Validation of a new risk stratification system-based management for methicillin-resistant Staphylococcus aureus bacteraemia: analysis of a multicentre prospective study.

PURPOSE: Distinguishing between complicated and uncomplicated Staphylococcus aureus bacteraemia (SAB) is therapeutically essential. However, this distinction has limitations in reflecting the heterogeneity of SAB and encouraging targeted diagnostics. Recently, a new risk stratification system for SAB metastatic infection, involving stepwise approaches to diagnosis and treatment, has been suggested. We assessed its applicability in methicillin-resistant SAB (MRSAB) patients. METHODS: We retrospectively analysed data of a 3-year multicentre, prospective cohort of hospitalised patients with MRSAB. We classified the patients into three risk groups: low, indeterminate, and high, based on the new system and compared between-group management and outcomes. RESULTS: Of 380 patients with MRSAB, 6.3% were classified as low-, 7.6% as indeterminate-, and 86.1% as high-risk for metastatic infection. No metastatic infection occurred in the low-, 6.9% in the indeterminate-, and 19.6% in the high-risk groups (P < 0.001). After an in-depth diagnostic work-up, patients were finally diagnosed as 'without metastatic infection (6.3%)', 'with metastatic infection (17.4%)', and 'uncertain for metastatic infection (76.3%)'. 30-day mortality increased as the severity of diagnosis shifted from 'without metastatic infection' to 'uncertain for metastatic infection' and 'with metastatic infection' (P = 0.09). In multivariable analysis, independent factors associated with metastatic complications were suspicion of endocarditis in transthoracic echocardiography, clinical signs of metastatic infection, Pitt bacteraemia score ≥ 4, and persistent bacteraemia. CONCLUSIONS: The new risk stratification system shows promise in predicting metastatic complications and guiding work-up and management of MRSAB. However, reducing the number of cases labelled as 'high-risk' and 'uncertain for metastatic infection' remains an area for improvement.

Hepatitis C virus infection in patients undergoing surgery in a single tertiary academic center.

BACKGROUND AND AIM: Lack of awareness disturbs proper care for hepatitis C virus (HCV) infections in patients undergoing surgery. We investigated the status of HCV screening, confirmation, and treatment in patients who underwent surgery. METHODS: Patients who underwent surgery at a tertiary academic center between 2019 and 2021 were eligible for this retrospective study. RESULTS: Between 2019 and 2021, 96 894 patients (40 121 males; 41.4%) who underwent surgery under general anesthesia were recruited. The median age of the participants was 55.0 years. Of the 83 920 (86.6%) patients who tested positive for anti-HCV antibodies, 576 (0.7%) showed positive results, with a higher proportion of patients with diabetes mellitus (32.6% vs 18.5%), hypertension (50.5% vs 28.6%), liver cirrhosis (13.2% vs 1.7%), and unfavorable laboratory test results when compared with those with negative results (all P < 0.05). HCV RNA was tested in 215 patients (37.3%), with a positivity rate of 20.5% (n = 44). Of the 44 patients, 42 (95.5%) were referred for antiviral treatment, and 29 (69.0%) were successfully treated with direct-acting antiviral therapy. HCV RNA confirmation rates were higher in the Department of Hepatobiliary and Transplant Surgery (76.6%) than in the other surgical departments (25.0-33.5%) (P < 0.001). CONCLUSIONS: The proportion of patients who were positive for anti-HCV antibodies and failed to receive proper management after surgery was not negligible. Increased awareness of HCV infection among surgeons through appropriate education may be required.

Incidence of metabolic dysfunction-associated steatotic liver disease and advanced fibrosis and impact of overweight/obesity in elderly population: a nationwide cohort study.

