Incidence of Clostridioides difficile Infections in Republic of Korea: A Prospective Study With Active Surveillance vs. National Data From Health Insurance Review & Assessment Service.

BACKGROUND: Since the emergence of hypervirulent strains of Clostridioides difficile, the incidence of C. difficile infections (CDI) has increased significantly. METHODS: To assess the incidence of CDI in Korea, we conducted a prospective multicentre observational study from October 2020 to October 2021. Additionally, we calculated the incidence of CDI from mass data obtained from the Health Insurance Review and Assessment Service (HIRA) from 2008 to 2020. RESULTS: In the prospective study with active surveillance, 30,212 patients had diarrhoea and 907 patients were diagnosed with CDI over 1,288,571 patient-days and 193,264 admissions in 18 participating hospitals during 3 months of study period; the CDI per 10,000 patient-days was 7.04 and the CDI per 1,000 admission was 4.69. The incidence of CDI was higher in general hospitals than in tertiary hospitals: 6.38 per 10,000 patient-days (range: 3.25-12.05) and 4.18 per 1,000 admissions (range: 1.92-8.59) in 11 tertiary hospitals, vs. 9.45 per 10,000 patient-days (range: 5.68-13.90) and 6.73 per 1,000 admissions (range: 3.18-15.85) in seven general hospitals. With regard to HIRA data, the incidence of CDI in all hospitals has been increasing over the 13-year-period: from 0.3 to 1.8 per 10,000 patient-days, 0.3 to 1.6 per 1,000 admissions, and 6.9 to 56.9 per 100,000 population, respectively. CONCLUSION: The incidence of CDI in Korea has been gradually increasing, and its recent value is as high as that in the United State and Europe. CDI is underestimated, particularly in general hospitals in Korea.

Clinical Characteristics and Risk Factors for Mortality in Critical COVID-19 Patients Aged 50 Years or Younger During Omicron Wave in Korea: Comparison With Patients Older Than 50 Years of Age.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has caused the death of thousands of patients worldwide. Although age is known to be a risk factor for morbidity and mortality in COVID-19 patients, critical illness or death is occurring even in the younger age group as the epidemic spreads. In early 2022, omicron became the dominant variant of the COVID-19 virus in South Korea, and the epidemic proceeded on a large scale. Accordingly, this study aimed to determine whether young adults (aged ≤ 50 years) with critical COVID-19 infection during the omicron period had different characteristics from older patients and to determine the risk factors for mortality in this specific age group. METHODS: We evaluated 213 critical adult patients (high flow nasal cannula or higher respiratory support) hospitalized for polymerase chain reaction-confirmed COVID-19 in nine hospitals in South Korea between February 1, 2022 and April 30, 2022. Demographic characteristics, including body mass index (BMI) and vaccination status; underlying diseases; clinical features and laboratory findings; clinical course; treatment received; and outcomes were collected from electronic medical records (EMRs) and analyzed according to age and mortality. RESULTS: Overall, 71 critically ill patients aged ≤ 50 years were enrolled, and 142 critically ill patients aged over 50 years were selected through 1:2 matching based on the date of diagnosis. The most frequent underlying diseases among those aged ≤ 50 years were diabetes and hypertension, and all 14 patients who died had either a BMI ≥ 25 kg/m² or an underlying disease. The total case fatality rate among severe patients (S-CFR) was 31.0%, and the S-CFR differed according to age and was higher than that during the delta period. The S-CFR was 19.7% for those aged ≤ 50 years, 36.6% for those aged > 50 years, and 38.1% for those aged ≥ 65 years. In multivariate analysis, age (odds ratio [OR], 1.084; 95% confidence interval [CI], 1.043-1.127), initial low-density lipoprotein > 600 IU/L (OR, 4.782; 95% CI, 1.584-14.434), initial C-reactive protein > 8 mg/dL (OR, 2.940; 95% CI, 1.042-8.293), highest aspartate aminotransferase > 200 IU/L (OR, 12.931; 95% CI, 1.691-98.908), and mechanical ventilation implementation (OR, 3.671; 95% CI, 1.294-10.420) were significant independent predictors of mortality in critical COVID-19 patients during the omicron wave. A similar pattern was shown when analyzing the data by age group, but most had no statistical significance owing to the small number of deaths in the young critical group. Although the vaccination completion rate of all the patients (31.0%) was higher than that in the delta wave period (13.6%), it was still lower than that of the general population. Further, only 15 (21.1%) critically ill patients aged ≤ 50 years were fully vaccinated. Overall, the severity of hospitalized critical patients was significantly higher than that in the delta period, indicating that it was difficult to find common risk factors in the two periods only with a simple comparison. CONCLUSION: Overall, the S-CFR of critically ill COVID-19 patients in the omicron period was higher than that in the delta period, especially in those aged ≤ 50 years. All of the patients who died had an underlying disease or obesity. In the same population, the vaccination rate was very low compared to that in the delta wave, indicating that non-vaccination significantly affected the progression to critical illness. Notably, there was a lack of prescription for Paxlovid for these patients although they satisfied the prescription criteria. Early diagnosis and active initial treatment was necessary, along with the proven methods of vaccination and personal hygiene. Further studies are needed to determine how each variant affects critically ill patients.

