Emerging resistance to ceftriaxone treatment owing to different ampD mutations in Enterobacter roggenkampii.

OBJECTIVES: The Enterobacter cloacae complex is responsible for a variety of infections in hospitalized patients and is resistant to ß-lactam antibiotics owing to the expression of AmpC ß-lactamase. We report emerging resistance in Enterobacter roggenkampii exposed to ceftriaxone and explore the mechanism underlying mutations responsible for this resistance. METHODS: Three strains were derived from different samples from one patient (blood and liver abscess fluid). Antimicrobial susceptibility was evaluated by standard broth microdilution, while ampC expression was determined via RT-PCR. Genetic relatedness was evaluated via pulsed-field gel electrophoresis (PFGE). Species identification and comparative genome analysis were performed via genome sequencing. Mutation rate testing and selection of AmpC-derepressed mutants were conducted to explore the mutation mechanism. RESULTS: E. roggenkampii F1247 was susceptible to third-generation cephalosporins (3GCs); F95 and F1057, found in blood sample on day 11 and liver abscess drainage fluid on day 25, were resistant. ampC expression was 341- and 642-fold higher in F95 and F1057, respectively, than in F1247. Three isolates were the same PFGE and sequence types (ST1778) and were highly homologous (2 and 4 core genome single nucleotide polymorphism differences). Compared to F1247, F95 possessed a 575 bp deletion, including 537 bp of ampD, whereas F1057 harbored only one amino acid mutation (Leu140Pro in ampD). The mutation rates from F1247 exposure to cefotaxime, ceftazidime, ceftriaxone, piperacillin-tazobactam, and cefepime were (1.90 ± 0.21) × 10-8, (3.18 ± 0.43) × 10-8, (2.00 ± 0.20) × 10-8, (2.92 ± 0.29) × 10-9, and zero, respectively. In vitro-selected mutations responsible for resistance were identified in ampD, ampR, and dacB. CONCLUSIONS: E. roggenkampii may develop resistance in vivo and in vitro upon exposure to 3GCs and to a lesser extent to piperacillin-tazobactam. 3GCs should not be used as a monotherapy for E. roggenkampii infections. Therapy using cefepime or carbapenems may be preferred to piperacillin-tazobactam in the treatment of E. roggenkampii, especially if source control is difficult.

Paeonol Derivatives and Pharmacological Activities: A Review of Recent Progress.

Paeonol, 2-hydroxy-4-methoxy acetophenone, is one of the main active ingredients of traditional Chinese medicine such as Cynanchum paniculatum, Paeonia suffruticosa Andr and Paeonia lactiflora Pall. Modern medical research has shown that paeonol has a wide range of pharmacological activities. In recent years, a large number of studies have been carried out on the structure modification of paeonol and the mechanism of action of paeonol derivatives has been studied. Some paeonol derivatives exhibit good pharmacological activities in terms of antibacterial, anti-inflammatory, antipyretic analgesic, antioxidant and other pharmacological effects. Herein, the research progress on paeonol derivatives and their pharmacological activities were systematically reviewed.

Two new triterpenoids from Gypsophila oldhamiana.

Two new triterpenoids (1-2) were isolated and elucidated from the roots of Gypsophila oldhamiana, together with four known triterpenoids (3-6). Their structures were identified to be 3ß-hydroxyolean-13(18)-ene-23, 28-dioic acid (1), 3ß, 12α-dihydroxy-23-carboxyolean-28, 13ß-olide (2), 3ß, 16α-dihydroxy-23-oxoolean-13(18)-en-28-oic acid (3), gypsogenin (4), quillaic acid (5) and gypsogenic acid (6) by spectral methods. All compounds were tested for their cytotoxicities against human tumour cell lines (lung cancer H460 and gastric cancer SGC-7901) and for their antiangiogenic effects using a zebra fish model. All compounds showed interesting antiangiogenic activities and the significant cytotoxicities against H460.

Bioactive ent-clerodane diterpenoids from Scutellaria barbata.

Four new ENT-clerodane diterpenoids were isolated from the whole plant of Scutellaria barbata D. Don. (Labiatae). Their structures were elucidated by chemical methods and spectral analyses. in vitro, the four new compounds showed significant cytotoxic activities against three human cancer lines (HONE-1 nasopharyngeal, KB oral epidermoid carcinoma, and HT29 colorectal carcinoma cells), and gave IC50 values in the range 3.1-7.2 microM.

[Isolation and structure identification of the chemical constituents from Gypsophila oldhamiana].

AIM: To study the constituents of the root of Gypsophila oldhamiana Miq. METHODS: Silica gel column chromatographic technique was used for the isolation and purification of compounds. The structures were elucidated on the basis of spectral data and chemical evidences. RESULTS: Five compounds were obtained and identified as the beta-D-glucoside of alpha-spinasterol (I), tetracosyl caffeate (II), sucrose (III), beta-sitosterol (IV) and daucosterol (V). CONCLUSION: Compound II is a new compound. Compound I was isolated from this plant for the first time.