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b lactamics

Seyedehameneh Jahanbakhsh, Nivedita B Singh, Juwon Yim, Warren E Rose, Michael J Rybak
Biofilm-producing methicillin-resistant Staphylococcus aureus (MRSA) infections are challenging due to increasing antibiotic resistance. Synergistic activity of lipopeptides and lipoglycopeptides with β-lactams has been demonstrated for MRSA, but little is known about biofilm-embedded organisms. Our objective was to evaluate two telavancin (TLV) dosage regimens (7.5 mg/kg and 10 mg/kg q 24h)alone and in combination with ceftaroline (CPT) (600 mg q 8 h) or rifampin (RIF) (450 mg q 12h) against two biofilm-producing MRSA (494 and N315)...
May 21, 2018: Antimicrobial Agents and Chemotherapy
Gregory Balabanian, Michael Rose, Nyla Manning, David Landman, John Quale
Imipenem with relebactam is a novel β-lactam-β-lactamase inhibitor that has activity against most KPC-producing Enterobacteriaceae. Using 10 isolates of KPC-possessing Klebsiella pneumoniae, we assessed the relationship between imipenem-relebactam minimum inhibitory concentrations (MICs) and mechanisms known to contribute to antimicrobial resistance. The effect of adding a second agent was assessed by time-kill experiments. Mutations affecting the genes encoding porins ompK35 and ompK36 and identification of β-lactamases were assessed by PCR...
May 21, 2018: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
Lisa Niemann, Petra Müller, Jasmin Brauns, Rolf Nathaus, Franziska Schäkel, Kerstin Kipschull, Doris Höltig, Michael Wendt, Stefan Schwarz, Kristina Kadlec
The collaboration project VASIB aims at reducing the antibiotic consumption in pig production by integrating information from consulting expertise in clinical inspection, hygiene, epidemiology, microbiology and pharmacology. In this VASIB subproject, we investigated the antimicrobial susceptibility and relatedness of porcine respiratory tract pathogens. Bordetella bronchiseptica (n = 47), Pasteurella multocida (n = 18) and Streptococcus suis (n = 58) were obtained from weaner pigs at two farms. Antimicrobial susceptibility testing was performed by broth microdilution according to CLSI standards...
June 2018: Veterinary Microbiology
M Ponraj, Biswajit Dubashi, B H Harish, S Kayal, S L Cyriac, Jogamaya Pattnaik, K Ranjith, Unni S Pillai, Naresh Jadhav, Kiran K Matta, Jagdeep Singh, Esha Jaffa, Bhanu Prakash
PURPOSE: Beta lactams are standard empirical therapy for febrile neutropenia (FN). The aim of this study was to evaluate the efficacy and safety of cefepime monotherapy compared with cefoperazone/sulbactam plus amikacin (CS + A) for empirical treatment of high risk FN. METHODS: One hundred seventy-five patients with 336 FN episodes were randomized to receive either cefepime (2 g q8h for adults and 50 mg/kg q8h for children) or CS (2 g q8h for adults and 50 mg/kg q8h for children) plus amikacin (15 mg/kg once a day)...
May 17, 2018: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
Ka Lip Chew, Michelle K L Tay, Bernadette Cheng, Raymond T P Lin, Sophie Octavia, Jeanette W P Teo
Newly approved Food and Drug Administration (FDA) β-lactam-β-lactamase inhibitor (βL-βLI) inhibitor combinations such as ceftazidime-avibactam and meropenem-vaborbactam are potent inhibitors of class A carbapenemase (typified by KPC [ Klebsiella pneumoniae carbapenemase]-like) (1, 2) but are ineffective against carbapenemase-producing Enterobacteriaceae (CPE) producing class B metallo-β-lactamases (MβLs) such as New Delhi metallo-β-lactamase (NDM) (1-4).….
May 14, 2018: Antimicrobial Agents and Chemotherapy
Anna Mette Hansen, Pai Peng, Mara Baldry, Iris Perez-Gassol, Simon B Christensen, Joachim Møllesøe Obel Vinther, Hanne Ingmer, Henrik Franzyk
Emergence of antibiotic-resistant bacteria constitutes an increasing threat to human health. For example, treatment options for Staphylococcus aureus infections is declining with the worldwide spreading of highly virulent community-associated methicillin-resistant S. aureus (CA-MRSA) strains. Anti-virulence therapy has been proposed as an alternative treatment strategy, as it typically involves inhibition of expression of virulence factors rather than direct bacterial killing, thereby attenuating the risk of resistance development...
April 28, 2018: European Journal of Medicinal Chemistry
B Roese de Lima, G F Nicoloso, C C Fatturi-Parolo, M B C Ferreira, F Montagner, L Casagrande
AIM: To determine the presence of Prevotella species, the cfxA/cfxA2, blaZ and blaTEM genes associated with resistance to lactamic agents in different oral niches of children with pulp necrosis. METHODOLOGY: Children with pulp necrosis in primary teeth had samples of saliva, supragingival, pulp chamber and root canal biofilms collected and tested for Prevotella species (P. intermedia, P nigrescens, P. tannerae) and for beta-lactam resistance genes (cfxA / cfxA2, blaZ and blaTEM)...