Veno-arterial extracorporeal membrane oxygenation for severe fever with thrombocytopenia syndrome with fulminant myocarditis: a case report.

BACKGROUND: The clinical spectrum of severe fever with thrombocytopenia syndrome (SFTS) is wide, which can range from fever to multiple organ failure. Conservative therapy plays a key role in the treatment of SFTS. However, severe cases of SFTS, such as fulminant myocarditis, may require mechanical hemodynamic support. CASE PRESENTATION: This report presents a case of a 59-year old woman diagnosed with SFTS by reverse-transcription polymerase chain reaction. The patient had no initial symptoms of cardiac involvement and rapidly developed hemodynamic instability 3 days after hospitalization. She suffered from chest pain and had elevated cardiac enzymes. In the absence of atrio-ventricular conduction abnormalities, left ventricular dysfunction, and coronary artery abnormalities by coronary angiography, she was diagnosed with fulminant myocarditis. At that time, her pulse rate nearly dropped to 0 bpm and she developed near complete akinesia of the heart despite vasopressor administration. Veno-arterial extracorporeal membrane oxygenation (ECMO) was initiated with other supportive measures and she fully recovered after 21 days. CONCLUSIONS: This case indicates that SFTS can cause fulminant myocarditis even without evidence of cardiac involvement at presentation. When symptoms and/or signs of acute heart failure develop in patients with SFTS, myocarditis should be suspected and the patient should be promptly evaluated. Additionally, mechanical hemodynamic support like ECMO can be a lifesaving tool in the treatment of fulminant myocarditis.

Air and Environmental Contamination Caused by COVID-19 Patients: a Multi-Center Study.

BACKGROUND: The purpose of this study was to determine the extent of air and surface contamination of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in four health care facilities with hospitalized coronavirus disease 2019 (COVID-19) patients. METHODS: We investigated air and environmental contamination in the rooms of eight COVID-19 patients in four hospitals. Some patients were in negative-pressure rooms, and others were not. None had undergone aerosol-generating procedures. On days 0, 3, 5, and 7 of hospitalization, the surfaces in the rooms and anterooms were swabbed, and air samples were collected 2 m from the patient and from the anterooms. RESULTS: All 52 air samples were negative for SARS-CoV-2 RNA. Widespread surface contamination of SARS-CoV-2 RNA was observed. In total, 89 of 320 (27%) environmental surface samples were positive for SARS-CoV-2 RNA. Surface contamination of SARS-CoV-2 RNA was common in rooms without surface disinfection and in rooms sprayed with disinfectant twice a day. However, SARS-CoV-2 RNA was not detected in a room cleaned with disinfectant wipes on a regular basis. CONCLUSION: Our data suggest that remote (> 2 m) airborne transmission of SARS-CoV-2 from hospitalized COVID-19 patients is uncommon when aerosol-generating procedures have not been performed. Surface contamination was widespread, except in a room routinely cleaned with disinfectant wipes.

