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Antimicrobial Agents and Chemotherapy

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https://www.readbyqxmd.com/read/29784853/carbapenem-non-susceptible-haemophilus-influenzae-with-penicillin-binding-protein-3-containing-amino-acid-insertion
#1
Kazuki Kitaoka, Kouji Kimura, Hiromitsu Kitanaka, Hirotsugu Banno, Wanchun Jin, Jun-Ichi Wachino, Yoshichika Arakawa
Prevalence of β-lactamase-negative ampicillin-resistant Haemophilus influenzae (BLNAR) has become a clinical concern. In BLNAR, amino acid substitutions in penicillin-binding protein 3 (PBP3) are relevant to the β-lactam resistance. Carbapenem-non-susceptible H. influenzae isolates have been rarely reported. Through antimicrobial susceptibility testing and nucleotide sequence analysis of ftsI , encoding PBP3, and utilizing a collection of H. influenzae clinical isolates in our laboratory, we obtained a carbapenem-non-susceptible clinical isolate (NUBL1772) that possessed an altered PBP3 containing V525_N526insM...
May 21, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29784852/plasma-and-intrapulmonary-concentrations-of-cefepime-and-zidebactam-following-intravenous-administration-of-wck-5222-to-healthy-adult-subjects
#2
Keith A Rodvold, Mark H Gotfried, Rakesh Chugh, Mugdha Gupta, Anasuya Patel, Rajesh Chavan, Ravindra Yeole, H David Friedland, Ashima Bhatia
WCK 5222 is a combination of cefepime and the novel beta-lactam enhancer zidebactam being developed for the treatment of serious Gram-negative infections. The objective of this study was to compare plasma (total), epithelial lining fluid (ELF), and alveolar macrophage (AM) concentrations of cefepime and zidebactam in healthy adult subjects. The WCK 5222 dosing regimen was 2 grams cefepime/1 gram zidebactam administered as a 1-hour intravenous infusion every 8 hours for a total of 7 doses. Subjects were assigned to one bronchoalveolar lavage (BAL) sampling time at 0...
May 21, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29784851/replacement-by-site-saturation-mutagenesis-of-residue-119-in-ndm-1-metallo-%C3%AE-lactamase-a-kinetic-study
#3
Francesca Marcoccia, Paola Sandra Mercuri, Moreno Galleni, Giuseppe Celenza, Gianfranco Amicosante, Mariagrazia Perilli
NDM-1 is a subclass B1 metallo-β-lactamase which exhibits a broad activity spectrum against β-lactam antibiotics. In this study we report the kinetic study of six Q119X variants obtained by site-directed mutagenesis on NDM-1. All Q119X variants were able to hydrolyze very efficiently carbapenems, penicillins and 1st , 2nd , 3rd and 4th generation cephalosporins. In particular, Q119E, Q119Y, Q119V and Q119K mutants showed an improvement of kcat/ Km towards penicillins respect to NDM-1. The catalytic efficiency of Q119K variant is about 65- and 70-fold higher than that of NDM-1 for benzylpenicillin and carbenicillin, respectively...
May 21, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29784850/molecular-analysis-of-a-bla-imp-1-harboring-class-3-integron-in-multidrug-resistant-pseudomonas-fulva
#4
Masaki Yamamoto, Yasufumi Matsumura, Ryota Gomi, Tomonari Matsuda, Satoshi Nakano, Miki Nagao, Michio Tanaka, Satoshi Ichiyama
A multidrug-resistant (MDR) Pseudomonas fulva was isolated in 2006 from a urine sample. The isolate harbored the bla IMP-1 gene, which was located in a chromosomal Tn 402 -like class 3 integron as a gene cassette array of aacA31 - fosE - bla IMP-1 Two mutations in gyrA and one mutation in parC were detected in quinolone resistance-determining regions (QRDRs). We report a full-length, novel bla IMP-1 -carrying class 3 integron. This integron and together with mutations in QRDRs could have influenced the MDR phenotypes...
May 21, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29784849/evaluation-of-telavancin-alone-and-combined-with-ceftaroline-or-rifampin-against-methicillin-resistant-staphylococcus-aureus-mrsa-in-an-in-vitro-biofilm-model
#5
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
https://www.readbyqxmd.com/read/29784848/-in-vitro-and-in-vivo-activity-of-contezolid-mrx-i-against-mycobacterium-tuberculosis
#6
Carolyn Shoen, Michelle DeStefano, Barry Hafkin, Michael Cynamon
The in vitro activity of contezolid (MRX-I) against clinical isolates of M. tuberculosis was evaluated using a microtiter broth dilution assay. MRX-I was as effective in vitro as linezolid (LZD). MRX-I and LZD were subsequently studied in BALB/c mice infected intranasally with M. tuberculosis Erdman. MRX-I and LZD at 100mg/kg significantly reduced the bacterial load in lungs compared to the untreated early and late controls.
