An outbreak related to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China in December 2019. An extremely high potential for dissemination resulted in ...the global coronavirus disease 2019 (COVID-19) pandemic in 2020. Despite the worsening trends of COVID-19, no drugs are validated to have significant efficacy in clinical treatment of COVID-19 patients in large-scale studies. Remdesivir is considered the most promising antiviral agent; it works by inhibiting the activity of RNA-dependent RNA polymerase (RdRp). A large-scale study investigating the clinical efficacy of remdesivir (200 mg on day 1, followed by 100 mg once daily) is on-going. The other excellent anti-influenza RdRp inhibitor favipiravir is also being clinically evaluated for its efficacy in COVID-19 patients. The protease inhibitor lopinavir/ritonavir (LPV/RTV) alone is not shown to provide better antiviral efficacy than standard care. However, the regimen of LPV/RTV plus ribavirin was shown to be effective against SARS-CoV in vitro. Another promising alternative is hydroxychloroquine (200 mg thrice daily) plus azithromycin (500 mg on day 1, followed by 250 mg once daily on day 2–5), which showed excellent clinical efficacy on Chinese COVID-19 patients and anti-SARS-CoV-2 potency in vitro. The roles of teicoplanin (which inhibits the viral genome exposure in cytoplasm) and monoclonal and polyclonal antibodies in the treatment of SARS-CoV-2 are under investigation. Avoiding the prescription of non-steroidal anti-inflammatory drugs, angiotensin converting enzyme inhibitors, or angiotensin II type I receptor blockers is advised for COVID-19 patients.
Infections caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria (GNB), including carbapenem-resistant (CR) Enterobacterales (CRE; harboring mainly
,
, and
...-like genes), CR- or MDR/XDR-
(production of VIM, IMP, or NDM carbapenemases combined with porin alteration), and
complex (producing mainly OXA-23, OXA-58-like carbapenemases), have gradually worsened and become a major challenge to public health because of limited antibiotic choice and high case-fatality rates. Diverse MDR/XDR-GNB isolates have been predominantly cultured from inpatients and hospital equipment/settings, but CRE has also been identified in community settings and long-term care facilities. Several CRE outbreaks cost hospitals and healthcare institutions huge economic burdens for disinfection and containment of their disseminations. Parenteral polymyxin B/E has been observed to have a poor pharmacokinetic profile for the treatment of CR- and XDR-GNB. It has been determined that tigecycline is suitable for the treatment of bloodstream infections owing to GNB, with a minimum inhibitory concentration of ≤ 0.5 mg/L. Ceftazidime-avibactam is a last-resort antibiotic against GNB of Ambler class A/C/D enzyme-producers and a majority of CR-
isolates. Furthermore, ceftolozane-tazobactam is shown to exhibit excellent
activity against CR- and XDR-
isolates. Several pharmaceuticals have devoted to exploring novel antibiotics to combat these troublesome XDR-GNBs. Nevertheless, only few antibiotics are shown to be effective
against CR/XDR-
complex isolates. In this era of antibiotic pipelines, strict implementation of antibiotic stewardship is as important as in-time isolation cohorts in limiting the spread of CR/XDR-GNB and alleviating the worsening trends of resistance.
Neurobiology underlying inter-regional variations - across the human cerebral cortex - in measures derived with multi-modal magnetic resonance imaging (MRI) is poorly understood. Here, we ...characterize inter-regional variations in a large number of such measures, including T1 and T2 relaxation times, myelin water fraction (MWF), T1w/T2w ratio, mean diffusivity (MD), fractional anisotropy (FA), magnetization transfer ratio (MTR) and cortical thickness. We then employ a virtual-histology approach and relate these inter-regional profiles to those in cell-specific gene expression. Virtual histology revealed that most MRI-derived measures, including T1, T2 relaxation time, MWF, T1w/T2w ratio, MTR, FA and cortical thickness, are associated with expression profiles of genes specific to CA1 pyramidal cells; these genes are enriched in biological processes related to dendritic arborisation. In addition, T2 relaxation time, MWF and T1w/T2w ratio are associated with oligodendrocyte-specific gene-expression profiles, supporting their use as measures sensitive to intra-cortical myelin. MWF contributes more variance than T1w/T2w ratio to the mean oligodendrocyte expression profile, suggesting greater sensitivity to myelin. These cell-specific MRI associations may help provide a framework for determining which MRI sequences to acquire in studies with specific neurobiological hypotheses.
