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Irene Galani, Konstantina Nafplioti, Marianthi Chatzikonstantinou, Maria Souli
PURPOSE: The aim of this study was to evaluate the in vitro activity of double-carbapenem combinations against OXA-48-producing Klebsiella pneumoniae clinical isolates. METHODOLOGY: Double combinations of ertapenem, meropenem and imipenem were evaluated for synergy and bactericidal activity using the time-kill methodology. All antibiotics were tested at 10 mg l-1 and at a sub-inhibitory concentration of 0.5× minimum inhibitory concentration (MIC) for isolates with a carbapenem MIC≤8 mg l-1 ...
March 21, 2018: Journal of Medical Microbiology
Xingyu Zhang, Di Chen, Guifeng Xu, Weichun Huang, Xing Wang
Infection by carbapenem-resistant Klebsiella pneumoniae (CR-KP) is a public health challenge worldwide, in particular among children, which was associated with high morbidity and mortality rates. There was limited data in pediatric populations, thus this study aimed to investigate molecular epidemiology and drug resistant mechanism of CR-KP strains from pediatric patients in Shanghai, China. A total of 41 clinical CR-KP isolates from sputum, urine, blood or drainage fluid were collected between July 2014 and May 2015 in Shanghai Children's Medical Center...
2018: PloS One
Deng-Yuan Li, Zheng-Lu Huang, Pei-Nian Liu
The heterobicyclic core retained hydroarylation of oxa/azabenzonorbornadienes with quinoline N-oxides has been achieved under rhodium catalysis, giving quinoline N-oxide substituted heterobicyclic structures with excellent regioselectivity and in good yields. As the first example of the direct introduction of quinoline N-oxides onto heterobicyclic structures, the strained heterobicyclic core was well retained in the reaction. The products could be successfully transformed into a series of useful compounds, including epibatidine analogues...
March 20, 2018: Organic Letters
Bahare Salehi, Hossein Goudarzi, Bahram Nikmanesh, Hamidreza Houri, Mostafa Alavi-Moghaddam, Zohreh Ghalavand
RATIONALE: Acinetobacter baumannii is one of the antibiotic-resistant superbugs that threatens hospitalized patients. Emergence and spread of the multidrug-resistant (MDR) and extensively drug-resistant (XDR) clones cause erratic outbreaks following environmental contamination of hospital settings. OBJECTIVE: The present study intended to characterize the antimicrobial resistant profiles and the genotypes of clinical and environmental isolates of A. baumannii as a result of dissemination of resistant strains...
March 16, 2018: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
Ledys S Copete-Pertuz, Jersson Plácido, Efraím A Serna-Galvis, Ricardo A Torres-Palma, Amanda Mora
In this work, Leptosphaerulina sp. (a Colombian native fungus) significantly removed three Isoxazolyl-Penicillin antibiotics (IP): oxacillin (OXA, 16000 μg L-1 ), cloxacillin (CLX, 17500 μg L-1 ) and dicloxacillin (DCX, 19000 μg L-1 ) from water. The biological treatment was performed at pH 5.6, 28 °C, and 160 rpm for 15 days. The biotransformation process and lack of toxicity of the final solutions (antibacterial activity (AA) and cytotoxicity) were tested. The role of enzymes in IP removal was analysed through in vitro studies with enzymatic extracts (crude and pre-purified) from Leptosphaerulina sp...
March 2, 2018: Science of the Total Environment
Joseph D Lutgring, Wenming Zhu, Tom J B de Man, Johannetsy J Avillan, Karen F Anderson, David R Lonsway, Lori A Rowe, Dhwani Batra, J Kamile Rasheed, Brandi M Limbago
Oxacillinase (OXA)-48-like carbapenemases remain relatively uncommon in the United States. We performed phenotypic and genotypic characterization of 30 Enterobacteriaceae producing OXA-48-like carbapenemases that were recovered from patients during 2010-2014. Isolates were collected from 12 states and not associated with outbreaks, although we could not exclude limited local transmission. The alleles β-lactamase OXA-181 (blaOXA-181 ) (43%), blaOXA-232 (33%), and blaOXA-48 (23%) were found. All isolates were resistant to ertapenem and showed positive results for the ertapenem and meropenem modified Hodge test and the modified carbapenem inactivation method; 73% showed a positive result for the Carba Nordmann-Poirel test...