May 21, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29784847/translation-elongation-factor-4-lepa-contributes-to-tetracycline-susceptibility-by-stalling-elongating-ribosomes
#7
Bin Liu, Chunlai Chen
Even though elongation factor 4 (EF4) is the third most conserved protein in bacteria, its physiological functions remain largely unknown and its proposed molecular mechanisms are conflicting among previous studies. In the present study we show that growth of an Escherichia coli strain is more susceptible to tetracycline than its EF4 knockout strain. In consistence with previous studies, our results suggested that EF4 affects ribosome biogenesis when tetracycline is present. Through ribosome profiling analysis, we discovered that EF4 causes 1-nucleotide shifting of ribosomal footprints on mRNA when cells have been exposed to tetracycline...
May 21, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29784846/pharmacokinetics-of-piperaquine-and-safety-profile-of-dihydroartemisinin-piperaquine-co-administered-with-antiretroviral-therapy-in-malaria-uninfected-hiv-positive-malawian-adults
#8
Clifford G Banda, Fraction Dzinjalamala, Mavuto Mukaka, Jane Mallewa, Victor Maiden, Dianne J Terlouw, David G Lalloo, Saye H Khoo, Victor Mwapasa
There are limited data on the pharmacokinetic and safety profiles of dihydroartemisinin-piperaquine (DHA-PQ) among human immunodeficiency virus infected (HIV+) individuals taking antiretroviral therapy (ART). In a two step (parallel-group) pharmacokinetic trial with intensive blood sampling, we compared area under the concentration-time curve (AUC0-28 days ) and safety outcomes of piperaquine among malaria-uninfected HIV+ adults. In step 1, half the adult dose of DHA-PQ was administered for three days as an intitial safety check in four groups (n=6/group) of HIV+ adults (age≥18 years): (i) antiretroviral-naïve, (ii) on nevirapine-based ART, (iii) on efavirenz-based ART, and (iv) on ritonavir-boosted lopinavir-based ART...
May 21, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29784845/interaction-of-bacterial-phenazines-with-colistimethate-in-bronchial-epithelial-cells
#9
Valeri V Mossine, Deborah L Chance, James K Waters, Thomas P Mawhinney
Multidrug-resistant bacterial infections are being increasingly treated in clinics with polymyxins, a class of antibiotics associated with adverse effects in the kidney, nervous system, or airways of a significant proportion of human and animal patients. Although many of the resistant pathogens display enhanced virulence, a hazard of cytotoxic interactions between polymyxin antibiotics and bacterial virulence factors (VFs) has not been assessed, to date. We report here on testing paired combinations of four Pseudomonas aeruginosa VF phenazine toxins, pyocyanin (PYO), 1-hydroxyphenazine (1-HP), phenazine-1-carboxylic acid (PCA), phenazine-1-carboxamide (PCN), and two commonly prescribed polymyxin drugs, colistimethate (CMS)/colistin and polymyxin B, in three human airway cell lines, BEAS-2B, HBE-1, and CFT-1...
May 21, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29784844/incidences-of-pseudomonas-associated-ventilator-associated-pneumonia-within-studies-of-respiratory-tract-applications-of-polymyxin-testing-the-stoutenbeek-concurrency-postulates
#10
James C Hurley
Regimens containing topical polymyxin appear highly effective at preventing Ventilator-associated pneumonia (VAP) overall and more-so, gram negative VAP. However, Soutenbeek's postulates, that VAP incidences within studies of topical antibiotics would depend on the context of whether the component (control and intervention) groups of each study were concurrent versus non-concurrent, remain untested.The literature was searched for concurrent control (CC) versus non-concurrent control (NCC) designed studies of respiratory tract applications of topical polymyxin to mechanically ventilated (MV) patients that reported Pseudomonas associated Ventilator-associated pneumonia (PsVAP) incidences...
May 21, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29784843/high-dose-and-delayed-treatment-with-bile-acids-ineffective-in-rml-prion-infected-mice
#11
Grant Norman, Jody Campeau, Valerie L Sim
Prion diseases are a group of neurodegenerative diseases associated with the misfolding of the cellular prion protein (PrPC ) into the infectious form (PrPSc ). There are currently no treatments for prion disease. Bile acids have the ability to protect hepatocytes from apoptosis and are neuroprotective in animal models of other protein folding neurodegenerative diseases including Huntington's, Parkinson's, and Alzheimer's disease. Importantly, bile acids are approved for clinical use in patients with cirrhosis, and have recently been shown to be safe and possibly effective in pilot trials of patients with amyotrophic lateral sclerosis (ALS)...
