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The present investigation deals with the evaluation for the first time of the in vitro antimicrobial and α-glucosidaseinhibitory potential of a series of 15 enantiopure cycloalkylglycines using agar well diffusion and spectrophotometricmethods, respectively. The obtained results were compared to the positive controls. The antimicrobial results revealedthat all compounds exerted strongly inhibitory activity, especially against Gram-positive bacterial strains with the mostpotent activity was ascribed to α-γ-hydroxy-α-amino acids 11–14 [minimum inhibitory concentration (MIC) = 1.58–12.50 mg/ml, minimum bactericidal concentration (MBC) = 3.17–100 mg/ml, and minimum fungicidal concentration(MFC) = 6.25–50 mg/ml], followed by both isoxazolidine 5–9 (MIC = 1.58–12.50 mg/ml, MBC = 6.25–100 mg/ml,and MFC = 25–100 mg/ml) and isoxazine 10 (MIC = 3.17–12.50 mg/ml, MBC = 3.17–50 mg/ml, and MFC = 25–50mg/ml) compounds, and slightly inhibitory effect with α-amino-γ-lactones series 1–4 (MIC = 3.17–25 mg/ml, MBC =6.25–100 mg/ml, and MFC = 25–100 mg/ml). All the derivatives exhibited a potent α-glucosidase inhibitory activitywith compound 10 (IC50 = 30.1 ± 0.6 μM) was found to be the most active. The druglikeness and pharmacokineticprofiles have been also predicted. The in silico results indicate that all derivatives showed a resemblance with severalparameters of the antimicrobial standards, especially in terms of molecular property, bioavailability, lipophilicity,medicinal chemistry, and enzymatic inhibitory effects as well as they agree with the different drug discovery rules suchas Lipinski (Pfizer), Ghose (Amgen), Veber (GlaxoSmithKline), Egan (Pharmacia), and Muegge (Bayer) displaying ahigher druglikeness behavior.
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Objective To understand the drug resistance of Mycobacterium tuberculosis(MTB)and susceptibility of multidrug-resistant MTB(MDR-MTB)to linezolid in Hebei Province, so as to guiding clinical treatment of MDR tuberculosis.Methods The isolated strains and clinical information of patients with tuberculosis in 6 hospitals of 5 cities in Hebei Province between January and December 2016 were collected, susceptibility of MTB to antituberculous drugs isoniazid(INH), rifampicin(RFP), streptomycin(SM), ethambutol(EMB), ofloxacin(OFX), and kanamycin(KM)were detected, 100 strains of MDR-MTB were selected by stratified random sampling method, susceptibility to linezolid was detected.Results Drug resistance rate and MDR rate of the initially treated cases were 26.6％(200/753)and 13.5％(102/753)respectively, drug resistance rate and MDR rate of the retreatment cases were 59.7％(132/221)and 53.4(118/221)respectively, drug resistance rate and MDR rate of the retreatment cases were both statistically higher than initially treated cases(χ2=83.7, P＜0.01;χ2=93.5, P＜0.01).Resistance rates of MTB to first-line antituberculous drugs INH, RFP, SM, and EMB were 25.8％, 23.7％, 16.7％, and 7.1％ respectively, to second-line antituberculous drugs OFX and KM were 4.7％(37/782)and 4.0％(31/782)respectively; susceptibility of MDR-MTB to linezolid was 80.8％ (59/73).Conclusion Drug resistance rate and MDR rate of the retreated tuberculosis patients are higher than initially treated patients, linezolid has good in vitro antimicrobial activity against MDR-MTB.
