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Antimicrobial Agents and Chemotherapy

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https://www.readbyqxmd.com/read/28320728/mutations-at-arg220-and-thr237-in-per-2-%C3%AE-lactamase-impact-on-conformation-activity-and-susceptibility-to-inhibitors
#1
Melina Ruggiero, Lucrecia Curto, Florencia Brunetti, Eric Sauvage, Moreno Galleni, Pablo Power, Gabriel Gutkind
PER-2 accounts for up to 10% of oxyimino-cephalosporin resistance in Klebsiella pneumoniae and Escherichia coli in Argentina, and hydrolyzes both cefotaxime and ceftazidime with high catalytic efficiencies (kcat/Km). Through crystallographic analyses, we recently proposed the existence of a hydrogen-bond network connecting Ser70-Gln69-oxyanion water-Thr237-Arg220 that might be important for the activity and inhibition of the enzyme. Mutations at Arg244 in most class A β-lactamases (as TEM and SHV) reduce susceptibility to mechanism-based inactivators, and Arg220 in PER β-lactamases is equivalent to Arg244...
March 20, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28320727/primary-clofazimine-and-bedaquiline-resistance-among-isolates-from-patients-with-multidrug-resistant-tuberculosis
#2
Jian Xu, Bin Wang, Minghao Hu, Fengmin Huo, Shaochen Guo, Wei Jing, Eric Nuermberger, Yu Lu
Clofazimine has been repurposed for the treatment of tuberculosis especially for MDR-TB. To test the susceptibility to clofazimine for Mycobacterium tuberculosis clinical isolates, MICs of clofazimine were determined using the microplate Alamar blue assay (MABA) method for 80 drug-resistant isolates and 10 drug-susceptible isolates for comparison. Five clofazimine-resistant strains isolated from previously treated pre-XDR and XDR-TB patients without prior exposure to clofazimine or bedaquiline had clofazimine MICs ≥1...
March 20, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28320726/glucantime%C3%A2-causes-oxidative-stress-derived-dna-damage-in-balb-c-mice-infected-by-leishmania-leishmania-infantum
#3
Vanessa Ribeiro Moreira, Luís Cláudio Lima de Jesus, Rossy-Eric Pereira Soares, Luis Douglas Miranda Silva, Bruno Araújo Serra Pinto, Maria Norma Melo, Antonio Marcus de Andrade Paes, Silma Regina Ferreira Pereira
Leishmaniasis is a neglected tropical disease caused by over 20 species of the protozoan parasite Leishmania Regarding treatment, Glucantime® is the first-choice drug recommended by the World Health Organization for the treatment of all types of leishmaniasis. However, the mechanisms of action and toxicity of pentavalent antimonials, including genotoxic effetcs, remain unclear. Therefore, the mechanism by which Glucantime® causes DNA damage was investigated in BALB/c mice infected by Leishmania (Leishmania) infantum and treated with Glucantime® (20 mg/kg for 20 days)...
March 20, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28320725/occurrence-of-acquired-16s-methyltransferase-mediated-aminoglycoside-resistance-in-clinical-isolates-of-enterobacteriaceae-within-a-tertiary-referral-hospital-of-northeast-india
#4
Jayalaxmi Wangkheimayum, Deepjyoti Paul, Debadatta Dhar, Rajlakshmi Nepram, Shiela Chetri, Deepshikha Bhowmik, Atanu Chakravarty, Amitabha Bhattacharjee
Objectives: Methylation of ribosomal target leads to a high level of resistance towards the entire clinically relevant aminoglycoside antibiotics, so early detection of these resistant determinants will help to reduce the treatment failure as well as will lessen the dissemination rate. Here, we characterize different 16s methyltransferase responsible for aminoglycoside resistance and their epidemiological background in clinical isolates of enterobacteriaceae in a tertiary referral hospital of India.Methods: All aminoglycoside resistant isolates were screened for different 16s methyltransferase by PCR assay and incompatibility typing of the conjugable plasmid harboring resistant genes was determined by PCR based replicon typing...
March 20, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28320724/piperacillin-tazobactam-versus-other-antibacterial-agents-for-treatment-of-bloodstream-infections-due-to-ampc-beta-lactamase-producing-enterobacteriaceae
#5
Lucy Cheng, Brian C Nelson, Monica Mehta, Nikhil Seval, Sarah Park, Marla J Giddins, Qiuhu Shi, Susan Whittier, Angela Gomez-Simmonds, Anne-Catrin Uhlemann
In vivo induction of AmpC beta-lactamases produces high-level resistance to many beta-lactam antibiotics in Enterobacteriaceae, often resulting in the use of carbapenems or cefepime (FEP). The clinical effectiveness of piperacillin-tazobactam (TZP), a weak inducer of AmpC beta-lactamases, is poorly understood. Here we conducted a case-control study of adult inpatients with bloodstream infections (BSIs) due to Enterobacter, Serratia, or Citrobacter spp. from 2009 to 2015 to assess outcomes following treatment with TZP compared to FEP or meropenem (MEM)...
