staphylococcus aureus (MRSA) and vancomycin resistant Enterococcus faecium (VRE) were inoculated onto copper, copper alloy and stainless steel plates. After 24 hours of incubation, colony-forming units (CFU) were counted in the laboratory. Two similar rooms were chosen in the ICU; one room had copper-containing surface, and the other room contained items with a stainless steel surfaces. Items were sampled weekly for 8 weeks when the rooms were not crowded and when the rooms were busier with healthcare workers or visitors. Results In vitro time-kill curves showed copper or, a copper alloy yielded a significant reduction in MRSA and VRE CFUs over 15 minutes. Upon exposure to stainless steel plates, CFUs were slowly reduced for 24 hours. In vivo, MRSA CFUs were lower in rooms with copper-containing surfaces compared with controls, both after cleaning and after patients had received visitors (p < 0.05). Analysis of VRE revealed similar results, but VRE CFUs from copper-containing surfaces of drug carts in the ICU did not decrease significantly. Conclusions Copper has antimicrobial activity and appears to reduce the number of multi-drug resistant microorganisms in a hospital environment. This finding suggests the potential of the use of copper fittings, instruments and surfaces in hospital.

Abstract Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) has emerged as an important cause of infection. We conducted a longitudinal study to evaluate changes in clinical and microbiological characteristics as well as outcomes of sequence type (ST) 72 MRSA bacteremia. We reviewed adult patients enrolled in a prospective cohort with ST72 MRSA bacteremia from August 2008 to December 2018 at Asan Medical Center, Seoul, South Korea. Changes in clinical characteristics, outcomes, and microbiological characteristics of patients over time were evaluated. Generalized linear and linear regression models were used to evaluate changes. Of the 1,760 isolates, 915 (62%) were MRSA bacteremia and 292 (31.9%) were ST72 MRSA. During the study period, the relative risk (RR) of MRSA bacteremia decreased annually by 3.7%; however, among MRSA bacteremia, RR of ST72 MRSA increased annually by 8.5%. Vancomycin minimum inhibitory concentration (MIC) decreased over the study period. Metastatic infection, persistent bacteremia, and recurrence of bacteremia within 12 weeks decreased significantly. There were no significant changes in 30-d and 12-week mortality. Antibiotic susceptibility of ST72 MRSA was evaluated, and the resistance rate to erythromycin decreased significantly. ST72 MRSA incidence increased annually; its vancomycin MIC and erythromycin resistance rate decreased over the 11 years.

BackgroundIsolation of COVID-19 patients is a crucial infection control measure to prevent further SARS-CoV-2 transmission, but determining an appropriate timing to end the COVID-19 isolation is a challenging. We evaluated the performance of the self-test rapid antigen test (RAT) as a potential proxy to terminate the isolation of COVID-19 patients.Materials and methodsSymptomatic COVID-19 patients were enrolled who were admitted to a regional community treatment center (CTC) in Seoul (South Korea). Self-test RAT and the collection of saliva samples were performed by the patients, on a daily basis, until patient discharge. Cell culture and subgenomic RNA detection were performed on saliva samples.ResultsA total of 138 pairs of saliva samples and corresponding RAT results were collected from 34 COVID-19 patients. Positivity of RAT and cell culture was 27% (37/138) and 12% (16/138), respectively. Of the 16 culture-positive saliva samples, seven (43.8%) corresponding RAT results were positive. Using cell culture as the reference standard, the overall percent agreement, percent positive agreement, and percent negative agreement of RAT were 71% (95% CI, 63–78), 26% (95% CI, 12–42), and 82% (95% CI, 76–87), respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of the RAT for predicting culture results were 44% (95% CI, 20–70), 75% (95% CI, 66–82), 18% (95% CI, 8–34), and 91% (95% CI, 84–96), respectively.ConclusionAbout half of the patients who were SARS-CoV-2 positive based upon cell culture results gave negative RAT results. However, the remaining positive culture cases were detected by RAT, and RAT showed relatively high negative predictive value for viable viral shedding.

