Risk factors for gastrointestinal colonization and acquisition of carbapenem-resistant gram-negative bacteria among patients in intensive care units in Thailand

This study was conducted to investigate the prevalence of and risk factors for colonization and acquisition of carbapenem-resistant (CR) Gram-negative bacteria (GNB) among patients admitted to intensive care units (ICUs) in two tertiary care hospitals in northern Thailand. Screening of rectal swab specimens for CR-GNB was performed on patients at ICU admission and discharge.</jats:p

Environmental dissemination of mcr-1 positive Enterobacteriaceae by Chrysomya spp. (common blowfly): An increasing public health risk

Until recently, the role of insects, and particularly flies, in disseminating antimicrobial resistance (AMR) has been poorly studied. In this study, we screened blowflies (Chrysomya spp.) from different areas near the city of Phitsanulok, Northern Thailand, for the presence of AMR genes and in particular, mcr-1, using whole genome sequencing (WGS). In total, 48 mcr-1-positive isolates were recovered, consisting of 17 mcr-1-positive Klebsiella pneumoniae (MCRPKP) and 31 mcr-1-positive Escherichia coli (MCRPEC) strains. The 17 MCRPKP were shown to be clonal (ST43) with few single poly nucleomorphs (SNPs) by WGS analysis. In in-vitro models, the MCRPKP were shown to be highly virulent. In contrast, 31 recovered MCRPEC isolates are varied, belonging to 12 different sequence types shared with those causing human infections. The majority of mcr-1 gene are located on IncX4 plasmids (29/48, 60.42%), sharing an identical plasmid backbone. These findings highlight the contribution of flies to the AMR contagion picture in low- and middle-income countries and the challenges of tackling global AMR

Antimicrobial Activity of the Green Tea Polyphenol (−)-Epigallocatechin-3-Gallate (EGCG) against Clinical Isolates of Multidrug-Resistant <i>Vibrio cholerae</i>

The spread of multidrug-resistant (MDR) Vibrio cholerae necessitates the development of novel prevention and treatment strategies. This study aims to evaluate the in vitro antibacterial activity of green tea polyphenol (−)-epigallocatechin-3-gallate (EGCG) against MDR V. cholerae. First, MIC and MBC values were evaluated by broth microdilution techniques against 45 V. cholerae strains. The checkerboard assay was then used to determine the synergistic effect of EGCG and tetracycline. The pharmaceutical mode of action of EGCG was clarified by time-killing kinetics and membrane disruption assay. Our results revealed that all of the 45 clinical isolates were susceptible to EGCG, with MIC and MBC values in the range of 62.5–250 µg/mL and 125–500 µg/mL, respectively. Furthermore, the combination of EGCG and tetracycline was greater than either treatment alone, with a fractional inhibitory concentration index (FICI) of 0.009 and 0.018 in the O1 and O139 representative serotypes, respectively. Time-killing kinetics analysis suggested that EGCG had bactericidal activity for MDR V. cholerae after exposure to at least 62.5 µg/mL EGCG within 1 h. The mode of action of EGCG might be associated with membrane disrupting permeability, as confirmed by scanning electron microscopy. This is the first indication that EGCG is a viable anti-MDR V. cholerae treatment

Risk factors for extended-spectrum β-lactamase-producing Enterobacteriaceae carriage in patients admitted to Intensive Care Unit in a Tertiary Care Hospital in Thailand

Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) are important causes of serious infections in intensive care unit (ICU). This study aimed to investigate the risk factors for intestinal carriage of ESBL-PE among patients admitted to ICU, subsequent ESBL-PE infections, and outcomes of these patients. This study prospectively collected rectal swabs from 215 ICU patients in Northern Thailand and ESBL-PE were isolated. A high prevalence of ESBL-PE carriage (134/215, 62.3%) at ICU admission was observed, with Escherichia coli representing the predominant organism (67.5%) followed by Klebsiella pneumoniae (19.4%). Multivariate logistic regression analysis identified chronic renal disease as the independent risk factor for ESBL-PE carriage (p = 0.009; adjusted odds ratio = 4.369; 95% confidence interval = 1.455–13.119). Among colonized patients, 2.2% (3/134) developed ESBL-PE infections during ICU stay. Phylogenetic analysis of E. coli (n = 108) showed that the predominant group was group A (38.0%), followed by groups B1 (17.6%), D (15.7%), B2 (14.8%), C (7.4%), and F (6.5%). Multilocus sequence typing analysis of the pathogenic groups B2, D, and F revealed 11 different sequence types (STs), with ST131 (n = 13) as the most prevalent, followed by ST648 (n = 5), ST38 (n = 4), ST393 (n = 3), and ST1193 (n = 3). These results are of concern since ESBL-PE may be a prerequisite for endogenous infections and potentially disseminate within the hospital. This is the first study describing ESBL-PE carriage among patients at ICU admission and subsequent ESBL-PE infections in Thailand

Dinactin: A New Antitumor Antibiotic with Cell Cycle Progression and Cancer Stemness Inhibiting Activities in Lung Cancer

Lung cancer, especially non-small cell lung cancer (NSCLC), is one of the most complex diseases, despite the existence of effective treatments such as chemotherapy and immunotherapy. Since cancer stem cells (CSCs) are responsible for chemo- and radio-resistance, metastasis, and cancer recurrence, finding new therapeutic targets for CSCs is critical. Dinactin is a natural secondary metabolite produced by microorganisms. Recently, dinactin has been revealed as a promising antitumor antibiotic via various mechanisms. However, the evidence relating to cell cycle progression regulation is constrained, and effects on cancer stemness have not been elucidated. Therefore, the aim of this study is to evaluate the new function of dinactin in anti-NSCLC proliferation, focusing on cell cycle progression and cancer stemness properties in Lu99 and A549 cells. Flow cytometry and immunoblotting analyses revealed that 0.1&ndash;1 &micro;M of dinactin suppresses cell growth through induction of the G0/G1 phase associated with down-regulation of cyclins A, B, and D3, and cdk2 protein expression. The tumor-sphere forming capacity was used to assess the effect of dinactin on the cancer stemness potential in NSCLC cells. At a concentration of 1 nM, dinactin reduced both the number and size of the tumor-spheres. The quantitative RT-PCR analyses indicated that dinactin suppressed sphere formation by significantly reducing expression of CSC markers (i.e., ALDH1A1, Nanog, Oct4, and Sox2) in Lu99 cells. Consequently, dinactin could be a promising strategy for NSCLC therapy targeting CSCs