March 20, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28320723/amoebicidal-activity-of-caffeine-and-maslinic-acid-by-the-induction-of-programmed-cell-death-in-acanthamoeba
#6
Carmen M Martín-Navarro, Atteneri López-Arencibia, Ines Sifaoui, María Reyes-Battle, Emilie Fouque, Antonio Osuna, Basilio Valladares, José E Piñero, Yann Héchard, Sutherland K Maciver, Jacob Lorenzo-Morales
Free living amoebae of the genus Acanthamoeba are the causal agents of a sight threatening ulceration of the cornea called Acanthamoeba keratitis, and the rare but usually fatal granulomatous amoebic encephalitis. Although there are many therapeutic options for the treatment of Acanthamoeba infections, they are generally lengthy and/or have limited efficacy. For the best clinical outcome, the treatments should target both the trophozoite and the cyst stages as the later are known to confer resistance to treatment...
March 20, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28320722/in-vitro-and-in-vivo-antibacterial-activities-of-patchouli-alcohol-a-natural-occurring-tricyclic-sesquiterpene-against-helicobacter-pylori-infection
#7
Y F Xu, D W Lian, Y Q Chen, Y F Cai, Y F Zheng, P L Fan, W K Ren, L J Fu, Y C Li, J H Xie, H Y Cao, B Tan, Z R Su, P Huang
This study further evaluated the in vitro and in vivo anti-Helicobacter pylori activity and potential underlying mechanism of patchouli alcohol (PA), a tricyclic sesquiterpene. In in vitro assay, the capacities of PA to inhibit and kill H. pylori were tested on three standard strains at different pH values and 12 clinical isolates. The effects of PA on H. pylori adhesion (and its alpA, alpB and babA genes), motility (and its flaA and flaB genes), ultrastructure and flagellation were investigated. Moreover, the H...
March 20, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28320721/a-library-of-seleno-compounds-and-leishmania-species-rising-evidences-towards-novel-agents
#8
Álvaro Martín-Montes, Daniel Plano, Rubén Martín-Escolano, Verónica Alcolea, Marta Díaz, Silvia Pérez-Silanes, Socorro Espuelas, Esther Moreno, Clotilde Marín, Ramón Gutiérrez-Sánchez, Carmen Sanmartín, Manuel Sánchez-Moreno
In vitro leishmanicidal activity of a series of forty-eight selenium derivatives, recently synthesized, was tested on Leishmania infantum and Leishmania braziliensis parasites, using promastigotes and intracellular amastigote forms. The cytotoxicity of the tested compounds on J774.2 macrophage cells was also measured in order to establish their selectivity. Six of the tested compounds (8, 10, 11, 15, 45 and 48) showed selectivity indexes higher than those of the reference drug Glucantime for both Leishmania species; in the case of L...
March 20, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28320720/moraxella-species-as-potential-sources-of-mcr-like-polymyxin-resistance-determinants
#9
Nicolas Kieffer, Patrice Nordmann, Laurent Poirel
Plasmid-mediated resistance to polymyxins mediated by the MCR-1/-2 determinants has been recently reported in Enterobacteriaceae worldwide. Using PCR-based and cloning strategies, a series of Moraxella species were screened for mcr-like genes. Moraxella spp. that are mainly animal pathogens but may also be human pathogens were identified as potential reservoirs of mcr-like genes.
March 20, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28320719/antibiotic-effects-on-methicillin-resistant-staphylococcus-aureus-cytoplasmic-peptidoglycan-intermediate-levels-evidence-for-potential-metabolite-level-regulatory-loops
#10
Harika Vemula, Navid J Ayon, Alloch Burton, William G Gutheil
Cytoplasmic peptidoglycan (PG) precursor levels were determined in methicillin resistant S. aureus (MRSA) after exposure to several cell wall targeting antibiotics. Three experiments were performed: 1) Exposure to 4x MIC levels (acute). 2) Exposure to sub-MIC levels (sub-acute). 3) A time course of the effect of vancomycin. In acute exposure experiments, fosfomycin increased UDP-GlcNAc, as expected, and resulted in substantially lower levels of total UDP-linked metabolite accumulation relative to other pathway inhibitors, indicating reduced entry into this pathway...
