Two novel genes identified by large-scale transcriptomic analysis are essential for biofilm and rugose colony development of Vibrio vulnificus.

Many pathogenic bacteria form biofilms to survive under environmental stresses and host immune defenses. Differential expression (DE) analysis of the genes in biofilm and planktonic cells under a single condition, however, has limitations to identify the genes essential for biofilm formation. Independent component analysis (ICA), a machine learning algorithm, was adopted to comprehensively identify the biofilm genes of Vibrio vulnificus, a fulminating human pathogen, in this study. ICA analyzed the large-scale transcriptome data of V. vulnificus cells under various biofilm and planktonic conditions and then identified a total of 72 sets of independently co-regulated genes, iModulons. Among the three iModulons specifically activated in biofilm cells, BrpT-iModulon mainly consisted of known genes of the regulon of BrpT, a transcriptional regulator controlling biofilm formation of V. vulnificus. Interestingly, the BrpT-iModulon additionally contained two novel genes, VV1_3061 and VV2_1694, designated as cabH and brpN, respectively. cabH and brpN were shared in other Vibrio species and not yet identified by DE analyses. Genetic and biochemical analyses revealed that cabH and brpN are directly up-regulated by BrpT. The deletion of cabH and brpN impaired the robust biofilm and rugose colony formation. CabH, structurally similar to the previously known calcium-binding matrix protein CabA, was essential for attachment to the surface. BrpN, carrying an acyltransferase-3 domain as observed in BrpL, played an important role in exopolysaccharide production. Altogether, ICA identified two novel genes, cabH and brpN, which are regulated by BrpT and essential for the development of robust biofilms and rugose colonies of V. vulnificus.

Direct interhemispheric cortical communication via thalamic commissures: a new white matter pathway in the primate brain.

Cortical neurons of eutherian mammals project to the contralateral hemisphere, crossing the midline primarily via the corpus callosum and the anterior, posterior, and hippocampal commissures. We recently reported and named the thalamic commissures (TCs) as an additional interhemispheric axonal fiber pathway connecting the cortex to the contralateral thalamus in the rodent brain. Here, we demonstrate that TCs also exist in primates and characterize the connectivity of these pathways with high-resolution diffusion-weighted MRI, viral axonal tracing, and fMRI. We present evidence of TCs in both New World (Callithrix jacchus and Cebus apella) and Old World primates (Macaca mulatta). Further, like rodents, we show that the TCs in primates develop during the embryonic period, forming anatomical and functionally active connections of the cortex with the contralateral thalamus. We also searched for TCs in the human brain, showing their presence in humans with brain malformations, although we could not identify TCs in healthy subjects. These results pose the TCs as a vital fiber pathway in the primate brain, allowing for more robust interhemispheric connectivity and synchrony and serving as an alternative commissural route in developmental brain malformations.

Severe Human Parainfluenza Virus Community- and Healthcare-Acquired Pneumonia in Adults at Tertiary Hospital, Seoul, South Korea, 2010-2019.

The characteristics of severe human parainfluenza virus (HPIV)-associated pneumonia in adults have not been well evaluated. We investigated epidemiologic and clinical characteristics of 143 patients with severe HPIV-associated pneumonia during 2010-2019. HPIV was the most common cause (25.2%) of severe virus-associated hospital-acquired pneumonia and the third most common cause (15.7%) of severe virus-associated community-acquired pneumonia. Hematologic malignancy (35.0%), diabetes mellitus (23.8%), and structural lung disease (21.0%) were common underlying conditions. Co-infections occurred in 54.5% of patients admitted to an intensive care unit. The 90-day mortality rate for HPIV-associated pneumonia was comparable to that for severe influenza virus-associated pneumonia (55.2% vs. 48.4%; p = 0.22). Ribavirin treatment was not associated with lower mortality rates. Fungal co-infections were associated with 82.4% of deaths. Clinicians should consider the possibility of pathogenic co-infections in patients with HPIV-associated pneumonia. Contact precautions and environmental cleaning are crucial to prevent HPIV transmission in hospital settings.

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.

The origin of sequence type 72 community-associated methicillin-resistant Staphylococcus aureus (MRSA) and fusidic acid (FA) resistant sequence type 5 MRSA: Analysis of FA resistance and spa type in a single center in South Korea.