BACKGROUND AND AIM: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing worldwide, coinciding with aging population. However, limited studies have evaluated its incidence and progression to advanced fibrosis in the elderly population. Therefore, our study aimed to investigate the incidence of MASLD and advanced fibrosis in this age group. METHODS: We included 878 686 individuals aged ≥60 years from the Korea National Health Insurance Service-Senior cohort. After excluding participants with preexisting MASLD, 329 388 individuals were finally analyzed. Participants were categorized into four groups based on the presence of overweight/obesity and additional risk factors (aRF) included in the cardiometabolic diagnostic criteria of MASLD. RESULTS: The overall incidence of MASLD was 1.94 per 100 person-years, and the incidence of advanced fibrosis in MASLD patients was 1.78 per 100 person-years. MASLD development was significantly higher in overweight/obese patients (2.65 per 100 person-years) compared to lean patients (1.09 per 100 person-years), and this trend persisted after stratification by the presence of aRF. Similarly, the incidence of advanced fibrosis among MASLD patients was higher in overweight/obese individuals (2.06 per 100 person-years) compared to lean counterparts (0.87 per 100 person-years), irrespective of aRF. CONCLUSIONS: The lower incidence of MASLD in the elderly population compared to the general population underscores the importance of identifying age-specific risk factors. Overweight/obesity emerged as a robust predictor of MASLD development and advanced fibrosis. Additionally, the presence of additional cardiometabolic risk factors further increased the risk of incident MASLD and advanced fibrosis among the elderly.

Pitfalls of a Multiplex PCR Panel for Identification of Bloodstream Pathogens.

BACKGROUND: We evaluated the diagnostic performance of the FilmArray Blood Culture Identification Panel (BCID; bioMerieux) for the detection of bloodstream pathogens. METHODS: From May to August 2022, up to 67 samples from positive blood cultures previously processed with BACTEC FX (BD) were collected and submitted to the BCID panel. BCID panel results were compared with traditional culture results. RESULTS: We tested 67 positive blood culture samples; 13 samples were from pediatric bottles of BACTEC Peds Plus/F media (BD). The overall sensitivity of the BCID panel was 89.9% (62/69; 95% CI, 80.2 - 95.3%). For blood-stream pathogens targeted by the BCID panel, sensitivity was 98.4% (62/63; 95% CI, 90.7 - > 99.9%). Interestingly, Proteus species were additionally detected in 6 samples from pediatric blood culture bottles. CONCLUSIONS: BCID demonstrated high clinical sensitivity for target pathogens, but positive findings for unexpected multiple targets or Proteus species require cautious interpretation to avoid false positives.

Clinical safety of remdesivir therapy in COVID-19 patients with renal insufficiency.

Though remdesivir benefits COVID-19 patients, its use in those with renal dysfunction is currently limited due to concerns about possible toxic effects of accumulated sulfobutylether-ß-cyclodextrin (SBECD) on liver and kidney. We examined renal and hepatic function for a month in renally-impaired COVID-19 patients who were treated or not treated with remdesivir to assess the safety of the drug. A retrospective study was performed in adult COVID-19 patients with glomerular filtration rates of <30 ml/min/1.73 m2 at admission to a tertiary care hospital between November 2020 and March 2022. Data on serum creatinine and liver chemistry were collected serially. A total of 101 patients with impaired renal function were analyzed, comprising 64 remdesivir-treated patients and 37 who did not receive any antiviral agent. Although remdesivir-treated patients were more likely to be infected with the Omicron variant (79.7% vs. 48.6%), baseline characteristics did not differ significantly between the two groups. Among patients who initially did not require dialysis, 18.4% (7/38) of remdesivir-treated patients developed acute kidney injury (AKI) at days 4-6, compared with 51.7% (15/29) of non-remdesivir-treated patients. Liver injury severity worsened in 3.1% (2/64) of remdesivir-treated patients and 5.4% (2/37) of non-remdesivir-treated patients at days 4-6. In addition, there was no significant increase in AKI and liver injury over time in remdesivir-treated patients, and there were no cases of discontinuation of remdesivir due to adverse reactions. Concerns regarding the safety of SBECD should not lead to hasty withholding of remdesivir treatment in renally-impaired COVID-19 patients.

Activated Leukocyte Cell Adhesion Molecule Regulates the Expression of Interleukin-33 in RSV Induced Airway Inflammation by Regulating MAPK Signaling Pathways.