Viral Load Kinetics of SARS-CoV-2 Infection in Saliva in Korean Patients: a Prospective Multi-center Comparative Study.

BACKGROUND: This study was performed to compare the viral load and kinetics of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in saliva with those in standard nasopharyngeal/oropharyngeal (NP/OP) swabs. METHODS: Fifteen patients with SARS-CoV-2 infection from four hospitals were prospectively enrolled and matched samples of nasopharyngeal/oropharyngeal swabs and saliva were collected at Day 1 of admission and every other day till consequently negative for two times. Real-time reverse transcription polymerase chain reaction (rRT-PCR) was performed to detect the envelope (E) and RNA-dependent RNA polymerase (RdRP) genes. RESULTS: The cycle threshold values of saliva were comparable to those of NP/OP swabs overall (P = 0.720, Mann-Whitney U test). However, the overall sensitivity of rRT-PCR using saliva was 64% (34/53), which is lower than the 77% (41/53) using NP/OP swabs. The sensitivity of rRT-PCR using saliva was especially lower in early stage of symptom onset (1-5 days; 8/15; 53%) and in patients who did not have sputum (12/22; 55%). CONCLUSION: Saliva sample itself is not appropriate for initial diagnosis of coronavirus disease 2019 (COVID-19) to replace NP/OP swabs, especially for the person who does not produce sputum. COVID-19 cannot be excluded when the test using saliva is negative, and it is necessary to retest using NP/OP swabs.

In Vitro Synergy and In Vivo Activity of Tigecycline-Ciprofloxacin Combination Therapy against Vibrio vulnificus Sepsis.

The mortality rate associated with Vibrio vulnificus sepsis remains high. An in vitro time-kill assay revealed synergism between tigecycline and ciprofloxacin. The survival rate was significantly higher in mice treated with tigecycline plus ciprofloxacin than in mice treated with cefotaxime plus minocycline. Thus, combination treatment with tigecycline-ciprofloxacin may be an effective novel antibiotic regimen for V. vulnificus sepsis.

Dysfunction of Circulating Natural Killer T Cells in Patients With Scrub Typhus.

Background: Human natural killer T (NKT) cells are known to serve as regulatory and/or effector cells in infectious diseases. However, little is known about the role of NKT cells in Orientia tsutsugamushi infection. Accordingly, the objective of this study was to examine the level and function of NKT cells in patients with scrub typhus. Methods: This study included 62 scrub typhus patients and 62 healthy controls (HCs). NKT cell level and function in peripheral blood samples were measured by flow cytometry. Results: Proliferation of NKT cells and their ability to produce interferon-γ and interleukin-4 (IL-4) were significantly lower in scrub typhus patients compared to those in HCs. However, circulating NKT cell levels were comparable between patients and HCs. Expression levels of CD69, programmed death-1 (PD-1), lymphocyte activation gene-3 (LAG-3), and T-cell immunoglobulin domain and mucin domain-containing molecule-3 (TIM-3) were significantly increased in scrub typhus patients. Elevated expression of CD69, PD-1, LAG-3, and TIM-3, impaired proliferation, and decreased IL-4 production by NKT cells were recovered in the remission phase. Conclusions: This study demonstrates that circulating NKT cells are numerically preserved but functionally impaired in scrub typhus patients. In addition, NKT cell dysfunction is recovered in the remission phase.

Case report: dual primary AIDS-defining cancers in an HIV-infected patient receiving antiretroviral therapy: Burkitt's lymphoma and Kaposi's sarcoma.