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@#This study aimed to isolate and prepare highly purified impurity C from doxycycline hyclate by a preparative HPLC method and to inspect the toxicity and in vitro antimicrobial activity of the impurity C of doxycycline hyclate. The solution of doxycycline hyclate treated with heat produced a solution containing 10% of impurity C which was firstly separated by the Sapphire C18(21. 2 mm×250 mm, 5 μm)column with 0. 1% acetic acid-acetonitrile(83 ∶17)as the mobile phase at 20 mL/min. Secondly, rotary evaporation of the eluted solution at the time of 8. 4 min was performed at 50 °C to remove organic solvent. Then the target product was prepared after freeze drying of evaporated solution adjusting pH to 1. 8 with formic acid. The target product was identified with ultraviolet absorbance(UV), infrared(IR), mass spectrometry(MS)and nuclear magnetic resonance(NMR), and its purity was be determined by HPLC. Meanwhile, cytotoxicity and genotoxicity in the Chinese hamster lung cells, toxicity on the development of zebrafish embryos and in vitro antimicrobial activity were compared among impurity C of doxycycline hyclate, doxycycline, metacycline and β-doxycycline. Results showed that prepared product was confirmed to be the impurity C of doxycycline hyclate. Its purity was 90. 1%, which had been the highest so far. In the cellular toxic tests and genetic toxic tests of Chinese hamster lung cells, impurity C of doxycycline hyclate, doxycycline, metacycline and β-doxycycline were somewhat toxic to Chinese hamster lung cells. Toxicity gradually decreased from doxycycline, impurity C of doxycycline hyclate, β-doxycycline to metacycline from -S9mix test results; toxicity gradually decreased from doxycycline, β-doxycycline, impurity C of doxycycline hyclate to metacycline from +S9mix test results; the aberration rate of all the tested related substances was less than 5%, and no obvious genotoxicity was found. According to test results of the development of zebrafish embryos, impurity C of doxycycline hyclate showed the strongest teratogenicity and lethality. Invitro antimicrobial tests revealed that impurity C of doxycycline hyclate had a weaker antimicrobial activity, and invitro antimicrobial activity potential of the tested compounds followed the order: metacycline, doxycycline, impurity C of doxycycline hyclate, β-doxycycline. Studies on safety and effectiveness indicated that impurity C of doxycycline hyclate belonged to toxic and ineffective impurity and need to be controlled individually in quality standard. A useful suggestion was given to revise the quality standard of doxycycline hyclate and its preparation in the current Pharmacopoeia of the People′s Republic of China.
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Aims and Study Design: Piper aduncum L. is a Brazilian plant with many biological properties attributed to its dillapiole-rich essential oil. Despite the development of antibiotics, bacterial and fungal infections are still a public health issue in the medical field. This study measured the antimicrobial activity of the dillapiole-rich essential oil of P. aduncum against pathogenic skin microorganisms. Place of Study: Faculty of Pharmacy and Graduate Program in Pharmaceutical Science, Federal University of Pará, Brazil. This work was performed in 2014. Methodology: Gas Chromatography (GC) and Gas Cromatography-Mass spectrometry (GC-MS) have analyzed the oil and its dillapiole-rich fraction. The determination of Minimum Inhibitory Concentration (MIC) and Minimum fungicidal concentration (MFC) values was carried out by microdilution method and counting of formed colonies. Results: For the strains of Trichophyton mentagrophytes (ATCC 9533 and clinical isolate), the oil and its dillapiole-rich fraction exhibited MIC values of 500 μg/ml while the MFC values were 1,500 μg/ml for the oil and 1,000 μg/ml for the fraction rich in dillapiole. For clinical isolates of T. rubrum and Epidermophyton floccosum, MIC values of 500 μg/ml and MFC 1,500 μg/ml were equal for the oil and the dillapiole-rich fraction, respectively. For clinical isolates of Microsporum canis and M. gypseum, the MIC and MFC values were 250 μg/ml and 500 μg/ml, respectively. For strains of Aspergillus fumigatus (ATCC 40152 and clinical isolate), the oil and its dillapiole-rich fraction have shown the same MIC value of 3.9 μg/ml while the MFC values were 7.8 μg/ml for the strain ATCC 40152, and 15.6 μg/ml for the clinical isolate. The oil and dillapiole-rich fraction did not show antibacterial activity against the strain of Staphylococcus aureus ATCC 6538 and its clinical isolate Conclusion: The dillapiole-rich essential oil of P. aduncum and its dillapiole-rich fraction demonstrates significant antifungal activity against dermatophytes, filamentous fungi and potent antifungal activity against non-dermatophyte filamentous fungi.