April 2018: Emerging Infectious Diseases
Mohammed Sami Alhaddad, Afnan Khalifah AlBarjas, Lolowah Ebraheem Alhammar, Abdullatif Sami Al Rashed, Lorina Ineta Badger-Emeka
Background: Acinetobacter baumannii , is an emerging nosocomial multidrug resistance pathogen with the rapid spread of clones being reported in health-care settings and hospitals worldwide. Carbapenem resistance in this bacterium has been attributed to D OXA β-lactamases with OXA-51-like β-lactamase, being present in all A. baumannii isolate. The present study looks into the antibiotics susceptibility and molecular characterization of clinical A. baumannii isolates from Intensive Care Unit (ICU) samples in Al-Hofuf, South-eastern region of Saudi Arabia...
January 2018: International Journal of Applied and Basic Medical Research
Carlos Hernán Rodríguez, Marcela Nastro, Angela Famiglietti
Carbapenem resistance in gram-negative bacteria by production of carbapenemases is one of the most challenging issues regarding healthcare worldwide. We review the epidemiology and prevalence of carbapenemases in carbapenem-resistant Acinetobacter baumannii isolates from Latin American countries. High resistance rates to antimicrobial agents, particularly to carbapenems, are observed in this region. OXA-23 is the most widely disseminated class D-carbapenemase; it is present in all the countries of the region and is frequently associated to endemic clones CC113/CC79, CC104/CC15, CC110/ST25 and CC109/CC1...
March 13, 2018: Revista Argentina de Microbiología
Pınar Sağıroğlu, Ufuk Hasdemir, Gülşen Altınkanat Gelmez, Burak Aksu, Onur Karatuna, Güner Söyletir
In this study, the performance of the "RESIST-3 O.K.N. K-SeT" (Coris BioConcept, Gembloux, Belgium) immunochromatographic assay was evaluated in 132 Klebsiella pneumoniae comprising 102 carbapenem resistant and 30 carbapenem susceptible isolates. Genotypically known isolates of Gram negative bacteria (n=22) including various species were also tested by the assay as controls. The isolates tested by the immunochromatographic assay and also were run PCR for blaKPC , blaIMP , blaVIM , blaNDM , and blaOXA-48 ...
March 1, 2018: Brazilian Journal of Microbiology: [publication of the Brazilian Society for Microbiology]
Laurent Dortet, Sandrine Bernabeu, Camille Gonzalez, Thierry Naas
The objective of this study was to assess the performance of the Carbapenemase Detection Set™ (CDS; Mast Diagnostics) in association with i) the EUCAST meropenem screening cut-off and ii) the faropenem-temocillin algorithm (FTa) for the screening of carbapenemase-producing Enterobacteriaceae (CPE). A total of 200 well-characterized enterobacterial isolates with reduced susceptibility to at least one carbapenem including 63 non-CPEs and 137 CPEs belonging to different Ambler classes were initially screened for CPEs using i) the EUCAST meropenem cut-off (diameter <25 mm) and ii) the FTa...
February 17, 2018: Diagnostic Microbiology and Infectious Disease
Omnia A Shaker, Howayda E Gomaa, Shereen A ElMasry, Rania M Abdel Halim, Amany H Abdelrahman, Jackline S Kamal
AIM: To evaluate the diagnostic performance of MDI and temocillin disk (30 μg) for detection of carbapenem-resistant Enterobacteriaceae in comparison to real-time PCR. MATERIAL AND METHODS: Fifty specimens submitted to the Microbiology Laboratory of Ain Shams University Hospitals and showed resistance to carbapenem drugs through routine culture and susceptibility testing, were assessed by both temocillin disk (30 μg) and MDI set to detect carbapenem-resistant Enterobacteriaceae ...