March 20, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28320718/3-hydroxypyrimidine-2-4-diones-as-novel-hepatitis-b-virus-antivirals-targeting-the-viral-ribonuclease-h
#11
Andrew D Huber, Eleftherios Michailidis, Jing Tang, Maritza N Puray-Chavez, Maria Boftsi, Jennifer J Wolf, Kelsey N Boschert, Megan A Sheridan, Maxwell D Leslie, Karen A Kirby, Kamalendra Singh, Hiroaki Mitsuya, Michael A Parniak, Zhengqiang Wang, Stefan G Sarafianos
Hepatitis B virus (HBV) ribonuclease H (RNH) is an appealing therapeutic target due to its essential role in viral replication. RNH inhibitors (RNHIs) could help more effectively control HBV infections. Here, we report 3-hydroxypyrimidine-2,4-diones as novel HBV RNHIs with antiviral activity. We synthesized and tested 52 analogs and found 4 that inhibit HBV RNH activity in infected cells. Importantly, 2 of these compounds inhibited HBV replication in the low micromolar range.
March 20, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28320717/in-vitro-activities-and-spectrum-of-the-novel-fluoroquinolone-lascufloxacin-krp-am1977
#12
Ryuta Kishii, Yuko Yamaguchi, Masaya Takei
Lascufloxacin showed a broad spectrum of activity against various clinical isolates. Especially, lascufloxacin showed the most potent activity against gram-positive bacteria among the quinolones tested. Furthermore, lascufloxacin showed incomplete cross-resistance against existing quinolone-resistant strains. Enzymatic analysis indicated that lascufloxacin showed potent inhibitory activity against both wild-type and mutated target enzymes. These results suggested that lascufloxacin may be useful in treating infections caused by various pathogens, including quinolone-resistant strains...
March 20, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28320716/in-vitro-activity-of-imipenem-relebactam-against-gram-negative-eskape-pathogens-isolated-by-clinical-laboratories-in-the-united-states-in-2015-results-from-the-smart-global-surveillance-program
#13
Sibylle H Lob, Meredith A Hackel, Krystyna M Kazmierczak, Katherine Young, Mary R Motyl, James A Karlowsky, Daniel F Sahm
Relebactam (formerly MK-7655) is an inhibitor of class A and C β-lactamases, including Klebsiella pneumoniae carbapenemase (KPC), and is currently in clinical development in combination with imipenem/cilastatin. Using Clinical and Laboratory Standards Institute (CLSI) defined broth microdilution methodology, we evaluated the in vitro activities of imipenem-relebactam, imipenem, and seven routinely tested parenteral antimicrobial agents against gram-negative ESKAPE pathogens (Pseudomonas aeruginosa, n = 845; Klebsiella pneumoniae, n = 689; Enterobacter spp...
March 20, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28320715/experimental-models-of-short-courses-of-liposomal-amphotericin-b-for-induction-therapy-for-cryptococcal-meningitis
#14
Jodi Lestner, Laura McEntee, Adam Johnson, Joanne Livermore, Sarah Whalley, Julie Schwartz, John R Perfect, Thomas Harrison, William Hope
Cryptococcal meningoencephalitis is a rapidly lethal infection in immunocompromised patients. Induction regimens are usually administered for 2-weeks. The shortest effective period of induction therapy with liposomal amphotericin B (LAmB) is unknown. The pharmacodynamics of LAmB were studied in murine and rabbit models of cryptococcal meningoencephalitis. The concentrations of LAmB in plasma and brain of mice were measured using HPLC. Histopathological changes were determined. The penetration of LAmB into the brain was determined by immunohistochemistry using an antibody directed to amphotericin B...
March 20, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28320714/variability-in-trough-total-and-unbound-teicoplanin-concentrations-and-achievement-of-therapeutic-drug-monitoring-targets-in-adult-patients-with-haematological-malignancy
#15
Catherine J Byrne, Jason A Roberts, Brett McWhinney, Jerome P Fennell, Philomena O'Byrne, Evelyn Deasy, Sean Egan, Ronan Desmond, Helen Enright, Sheila A Ryder, Deirdre M D'Arcy, Johnny McHugh
Objectives: To explore the following aspects of teicoplanin use in patients with haematological malignancy: early attainment of target trough concentrations with current high dose teicoplanin regimens; variability in unbound teicoplanin fractions; factors associated with observed total and unbound trough concentrations; efficacy and toxicity; and renal function estimation.Methods: This was a single-centre, prospective study. Trough samples were taken on Days 3, 4, 7 and 10. Total and unbound teicoplanin concentrations were determined using validated HPLC methods...