May 8, 2018: International Endodontic Journal
Shusuke Tomoshige, David A Dik, Masaaki Akabane-Nakata, Chinedu Madukoma, Jed F Fisher, Joshua D Shrout, Shahriar Mobashery
The bulgecins are iminosaccharide secondary metabolites of the Gram-negative bacterium Paraburkholderia acidophila and inhibitors of lytic transglycosylases of bacterial cell-wall biosynthesis and remodeling. The activities of the bulgecins are intimately intertwined with the mechanism of a co-biosynthesized β-lactam antibiotic. β-Lactams inhibit the penicillin-binding proteins, enzymes also critical to cell-wall biosynthesis. The simultaneous loss of the lytic transglycosylase (by bulgecin) and penicillin-binding protein (by β-lactams) activities results in deformation of the septal cell wall, observed microscopically as a bulge preceding bacterial cell lysis...
May 1, 2018: ACS Infectious Diseases
Dhruvitkumar S Sutaria, Bartolome Moya, Kari B Green, Tae Hwan Kim, Xun Tao, Yuanyuan Jiao, Arnold Louie, George L Drusano, Jürgen B Bulitta
Penicillin-binding proteins (PBPs) are the high affinity target sites of all β-lactam antibiotics in bacteria. It is well known that each β-lactam covalently binds to and thereby inactivates different PBPs with varying affinity. Despite β-lactams serving as cornerstone of our therapeutic armamentarium against Klebsiella pneumoniae , PBP binding data are missing for this pathogen. We aimed to generate the first PBP binding data on 13 chemically diverse and clinically relevant β-lactams and β-lactamase inhibitors in K...
April 30, 2018: Antimicrobial Agents and Chemotherapy
Stephanie M Forget, Andrew W Robertson, Steven R Hall, Jeanna M MacLeod, David P Overy, Russell G Kerr, Kerry B Goralski, David L Jakeman
Herein, we report the characterization and antimicrobial activity of a previously unreported jadomycin (1) obtained from a culture of S. venezuelae ISP5230 with L-ornithine (Orn). 1 arises from the rearrangement of a putative five-membered ring containing jadomycin incorporating Orn, whereby intramolecular attack of the E-ring carbonyl from the δ-NH2 group of the Orn side chain results in collapse of the oxazolone ring and formation of a stable six-membered lactam. This rearrangement produces a jadomycin with a 3a hemiaminal position that is susceptible to solvolysis...
April 26, 2018: Journal of Antibiotics
I M Leon, S D Lawhon, K N Norman, D S Threadgill, N Ohta, J Vinasco, H M Scott
Although Salmonella enterica can produce life-threatening colitis in horses, certain serotypes are more commonly associated with clinical disease. Our aim was to evaluate the proportional morbidity attributed to different serotypes, as well as phenotypic and genotypic antimicrobial resistance (AMR) of Salmonella isolated from patients at an equine referral hospital in the southern United States. Two-hundred-fifty-five Salmonella isolates were obtained from clinical samples of patients admitted to the hospital between 2007 and 2015...
April 20, 2018: Applied and Environmental Microbiology
Asabe Halimat Momoh, Jacob K P Kwaga, Mohammed Bello, Anthony K B Sackey, Anders Rhod Larsen
Staphylococcus aureus is a commensal and pathogenic bacterium with impact on public health and livestock industry. The study investigated nasal carriage, antibiotic resistance, and molecular characterization of S. aureus in pigs and pig workers. Nasal swabs from 300 backyard-raised pigs and 101 pig workers were used for the study. Resulting isolates were confirmed using MALDI-TOF MS, tested for antibiotic resistance, and three different multiplex PCRs were used to detect enterotoxin, mecA, spaA, scn, and pvl genes...
April 19, 2018: Tropical Animal Health and Production
Vivek Keshri, Arup Panda, Anthony Levasseur, Jean-Marc Rolain, Pierre Pontarotti, Didier Raoult
β-lactamases are enzymes which are commonly produced by bacteria and which degrade the β-lactam ring of β-lactam antibiotics, namely penicillins, cephalosporins, carbapenems, and monobactams, and inactivate these antibiotics. We performed a rational and comprehensive investigation of β-lactamases in different biological databases. In this study, we constructed hidden Markov model profiles as well as the ancestral sequence of four classes of β-lactamases (A, B, C, and D), which were used to identify potential β-lactamases from environmental metagenomic (1206), human microbiome metagenomic (6417), human microbiome reference genome (1310), and NCBI's nonredundant databases (44101)...