IntroductionDespite vaccine development, the COVID-19 pandemic is ongoing due to immunity-escaping variants of concern (VOCs). Estimations of vaccine-induced protective immunity against VOCs are essential for setting proper COVID-19 vaccination policy.MethodsWe performed plaque-reduction neutralizing tests (PRNTs) using sera from healthcare workers (HCWs) collected from baseline to six months after COVID-19 vaccination and from convalescent COVID-19 patients. The 20.2% of the mean PRNT titer of convalescent sera was used as 50% protective value, and the percentage of HCWs with protective immunity for each week (percent-week) was compared among vaccination groups. A correlation equation was deduced between a PRNT 50% neutralizing dose (ND50) against wild type (WT) SARS-CoV-2 and that of the Delta variant.ResultsWe conducted PRNTs on 1,287 serum samples from 297 HCWs (99 HCWs who received homologous ChAdOx1 vaccination (ChAd), 99 from HCWs who received homologous BNT162b2 (BNT), and 99 from HCWs who received heterologous ChAd followed by BNT (ChAd-BNT)). Using 365 serum samples from 116 convalescent COVID-19 patients, PRNT ND50 of 118.25 was derived as 50% protective value. The 6-month cumulative percentage of HCWs with protective immunity against WT SARS-CoV-2 was highest in the BNT group (2297.0 percent-week), followed by the ChAd-BNT (1576.8) and ChAd (1403.0) groups. In the inter-group comparison, protective percentage of the BNT group (median 96.0%, IQR 91.2–99.2%) was comparable to the ChAd-BNT group (median 85.4%, IQR 15.7–100%; P =0.117) and significantly higher than the ChAd group (median 60.1%, IQR 20.0–87.1%; P

AbstractBackground Q fever endocarditis is a major cause of culture-negative endocarditis. The role of Coxellia burnetii is underestimated because it is difficult to diagnose. We investigated the significance of C. burnetii as the cause of culture-negative endocarditis and vascular infection by examining blood and tissue specimens using serological testing and polymerase chain reaction (PCR).Methods All patients with infective endocarditis or large vessel vasculitis were prospectively enrolled at a tertiary-care hospital from May 2016 through September 2020. Q fever endocarditis and vascular infection were diagnosed based on: (1) positive PCR for a cardiac valve or vascular tissue, (2) positive PCR for blood or phase I immunoglobulin G (IgG) ≥ 6400, or (3) phase I IgG ≥ 800 and < 6400 with morphologic abnormality. PCR targeted C. burnetii transposase gene insertion element IS1111a.Results Of the 163 patients, 40 (25%) had culture-negative endocarditis (n = 35) or vascular infection (n = 5). Of the 40 patients, 24 (60%) were enrolled. Eight (33%) were diagnosed with Q fever endocarditis or vascular infection. Of these 8 patients, 6 had suspected acute Q fever endocarditis or vascular infection with negative phase I IgG. Six patients were not treated for C. burnetii, 4 were stable after surgery. One patient died due to surgical site infection after 5 months post-operatively and one died due to worsening underlying disease.Conclusions Approximately one-third of patients with culture-negative endocarditis and vascular infection was diagnosed as Q fever. Q fever endocarditis and vascular infection may be underestimated in routine clinical practice in South Korea.KEY MESSAGEQ fever endocarditis and vascular infection may be underestimated in routine clinical practice, thus, try to find evidence of C. burnetti infection in suspected patients by all available diagnostic tests including PCR.