BACKGROUND: The incidence of AIDS-defining cancers (ADCs) has decreased markedly in the era of highly active antiretroviral therapy (HAART). The occurrence of two ADCs is rare in people living with HIV or AIDS (PWHA) who are severely immunosuppressed or have incomplete virologic suppression. CASE PRESENTATION: We report a case of dual primary ADCs, especially NHL followed by KS, in a 70-year-old HIV-infected man who was on antiretroviral therapy and had successful virologic suppression. During HAART, he presented with generalized myalgia and abdominal pain. Multiple liver masses were detected and a biopsy revealed Burkitt's lymphoma. After three cycles of anticancer chemotherapy with a favorable response, he was diagnosed with cytomegalovirus retinitis and the anti-cancer chemotherapy was discontinued. Despite successful virologic suppression with HAART, human herpes virus-8 associated Kaposi's sarcoma was diagnosed in his right thigh. He underwent radiation therapy. CONCLUSION: These findings suggest that multiple ADCs can occur in PWHA who are receiving HAART and have successful virologic suppression. Healthcare providers caring for PWHA should maintain vigilance for the development of a broad spectrum of cancers.

Case report: detection of the identical virus in a patient presenting with severe fever with thrombocytopenia syndrome encephalopathy and the tick that bit her.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease. Haemophysalis longicornis ticks have been considered the vector of severe fever with thrombocytopenia syndrome virus (SFTSV). However, clear data on the transmission of SFTS from ticks to humans are limited. CASE PRESENTATION: We report an 84-year-old woman who presented with fever and altered mentality, which was confirmed as SFTS with encephalopathy by reverse-transcription polymerase chain reaction in blood and cerebrospinal fluid. The SFTSV was also identified in the tick that bit her, H. longicornis. Phylogenetic analyses indicated that the SFTSV from the patient and the tick was identical. The patient gradually recovered with treatments of corticosteroids and immunoglobulin. CONCLUSION: These findings provide further evidence of SFTS viral transmission from H. longicornis to human.

First Imported Case of Zika Virus Infection into Korea.

Since Zika virus has been spreading rapidly in the Americas from 2015, the outbreak of Zika virus infection becomes a global health emergency because it can cause neurological complications and adverse fetal outcome including microcephaly. Here, we report clinical manifestations and virus isolation findings from a case of Zika virus infection imported from Brazil. The patient, 43-year-old Korean man, developed fever, myalgia, eyeball pain, and maculopapular rash, but not neurological manifestations. Zika virus was isolated from his semen, and reverse-transcriptase PCR was positive for the virus in the blood, urine, and saliva on the 7th day of the illness but was negative on the 21st day. He recovered spontaneously without any neurological complications. He is the first case of Zika virus infection in Korea imported from Brazil.

Outcome of intravenous azithromycin therapy in patients with complicated scrub typhus compared with that of doxycycline therapy using propensity-matched analysis.

There are no well-matched, controlled studies comparing azithromycin with doxycycline for the treatment of complicated scrub typhus. A retrospective propensity score-matched case-control study was performed for patients who presented with complicated scrub typhus and were treated with doxycycline or azithromycin between 2001 and 2011. Data on comorbidities, clinical manifestations, laboratory studies, treatments, and outcomes were extracted for analysis. The clinical characteristics and outcomes of the azithromycin-treated group (n=73) were compared to those of the doxycycline-treated group (n=108). Of 181 patients, 73 from each group were matched by propensity scores. There were no significant differences in baseline characteristics between the matched groups. The treatment success and survival rates were not significantly different (89% [65/73 patients] versus 96% [70/73 patients] and 96% [70/73 patients] versus 96% [70/73 patients], respectively [P>0.05]). No difference was observed in the time to defervescence or length of hospital stay between the two groups (P>0.05). In complicated scrub typhus patients (n=181), multivariate analysis showed that only APACHE II score was an independent risk factor for mortality (95% confidence interval, 1.11 to 1.56; P<0.001). Our data suggest that outcomes of azithromycin therapy are comparable to those of doxycycline therapy in patients with complicated scrub typhus.

The microbiology of periprosthetic joint infections as revealed by sonicate cultures in Korea: Routine use of fungal and mycobacterial cultures is necessary?