INTRODUCTION: We investigated the prevalence of fusidic acid (FA) resistance in MSSA and MRSA stratified by sequence (ST) and spa types, and determined the prevalence of FA resistance mechanisms. METHODS: From August 2014 to April 2020, S. aureus blood isolates were collected in Asan Medical Center, Seoul, South Korea. Antimicrobial susceptibility tests were performed using broth microdilution and interpreted according to EUCAST's FA criteria. We performed spa typing for fusA mutation presence and acquired FA resistance determinants (fusB, fusC, and fusD) by PCR. RESULTS: Of the 590 MRSA isolates, 372 were FA resistant, and among 425 MSSA isolates, 136 were resistant. Of the 380 ST5-MRSA isolates, 350 were FA resistant, whereas only 1 of 14 ST5-MSSA isolates was FA resistant. Conversely, of the 163 ST72-MRSA isolates, only 8 were resistant, whereas 37 of 42 ST72-MSSA were resistant. The fusA mutation (80%) was the most common determinant. The one FA resistant ST5-MSSA isolate belonged to the t2460 spa type, the most common spa type (24 of 35 isolates) of FA resistant ST5-MRSA. In addition, t324 and t148, which are minor spa types of ST72-MSSA, were susceptible to FA, in contrast to other ST72-MSSA spa types, and the major spa type of ST72-MRSA (110 of 163 isolates). CONCLUSIONS: FA resistance was common in ST5-MRSA and ST72-MSSA, and rare in ST5-MSSA and ST72-MRSA. Our findings suggest that minor clones of ST5-MSSA isolates, with the fusA mutation and minor clones of ST72-MSSA susceptible to FA, may have evolved to harbor the mecA gene.

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.

Pathogenic potential assessment of the Shiga toxin-producing Escherichia coli by a source attribution-considered machine learning model.

Instead of conventional serotyping and virulence gene combination methods, methods have been developed to evaluate the pathogenic potential of newly emerging pathogens. Among them, the machine learning (ML)-based method using whole-genome sequencing (WGS) data are getting attention because of the recent advances in ML algorithms and sequencing technologies. Here, we developed various ML models to predict the pathogenicity of Shiga toxin-producing Escherichia coli (STEC) isolates using their WGS data. The input dataset for the ML models was generated using distinct gene repertoires from positive (pathogenic) and negative (nonpathogenic) control groups in which each STEC isolate was designated based on the source attribution, the relative risk potential of the isolation sources. Among the various ML models examined, a model using the support vector machine (SVM) algorithm, the SVM model, discriminated between the two control groups most accurately. The SVM model successfully predicted the pathogenicity of the isolates from the major sources of STEC outbreaks, the isolates with the history of outbreaks, and the isolates that cannot be assessed by conventional methods. Furthermore, the SVM model effectively differentiated the pathogenic potentials of the isolates at a finer resolution. Permutation importance analyses of the input dataset further revealed the genes important for the estimation, proposing the genes potentially essential for the pathogenicity of STEC. Altogether, these results suggest that the SVM model is a more reliable and broadly applicable method to evaluate the pathogenic potential of STEC isolates compared with conventional methods.

Comparative Analysis of CT Findings and Clinical Outcomes in Adult Patients With Disseminated and Localized Pulmonary Nocardiosis.