Of various rodent-borne hantaviruses, Seoul orthohantavirus (SEOV) causes haemorrhagic fever with renal syndrome (HFRS), as does Hantaan orthohantavirus (HTNV). Given global-scale of cases of human infection with SEOV, it is of great clinical importance to distinguish SEOV from other HFRS-causing hantaviruses. In May 2019, a middle-aged patient who had lived in a suburban area of Chungcheong Province, Republic of Korea and enjoyed outdoor activities was transferred to Asan Medical Center in Seoul, Republic of Korea with HFRS; his symptoms included high fever and generalized myalgia. The rapid diagnostic test performed immediately after his transfer detected HTNV-specific antibodies, and the patient was treated accordingly. However, two consecutive IFAs performed at ten-day intervals showed no HTNV-specific immunoglobulin (Ig) G. During continuous supportive care, next-generation sequencing successfully identified viral genomic sequences in the patient's serum, which were SEOV and not HTNV. Phylogenetic analysis grouped the L, M, and S genes of this SEOV strain together with those of rat- or human-isolated Korean strains reported previously. Given global outbreaks and public health threats of zoonotic hantaviruses, a causative pathogen of hantavirus HFRS should be identified correctly at the time of diagnosis and by point-of-care testing.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tickborne disease in East Asia that is causing high mortality. The Gn glycoprotein of the SFTS virus (SFTSV) has been considered to be an essential target for virus neutralization. However, data on anti-Gn glycoprotein antibody kinetics are limited. Therefore, we investigated the kinetics of Gn-specific antibodies compared to those of nucleocapsid protein (NP)-specific antibodies. A multicenter prospective study was performed in South Korea from January 2018 to September 2021. Adult patients with SFTS were enrolled. Anti-Gn-specific IgM and IgG were measured using an enzyme-linked immunosorbent assay. A total of 111 samples from 34 patients with confirmed SFTS were analyzed. Anti-Gn-specific IgM was detected at days 5–9 and peaked at day 15–19 from symptom onset, whereas the anti-NP-specific IgM titers peaked at days 5–9. Median seroconversion times of both anti-Gn- and NP-specific IgG were 7.0 days. High anti-Gn-specific IgG titers were maintained until 35–39 months after symptom onset. Only one patient lost their anti-Gn-specific antibodies at 41 days after symptom onset. Our data suggested that the anti-Gn-specific IgM titer peaked later than anti-NP-specific IgM, and that anti-Gn-specific IgG remain for at least 3 years from symptom onset.

β-lactam–avibactam combinations have been proposed as carbapenem-sparing therapies, but little data exist on their in vitro activities in infections with high bacterial inocula. We investigated the in vitro efficacies and the inoculum effects of ceftazidime–avibactam and aztreonam–avibactam against extended-spectrum β-lactam-resistant Enterobacterales blood isolates. A total of 228 non-repetitive extended-spectrum β-lactam-resistant Escherichia coli and Klebsiella pneumoniae blood isolates were prospectively collected in a tertiary center. In vitro susceptibilities to ceftazidime, aztreonam, meropenem, ceftazidime–avibactam, and aztreonam–avibactam were evaluated by broth microdilution method using standard and high inocula. An inoculum effect was defined as an eightfold or greater increase in MIC when tested with the high inoculum. Of the 228 isolates, 99% were susceptible to ceftazidime–avibactam and 99% had low aztreonam–avibactam MICs (≤8 mg/L). Ceftazidime–avibactam and aztreonam–avibactam exhibited good in vitro activities; MIC50/MIC90 values were 0.5/2 mg/L, 0.125/0.5 mg/L, and ≤0.03/0.25 mg/L, respectively, and aztreonam–avibactam was more active than ceftazidime–avibactam. The frequencies of the inoculum effect with ceftazidime–avibactam and aztreonam–avibactam were lower than with meropenem (14% vs. 38%, p < 0.001 and 30% vs. 38%, p = 0.03, respectively). The β-lactam-avibactam combinations could be useful as carbapenem-sparing strategies, and aztreonam–avibactam has the better in vitro activity but is more subject to the inoculum effect than ceftazidime–avibactam.