April 1, 2018: Genome Biology and Evolution
Daniëlle Copmans, Mostafa Rateb, Jioji N Tabudravu, Mercedes Pérez-Bonilla, Nina Dirkx, Riccardo Vallorani, Caridad Diaz, José Pérez Del Palacio, Alan J Smith, Rainer Ebel, Fernando Reyes, Marcel Jaspars, Peter A M de Witte
In search for novel antiseizure drugs (ASDs), the European FP7-funded PharmaSea project used zebrafish embryos and larvae as a drug discovery platform to screen marine natural products to identify promising antiseizure hits in vivo for further development. Within the framework of this project, seven known heterospirocyclic γ-lactams, namely, pseurotin A, pseurotin A2 , pseurotin F1, 11- O-methylpseurotin A, pseurotin D, azaspirofuran A, and azaspirofuran B, were isolated from the bioactive marine fungus Aspergillus fumigatus, and their antiseizure activity was evaluated in the larval zebrafish pentylenetetrazole (PTZ) seizure model...
April 19, 2018: ACS Chemical Neuroscience
Lenka Sedláčková, Miroslav Průcha, Ingrid Poláková, Blanka Míková
The current diagnostic algorithm for beta-lactam allergy is based on skin and provocation tests, both of which carry a certain risk of inducing hypersensitivity reactions. Thus, non-invasive in vitro tests reliable enough to replace skin and provocation tests at least in a portion of patients are desirable. We aimed to verify the utility of IFN-γ ELISPOT as a first-line test in patients with suspected non-immediate hypersensitivity reaction to amoxicillin (AMX) and penicillin (PNC). The prospective observational study included 24 patients with recent, suspected non-immediate hypersensitivity reaction to AMX or PNC and 6 recently-exposed healthy subjects...
2018: Prague Medical Report
Eva Soršak, Julija Volmajer Valh, Špela Korent Urek, Aleksandra Lobnik
This study presents chemical modification of a Rhodamine B (RhB) sensor probe by ethylenediamine (EDA), and investigation of its spectral as well as sensor properties to the various metals. The synthesised N -(Rhodamine-B)-lactam-ethylenediamine (RhB-EDA) fluorescent probe shows interesting optical sensor properties, and high sensitivity and selectivity to Ag⁺ ions among all the tested metal ions (K⁺, Mg2+ , Cu2+ , Ni2+ , Fe2+ , Pb2+ , Na⁺, Mn2+ , Li⁺, Al3+ , Co2+ , Hg2+ , Sr2+ , Ca2+ , Ag⁺, Cd2+ and Zn2+ ), while the well-known Rhodamine B (RhB) fluorescent probe shows much less sensitivity to Ag⁺ ions, but high sensitivity to Fe2+ ions...
April 14, 2018: Sensors
Margareth Sidarta, Dongdong Li, Lars Hederstedt, Ewa Bukowska-Faniband
SpoVD and PBP4b are structurally very similar high molecular weight, class B, penicillin-binding proteins produced early during sporulation in Bacillus subtilis SpoVD is known to be essential for endospore cortex synthesis and thereby production of heat-resistant spores. The role of PBP4b is still enigmatic. Both proteins are synthesized in the cytoplasm of the mother cell. PBP4b remains in the cytoplasmic membrane of the mother cell whereas SpoVD accumulates in the forespore outer membrane. By the use of SpoVD/PBP4b chimeras with swapped protein domains we show that the N-terminal part of SpoVD, containing the single transmembrane region, determines forespore targeting of the protein...
April 16, 2018: Journal of Bacteriology
Nurul Iman Mohamad, Azian Harun, Habsah Hasan, Zakuan Zainy Deris
Although doxycycline is active against Burkholderia pseudomallei and has been used in the eradication stage of melioidosis therapy, it is not regularly used during the initial intensive phase. In order to assess its potential use in intensive phase therapy, we investigated in vitro pharmacodynamic activity of doxycycline and β-lactams alone and in combination against four Malaysian strains of B. pseudomallei. Using a checkerboard assay, the combinations of doxycycline and imipenem, doxycycline and ceftazidime, and doxycycline and amoxicillin-clavulanate tested against four strains showed indifferent effects with summation fractional inhibitory concentration values ranging from 0...
June 2018: Indian Journal of Microbiology
Juri Katchanov, Lucia Asar, Eva-Maria Klupp, Anna Both, Camilla Rothe, Christina König, Holger Rohde, Stefan Kluge, Florian P Maurer
OBJECTIVES: To determine the spectrum of infections with multidrug-resistant Gram-negative bacteria (MDR-GNB) and the clinical impact of the newly available betalactam/betalactamase inhibitor combinations ceftolozane/tazobactam and ceftazidime/avibactam in a German academic tertiary care center. METHODS: Retrospective analysis. RESULTS: Between September 1, 2015 and August 31, 2016, 119 individual patients (0.22% of all hospital admissions) were colonized or infected with carbapenem-resistant MDR-GNB...
2018: PloS One
Dmitry V Amakhin, Elena B Soboleva, Aleksey V Zaitsev
Cephalosporins are beta-lactam antibiotics that are extensively used in medical practice and are reported to cause epileptic seizures in some patients. The primary cause of cephalosporin-induced convulsions is believed to be their ability to block GABAa receptors. However, direct evidence for the involvement of this mechanism has not yet been provided. The present study aims to investigate the ability of two cephalosporins - cefepime and ceftriaxone - to block inhibitory synaptic transmission in entorhinal cortex slices of rats...
April 3, 2018: Biochemical and Biophysical Research Communications
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