Unfortunately, the options for treating multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) infections are extremely limited. Recently, fosfomycin and minocycline were newly introduced ...as a treatment option for MDR A. baumannii infection. Therefore, we investigated the efficacy of the combination of colistin with fosfomycin and minocycline, respectively, as therapeutic options in MDR A. baumannii pneumonia. We examined a carbapenem-resistant A. baumannii isolated from clinical specimens at Severance Hospital, Seoul, Korea. The effect of colistin with fosfomycin, and colistin with minocycline on the bacterial counts in lung tissue was investigated in a mouse model of pneumonia caused by MDR A. baumannii. In vivo, colistin with fosfomycin or minocycline significantly (p < 0.05) reduced the bacterial load in the lungs compared with the controls at 24 and 48 h. In the combination groups, the bacterial loads differed significantly (p < 0.05) from that with the more active antimicrobial alone. Moreover, the combination regimens of colistin with fosfomycin and colistin with minocycline showed bactericidal and synergistic effects compared with the more active antimicrobial alone at 24 and 48 h. This study demonstrated the synergistic effects of combination regimens of colistin with fosfomycin and minocycline, respectively, as therapeutic options in pneumonia caused by MDR A. baumannii.
Developing new antibody assays for emerging SARS‐CoV‐2 variants is challenging. SARS‐CoV‐2 surrogate virus neutralization tests (sVNT) targeting Omicron BA.1 and BA.5 have been devised, but their ...performance needs to be validated in comparison with quantitative immunoassays. First, using 1749 PRNT‐positive sera, we noticed that log‐transformed optical density (OD) ratio of wild‐type (WT) sVNT exhibited better titer‐correlation with plaque reduction neutralization test (PRNT) than % inhibition value. Second, we tried 798 dilutional titration tests with 103 sera, but nonlinear correlation between OD ratio and antibody concentration limited titration of sVNT. Third, the titer‐correlations of two sVNT kits for BA.1 and two quantitative immunoassays for WT were evaluated with BA.1 and BA.5 PRNT. All tested kits exhibited a linear correlation with PRNT titers, but the sVNT kits exhibited high false‐negative rates (cPass‐BA.1 kit, 45.4% for BA.1 and 44.2% for BA.5; STANDARD F‐BA.1 kit, 1.9% for BA.1 and 2.2% for BA.5), while quantitative immunoassays showed 100% sensitivity. Linear mixed‐effects model suggested superior titer‐correlation with PRNT for quantitative immunoassays compared to sVNT kits. Taken together, the use of quantitative immunoassays for WT, rather than rapid development of new kits, would be practical for predicting neutralizing activities against emerging new variants.
Stenotrophomonas maltophilia is an important nosocomial pathogen. This pathogen has intrinsic or acquired resistance to a number of antibiotics classes. Furthermore, Stenotrophomonas infections have ...been associated with high mortality, mainly in immunocompromised patients. Accordingly, we conducted a retrospective cohort study on the clinical data, microbiological characteristics, and outcomes of patients with S. maltophilia (SM) bacteremia.
A retrospective cohort study was conducted at two tertiary care referral hospitals in Seoul, South Korea. Data were collected between January 2006 and December 2015 from electric medical records. Our analysis aimed to identify the risk factors associated with crude mortality, as well as the predictive factors of quinolone-resistant strains in SM bacteremia patients.
A total of 126 bacteremia patients were enrolled in the study. The mortality rate was 65.1%. On multivariable analysis, hypoalbuminemia (odds ratio OR, 5.090; 95% confidence interval CI, 1.321-19.621; P = 0.018), hematologic malignancy (OR, 35.567; 95% CI, 2.517-502.515; P = 0.008) and quinolone-resistant strains (OR, 7.785; 95% CI, 1.278-47.432; P = 0.026) were independent risk factors for mortality. Alternatively, usage of an empirical regimen with quinolone (OR, 0.172; 95% CI, 0.034-0.875; P = 0.034) was an independent protective factor for mortality. The multivariable analysis of predictive factors revealed that high Charlson comorbidity index (OR, 1.190; 95% CI, 1.040-1.361; P = 0.011) and indwelling of a central venous catheter (CVC) (OR, 3.303; 95% CI, 1.194-9.139; P = 0.021) were independent predisposing factors associated with quinolone-resistant strains in SM bacteremia patients.