February 15, 2018: Open Access Macedonian Journal of Medical Sciences
Martin Everett, Nicolas Sprynski, Alicia Coelho, Jérôme Castandet, Maëlle Bayet, Juliette Bougnon, Clarisse Lozano, David T Davies, Simon Leiris, Magdalena Zalacain, Ian Morrissey, Sophie Magnet, Kirsty Holden, Peter Warn, Filomena De Luca, Jean-Denis Docquier, Marc Lemonnier
Infections caused by carbapenem-resistant Enterobacteriaceae (CRE) are increasingly prevalent and have become a major worldwide threat to human health. Carbapenem resistance is driven primarily by the acquisition of β-lactamase enzymes which are able to degrade carbapenem antibiotics (hence termed carbapenemases) and can result in high levels of resistance and treatment failure. Clinically relevant carbapenemases include both serine-β-lactamases (SBLs, e.g. KPC-2 and OXA-48) and metallo-β-lactamases (MBLs), such as NDM-1...
March 12, 2018: Antimicrobial Agents and Chemotherapy
Carole Ayoub Moubareck, Shaimaa F Mouftah, Tibor Pál, Akela Ghazawi, Dalal H Halat, Anju Nabi, Mouza A AlSharhan, Zulfa O AlDeesi, Christabel C Peters, Handan Celiloglu, Manjunath Sannegowda, Dolla K Sarkis, Ágnes Sonnevend
Few studies have addressed the molecular epidemiology of carbapenem resistant Enterobacteriaceae (CRE) isolates in the Arabian Peninsula, and such investigations have been missing from Dubai, a major economical, tourism and medical centre of the region. The antibiotic susceptibility, the carbapenemase type produced, and the clonality of 89 CRE strains isolated in five major Dubai hospitals in June 2015 - June 2016 were determined. Thirty three percent of the collection of 70 K. pneumoniae, 13 E. coli and 6 other Enterobacteriaceae were extremely drug resistant, 27% were resistant to colistin, and 4...
March 9, 2018: International Journal of Antimicrobial Agents
Michelle H Fung, Kārlis Bērziņš, Raj Suryanarayanan
In an earlier investigation, coamorphous systems of ketoconazole (KTZ) prepared with each oxalic (OXA), tartaric (TAR), citric (CIT) and succinic (SUC) acid, revealed drug-acid ionic and/or hydrogen bonding interactions in the solid-state (Fung et al, Mol Pharmaceutics, 2018, 15(x), xxxx-yyyy). We showed that the drug-acid interactions in KTZ-TAR were the strongest, followed by KTZ-OXA, KTZ-CIT and KTZ-SUC. In this study, we investigated the crystallization propensity and dissolution behavior of the KTZ-acid coamorphous systems...
March 12, 2018: Molecular Pharmaceutics
Aliakbar Rezaei, Hossein Fazeli, Mehdi Moghadampour, Mehrdad Halaji, Jamshid Faghri
Acinetobacter baumannii is one of the most important bacterial species with the ability to produce OXA-type carbapenemases. We aimed to evaluate the prevalence of OXA-type carbapenemases among clinical isolates of A. baumannii in three major hospitals of Isfahan. In this cross-sectional descriptive study, 153 non-repeated strains of A. baumannii were isolated from various clinical samples of hospitalized patients in Al-Zahra, Imam Mousa Kazem, and Shariati hospitals from October 2015 to October 2016. Antimicrobial susceptibility testing for imipenem, meropenem, ertapenem, cefepime, ceftazidime, ceftriaxone, piperacillin-tazobactam, gentamicin, amikacin, ciprofloxacin, and tetracycline was performed using the disk diffusion method...
