Teniposide

Environmental phenols are a group of typical endocrine disruptors, and widely detectable in human breast milk and infant formulas. However, exposures data are scarce in early infancy, a particularly sensitive period to environmental pollutants exposures. We aimed to prospectively assess urinary concentrations of eighteen environmental phenols in infants from birth to 6 months of age and their associations with feeding patterns (breastfeeding, formula and mixed-feeding). This study included 197 mother-infant pairs. Urinary concentrations of six parabens (PBs), seven bisphenols, four benzophenones (BPs) and triclosan were measured in infants at the ages of 3 days, 42 days, 3 and 6 months by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Multivariable linear regression models were applied to evaluate the associations between infant feeding types and urinary phenol concentrations in log₁₀-transformed scale. The detection rates of bisphenol A and S, methyl 4-hydroxybenzoate (MeP), ethyl 4-hydroxybenzoate (EtP), and propyl 4-hydroxybenzoate (PrP) were persistently high (ranged 48.7%-100.0%) across all ages (3 days, 42 days, 3 and 6 months). The detection rates of bisphenol P, B and AP were high (ranged 76.9%-95.9%) at age 3 days, and lower (14.4%-88.0%) at later ages. Compared to exclusive breastfeeding, mixed feeding was associated with 0.32 (95% CI: 0.01, 0.62, p < 0.05) higher log (BPA) (μg/g creatinine) at 42 days, 0.69 (0.03, 1.35) higher log (TCS) (μg/g creatinine) at 3 months, 0.54 (0.08, 1.00) higher log (EtP) (μg/g creatinine) at 6 months; formula feeding was associated with 1.30 (0.59, 2.00) and 0.91 (0.22, 1.60) higher log (BPB) (μg/g creatinine) at the age of 42 days and 3 months respectively, 1.19 (0.003-2.37) higher log (BPP) and 0.95 (0.27-1.64) higher log (BPS) (μg/g creatinine) at 3 months. In conclusion, exposures to BPA and its analogs, and parabens (MeP, EtP, and PrP) were extensive in early postnatal life of infants. Breastfeeding might be a safer form of feeding for infants against exposure to some phenols.

Carbapenem-resistant Enterobacterales (CRE), specifically those resistant to only ertapenem among carbapenems (ETP-mono-resistant), are increasingly reported, while the optimal therapy options remain uncertain. To investigate the prevalence and characteristics of ETP-mono-resistant CRE, CRE strains were systematically collected from 102 hospitals across China between 2018 and 2021. A 1:1 randomized matching study was conducted with ETP-mono-resistant strains to meropenem- and/or imipenem-resistant (MEM/IPM-resistant) strains. Antimicrobial susceptibility testing, whole-genome sequencing, carbapenem-hydrolysing activity and the expression of carbapenemase genes were determined. In total, 18.8% of CRE strains were ETP-mono-resistant, with relatively low ertapenem MIC values. ETP-mono-resistant strains exhibited enhanced susceptibility to β-lactams, β-lactam/β-lactamase inhibitor combinations, levofloxacin, fosfomycin, amikacin and polymyxin than MEM/IPM-resistant strains (P < 0.05). Phylogenetic analysis revealed high genetic diversity among ETP-mono-resistant strains. Extended-spectrum β-lactamases (ESBLs) and/or AmpC, as well as porin mutations, were identified as potential major mechanisms mediating ETP-mono-resistance, while the presence of carbapenemases was found to be the key factor distinguishing the carbapenem-resistant phenotypes between the two groups (P < 0.001). Compared with the MEM/IPM-resistant group, limited carbapenemase-producing CRE (CP-CRE) strains in the ETP-mono-resistant group showed a significantly lower prevalence of ESBLs and porin mutations, along with reduced expression of carbapenemase. Remarkably, spot assays combined with modified carbapenem inactivation method indicated that ETP-mono-resistant CP-CRE isolates grew at meropenem concentrations eightfold above their corresponding MIC values, accompanied by rapidly enhanced carbapenem-hydrolysing ability. These findings illustrate that ETP-mono-resistant CRE strains are relatively prevalent and that caution should be exercised when using meropenem alone for treatment. The detection of carbapenemase should be prioritized.