BACKGROUND: Pulmonary nocardiosis is a rare opportunistic infection with occasional systemic dissemination. This study aimed to investigate the computed tomography (CT) findings and prognosis of pulmonary nocardiosis associated with dissemination. METHODS: We conducted a retrospective analysis of patients diagnosed with pulmonary nocardiosis between March 2001 and September 2023. We reviewed the chest CT findings and categorized them based on the dominant CT findings as consolidation, nodules and/or masses, consolidation with multiple nodules, and nodular bronchiectasis. We compared chest CT findings between localized and disseminated pulmonary nocardiosis and identified significant prognostic factors associated with 12-month mortality using multivariate Cox regression analysis. RESULTS: Pulmonary nocardiosis was diagnosed in 75 patients, of whom 14 (18.7%) had dissemination, including involvement of the brain in 9 (64.3%) cases, soft tissue in 3 (21.4%) cases and positive blood cultures in 3 (21.4%) cases. Disseminated pulmonary nocardiosis showed a higher frequency of cavitation (64.3% vs. 32.8%, P = 0.029) and pleural effusion (64.3% vs. 29.5%, P = 0.014) compared to localized infection. The 12-month mortality rate was 25.3%. The presence of dissemination was not a significant prognostic factor (hazard ratio [HR], 0.80; confidence interval [CI], 0.23-2.75; P = 0.724). Malignancy (HR, 9.73; CI, 2.32-40.72; P = 0.002), use of steroid medication (HR, 3.72; CI, 1.33-10.38; P = 0.012), and a CT pattern of consolidation with multiple nodules (HR, 4.99; CI, 1.41-17.70; P = 0.013) were associated with higher mortality rates. CONCLUSION: Pulmonary nocardiosis with dissemination showed more frequent cavitation and pleural effusion compared to cases without dissemination, but dissemination alone did not affect the mortality rate of pulmonary nocardiosis.

Comparison of the Clinical Outcomes Between Early and Delayed Transplantation After SARS-CoV-2 Infection.

Our study analyzed 95 solid organ transplant (SOT) and 78 hematopoietic stem cell transplant (HSCT) recipients with prior coronavirus disease 2019 (COVID-19). Patients who underwent transplantation within 30 days of COVID-19 infection comprised the early group, and those who underwent transplantation post-30 days of COVID-19 infection comprised the delayed group. In the early transplantation group, no patient, whether undergoing SOT and HSCT, experienced COVID-19-associated complications. In the delayed transplantation group, one patient each from SOT and HSCT experienced COVID-19-associated complications. Additionally, among early SOT and HSCT recipients, two and six patients underwent transplantation within seven days of COVID-19 diagnosis, respectively. However, no significant differences were observed in the clinical outcomes of these patients compared to those in other patients. Early transplantation following severe acute respiratory syndrome coronavirus 2 infection can be performed without increased risk of COVID-19-associated complications. Therefore, transplantation needs not be delayed by COVID-19 infection.

Early molecular events of autosomal-dominant Alzheimer's disease in marmosets with PSEN1 mutations.

INTRODUCTION: Fundamental questions remain about the key mechanisms that initiate Alzheimer's disease (AD) and the factors that promote its progression. Here we report the successful generation of the first genetically engineered marmosets that carry knock-in (KI) point mutations in the presenilin 1 (PSEN1) gene that can be studied from birth throughout lifespan. METHODS: CRISPR/Cas9 was used to generate marmosets with C410Y or A426P point mutations in PSEN1. Founders and their germline offspring are comprehensively studied longitudinally using non-invasive measures including behavior, biomarkers, neuroimaging, and multiomics signatures. RESULTS: Prior to adulthood, increases in plasma amyloid beta were observed in PSEN1 mutation carriers relative to non-carriers. Analysis of brain revealed alterations in several enzyme-substrate interactions within the gamma secretase complex prior to adulthood. DISCUSSION: Marmosets carrying KI point mutations in PSEN1 provide the opportunity to study the earliest primate-specific mechanisms that contribute to the molecular and cellular root causes of AD onset and progression. HIGHLIGHTS: We report the successful generation of genetically engineered marmosets harboring knock-in point mutations in the PSEN1 gene. PSEN1 marmosets and their germline offspring recapitulate the early emergence of AD-related biomarkers. Studies as early in life as possible in PSEN1 marmosets will enable the identification of primate-specific mechanisms that drive disease progression.