PURPOSE: The respiratory syncytial virus (RSV) is a common respiratory virus that causes acute lower respiratory tract infectious diseases, particularly in young children and older individuals. Activated leukocyte cell adhesion molecule (ALCAM) is a membrane glycoprotein expressed in various cell types, including epithelial cells, and is associated with inflammatory responses and various cancers. However, the precise role of ALCAM in RSV-induced airway inflammation remains unclear, and our study aimed to explore this gap in the literature. METHODS: C57BL/6 wild-type, ALCAM knockout mice and airway epithelial cells were infected with RSV and the expression of ALCAM and inflammatory cytokines were measured. We also conducted further experiments using Anti-ALCAM antibody and recombinant ALCAM in airway epithelial cells. RESULTS: The expression levels of ALCAM and inflammatory cytokines increased in both RSV-infected mice and airway epithelial cells. Interestingly, IL-33 expression was significantly reduced in ALCAM-knockdown cells compared to control cells following RSV infection. Anti-ALCAM antibody treatment also reduced IL-33 expression following RSV infection. Furthermore, the phosphorylation of ERK1/2, p38, and JNK was diminished in ALCAM-knockdown cells compared to control cells following RSV infection. Notably, in the control cells, inhibition of these pathways significantly decreased the expression of IL-33. In vivo study also confirmed a reduction in inflammation induced by RSV infection in ALCAM deficient mice compared to wild-type mice. CONCLUSION: These findings demonstrate that ALCAM contributes to RSV-induced airway inflammation at least partly by influencing IL-33 expression through mitogen-activated protein kinase signaling pathways. These results suggest that targeting ALCAM could be a potential therapeutic strategy for alleviating IL-33-associated lung diseases.

Characterization of Ceftriaxone-Resistant Haemophilus influenzae Among Korean Children.

BACKGROUND: Haemophilus influenzae is a frequently encountered pathogen responsible for respiratory tract infections in children. Following the detection of ceftriaxone-resistant H. influenzae at our institution, we aimed to investigate the resistance mechanisms of ceftriaxone in H. influenzae, with a particular focus on alterations in penicillin-binding protein 3 (PBP3) and ß-lactamase production. METHODS: Among H. influenzae isolates collected at Asan Medical Center Children's Hospital from March 2014 to April 2019, ceftriaxone-resistant strains by the disk-diffusion test were included. Ceftriaxone minimum inhibitory concentrations (MICs) were determined using the E-test according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. The presence of ß-lactamase was assessed through cefinase test and TEM-1/ROB-1 polymerase chain reaction (PCR). PBP3 alterations were explored via ftsI gene sequencing. RESULTS: Out of the 68 collected strains, 21 exhibited resistance to ceftriaxone in disk diffusion tests. Two strains were excluded due to failed subculture. Among 19 ceftriaxone-resistant H. influenzae isolates, eighteen were non-typeable H. influenzae, and twelve were positive for TEM-1 PCR. Isolates were classified into groups II (harboring only N526K, n = 3), III (N526K+S385T, n = 2), III+ (S385T+L389F+N526K, n = 11), and III-like+ (S385T+L389F+R517H, n = 3) according to the PBP3 alteration pattern. With a median ceftriaxone MIC of 0.190 mg/L (range, 0.008-0.750), the median ceftriaxone MIC was the highest in group III-like+ (0.250 mg/L), followed by groups III+ (0.190 mg/L), III (0.158 mg/L), and II (0.012 mg/L). All three strains belonging to group II, which did not harbor the S385T substitution, had ceftriaxone MICs of ≤ 0.125 mg/L. CONCLUSION: The emergence of ceftriaxone-resistant H. influenzae with ceftriaxone MIC values of up to 0.75 mg/L was observed even in children in South Korea, with most associated with S385T and L389F substitutions. The N526K mutation alone does not significantly impact ceftriaxone resistance. Further large-scale studies are essential to investigate changes in antibiotic resistance patterns and factors influencing antibiotic resistance in H. influenzae isolated from pediatric patients in Korea.

Evolution of blaKPC Under the Pressure of Carbapenems and Ceftazidime/Avibactam in a Patient With Persistent Bacteremia Caused by Klebsiella pneumoniae.