March 20, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28320713/antimicrobial-percutaneous-nephrostomy-catheters-for-the-prevention-of-renal-infections-in-vitro-studies
#16
Nylev Vargas-Cruz, Ruth A Reitzel, Joel Rosenblatt, Mohamed Jamal, Ariel D Szvalb, Anne-Marie Chaftari, Ray Hachem, Issam Raad
Purpose - Percutaneous nephrostomy (PCN) catheters are the primary method for draining ureters obstructed by malignancy and preventing a decline of the renal function. However, PCN-related infections such as pyelonephritis and urosepsis remain a significant concern. Currently no antimicrobial PCNs are available for preventing infectious complications. Vascular catheters impregnated with Minocycline/Rifampin (M/R) and M/R with Chlorhexidine coating (M/R+CHD) have previously demonstrated antimicrobial activity...
March 20, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28320712/efficacy-of-telavancin-alone-and-in-combination-with-ampicillin-in-a-rat-model-of-enterococcus-faecalis-endocarditis
#17
Truc T Tran, Vincent H Tam, Barbara E Murray, Cesar A Arias, Kavindra V Singh
We first assessed telavancin (TLV) pharmacokinetics after a single subcutaneous dose of 35 mg/kg. The pharmacokinetic data were used to predict a TLV dose that simulates human exposure and the efficacy of TLV was then evaluated using TLV 21 mg/kg Q 12 h against Enterococcus faecalis OG1RF (TLV MIC of 0.06 μg/ml) in a rat endocarditis model with an indwelling catheter. Therapy was given for 3 days with TLV, daptomycin (DAP) or ampicillin (AMP) monotherapy and with combinations of TLV plus AMP, AMP plus gentamicin (GEN), and AMP plus ceftriaxone (CRO); rats were sacrificed 24 h after the last dose...
March 20, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28320711/a-novel-hybrid-plasmid-carrying-multiple-antimicrobial-resistance-and-virulence-genes-in-salmonella-dublin
#18
Chand S Mangat, Sadjia Bekal, Rebecca J Irwin, Michael R Mulvey
Virulence plasmids and antibiotic resistance plasmids are usually maintained separately in Salmonella spp., however we report an instance of a hybrid plasmid (pN13-01125) in Salmonella Dublin. The complete sequence of the 172,265 bp plasmid suggested that pN13-01125 is comprised of the previously described pSDVr and pSH696_135 plasmids and that the mechanism of hybridization likely involved IS6 (IS26) insertion sequence elements. The plasmid has a low conjugation frequency, confers resistance to six classes of antimicrobials, and contains a complete spv virulence operon...
March 20, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28289036/characterizing-the-antimicrobial-activity-of-n-2-n-4-disubstituted-quinazoline-2-4-diamines-towards-multidrug-resistant-acinetobacter-baumannii
#19
Renee Fleeman, Kurt S Van Horn, Megan M Barber, Whittney N Burda, David L Flanigan, Roman Manetsch, Lindsey N Shaw
We previously reported a series of N(2) ,N(4) -disubstituted quinazoline-2,4-diamine as dihydrofolate reductase inhibitors, with potent in vitro and in vivo antibacterial activity against MRSA strains. In this work we extend our previous study to the Gram-negative pathogen Acinetobacter baumannii We determined that optimized N(2) ,N(4) -disubstituted quinazoline-2,4-diamines are strongly antibacterial against multi-drug resistant A. baumannii strains when the 6-position is substituted with a halide or an alkyl substituent...
March 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28289035/wck-5107-zidebactam-wck-5153-novel-inhibitors-of-pbp2-showing-potent-%C3%AE-lactam-enhancer-activity-against-pseudomonas-aeruginosa-including-multidrug-resistant-metallo-%C3%AE-lactamase-producing-high-risk-clones
#20
Bartolome Moya, Isabel M Barcelo, Sachin Bhagwat, Mahesh Patel, German Bou, Krisztina M Papp-Wallace, Robert A Bonomo, Antonio Oliver
Zidebactam and WCK 5153 are novel β-lactam enhancers that are bicyclo-acyl hydrazides (BCH), derivatives of diazabicyclooctane (DBO) scaffold, targeted for the treatment of serious infections caused by highly drug-resistant Gram-negative pathogens. In this report, we determined the PBP inhibition profiles and the antimicrobial activity of zidebactam and WCK 5153 against P. aeruginosa, including multidrug-resistant (MDR) metallo-β-lactamase (MBL)-producing high-risk clones. MICs and time-kill assays were conducted for zidebactam, WCK 5153 and antipseudomonal β-lactams using wild-type PAO1 strain, MexAB-OprM-hyperproducing (mexR), porin deficient (oprD) and AmpC-hyperproducing (dacB) derivatives of PAO1 and MBL-expressing clinical strains, ST175 (blaVIM-2) and ST111 (blaVIM-1)...
March 13, 2017: Antimicrobial Agents and Chemotherapy
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