Our findings suggest that a high Charlson comorbidity score and indwelling of a CVC were significantly independent predictors of quinolone-resistant strains in SM bacteremia patients. Therefore, we need to carefully consider the antibiotic use in SM bacteremia patients with these predictive factors.
Abstract
Extracorporeal membrane oxygenation (ECMO) provides hemodynamic and oxygenation support to critically ill patients. Due to multiple catheter cannulations, patients on ECMO are vulnerable to ...bloodstream infections (BSIs). We aimed to investigate the incidence, clinical characteristics, risk factors, and microorganisms associated with BSIs during ECMO. This single-center retrospective cohort study was conducted between January 2015 and May 2021. Patients aged 18 years or older with an ECMO duration of > 48 h for cardiogenic or respiratory support were included in the study. Patients who developed bacteremia or candidemia from 12 h after ECMO cannulation to 7 days after de-cannulation were included. The clinical factors between non-BSI and BSI were compared, along with an analysis of the risk factors associated with BSI during ECMO. A total of 480 patients underwent ECMO for cardiogenic shock (n = 267, 55.6%) or respiratory failure (n = 213, 44.4%) during the study period. The incidence was 20.0 episodes per 1000 ECMO-days. Approximately 20.2% (97/480) and 5.4% (26/480) of the patients developed bacteremia and candidemia, respectively. The median numbers of days of BSI development were 8.00 days for bacteremia and 11.0 days for candidemia. The most common pathogens were methicillin-resistant coagulase-negative staphylococci (n = 24), followed by vancomycin-resistant
Enterococcus
(n = 21). Multivariable logistic analysis demonstrated that hemodialysis (odds ratio OR 2.647, p < 0.001), veno-arterial-venous mode (OR 1.911, p = 0.030), and total ECMO duration (OR 1.030, p = 0.007) were significant risk factors for bacteremia. The total ECMO duration was the only risk factor associated with candidemia (OR 1.035, p = 0.010). The mortality rate was significantly higher in the bacteremia (57.7%) and candidemia (69.2%) groups than that in the non-BSI group (43.6%). BSI is a common complication of patients receiving ECMO support and is associated with poor clinical outcomes. Determining the type of frequently isolated organisms and the median onset time of BSI would help in the selection of appropriate prophylactic antibiotics or antifungal agents.
Progressive multifocal leukoencephalopathy (PML) is a rare but fatal opportunistic infection and mainly occurs in patients with immunosuppressive conditions. Despite the increasing number of patients ...receiving immunosuppressive treatments, studies on PML are still lacking due to its low prevalence and incidence. We retrospectively reviewed patients diagnosed with PML in two tertiary hospitals in South Korea from 1999 to 2021. Total of 47 PML patients were included. Of 27 patients (57.4%) were diagnosed with human immunodeficiency virus (HIV). Median last follow-up modified Rankin Scale (mRS) score was higher in the non-HIV PML group than that in the HIV group (5 vs. 4, p = 0.020). Median survival duration was lower in the non-HIV group (184 vs. 1,564 days). The 1-year and overall mortality rates of PML patients were significantly higher in the non-HIV group than that in HIV group (60.0% vs. 25.9%, p = 0.019; 80.0% vs. 40.7%, p = 0.007). Initial mRS score (HR 1.685, p = 0.038) and highly active antiretroviral therapy (HAART) in HIV patients (HR 0.374, p = 0.013) had a significant effect on overall mortality. Our findings suggest that early detection of PML with low mRS score and early initiation of HAART in patients with HIV may improve prognosis.