March 1, 2018: Le Infezioni in Medicina
Violeta Beleva Guthrie, David L Masica, Andrew Fraser, Joseph Federico, Yunfan Fan, Manel Camps, Rachel Karchin
The evolution of new biochemical activities frequently involves complex dependencies between mutations and rapid evolutionary radiation. Mutation co-occurrence and co-variation have previously been used to identify compensating mutations that are the result of physical contacts and preserve protein function and fold. Here, we model pairwise functional dependencies and higher order interactions that enable evolution of new protein functions. We use a network model to find complex dependencies between mutations resulting from evolutionary trade-offs and pleiotropic effects...
March 7, 2018: Molecular Biology and Evolution
Hamid Solgi, Farzad Badmasti, Christian G Giske, Shadi Aghamohammad, Fereshteh Shahcheraghi
Objectives: Despite the fact that the blaOXA-48 and blaNDM-1 genes have successfully disseminated among Klebsiella pneumoniae isolates worldwide, outbreaks remain unidentified in Iran. Here we examined the molecular epidemiology of 96 carbapenem-resistant K. pneumoniae recovered from an Iranian hospital. Methods: A total of 96 non-replicate carbapenem-resistant K. pneumoniae were recovered from clinical specimens in a university hospital. Detection of ESBLs and carbapenemases produced by studied strains was performed using PCR and DNA sequencing...
March 6, 2018: Journal of Antimicrobial Chemotherapy
Michael A Pfaller, Michael D Huband, Rodrigo E Mendes, Robert K Flamm, Mariana Castanheira
We evaluated meropenem-vaborbactam activity against 11,559 Enterobacteriaceae isolates, including 330 carbapenem-resistant phenotypes (CRE) and carbapenemase genotypes collected worldwide during 2015. Meropenem-vaborbactam (inhibitor at 8 mg/L) and comparators were susceptibility tested using reference broth microdilution methods. CRE isolates were screened for the presence of genes encoding carbapenemases and 292 (88.5%) of the CRE isolates carried these resistance genes. A total of 209 (63.3% of the CRE; 1...
March 3, 2018: International Journal of Antimicrobial Agents
Yu Chen, Christian Paetz, Bernd Schneider
Phenylbenzoisochromenone glucosides (oxa-phenylphenalenone glucosides) occurring in some phenylphenalenone-producing plants of the Haemodoraceae undergo conversion to phenylbenzoisoquinolindiones (aza-phenylphenalenones) in extracts of Xiphidium caeruleum. Precursor-directed biosynthetic experiments were used to generate a series of new phenylbenzoisoquinolindiones from native phenylbenzoisochromenone glucosides and external amines, amino acids, and peptides. Intermediates of the conversion were isolated, incubated with cell-free extracts, and exposed to reactions under oxidative or inert conditions, respectively, to elucidate the entire pathway from phenylbenzoisochromenones to phenylbenzoisoquinolindiones...
March 6, 2018: Journal of Natural Products
Tian-Wen Sun, Dong-Dong Liu, Kuang-Yu Wang, Bingqi Tong, Jia-Xin Xie, Yanlong Jiang, Yong Li, Bo Zhang, Yi-Fan Liu, Yuan-Xian Wang, Jia-Jun Zhang, Jia-Hua Chen, Zhen Yang
The stereoselective construction of the CDEFGH ring system of lancifodilactone G is described. The key steps in this synthesis are i) ring-closing metathesis for formation of the oxa-bridged eight-membered ring; ii) an intramolecular Pauson-Khand reaction for construction of the sterically congested F ring; and iii) sequential cross-metathesis, hydrogenation, and lactonization reactions for installation of the anomerically stabilized bis-spiro ketal fragment of lancifodilactone G.
March 6, 2018: Journal of Organic Chemistry
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