BACKGROUND: Although sonication is a valuable diagnostic tool for periprosthetic joint infections (PJI), it is not commonly utilized. We analyzed sonicate and intraoperative tissue culture results obtained from three hospitals to define the microbial etiology of PJIs in Korea. Furthermore, we investigated necessity of conducting regular fungal and mycobacterial cultures. METHODS: We retrospectively analyzed data for patients with suspected orthopedic-related infections between 2017 and 2022, who had undergone prostheses removal surgery. We included 193 patients with suspected PJIs, and bacterial (n = 193), fungal (n = 193), and mycobacterial (n = 186) cultures were conducted on both sonicate and intraoperative tissue samples. The diagnosis of PJI was based on the European Bone and Joint Infection Society (EBJIS) criteria. RESULTS: Out of 193 patients, 121 (62.7%) had positive sonicate cultures, while 112 (58.0%) had positive periprosthetic tissue cultures. According to EBJIS criteria, a total of 181 patients were diagnosed with PJI, and 141 patients received microbiological confirmation through sonicate fluid culture or tissue culture. Of the 181 patients, 28 were classified with acute PJI (within 3 months of implantation) and 153 with chronic PJI. Among 141 patients, staphylococci were the most common organisms, accounting for 51.8% of cases, followed by Gram-negative organisms (15.6%), fungus (8.5%), and mycobacteria (3.5%). Nearly 91.7% of fungal isolates were Candida species, which also grew in bacterial cultures. In total, 11 cases cultured positive only in tissue culture, whereas 20 cases cultured positive only in sonicate culture. The antibiotic treatment plans were adjusted according to culture results. CONCLUSIONS: Utilizing sonicate culture has greatly assisted in identifying pathogens responsible for chronic indolent PJIs, allowing suitable antimicrobial treatment. Based on few cases involving non-Candida and mycobacterial infections, it appears that routine fungal and mycobacterial cultures may not be necessary.

Comparative Study on the Immunogenicity of COVID-19 mRNA Vaccines in Patients Receiving Adjuvant and Palliative Chemotherapy.

This study was conducted to investigate potential differences in vaccine efficacy between patients undergoing palliative chemotherapy and receiving adjuvant chemotherapy. Additionally, the study proved the influence of vaccination timing on vaccine efficacy during active chemotherapy. Anti-receptor-binding domain (RBD) IgG binding antibody assays and surrogate neutralizing antibody assays were performed after BNT162b2 or mRNA-1273 vaccination in 45 solid cancer patients (23 adjuvant and 22 palliative chemotherapy) and in 24 healthy controls before vaccination (baseline), at every two to four weeks after the first (post-dose 1) and the second vaccination (post-dose 2). The levels of anti-RBD IgG and neutralizing antibodies increased significantly from baseline through post-dose 1 to post-dose 2 in all three groups. At the post-dose 1, the anti-RBD IgG and neutralizing antibody levels were significantly lower in cancer patients than in healthy controls. However, by post-dose 2, the seropositivity of anti-RBD IgG and neutralizing antibodies uniformly reached 100% across all groups, with no significant disparity in antibody levels among the three groups. Moreover, the antibody titers were not significantly different between patients with a vaccine and chemotherapy interval of more than 14 days or those with less than 14 days. This study demonstrated that after second doses of mRNA COVID-19 vaccines, humoral immune responses in patients receiving chemotherapy were comparable to those of healthy controls, regardless of whether the purpose of the anti-cancer treatment was palliative or adjuvant. Furthermore, the timing of vaccination did not affect the level of humoral immunity after the second vaccination.

Inappropriateness of quinolone in scrub typhus treatment due to gyrA mutation in Orientia tsutsugamushi Boryong strain.