Efficacy of Doxycycline for Mild-to-Moderate Community-Acquired Pneumonia in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Doxycycline has been recommended as a treatment option for non-severe community-acquired pneumonia (CAP) in adults. We sought to review the evidence for the efficacy of doxycycline in adult patients with mild-to-moderate CAP. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) of doxycycline versus comparator to assess the clinical efficacy. The primary outcome was the clinical cure rate. Random effects model meta-analyses were used to generate pooled odds ratio (OR) and evaluate heterogeneity (I2). Risk of bias (RoB) and quality of evidence (QoE) were evaluated using the Cochrane Risk of Bias 2.0 tool and GRADE methods, respectively. RESULTS: We included 6 RCTs with 834 clinically evaluable patients. The trials were performed between 1984 and 2004. Comparators were 3 macrolides (roxithromycin, spiramycin, and erythromycin) and 3 fluoroquinolones (ofloxacin, fleroxacin, and levofloxacin). Four trials had an overall high RoB. The clinical cure rate was similar between the doxycycline and comparator groups (87.2% [381/437] vs 82.6% [328/397]; OR 1.29 [95% confidence interval {CI}: .73-2.28]; I2 = 30%; low QoE). Subgroup analysis of two studies with a low RoB showed significantly higher clinical cure rates in the doxycyline group (87.1% [196/225] vs 77.8% [165/212]; OR 1.92 [95% CI: 1.15-3.21]; P = .01; I2 = 0%). Adverse event rates were comparable between the doxycycline and comparator groups. CONCLUSIONS: The efficacy of doxycycline was comparable to macrolides or fluoroquinolones in mild-to-moderate CAP and thus represents a viable treatment option. Considering the lack of recent trials, it warrants large-scale clinical trials.

Routine ophthalmologic examination in Klebsiella pneumoniae bacteremia is not necessary: incidence of and risk factors for ocular involvement.

Klebsiella pneumoniae bacteremia is known to present a virulent clinical course, including multiple metastatic infections, which is not uncommon in Asia. However, there are limited data on the incidence and risk factors for ocular involvement in K. pneumoniae bacteremia. We retrospectively reviewed the medical records of all patients with K. pneumoniae bacteremia who underwent ophthalmologic examination in a tertiary center in Seoul, Korea, from February 2012 to December 2020. Two retinal specialists reviewed the findings of the ophthalmologic examinations and classified them as endophthalmitis, chorioretinitis, and no ocular involvement. Of 689 patients, 56 [8.1%; 95% confidence interval (CI) 6.2-10.4] had ocular involvement, and 9 (1.3%; 95% CI 0.6-2.5) were diagnosed with endophthalmitis. Of 47 patients with chorioretinitis, 45 (95.7%) improved with systemic antibiotic therapy alone. Community-onset bacteremia (100% vs 62.1% vs 57.4%, P = 0.04), cryptogenic liver abscess (55.6% vs 11.8% vs 8.5%, P = 0.003), and metastatic infection (66.7% vs 5.8% vs 10.6%, P < 0.001) were more common in endophthalmitis than in no ocular involvement or chorioretinitis. In the multivariable analysis, cryptogenic liver abscess [adjusted odds ratio (aOR), 6.63; 95% CI 1.44-35.20] and metastatic infection (aOR, 17.52; 95% CI 3.69-96.93) were independent risk factors for endophthalmitis. Endophthalmitis was not associated with 30-day mortality. Endophthalmitis is rare in Asian patients with K. pneumoniae bacteremia. Targeted ophthalmologic examination in those with cryptogenic liver abscess, metastatic infection, or ocular symptoms may be more appropriate than routine examination of all patients.

Clinical and microbiological characteristics of rifampicin-resistant MRSA bacteraemia.

OBJECTIVES: The clinical significance of rifampicin resistance in Staphylococcus aureus infections has not been demonstrated. Here, we evaluated the clinical characteristics of rifampicin-resistant S. aureus infection. METHODS: Data were collected from adult patients who were hospitalized with MRSA bacteraemia between March 2007 and May 2020 at a tertiary hospital in South Korea. The clinical characteristics and treatment outcomes of patients infected with rifampicin-resistant MRSA were compared with those of rifampicin-susceptible isolates. All-cause death and recurrence of MRSA infection were assessed for 90 days. RESULTS: Of the 961 patients with MRSA bacteraemia, 61 (6.3%) were infected by rifampicin-resistant isolates. The type of infection focus and duration of bacteraemia did not significantly differ between the two groups. Rifampicin-resistant MRSA isolates were more likely to have multidrug resistance and a higher vancomycin MIC relative to the rifampicin-susceptible isolates. The 90-day recurrence rate was higher in the patients infected with rifampicin-resistant MRSA compared with those with rifampicin-susceptible MRSA (18.0% versus 6.2%, P < 0.001), whereas the 90-day mortality was comparable between the two groups (27.9% versus 29.2%, P = 0.94). After adjusting for potential confounding factors, rifampicin resistance was significantly associated with 90-day recurrence (subdistributional HR: 2.31; 95% CI: 1.05-5.10; P = 0.04). CONCLUSIONS: Rifampicin-resistant MRSA isolates showed distinct microbiological features in terms of multidrug resistance and a high vancomycin MIC. Although the management of MRSA bacteraemia was not significantly different between the two groups, recurrence was significantly more common in the rifampicin-resistant group. Rifampicin resistance may play a significant role in infection recurrence.