Background Brain abscess can be life-threatening and manifest various neurological findings, although the mortality rate has decreased recently. We investigated the risk factors for unfavorable ...outcomes of patients with brain abscess. Methods A retrospective cohort study examined patients with brain abscess seen from May 2005 to December 2018 in a tertiary care hospital in Seoul, South Korea. We reviewed the medical records for clinical findings, therapeutic modalities, and prognostic factors of brain abscess. Unfavorable clinical outcomes were defined as death, moderate to severe disability with neurological deficits, or vegetative state at 1 year or at the time of discharge from outpatient follow-up. Results The study enrolled 135 patients: 65.2% were males; the mean age was 56 years. 35.6% had unfavorable outcomes. In multivariate analysis, higher Sequential Organ Failure Assessment (SOFA) (p < 0.001), pre-existing hemiplegia (p = 0.049), and higher Charlson comorbidity index (CCI) (p = 0.028) were independently associated with unfavorable outcomes. Conclusions Higher SOFA, pre-existing hemiplegia and higher Charlson comorbidity index were significant risk factors for unfavorable clinical outcomes in patients with brain abscess.
Spinal tuberculosis (TB) remains an important concern. Although spinal TB often has sequelae such as myelopathy after treatment, the predictive factors affecting such unfavourable outcomes are not ...yet established. We investigated the clinical manifestations and predictors of unfavourable treatment outcomes in patients with spinal TB.
We performed a multicentre retrospective cohort study of patients with spinal TB. Unfavourable outcome was defined according to previous studies. The prognostic factors for unfavourable outcomes as the primary outcome were determined using multivariable logistic regression analysis and a linear mixed model was used to compare time course of inflammatory markers during treatment. A total of 185 patients were included, of whom 59 patients had unfavourable outcomes.
In multivariate regression analysis, the factors associated with unfavourable outcome were old age (odds ratio (OR) 2.51; 95% confidence interval (CI) 1.07 to 5.86; p = 0.034), acid-fast bacilli (AFB) smear positivity in specimens obtained through biopsy (OR 3.05; 95% CI 1.06 to 8.80; p = 0.039), and elevated erythrocyte sedimentation rate (ESR) at the end of treatment (OR 3.85; 95% CI 1.62 to 9.13; p = 0.002). Patients with unfavourable outcomes had a significant trend toward higher ESR during treatment compared with patients with favourable outcome (p = 0.009). Duration of anti-TB and surgical treatment did not affect prognosis.
Elevated ESR at the end of treatment could be used as a marker to identify spinal TB patients with a poor prognosis. Patients whose ESR is not normalized during treatment, as well as those with old age and AFB smear positivity, should be aware of unfavourable outcomes. Cite this article:
2019;101-B:1542-1549.
Recent studies disputed the effectiveness of efforts to comply with contact precautions and isolation (CPI) considering relatively low intra-hospital transmission rate of healthcare ...facility-associated Clostridioides difficile infection (HCFA-CDI). We evaluated the potential causal effect of CPI on HCFA-CDI occurrence by comparing the incidence rate (IR) for different time periods with and without CPI implementation.
Long-term observational time-series data were separated into three periods (pre-CPI: January 2012–March 2016, CPI: April 2016–April 2021, post-CPI: May 2021–December 2022). CPI was suspended owing to the restriction of isolation rooms during the COVID-19 pandemic. We inferred potential causal outcomes by comparing predicted and observed IRs of HCFA-CDI using interrupted time-series analyses, including the Bayesian structural time-series or autoregressive integrated moving average (ARIMA) model in the R-language or SAS software.
The monthly observed IR (44.9/100,000 inpatient-days) during the CPI period was significantly lower than the predicted IR (90.8) (−50.6% relative effect, P = 0.001). However, the observed IR (52.3) during the post-CPI period was significantly higher than the predicted IR (39.1) (33.6%, P = 0.001). The HCFA-CDI IR decreased during CPI (−14.3, P < 0.001) and increased post-CPI (5.4, P < 0.001) in the multivariable ARIMA model, which controlled for antibiotic usage, handwashing with soap and water, and number of toxin tests.
Various time-series models revealed that CPI implementation had a potential causal effect on the reduction of HCFA-CDI incidence.