The use of quinolone for treatment of rickettsial diseases remains controversial. Recent clinical studies suggest that quinolone is not as effective as others in patients with rickettsial diseases including scrub typhus, although the mechanism is not well understood. In this study, we evaluated the mutation in gyrA associated with quinolone resistance. We prospectively enrolled scrub typhus patients, collected blood samples and clinical data from October, 2010 to November, 2011. Among the 21 patients enrolled, one initially received ciprofloxacin for 3 days but was switched to doxycycline due to clinical deterioration. We obtained the gyrA gene of Orientia tsutsugamushi from 21 samples (20 Boryong strain, 1 Kato strain) and sequenced the quinolone resistance-determining region. All of 21 samples had the Ser83Leu mutation in the gyrA gene, which is known to be associated with quinolone resistance. This suggests that quinolones may be avoided for the treatment of serious scrub typhus.

Nosocomial Outbreak of COVID-19 from a Kidney Transplant Patient: Necessity of a Longer Isolation Period in Immunocompromised Patients.

BACKGROUND: Determination of the release from isolation for coronavirus disease 2019 (COVID-19) in immunocompromised patients who need additional hospitalization for treatment of non-COVID-19 related disease is important to prevent nosocomial transmission. However, there is insufficient evidence for an extended isolation period. MATERIALS AND METHODS: In September 2021, when the Delta variant was dominant, a nosocomial outbreak of COVID-19 occurred in the nephrology ward of a tertiary hospital in Gwangju, Korea. We conducted epidemiological investigations and whole-genome sequencing (WGS) of this virus. RESULTS: A man who underwent kidney transplantation was admitted to our hospital for the treatment of acute kidney injury. He was diagnosed with asymptomatic COVID-19 infection during a pre-admission screening test on September 1, 2021 and underwent isolation. After 10 days of isolation in the COVID-19-designated ward, he was transferred to the general nephrology ward. He underwent steroid pulse therapy (September 17 to September 23, >60 mg/day prednisolone) due to acute T-cell rejection. On September 28, 2021, the first patient with COVID-19 was identified in the nephrology ward, and a rapid-response team was activated to identify additional patients with COVID-19 and prevent the spread of COVID-19. Epidemiological investigations revealed that 12 patients, two caregivers, and three healthcare workers from the nephrology ward were diagnosed with COVID-19. The WGS of specimens from 14 nosocomial outbreak samples and released an index patient exhibited the same Delta variant originating from the B.1.617.2 lineage. This hospital-acquired COVID-19 outbreak in the nephrology ward resulted in two (11.7%) deaths in patients who underwent kidney transplantation. CONCLUSION: We demonstrated that an immunocompromised patient can cause a nosocomial outbreak due to the prolonged shedding of infectious viruses. Prolonged isolation in patients under active immunosuppressive therapy may be necessary to prevent transmission, especially in the hospital setting.

Coinfection With Severe Fever With Thrombocytopenia Syndrome and Scrub Typhus in Korea.

Background: Scrub typhus and severe fever with thrombocytopenia syndrome (SFTS) are the 2 most common tick-borne infectious diseases in Korea. Every year, an increasing number of cases are reported, which is a public health concern. Therefore, we aimed to investigate the prevalence of SFTS-scrub typhus coinfection in patients with SFTS. Methods: Clinical samples were collected from 129 patients with SFTS. One-step reverse-transcription polymerase chain reaction (PCR) was performed to identify the SFTS virus (SFTSV), and real-time PCR followed by nested PCR was performed to detect the Orientia tsutsugamushi gene for scrub typhus. Phylogenetic analysis was conducted to confirm the evolutionary relationships among different species. Results: Among 129 SFTS cases, 2 patients with SFTSV were positive for O. tsutsugamushi with a prevalence of coinfection of 1.6% (95% confidence interval, .001-.06). Phylogenetic analysis confirmed these as O. tsutsugamushi strain Boryong. Conclusions: Our study found that 1.6% of patients were coinfected with SFTS and scrub typhus infection. We believe that this information will add a new dimension to clinical diagnosis, which should be considered for better public health management. Further research is needed to better understand the ecological transmission dynamics and geographical distribution of SFTSV and O. tsutsugamushi in endemic countries.

Clinically differential diagnosis of human granulocytic anaplasmosis and severe fever with thrombocytopenia syndrome.