A 30-year-old Korean man with myelodysplastic syndrome admitted hospital due to undifferentiated fever and recurrent skin lesions. He received combination therapy with high doses of meropenem, tigecycline and amikacin, yielding carbapenem resistant Klebsiella pneumoniae (CRKP) harboring K. pneumoniae carbapenemase (KPC)-2 from blood cultures on hospital day (HD) 23. Ceftazidime/avibactam was started at HD 37 and CRKP was eradicated from blood cultures after 5 days. However, ceftazidime/avibactam-resistant CRKP carrying KPC-44 emerged after 26 days of ceftazidime/avibactam treatment and then ceftazidime/avibactam-resistant, carbapenem-susceptible K. pneumoniae carrying KPC-135 was isolated on HD 65. The 3-D homology of KPC protein showed that hot spot changes in the omega loop could be attributed to ceftazidime/avibactam resistance and loss of carbapenem resistance. Whole genome sequencing of serial isolates supported that phenotypic variation was due to clonal evolution than clonal replacement. The treatment regimen was changed from CAZ/AVI to meropenem-based therapy (meropenem 1 g iv q 8 hours and amikacin 600 mg iv per day) starting with HD 72. CAZ/AVI-susceptible CRKP was presented again from blood cultures on HD 84, and the patient expired on HD 85. This is the first Korean report on the acquisition of ceftazidime/avibactam resistance through the emergence of blaKPC variants.

Diabetic MAFLD is associated with increased risk of hepatocellular carcinoma and mortality in chronic viral hepatitis patients.

Metabolic dysfunction-associated fatty liver disease (MAFLD) can coexist with chronic viral hepatitis. MAFLD is a heterogeneous disease because the diagnostic criteria include various metabolic traits. We aimed to identify patients at high risk of poor long-term outcomes based on MAFLD subgroups in chronic viral hepatitis patients. We evaluated 63 273 chronic hepatitis B and C patients. Patient with a fatty liver index ≥30 was defined to have hepatic steatosis. MAFLD was defined as the presence of hepatic steatosis with any one of the following three conditions, overweight/obesity, type 2 diabetes or ≥2 metabolic risk factors. The prevalence of MAFLD was 38.4% (n = 24 290). During a median 8.8-year follow-up, 1839 HCCs and 2258 deaths were documented in MAFLD patients. Among MAFLD patients, diabetes could identify patients at high risk of HCC and mortality, whereas overweight/obesity and metabolic risk factors did not. Compared with non-MAFLD patients, risk of HCC and mortality was significantly higher in diabetic MAFLD patients (adjusted hazard ratio [aHR] = 1.34, 95% confidence interval [CI] = 1.26-1.43 for HCC; aHR = 1.15, 95% CI = 1.08-1.22 for mortality). Risk of HCC and mortality was significantly higher in diabetic MAFLD patients (aHR = 1.40, 95% CI = 1.26-1.55 for HCC; aHR = 1.77, 95% CI = 1.63-1.93 for mortality) compared with non-diabetic MAFLD patients. Diabetic MAFLD is associated with increased risk of HCC and mortality among chronic viral hepatitis patients. Our findings highlight the need for close surveillance and effective treatment for these high-risk patients to reduce HCC and mortality in patients with chronic viral hepatitis.

Five-year on-treatment variables-based PPACS model predicts subsequent hepatocellular carcinoma in entecavir/tenofovir-treated patients.

Considering the lower risk of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients receiving long-term potent antiviral therapy, models predicting HCC after 5 years of therapy are needed. We conducted a multicenter retrospective cohort study to construct and validate a model predicting HCC after 5 years of entecavir (ETV) or tenofovir (TFV) therapy for CHB. The endpoint was HCC after 5 years of ETV/TFV therapy. Information on age, sex, liver cirrhosis (assessed by diagnosis code and confirmed by clinical findings) and type of antiviral agent was obtained at baseline (initiation of ETV/TFV). Laboratory values were collected at baseline and 5 years. Risk factors for HCC were identified in the training set and the final prediction model was validated using the test set. Among 7542 patients, 345 (4.6%) developed HCC after 5 years of ETV/TFV therapy. HCC risk after 5 years of ETV/TFV therapy was increased by 4-fold in patients with liver cirrhosis than in those without cirrhosis at baseline. Furthermore, Platelet counts and Prothrombin time at 5 years, Age at baseline and Sex were associated with risk of HCC and were incorporated into a prediction model, PPACS. PPACS showed a good performance with a time-dependent area under the curve of 0.80 (95% confidence interval, 0.75-0.85) at 8-year of ETV/TFV therapy, a Brier score of 0.031 and an integrated Brier score of 0.006 in the test set. In conclusion, the PPACS model provides a reliable assessment of HCC risk after 5 years of ETV/TFV therapy (https://ppacs.shinyapps.io/shiny_app_up/).