Septicaemia likely results in high case-fatality rates in the present multidrug-resistant (MDR) era. Amongst them are hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), two ...frequent fatal septicaemic entities amongst hospitalised patients. We reviewed the PubMed database to identify the common organisms implicated in HAP/VAP, to explore the respective risk factors, and to find the appropriate antibiotic choice. Apart from methicillin-resistant
and
, extended-spectrum β-lactamase-producing Enterobacteriaceae spp., MDR or extensively drug-resistant (XDR)-
complex spp., followed by
,
, and
are ranked as the top Gram-negative bacteria (GNB) implicated in HAP/VAP. Carbapenem-resistant Enterobacteriaceae notably emerged as an important concern in HAP/VAP. The above-mentioned pathogens have respective risk factors involved in their acquisition. In the present XDR era, tigecycline, colistin, and ceftazidime-avibactam are antibiotics effective against the
carbapenemase and oxacillinase producers amongst the Enterobacteriaceae isolates implicated in HAP/VAP. Antibiotic combination regimens are recommended in the treatment of MDR/XDR-
or
complex isolates. Some special patient populations need prolonged courses (>7-day) and/or a combination regimen of antibiotic therapy. Implementation of an antibiotic stewardship policy and the measures recommended by the United States (US) Institute for Healthcare were shown to decrease the incidence rates of HAP/VAP substantially.
Lemierre's syndrome, also known as post-anginal septicemia or necrobacillosis, is characterized by bacteremia, internal jugular vein thrombophlebitis, and metastatic septic emboli secondary to acute ...pharyngeal infections. Modern physicians have “forgotten” this disease. The most common causative agent of Lemierre's syndrome is Fusobacterium necrophorum, followed by Fusobacterium nucleatum and anaerobic bacteria such as streptococci, staphylococci, and Klebsiella pneumoniae. The causative focus mostly originated from pharyngitis or tonsillitis, accounting for over 85% of the cases of Lemierre's syndrome. Pneumonia or pleural empyema is the most common metastatic infection in Lemierre's syndrome. Antimicrobial therapy should be prescribed for 3–6 weeks. The treatment regimens include metronidazole and β-lactam antibiotics. In recent years, the antibiotic stewardship program has resulted in decreased antibiotic prescription for upper respiratory tract infections. The incidence of Lemierre's syndrome has increased over the past decade. F. necrophorum is an underestimated cause of acute pharyngitis or tonsillitis. A high index of suspicion is required for the differential diagnosis of acute tonsillopharyngitis with persistent neck pain and septic syndrome.
Epidemiological studies have suggested the effects of ambient fine particles (PM
2.5
) on asthma, but the effects of specific components of PM
2.5
on asthma remain to be explored. Here, we studied ...the effect of PM
2.5
-bound polycyclic aromatic hydrocarbons (PAHs) on asthma acute exacerbation. The data on daily counts of emergency room visits (ERVs) were obtained from Wan Fang Medical Center, Taipei, Taiwan, from 2012 to 2015. The daily concentrations of PM
2.5
and pollutant gases were obtained from a local air quality monitoring station. The levels of PM
2.5
-bound PAH were estimated by an established grid-scale model. Relative risks for ERVs as the increase in the level of ambient pollutants were calculated by using a generalized additive model of Poisson regression. In the present study, we observed statistically significant positive associations between PM
2.5
and asthma ERVs for all age groups. PM
2.5
-bound PAH was also associated with asthma ERVs for all age groups. In the adult subgroup analysis, there was a significant association between PM
2.5
-bound PAH and asthma ERVs at lags 1 and 2 (RR 1.289, 95% CI 1.050–1.582 and RR 1.242, 95% CI 1.039–1.485). The impacts of air pollution on the risk of pediatric asthma ERV were found to be significant for PM
2.5
at lag day 0 (RR 1.310, 95% CI 1.069–1.606). Moreover, pediatric asthma ERVs were significantly associated with the levels of PM
2.5
-bound PAH at lag 1 and 2 days (RR 1.576, 95% CI 1.371–1.810 and RR 1.426, 95% CI 1.265–1.607). The study provides evidence that PM
2.5
-bound PAHs were associated with an increased risk of asthma attacks. Our data further suggested that traffic exhaust is a primary source of PM
2.5
-bound PAHs.
Highlights • A total of 9599 isolates of Gram-negative bacteria (GNB) causing urinary tract infections (UTIs) were collected from 61 centres in 13 countries in the Asia-Pacific region from 2010–2013. ...• China, Vietnam, India, Thailand and the Philippines had the highest rates of GNB species producing extended-spectrum β-lactamases (ESBLs) and of cephalosporin resistance. • ESBL production and hospital-acquired infection significantly compromised the susceptibility of E. coli and K. pneumoniae to ciprofloxacin, levofloxacin and most β-lactams, with the exception of imipenem and ertapenem.
To explore the in vitro antimicrobial susceptibility among clinically important Gram-negative bacteria (GNB) in Taiwan.
From 2016 through 2018, a total of 5458 GNB isolates, including Escherichia ...coli (n = 1545), Klebsiella pneumoniae (n = 1255), Enterobacter species (n = 259), Pseudomonas aeruginosa (n = 1127), Acinetobacter baumannii complex (n = 368), and Stenotrophomonas maltophilia (n = 179), were collected. The susceptibility results were summarized by the breakpoints of minimum inhibitory concentration (MIC) of CLSI 2020, EUCAST 2020 (for colistin), or published articles (for ceftolozane/tazobactam). The resistance genes among multidrug-resistant (MDR) or extensively drug-resistant (XDR)-GNB were investigated by multiplex PCR.