This study analyzed HGA and SFTS in patients with suspected tick-borne infection by focusing on key differences that clinicians can easily recognize. A retrospective analysis was performed on confirmed patients with HGA or SFTS in 21 Korean hospitals from 2013 to 2020. A scoring system was developed by multivariate regression analysis and accuracy assessment of clinically easily discriminable parameters was performed. The multivariate logistic regression analysis revealed that sex (especially male sex) (odds ratio [OR] 11.45, P = 0.012), neutropenia (< 1500) (OR 41.64, P < 0.001), prolonged activated partial thromboplastin time (OR 80.133, P < 0.001), and normal C-reactive protein concentration (≤ 1.0 mg/dL; OR 166.855, P = 0.001) were significantly associated with SFTS but not with HGA. Each factor, such as meaningful variables, was given 1 point, and a receiver-operating characteristic curve with a cutoff value (> 1) in a 5-point scoring system (0-4 points) was analyzed to evaluate the accuracy of differentiation between HGA and SFTS. The system showed 94.5% sensitivity, 92.6% specificity, and an area under the receiver-operating characteristic curve of 0.971 (0.949-0.9). Where HGA and SFTS are endemic, the scoring system based on these four parameters such as sex, neutrophil count, activated partial thromboplastin time, and C-reactive protein concentration will facilitate the differential diagnosis of HGA and SFTS in the emergency room in patients with suspected tick-borne infectious diseases.

Rifamycin resistance, rpoB gene mutation and clinical outcomes of Staphylococcus species isolates from prosthetic joint infections in Republic of Korea.

OBJECTIVES: We conducted an in vitro investigation of the activity of rifamycins against planktonic and biofilm states of Staphylococcus aureus and Staphylococcus epidermidis isolates from patients with prosthetic joint infections (PJIs), characterised their rpoB gene mutations, and analysed the clinical outcomes of rifampicin-resistant isolates. METHODS: A total of 110 staphylococcal isolates were collected from patients with PJI. Antimicrobials tested using the broth microdilution method included rifampicin, rifabutin, rifapentine and rifaximin. We evaluated rpoB gene mutations to identify rifampicin resistance mechanisms. Clinical outcomes were assessed in rifampicin-resistant isolates. RESULTS: The 110 staphylococcal isolates included 85 S. aureus (55% methicillin-resistant) and 25 S. epidermidis (100% methicillin-resistant). Seven S. aureus isolates and two S. epidermidis isolates were resistant to rifampicin [minimum inhibitory concentration (MIC) ≥2 µg/mL] and these isolates exhibited rpoB gene mutations. Among the 78 rifampicin-susceptible S. aureus isolates and 23 S. epidermidis isolates, 76 S. aureus isolates (97.4%) and all S. epidermidis isolates (100%) were highly susceptible (MIC ≤ 0.06 µg/mL) to other rifamycins. The minimum biofilm bactericidal concentrations for ≥50% of isolates (MBBC50) to rifampicin, rifabutin, rifapentine and rifaximin were 4, 1, 2 and 4 µg/mL for S. aureus and 1, 0.125, 0.25 and 0.5 µg/mL for S. epidermidis, respectively, among rifampicin-susceptible isolates. Among nine patients bearing rifampicin-resistant isolates, only three (33%) had successful outcomes. CONCLUSION: Rifamycins other than rifampicin show promising antistaphylococcal activity, including antibiofilm activity. Rifamycin-resistant staphylococci exhibit rpoB gene mutations.

Replacement of the Dominant ST191 Clone by ST369 Among Carbapenem-Resistant Acinetobacter baumannii Bloodstream Isolates at a Tertiary Care Hospital in South Korea.