Background
Despite medical advances, septic shock remains one of the main causes of high mortality in critically ill patients. Although sarcopenia is considered a predictor of mortality in septic ...shock patients, most studies have only investigated short‐term mortality, and those on long‐term prognosis are limited. We investigated the impact of sarcopenia on long‐term mortality in a large patient population with septic shock.
Methods
A retrospective cohort study comprising 905 patients with septic shock was conducted from 2008 to 2019. Sarcopenia was defined based on the measurement of the total abdominal muscle area, assessed using abdominal computed tomography scans. Thereafter, we stratified the patients into two groups—sarcopenia and non‐sarcopenia groups—and compared the impact of sarcopenia on short‐term (28 days) and long‐term (1 year and overall) mortality using multivariable Cox proportional analysis.
Results
A total of 905 patients were included, and the mean age was 65.7 ± 15.1 years. Among them, 430 (47.5%) patients were male and 407 (45.0%) had sarcopenia. We found that the 28 day, 1 year, and overall mortality rates in the sarcopenia group were significantly higher than those in the non‐sarcopenia group (13.8% vs. 6.4%, P < 0.001; 41.8% vs. 21.7%, P < 0.001; 62.2% vs. 35.7%, P < 0.001, respectively). Univariable Cox analysis showed that the sarcopenia group had a significant association with the increase in each mortalities compared with the non‐sarcopenia group (28 day mortality, hazard ratio (HR) = 2.230, 95% confidence interval (CI) 1.444–3.442, P < 0.001; 1 year mortality, HR = 2.189, 95% CI 1.720, 2.787, P < 0.001; overall mortality, HR = 2.254, 95% CI 1.859, 2.734, P < 0.001). Multivariable Cox analysis showed that both the short‐term and long‐term mortality rates remained significantly higher in the sarcopenia group than in the non‐sarcopenia group, even after adjusting for confounding variables (28 day mortality, HR = 2.116, 95% CI 1.312, 3.412, P = 0.002; 1 year mortality, HR = 1.679, 95% CI 1.291, 2.182, P < 0.001; overall mortality, HR = 1.704, 95% CI 1.381, 2.102, P < 0.001).
Conclusions
Sarcopenia was associated with both short‐term and long‐term mortality in patients with septic shock. In clinical settings, close attention should be paid to these patients for both short‐term and long‐term outcomes.
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Glioblastoma multiform (GBM) is the most frequent and aggressive form of brain tumors in adults. However, the development of more efficient and safe nonviral vector gene therapy ...represents a promising therapeutic approach, using a tumor-specific killer gene, named apoptin. In this study, we describe the efficacy of non-viral gene delivery vectors, the amino acid-conjugated PAMAM derivatives (PAMAM-H-R and PAMAM-H-K) in delivering a therapeutic gene, displaying affinity toward human primary glioma cells (GBL-14 cells) and dermal fibroblasts. We analyzed transfection efficiency, using luciferase (Luci) and a pDNA encoding for enhanced fluorescent protein (EGFP), and cytotoxicity in both cells. The results show that transfection efficiency of PAMAM-H-R improved compared to native PAMAM dendrimer, but cytotoxicity of PAMAM-H-R and PAMAM-H-K were very low. We treated both cells with a polyplex formation of PAMAM-H-R or PAMAM-H-K/apoptin, and analyzed their cellular uptake and localization by flow cytometry and confocal microscopy. Furthermore, we analyzed the endosomal escape effect using TEM images, and found that PAMAM-H-R showed very fast escape from endosome to the cytosol. Caspase 3 activity assay, cell cycle distribution, and JC-1 analysis showed apoptosis induced by apoptin in GBL-14 cells. This indicates that PAMAM-H-R can be a potential nonviral vector gene delivery carrier for brain tumor therapy. The present study demonstrates that PAMAM-H-R/apoptin gene polyplex can be used as an effective therapeutic candidate for GBM due to its selective induction of apoptosis in primary glioma cells as a potential nonviral gene delivery carrier for brain tumor therapy.
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