Three new compounds from the flower branch of Gastrodia elata Blume and anti-microbial activity.

Three new compounds (1-3), including novel tetra-p-cresol substituted cyclopenta[a]naphthalene derivatives, named gastrodinol (1), 2-(4'-hydroxybenzoyl)-3-hydroxyethyl indole (2), 2-(4'-hydroxybenzoyl)-3-(4''-hydroxybenzyl)indole (3) were isolated from the flower branch of G. elata, along with five known compounds (4-8). Among them, compound 1 exhibited the most anti-microbial activity against Streptococcus agalactiae, with the minimum inhibitory concentration of 1 µg ml-1. This study demonstrated that the novel gastrodinol 1 found in the flower branch of G. elata may be responsible for the anti-microbial effect. It will lead to the development of new antibiotics, and how to utilize the TCM ''Tianma'' better.

The Diagnostic Value of Procalcitonin Versus Other Biomarkers in Prediction of Bloodstream Infection.

BACKGROUND: We compared the diagnostic utility of procalcitonin (PCT), C-reactive protein (CRP), and hematological markers, including white blood cell count (WBC), neutrophils (NEU), percentage of neutrophils (NEU%), lymphocytes (LYM), neutrophil-lymphocyte count ratio (NLCR), and platelet count (PLT) for predicting bloodstream infection (BSI), which was confirmed by blood culture (BC). METHODS: A retrospective analysis was conducted for 1807 inpatients. The level of PCT, CRP, blood cells, and blood culture results were compared between the positive blood culture group and negative blood culture group; each indicator was analyzed in the performance of bacterial BSI diagnosis by drawing ROC curves. RESULTS: Blood cultures were positive in 230 patients; hence, the prevalence of bacteremia was 12.7%. There were significant differences in the median value for each marker between positive group BCs and negative group BCs (p < 0.05). The areas under the receiver operating characteristic curves (ROC-AUCs) of PCT, CRP, WBC, NEU, NUE%, LYM, NLCR, and PLT for discriminating positive BCs from negative BCs were 0.811, 0.654, 0.612, 0.634, 0.684, 0.595, 0.682, and 0.633 respectively. PCT concentrations of gram-negative (14.94 ng/mL, IQR 2.93  48.76) were significantly higher than gram-positive (4.74 ng/mL, IQR 1.22  17.5) and fungal (1.47 ng/mL, IQR 0.66  35.34). CONCLUSIONS: PCT proved to be the most reliable predictor of BSI, second were NEU% and NLCR. A higher PCT level was found in patients with a gram-negative BSI compared to gram-positive BSI and fungal BSI.

Overexpression of MexAB-OprM efflux pump in carbapenem-resistant Pseudomonas aeruginosa.

Efflux pump systems are one of the most important mechanisms conferring multidrug resistance in Pseudomonas aeruginosa. MexAB-OprM efflux pump is one of the largest multi-drug resistant efflux pumps with high-level expression, which is controlled by regulatory genes mexR, nalC, and nalD. This study investigated the role of efflux pump MexAB-OprM in 75 strains of carbapenem-resistant P. aeruginosa and evaluated the influence of point mutation of the regulatory genes. The minimum inhibitory concentrations of imipenem and meropenem, with or without MC207110, an efflux pump inhibitor, were determined by agar dilution method to select the positive strains for an overexpressed active efflux pump. Carba NP test and EDTA-disk synergy test were used for the detection of carbapenemase and metallo-ß-lactamases, respectively. The gene mexA, responsible for the fusion protein structure, and the reference gene rpoD of the MexAB-OprM pump were amplified by real-time PCR. The quantity of relative mRNA expression was determined simultaneously. By PCR method, the efflux regulatory genes mexR, nalC, and nalD and outer membrane protein OprD2 were amplified for the strains showing overexpression of MexAB-OprM and subsequently analyzed by BLAST. Among the 75 P. aeruginosa strains, the prevalence of efflux pump-positive phenotype was 17.3 % (13/75). Carba NP test and EDTA-disk synergy test were all negative in the 13 strains. PCR assay results showed that ten strains overexpressed the MexAB-OprM efflux pump and were all positive for the regulatory genes mexR, nalC, and nalD. Sequence analysis indicated that of the ten isolates, nine had a mutation (Gly â†’ Glu) at 71st amino acid position in NalC, and eight also had a mutation (Ser â†’ Arg) at 209th position in NalC. Only one strain had a mutation (Thr â†’ Ile) at the 158th amino acid position in NalD, whereas eight isolates had mutations in MexR. In conclusion, overexpression of efflux pump MexAB-OprM plays an important role in carbapenem-resistant P. aeruginosa. The mutations of regulatory genes may be a main factor contributing to overexpression of MexAB-OprM.

[Mechanisms of pandrug-resistance of Pseudomonas aeruginosa].

OBJECTIVE: To explore the mechanisms of pandrug-resistance (PDR) of Pseudomonas aeruginosa (PA). METHODS: Nineteen strains of PA were collected from Huashan Hospital, Shanghai. Agar dilution method was used to detect the levels of minimum inhibitory concentration (MIC) of 14 antimicrobial drugs to the PA strains. Strain homology was investigated by enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR). To analyze the beta-lactam resistant mechanisms, genes of extended-spectrum beta-lactamases (ESBLs), carbapenemase, and plasmid-mediated AmpC were amplified and analyzed by PCR and DNA sequencing. To analyze the aminoglycoside resistant mechanisms, 16 aminoglycoside modifying enzyme were screened by PCR. PCR and DNA sequencing were used to amplify and analyze the genes of DNA gyrase genes gyrA and gyrB, topoisomerase IV genes parC and pare, and qnr gene for the fluoroquinolone resistance mechanisms, to amplify and analyze study the oprD2 coding genes and inhibitor MC207110 were used to detect efflux pump for the carbapenem resistance mechanisms. RESULTS: Five types were identified in the 19 PDR-PA by ERIC-PCR, mainly type A (n=6) and type B (n=7). 17 of the 19 PDR-PA strains produced VEB-3 type ESBL, 1 strain of which also produced OXA-10 type ESBL simultaneously. Both of the carbapenemase and plasmid-mediated AmpC were negative. All of the 19 PDR-PA strains produced aminoglycoside modifying enzyme, yielding ant (3") I and 18 strains of which produced aac (3) II simultaneously. All 19 PDR-PA strains carried gyrA mutations, 14 of which carried parC mutation simultaneously, qnr gene was negative. OprD2 coding gene sequencing analysis revealed that small fragment missing occurred to all oprD2 genes of the 19 strains. 16 strains showed efflux pump mechanism. CONCLUSION: The resistance mechanism of PDR-PA to cephalosporins, beta-lactam/beta-lactamase inhibitor, carbapenem, fluoroquinolones, and aminoglycosides are due to production of VEB-3-ESBL, aac (3) II, and ant (3") I aminoglycoside modifying enzyme, mutations of DNA gyrase gyrA and topoisomerase parC gene, OprD2 protein deficiencies, and efflux pump overexpression.