The clonal dissemination of carbapenem-resistant Acinetobacter baumannii (CRAB) bacteremia is a serious clinical problem worldwide. However, the factors related to the emergence and replacement of predominant CRAB clones in nosocomial settings are unclear. By multilocus sequence typing (MLST), we evaluated the genetic relatedness of CRAB bloodstream isolates at a tertiary care hospital over a 3.5-year period and investigated the clinical and microbiologic characteristics of the predominant sequence types (STs). One hundred and seventy-nine CRAB bloodstream isolates were collected from June 2016 to December 2019, and their MLSTs according to Oxford scheme and clinical data were obtained. The predominant STs were assessed for in vitro growth, competitive growth, and virulence in a mouse model of intraperitoneal infection. Two dominant clones-ST369 (n = 98) and ST191 (n = 48)-belonging to international clone 2 (IC2) were recovered from patients admitted to intensive care units (ICUs) or wards. ST191 predominated (61%, 27/43) from June 2016 to July 2017, whereas ST369 (72%, 98/136), which was first isolated from a patient admitted to the emergency room, replaced ST191 (15%, 21/136) after August 2017. In a multivariate analysis, leukopenia (OR = 3.62, 95% CI 1.04-12.6, p = 0.04) and ST191 or 369 (OR = 5.32, 95% CI 1.25-22.65, p = 0.02) were independent risk factors for 7-day mortality. Compared with non-ST369, ST369 was associated with a shorter time to bacteremia from ICU admission (7 vs. 11 days, p = 0.01), pneumonia as an origin of bacteremia (67 vs. 52%, p = 0.04), leukopenia (28 vs. 11%, p < 0.01), and a lower 7-day survival rate (41 vs. 70%, p < 0.01). In vitro, ST 369 isolates had significantly higher growth rates and enhanced competitive growth compared to ST191. Finally, ST369 had greater virulence and a higher mortality rate than other STs in a mouse infection model. We report almost-complete replacement of the predominant ST191 clone by ST369 within an 8-month period at our hospital. ST369 had a high incidence density rate of CRAB bacteremia, a short time to bacteremia after ICU admission, and a high early mortality rate, which may be in part explained by its faster competitive growth rate and higher virulence than ST191.

Weight Gain and Lipid Profile Changes in Koreans with Human Immunodeficiency Virus undergoing Integrase Strand Transfer Inhibitor-Based Regimens.

BACKGROUND: This study explored the relationship between integrase strand transfer inhibitor (INSTI)-based anti-retroviral agents and weight gain over time, and the risk factors for weight gain in Korean people living with human immunodeficiency virus (PLWH). MATERIALS AND METHODS: The study was conducted retrospectively in PLWHs 18 years of age or older who took one of three INSTI-based single-tablet regimens (STRs) (tenofovir disoproxil fumarate/emtricitabine/elvitegravir/cobicistat [TDF/F/EVG/c], tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat [TAF/F/EVG/c], and abacavir/lamivudine/dolutegravir [ABC/3TC/DTG]) for more than 2 years at three university-affiliated hospitals in South Korea from May 2014 to December 2020. Analysis was performed in the treatment-naïve and treatment-experienced groups, respectively. RESULTS: Individual INSTI-based STRs were associated with weight gain at the 24-month follow up in both treatment-naïve (n = 179) and treatment-experienced (n = 290) groups. Body mass index (BMI) categories changed over time for TAF/F/EVG/c and ABC/3TC/DTG, with significant increases in the rates of overweight and obesity in treatment-naïve patients, whereas there was no change for TDF/F/EVG/c. TAF/F/EVG/c significantly increased total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) compared to other regimens over 24 months. In the treatment-naïve group, a baseline CD4+ T cell count <100 cells/mm3, human immunodeficiency virus (HIV) viral load (VL) ≥100,000 copies/mL, no physical exercise, and TAF/F/EVG/c (vs. TDF/F/EVF/c) were risk factors for ≥10% weight gain. In the treatment-experienced group, age <45 years, BMI <25 kg/m², and no physical exercise were risk factors for ≥5% weight gain. CONCLUSION: INSTI-based STR continued to increase body weight at the 24-month follow up in treated and untreated Korean PLWH. Exercise, together with demographic-, HIV-, and anti-retroviral therapy-related factors, influenced weight gain. Therefore, when prescribing an INSTI-based STR, weight gain and metabolic changes should be closely monitored in PLWH with these risk factors.