Comparison of secondary attack rate and viable virus shedding between patients with SARS-CoV-2 Delta and Omicron variants: A prospective cohort study.

There are limited data comparing the transmission rates and kinetics of viable virus shedding of the Omicron variant to those of the Delta variant. We compared these rates in hospitalized patients infected with Delta and Omicron variants. We prospectively enrolled adult patients with COVID-19 admitted to a tertiary care hospital in South Korea between September 2021 and May 2022. Secondary attack rates were calculated by epidemiologic investigation, and daily saliva samples were collected to evaluate viral shedding kinetics. Genomic and subgenomic SARS-CoV-2 RNA was measured by PCR, and virus culture was performed from daily saliva samples. A total of 88 patients with COVID-19 who agreed to daily sampling and were interviewed, were included. Of the 88 patients, 48 (59%) were infected with Delta, and 34 (41%) with Omicron; a further 5 patients gave undetectable or inconclusive RNA PCR results and 1 was suspected of being coinfected with both variants. Omicron group had a higher secondary attack rate (31% [38/124] vs. 7% [34/456], p < 0.001). Survival analysis revealed that shorter viable virus shedding period was observed in Omicron variant compared with Delta variant (median 4, IQR [1-7], vs. 8.5 days, IQR [5-12 days], p < 0.001). Multivariable analysis revealed that moderate-to-critical disease severity (HR: 1.96), and immunocompromised status (HR: 2.17) were independent predictors of prolonged viral shedding, whereas completion of initial vaccine series or first booster-vaccinated status (HR: 0.49), and Omicron infection (HR: 0.44) were independently associated with shorter viable virus shedding. Patients with Omicron infections had higher transmission rates but shorter periods of transmissible virus shedding than those with Delta infections.

Clinical significance and outcomes of Clostridium tertium bacteremia: analysis of 62 cases in neutropenic and non-neutropenic patients.

The clinical significance of Clostridium tertium bacteremia is still uncertain. We evaluated the incidence, clinical characteristics, and outcomes of C. tertium bacteremia and identified differences between neutropenia and non-neutropenia. All adult patients with C. tertium bacteremia in a 2700-bed tertiary center between January 2004 and November 2021 were retrospectively enrolled. The first episode of C. tertium bacteremia in each patient was included in the analysis. Among 601 patients with Clostridium species bacteremia, 62 (10%) had C. tertium bacteremia, and of these 62 patients, 39 (63%) had had recent chemotherapy, and 31 (50%) had neutropenia or hematologic malignancy. C. tertium bacteremia originated frequently from a gastrointestinal tract infection such as enterocolitis (34%), primary bacteremia (29%), and secondary peritonitis (18%), and 34% of patients had polymicrobial bacteremia. Hematologic malignancy, prior antibiotic treatment, neutropenic enterocolitis, and primary bacteremia were significantly associated with C. tertium bacteremia in neutropenic patients, whereas solid tumor, hepatobiliary disease, secondary peritonitis, polymicrobial bacteremia, and a higher frequency of eradicable infection foci were significantly associated with C. tertium bacteremia in non-neutropenic patients. There was 15% 30-day mortality. APACHE II score (adjusted odds ratio [aOR], 1.5; 95% confidence interval [CI], 1.1-2.1) and secondary peritonitis (aOR, 25.9; 95% CI, 3.0-224.7) were independent risk factors for 30-day mortality. The prevalence of C. tertium bacteremia is low, and the characteristics of C. tertium bacteremia are significantly different between neutropenic and non-neutropenic patients. Appropriate investigation for gastrointestinal mucosal injury should be performed to improve treatment outcomes in this form of bacteremia.