Significantly higher rates of non-susceptibility (NS) to ertapenem and carbapenemase production, predominantly KPC and OXA-48-like beta-lactamase, were observed in Enterobacterales isolates causing respiratory tract infection than those causing complicated urinary tract or intra-abdominal infection (12.7%/3.44% vs. 5.7%/0.76% or 7.7%/0.97%, respectively). Isolates of Enterobacter species showed higher rates of phenotypic extended-spectrum β-lactamase and NS to ertapenem than E. coli or K. pneumoniae isolates. Although moderate activity (54–83%) was observed against most potential AmpC-producing Enterobacterales isolates, ceftolozane/tazobactam exhibited poor in vitro (44.7–47.4%) activity against phenotypic AmpC Enterobacter cloacae isolates. Additionally, 251 (22.3%) P. aeruginosa isolates exhibited the carbapenem-NS phenotype, and their MDR and XDR rate was 63.3% and 33.5%, respectively. Fifteen (75%) of twenty Burkholderia cenocepacia complex isolates were inhibited by ceftolozane/tazobactam at MICs of ≤4 μg/mL.
With the increase in antibiotic resistance in Taiwan, it is imperative to periodically monitor the susceptibility profiles of clinically important GNB.
The emergence of carbapenem-resistant Enterobacterales (CRE) has become a major public health concern. Moreover, its colonization among residents of long-term care facilities (LTCFs) is associated ...with subsequent infections and mortality. To further explore the various aspects concerning CRE in LTCFs, we conducted a literature review on CRE colonization and/or infections in long-term care facilities. The prevalence and incidence of CRE acquisition among residents of LTCFs, especially in California, central Italy, Spain, Japan, and Taiwan, were determined. There was a significant predominance of CRE in LTCFs, especially in high-acuity LTCFs with mechanical ventilation, and thus may serve as outbreak centers. The prevalence rate of CRE in LTCFs was significantly higher than that in acute care settings and the community, which indicated that LTCFs are a vital reservoir for CRE. The detailed species and genomic analyses of CRE among LTCFs reported that
is the primary species in the LTCFs in the United States, Spain, and Taiwan. KPC-2-containing
strains with sequence type 258 is the most common sequence type of KPC-producing
in the LTCFs in the United States. IMP-11- and IMP-6-producing CRE were commonly reported among LTCFs in Japan. OXA-48 was the predominant carbapenemase among LTCFs in Spain. Multiple risk factors associated with the increased risk for CRE acquisition in LTCFs were found, such as comorbidities, immunosuppressive status, dependent functional status, usage of gastrointestinal devices or indwelling catheters, mechanical ventilation, prior antibiotic exposures, and previous culture reports. A high CRE acquisition rate and prolonged CRE carriage duration after colonization were found among residents in LTCFs. Moreover, the patients from LTCFs who were colonized or infected with CRE had poor clinical outcomes, with a mortality rate of up to 75% in infected patients. Infection prevention and control measures to reduce CRE in LTCFs is important, and could possibly be controlled
active surveillance, contact precautions, cohort staffing, daily chlorhexidine bathing, healthcare-worker education, and hand-hygiene adherence.
Objectives. Acute respiratory distress syndrome (ARDS) is a critical complication in severe COVID-19 patients. The intravenous infusion (IVF) of umbilical cord- (UC-) mesenchymal stem cells (MSCs), ...validated to substantially reduce the release of several inflammatory cytokines in vivo, was also shown to exhibit benefits in improving hypoxemia among severe COVID-19 patients. A single dose of IVF-UC-MSCs therapy for severe COVID-19 patients was shown to alleviate the initial ARDS severity, but have 50%–67% case-fatality rates. In Taiwan, few adult patients with severe COVID-19-induced ARDS receiving compassionate adjuvant treatment consisting of either a single dose (1–10 × 106 cells/kg body weight (kg BW)) or three doses (5 × 106 cells/kg BW in each dose) of IVF-UC-MSCs had good outcomes. However, the optimal dosage and rounds of IVF-UC-MSCs administration for the treatment of severe COVID-19 patients with ARDS are undetermined. Methods. We reviewed the 2020–2022 PubMed literature database concerning the clinical efficacy of IVF-UC-MSCs among severe COVID-19 patients. Results. The data of COVID-19 case series in the PubMed literature revealed a notable heterogeneity in the therapeutic dosage (a single dose: 1–10 × 106 cells/kg BW; and three doses: 50–200 × 106 cells/kg BW in each dose) and the post-ARDS days of IVF-UC-MSCs administration (a single dose: 1–12; and multiple doses: 5–14) for the treatment of severe COVID-19-associated ARDS. The survival rates among these severe COVID-19 patients ranged from 50% to 76%. However, an overall rate of 93.1% of significant improvement in hypoxemia was observed for the COVID-19 survivors receiving IVF-UC-MSCs at the initial ARDS stage. Conclusions. According to our analysis, the ideal treatment dosage of IVF-UC-MSCs for severe COVID-19-induced ARDS is likely 5 × 106 cells/kg BW for three cycles within 5 days of ARDS onset in severe COVID-19 patients.
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