http://creativecommons.org/licenses/by-nc-nd/4.0/ ) 116 D.M. Tran, M. Larsson and L. Olson et al. / Journal of Infection 79 (2019) 115-122 Conclusion: These data indicate that there is an epidemic spread of CRE in Vietnamese hospitals with rapid transmission to hospitalised patients.

Background: Carbapenem-resistant Enterobacteriaceae (CRE) is an increasing problem worldwide, but particularly problematic in low-and middle-income countries (LMIC) due to limitations of resources for surveillance of CRE and infection prevention and control (IPC). Methods: A point prevalence survey (PPS) with screening for colonisation with CRE was conducted on 2233 patients admitted to neonatal, paediatric and adult care at 12 Vietnamese hospitals located in northern, central and southern Vietnam during 2017 and 2018. CRE colonisation was determined by culturing of faecal specimens on selective agar for CRE. Risk factors for CRE colonisation were evaluated. A CRE admission and discharge screening sub-study was conducted among one of the most vulnerable patient groups; infants treated at an 80-bed Neonatal ICU from March throughout June 2017 to assess CRE acquisition, hospital-acquired infection (HAI) and treatment outcome. Results: A total of 1165 (52%) patients were colonised with CRE, most commonly Klebsiella pneumoniae (n = 805), Escherichia coli (n = 682) and Enterobacter spp. (n = 61). Duration of hospital stay, HAI and treatment with a carbapenem were independent risk factors for CRE colonisation. The PPS showed that the prevalence of CRE colonisation increased on average 4.2% per day and mean CRE colonisation rates increased from 13% on the day of admission to 89% at day 15 of hospital stay. At the NICU, CRE colonisation increased from 32% at admission to 87% at discharge, mortality was significantly associated (OR 5 •5, P < 0 •01) with CRE colonisation and HAI on admission.

Staphylococcus aureus may cause relapsing infections. We previously showed that S. aureus SH1000 surviving intracellularly to bactericidal antibiotics are persisters. Here, we used 54 non-duplicate clinical isolates to assess links between persistence, resistance evolution, and intracellular survival, using moxifloxacin throughout as test bactericidal antibiotic. The relative persister fraction (RPF: percentage of inoculum surviving to 100× MIC moxifloxacin in stationary phase culture for each isolate relative to ATCC 25923) was determined to categorize isolates with low (≤10) or high (&gt;10) RPF. Evolution to resistance (moxifloxacin MIC ≥ 0.5 mg/L) was triggered by serial passages at 0.5× MIC (with daily concentration readjustments). Intracellular moxifloxacin maximal efficacy (Emax) was determined by 24 h concentration-response experiments [pharmacodynamic model (Hill-Langmuir)] with infected THP-1 monocytes exposed to moxifloxacin (0.01 to 100× MIC) after phagocytosis. Division of intracellular survivors was followed by green fluorescence protein dilution (FACS). Most (30/36) moxifloxacin-susceptible isolates showed low RPF but all moxifloxacin-resistant (n = 18) isolates harbored high RPF. Evolution to resistance of susceptible isolates was faster for those with high vs. low RPF (with SOS response and topoisomerase-encoding genes overexpression). Intracellularly, moxifloxacin Emax was decreased (less negative) for isolates with high vs. low RPF, independently from resistance. Moxifloxacin intracellular survivors were non-dividing. The data demonstrate and quantitate persisters in clinical isolates of S. aureus, and show that this phenotype accelerates resistance evolution and is associated with intracellular survival in spite of high antibiotic concentrations. Isolates with high RPF may represent a possible cause of treatment failure not directly related to resistance in patients receiving active antibiotics.

!A primary functional receptor screening assay was performed to examine the effects of methanolic extracts from ten Vietnamese medicinal plants on the human neurokinin-1 receptor expressed from Semliki Forest virus vectors in Chinese hamster ovary cells. Extracts from Piper nigrum, Stephania cambodica and Styphnolobium japonicum were found to exert inhibition on agonist-induced human neurokinin-1 receptor activity. Secondary assays and high performance liquid chromatography of the lead compounds addressed a possible association between pharmacological responses and these chemical compounds. Strong inhibition of human neurokinin-1 receptor was observed for extracts revealing the highest inhibitory potency for rotundine (tetrahydropalmatine) in S. cambodica extracts with IC 50 of 0.88 µM, followed by piperine and capsaicin in P. nigrum extracts with IC 50 values of approximately 2 µM, whereas rutin in S. japonicum extracts failed to inhibit hNK1R up to 100 µM. [4]. Since the hNK1R is known to be present in both the CNS and a number of other tissues and has been the target for development of drugs for migraine, emesis, anti-inflammation and psychiatric disorders [5,6], the potential interaction between plant extracts and the hNK1R is of significant interest. In this study, we employed the SFV system for overexpression of the hNK1R in CHO cells to investigate the effects of plant extracts on agonist-induced receptor activity. The methanolic extracts of the ten Vietnamese medicinal plants were subjected to a preliminary screening for their effects on receptors in presence of the agonist Substance P (SP). Extracts from three species, namely P. nigrum, S. japonicum and S. cambodica, were further selected and examined for probable associations between different geographical locations (accessions) with biological activity. Moreover, lead compounds of plant extracts from these three species were analyzed by HPLC and examined in functional receptor assays to elucidate whether extracts derived from different locations exert different activities in relation to their concentrations of lead compounds. HPLC was applied to determine the amount of piperine and capsaicin in P. nigrum, rotundine in S. cambodica, and rutin in S. japonicum collected from five different geographical locations (l " Fig. 1 and Table 1). The fruit extracts from P. nigrum, capsaicin and piperine showed the most consistent amounts of analyzed compounds ranging between 0.14 ± 0.01 % and 0.24 ± 0.01 % and between 1.51 ± 0.11 % and 2.22 ± 0.08 %, respectively. For tuber and root extracts from S. cambodica, the range of rotundine was between 0.98 ± 0.18 % and 4.69 ± 0.15 %, and moderately variable. In flower bud extracts from S. japonicum, rutin ranged from 0.17 ± 0.01 % to 6.14 ± 0.18 % showing the largest variation among analyzed compounds. The degree of variability within each species appeared to be influenced by not only the genotype, but also the plant parts examined. In this context, extracts of fruits (P. nigrum) showed the least variation, tu...