Clinical impact of metformin exposure during Staphylococcus aureus bacteremia in patients with diabetes mellitus.

PURPOSE: Increasing evidence has suggested that metformin may play positive roles in a wide range of infectious diseases. This study aimed to investigate the clinical impact of metformin exposure during Staphylococcus aureus bacteremia (SAB) in patients with diabetes. METHODS: A 3-year observational cohort study of 452 patients (aged ≥ 16 years) with SAB was performed at a tertiary care hospital. Metformin exposure was defined as receiving metformin during SAB, regardless of metformin use before the onset of bacteremia. RESULTS: Of 452 patients, 51 (11.3%) were classified in Group A (diabetes with metformin exposure), 115 (25.4%) in Group B (diabetes without metformin exposure), and 286 (63.3%) in Group C (no diabetes). The 30-day mortality rate in Group A was significantly lower than that in Group B (3.9% [2/51] versus 14.8% [17/115]; p = 0.04) and lower than that in Group C (3.9% [2/51] versus 17.1% [49/286]; p = 0.02). The mortality rates did not differ between Group B and Group C (14.8% [17/115] versus 17.1% [49/286]; p = 0.57). The rates of persistent and recurrent bacteremia were comparable among the three groups. Multivariate analysis indicated that metformin exposure was significantly associated with reduced mortality (adjusted odds ratio, 0.20; 95% confidence interval, 0.04-0.88; p = 0.03). CONCLUSIONS: Metformin exposure during SAB appears to be an independent predictor of survival in patients with diabetes.

False positive Aspergillus galactomannan assay results caused by specific parenteral nutrition.

In September 2022, the proportion of clinically false positive results with high index values for the galactomannan (GM) assay increased dramatically in our hospital and remained high until November 2022. We aimed to identify the possible causative agent that led to the dramatic increase in false positivity in GM assay. A case-control-control study was conducted, and patients admitted to two intensive care units between September and November 2022 were included. We defined each time point at which the GM assay was conducted in a patient as an episode and classified episodes into strong-positive (≥10.0 index; case), positive (control), and negative (<0.5 index; control) groups. We compared the medications administered in three groups and measured GM levels in relevant medications, including parenteral nutrition (PN). In total, 118 episodes in 33 patients were classified into three groups. There were 46 negative, 23 positive, and 49 strong-positive episodes, and there was a significant difference in the use of Winuf® PNs (P < .001) between the three groups. Forty episodes (82%) in the strong-positive group received Winuf®, compared with three (6.5%) in the negative group and one (4.3%) in the positive group (P < .001). All samples of Winuf® PNs used in the five patients whose GM results were repeatedly strong-positive were strongly positive for GM. False positivity in GM assay can be caused by the administration of specific PNs. A thorough investigation of prescribed medications should be considered when there is an abrupt increase in the proportion of strong-positive or positive GM results.

Clinical characteristics and outcomes of invasive and non-invasive fusariosis in South Korea.

BACKGROUND: Invasive fusariosis mainly affects immunocompromised patients including haematopoietic stem cell transplant recipients and those with haematologic malignancy. There are limited studies on invasive fusariosis in the Asia-Pacific region. OBJECTIVE: To describe the clinical characteristics and outcomes of invasive and non-invasive fusariosis in South Korea. PATIENTS/METHODS: From 2005 to 2020, patients with fusariosis who met the revised European Organisation for Research and Treatment of Cancer and the Mycoses Study Group criteria for the definition of proven or probable invasive fusariosis, and those with non-invasive fusariosis were retrospectively reviewed in a tertiary medical centre in Seoul, South Korea. RESULTS: Overall, 26 and 75 patients had invasive and non-invasive fusariosis, respectively. Patients with invasive fusariosis commonly had haematologic malignancy (62%), were solid organ transplant recipients (23%), and had a history of immunosuppressant usage (81%). In non-invasive fusariosis, diabetes mellitus (27%) and solid cancer (20%) were common underlying conditions. Disseminated fusariosis (54%) and invasive pulmonary disease (23%) were the most common clinical manifestations of invasive fusariosis; skin infection (48%) and keratitis (27%) were the most common manifestations of non-invasive fusariosis. Twenty-eight-day and in-hospital mortalities were high in invasive fusariosis (40% and 52%, respectively). In multivariate analysis, invasive fusariosis (adjusted odds ratio, 9.6; 95% confidence interval 1.3-70.8; p = .03) was an independent risk factor for 28-day mortality. CONCLUSIONS: Patients with invasive fusariosis were frequently immunocompromised, and more than half had disseminated fusariosis. Invasive fusariosis was associated with poor prognosis.