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Microbiological surveillance program is currently performed at our tertiary-care teaching Hospital. The temporal trend of microbial isolates from patients admitted during the last four calendar years (2004 to 2007), has been analyzed according to the main bacterial and fungal cultured organisms. The same pathogens isolated more than once from the same patient within one month, have been considered only once. On the whole, the main pathogen group remained that of Enterobacteriaceae (6,608 isolations out of 19,666: 33.6%, with Escherichia coli retrieved in 60-75% of cases), with no significant difference over time. Staphylococci (4,150 isolates), and enterococci (3,276 isolates), were the two largest groups after Enterobacteriaceae, but staphylococci significantly declined during the examined four-year period (p<.001), mainly due to a progressively reduced isolation of coagulase-negative staphylococci. On the other hand, a slight increase of enterococci occurred (p<.05). Based on the frequency of isolation, Gram-negative oxydasepositive organisms accounted for 2,109 episodes, followed by other aerobe Gram-positive organisms other than Staphylococci-Enterococci (613 isolates), and anaerobes (583 isolates): no significant temporal variations occurred over time for these last microbial groups. With regard to Gram-negative oxydase-negative microorganisms (567 isolates), non-betahemolytic streptococci (464 cases), and beta-hemolytic streptococci (260 isolates), a significant trend towards a reduction of frequency occurred from the year 2004 to 2007 (p<.05 to p<.001)
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Female , Cross Infection , Enterobacteriaceae , Microbiological Techniques , Infection Control , Pharmacology, ClinicalABSTRACT
OBJECTIVE To investigate in vitro antibacterial activity of meropenem in Gram-negative bacilli isolated from clinical specimens.METHODS Gram-negative bacilli were isolated from various clinical specimens in our hosptial from Jan 2008 to Dec 2008.The identification test was determined by VITEK-32 Full Automated Microbiology Analyzer,the antimicrobiol susceptibility was detected by K-B method.RESULTS The resistance rate of Enterobacteriaceae to meropenem was extremly low.The resistance rates of Escherichia coli,Klebsiella pneumoniae and Enterobacter cloacae to meropenem were 0,27.6% and 4.2%.The resistance rates of Stenotrophomonas maltophilia,Burkholderia cepacia,Chryseobacterium meningosepticum,Pseudomonas aeruginosa and Acinetobacter baumannii to meropenem were 100.00%,48.81%,94.12%,21.85% and 31.72% respectively.CONCLUSIONS Meropenem has high in vitro antimicrobial activity to Enterobacteriaceae.but generally low to non-fermentative Gram-negative bacilli.
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BACKGROUND: Ventilator-associated pneumonia caused by multi-drug resistant Acinetobacter baumannii has been increasing and growing as a threat in intensive care units. Limited therapeutic options have forced clinicians to choose colistin with or without combination of other antibiotics. We tried to compare the effectiveness between colistin monotherapy and combination therapy based on in vitro synergistic tests. METHODS: From January 2006 to December 2007 in medical ICU of a tertiary care hospital in Korea, We reviewed the medical records of patients treated with intravenous colistin due to ventilator-associated pneumonia caused by multi-drug resistant Acinetobacter baumannii. RESULTS: A total of 41 patients were analyzed. 22 patients had been treated with colistin monotherapy and 19 patients with colistin and combination antibiotics that were found to have in vitro synergistic effects. Baseline characteristics were similar in both groups but the mean duration of colistin administration was significantly longer in the combination group (19.1+/-11.2 days vs. 12.3+/-6.8 days, p=0.042). There were no significant differences in outcome variables between the two groups. CONCLUSION: Combination treatment based on the in vitro antimicrobial synergy test did not show better outcomes compared with colistin monotherapy in VAP caused by multi-drug resistant A. baumannii.