We conducted a prospective cohort study at a community facility designated for the isolation of individuals with asymptomatic or mild COVID-19 between 10 January and 22 February 2021 to investigate the relationship of viral shedding with symptom changes of COVID-19. In total, 89 COVID-19 adult patients (12 asymptomatic, 16 presymptomatic, 61 symptomatic) were enrolled. Symptom scores, the genomic RNA and subgenomic RNA of SARS-CoV-2 from saliva samples with a cell culture were measured. Asymptomatic COVID-19 patients had a similar viral load to symptomatic patients during the early course of the disease, but exhibited a rapid decrease in viral load with the loss of infectivity. Subgenomic RNA and viable virus by cell culture in asymptomatic patients were detected only until 3 days after diagnosis, and the positivity of the subgenomic RNA and cell culture in symptomatic patients gradually decreased in both from 40% in the early disease course to 13% at 10 days and 4% at 8 days after the symptom onset, respectively. In conclusion, symptomatic patients have a high infectivity with high symptom scores during the early disease course and gradually lose infectivity depending on the symptom. Conversely, asymptomatic patients exhibit a rapid decrease in viral load with the loss of infectivity, despite a similar viral load during the early disease course.

Background: To evaluate the role of hydroxychloroquine (HCQ) as pre-exposure prophylaxis against coronavirus disease 2019 (COVID-19), we investigated the prevalence of positive test results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing according to recent HCQ use in patients who had been tested using nationwide health-insurance data of South Korea. Methods: All adults tested for SARS-CoV-2 from 20 January 2020 to 15 May 2020 were identified. HCQ users were defined as patients who had been pretreated with HCQ for at least 30 days until the date of SARS-CoV-2 testing. The prevalence of positive PCR results for SARS-CoV-2 was compared between HCQ users and nonusers. Results: Of a total of 216,686 individuals who had been tested for SARS-CoV-2, 743 (0.3%) were pretreated with HCQ. The prevalence of positive results was not significantly different between HCQ users (2.2%) and nonusers (2.7%; P = 0.35), with an odds ratio of 0.79 (95% confidence interval (CI), 0.48–1.30). Propensity score-matched-cohort analysis showed similar results in terms of the prevalence of positive results (2.2% in HCQ users vs. 3.1% in nonusers; P = 0.18), with an odds ratio of 0.69 (95% CI, 0.40–1.19). The rate of positive PCR was not significantly different in long-term HCQ users (more than 3 or 6 months) compared with nonusers. Conclusions: In this population-based study, recent exposure to HCQ was not significantly associated with a lower risk of SARS-CoV-2 infection. Our data do not support the use of HCQ as pre-exposure prophylaxis against COVID-19.

Background: There are limited data on the clinical characteristics and the vertical transmission rate of pregnant women with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and their neonates in Korea. Materials and Methods: Pregnant women who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were retrospectively reviewed in Asan Medical Center from September 1, 2020, to April 26, 2022. All neonates and infected women underwent a polymerase chain reaction test for severe acute respiratory syndrome corona virus 2 within 24 hours of birth and at 48-hour interval if they stayed in the hospital. Results: A total of 60 pregnant women gave birth by cesarean section (n = 40, 66.7%) or vaginal delivery (n = 20, 33.3%). Among them, 3 women gave birth to twins. Delivery occurred, on average, at 38+2 weeks (± 2+0) of gestational age, and 9 patients (15.0%) had underlying diseases. Of these 60 patients, 9 (15.0%) received coronavirus disease 2019 vaccinations. Pneumonia was confirmed by a chest radiograph in 7 patients (11.7%), and 2 patients (3.3%) required supplemental oxygen therapy, both of whom eventually recovered. The mean birthweight of the neonates was 3,137 g (± 557.6). Further, 8 neonates (12.7%) were of low-birth weight (< 2,500 g), and 11 neonates (17.5%) were preterm (<37 weeks of gestation). Apgar score was median 8 (8 - 9) at 1 minute and 9 (9 – 9.5) at 5 minutes. Four neonates (6.3%) required invasive mechanical ventilation. All neonates had negative SARS-CoV-2 test results. Therefore, there was no vertical transmission in 63 of the neonates (0%, 95% confidence interval [CI]: 0 - 6) Conclusion: Pregnant Korean women with SARS-CoV-2-infection had favorable obstetric outcomes, and the risk of vertical transmission to their neonates was low. Managing the infection risks of pregnant women and their neonates during the coronavirus disease 2019 pandemic are required. [ABSTRACT FROM AUTHOR]