The relationship between organising pneumonia and invasive mould disease in patients with haematologic malignancy.

BACKGROUND: Organising pneumonia (OP) is reported in patients with haematologic malignancy suspected of having invasive mould disease, yet little is known about this relationship. OBJECTIVE: To investigate molecular evidence of invasive mould pneumonia in paraffin-embedded lung tissues from histologically diagnosed OP patients with suspected invasive mould pneumonia. PATIENTS/METHODS: Patients with haematologic malignancy suspected to have invasive pulmonary mould disease who underwent lung biopsy at a tertiary hospital, Seoul, South Korea, between 2008 and 2020, were retrospectively reviewed. To find molecular evidence of fungal infection, PCR assay was used to detect Aspergillus- and Mucorales-specific DNA within OP lung tissue sections. RESULTS: Forty-seven patients with suspected invasive mould pneumonia underwent lung biopsy and 15 (32%) were histologically diagnosed as OP without any evidence of fungal hyphae. Of these 15 patients, 3 (20%) received allogenic haematopoietic stem cell transplantation prior to developing OP. Before biopsy, 2 and 13 patients had probably and possible invasive mould disease, respectively. The median antifungal treatment length was 81 [8-114] days, and the median steroid treatment dosage was 0.35 mg/kg/day for 36 days (methylprednisolone equivalent doses), respectively. After biopsy, three patients with possible invasive mould infection revealed probable invasive pulmonary aspergillosis. From the 15 paraffin-embedded lung tissues, 6 (40%) exhibited positive PCR assay results for detecting Aspergillus- and Mucorales-specific DNA. CONCLUSIONS: More than one third of OP cases in patients with suspected invasive mould pneumonia exhibited molecular evidence of invasive mould infection by fungus-specific PCR in lung tissues, likely associated with concurrent or prior fungal infection.

Bacterial Co-Infection and Empirical Antibacterial Therapy in Patients With COVID-19.

BACKGROUND: The rate and composition of bacterial co-infection in patients with coronavirus disease 2019 (COVID-19) were evaluated when microbiological testing was conducted on the majority of patients. We also evaluated whether the use of empirical antibacterials was associated with mortality. METHODS: In this retrospective study, all of the adult patients with COVID-19 hospitalized in a single tertiary hospital in South Korea between February 2020 and December 2021 were included. Bacterial co-infection was assessed by sputum cultures, blood cultures, and molecular testing, including polymerase chain reaction sputum testing and urinary antigen tests. Mortality was compared between patients who received empirical antibacterials and those who did not. RESULTS: Of the 367 adult patients admitted during the study period, 300 (81.7%) had sputum culture results and were included in the analysis. Of these 300 patients, 127 (42.3%) had a history of antibiotic exposure. The co-infection rate within 48 hours was 8.3% (25/300): 6.4% (11/173) of patients without prior antibiotic exposure and 11% (14/127) of patients with prior antibacterial exposure. The co-infected bacteria were different according to antibacterial exposure before admission, and multi-drug resistant pathogens were detected exclusively in the antibacterial exposed group. Among the patients without positive results for the microbiological tests, empirical antibacterials were used in 33.3% of cases (100/300). Empirical antibacterial therapy was not significantly related to the 30-day mortality or in-hospital mortality rates in the study cohort before or after the propensity score-matching. CONCLUSION: In this study including only patients underwent microbiological testing, bacterial co-infection was not frequent, and the co-infected organisms varied depending on previous antibacterial exposures. Given the rarity of co-infection and the lack of potential benefits, empiric antibacterial use in COVID-19 should be an important target of antibiotic stewardship.