May 21, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29784842/eucast-determination-of-olorofim-f901318-susceptibility-of-mould-species-method-validation-and-mics
#12
Karin Meinike Jørgensen, Karen M T Astvad, Rasmus Krøger Hare, Maiken Cavling Arendrup
Olorofim is a novel antifungal agent with in vitro activity against Aspergillus and some other moulds. Here we addressed technical aspects for EUCAST olorofim testing and generated contemporary MIC data.EUCAST E.Def 9.3.1 testing was performed comparing two plate preparation methods (serial-dilution in medium (serial-plates) versus pre-dilution in DMSO (ISO-plates)), two lots of olorofim, visual (visual-MIC) versus spectrophotometer (spec-MIC) reading and four polystyrene plates using 34-53 Aspergillus isolates from five genera...
May 21, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29784841/the-metabolism-of-piperaquine-to-its-antiplasmodial-metabolites-and-their-pharmacokinetic-profiles-in-healthy-volunteers
#13
Huixiang Liu, Hongchang Zhou, Tianyu Cai, Aijuan Yang, Meitong Zang, Jie Xing
As a partner antimalarial for artemisinin drug-based combination therapy (ACT), piperaquine (PQ) can be metabolized into two major metabolites, including piperaquine N -oxide (M1) and N , N -dioxide (M2). To better understand the antimalarial potency of PQ, the antimalarial activity of PQ metabolites (M1 and M2) was studied in vitro ( Plasmodium strains Pf 3D7 and Pf Dd2) and in vivo (murine Plasmodium yoelii ) in this study. The recrudescence and survival time of infected mice were also recorded after drug treatment...
May 21, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29784840/oxidative-stress-and-first-line-antituberculosis-drug-induced-hepatotoxicity
#14
Wing Wai Yew, Kwok Chiu Chang, Denise P Chan
Hepatotoxicity induced by antituberculosis drugs is a serious adverse reaction with significant morbidity and even rarely mortality. This form of toxicity potentially impacts the treatment outcome of tuberculosis in some patients. Confining to first-line antituberculosis drugs, this review addresses whether and how oxidative stress, and more broadly, disturbance in redox homeostasis alongside mitochondrial dysfunction, may contribute to the hepatotoxicity induced by them. Risk factors for such toxicity that have been identified, in addition to genetic factors, principally include old age, malnutrition, alcoholism, chronic hepatitis C and chronic hepatitis B infection, HIV infection and pre-existing liver disease...
May 21, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29784839/clonal-spread-in-candida-glabrata-bloodstream-isolates-and-fluconazole-resistance-affected-by-prolonged-exposure-a-12-year-single-center-study-in-belgium
#15
Berdieke Goemaere, Katrien Lagrou, Isabel Spriet, Marijke Hendrickx, Pierre Becker
Candida glabrata is a major cause of candidemia in immunocompromised patients and is characterized by a high-level of fluconazole resistance. In the present study, acquisition of antifungal resistance and potential clonal spread of C. glabrata were explored at a single center over a 12-year period by analyzing 187 independent clinical C. glabrata bloodstream isolates. One strain was found to be micafungin resistant due to a mutation in the FKS2 gene. Fluconazole resistance remained stable throughout the period and was observed in 20 (10...
May 21, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29784838/in-vivo-and-in-vitro-effects-of-a-clpp-activating-antibiotic-against-vancomycin-resistant-enterococci
#16
Autumn Brown Gandt, Elizabeth C Griffith, Ida M Lister, Lisa L Billings, Angel Han, Rajendra Tangallapally, Ying Zhao, Aman P Singh, Richard E Lee, Michael D LaFleur
Antibiotics with novel bactericidal mechanisms of action are urgently needed. The antibiotic acyldepsipeptide 4 (ADEP4) activates the ClpP protease and causes cells to self-digest. The effects of ADEP4 and ClpP activation have not been sufficiently characterized for the enterococci, which are important pathogens known for high levels of acquired and intrinsic antibiotic resistance. In the present study, ADEP4 was found to be potently active against both Enterococcus faecalis and Enterococcus faecium with an MIC90 of 0...
May 21, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29784837/the-inoculum-effect-in-the-era-of-multidrug-resistance-minor-differences-in-inoculum-have-dramatic-effect-on-minimal-inhibitory-concentration-determination
#17
Kenneth P Smith, James E Kirby
The observed MIC may depend on the number of bacteria initially inoculated into the assay. This phenomenon is termed the inoculum effect (IE) and is often most pronounced for β-lactams in strains expressing β-lactamase enzymes. The Clinical and Laboratory Standards Institute (CLSI) recommended inoculum is 5 x 105 CFU mL-1 with an acceptable range of 2-8 x 105 CFU mL-1 IE testing is typically performed using an inoculum 100-fold greater than the CLSI recommended inoculum. Therefore, it remains unknown whether the IE influences MICs during testing performed according to CLSI guidelines...
May 21, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29760148/bacterial-silver-resistance-gained-by-cooperative-interspecies-redox-behavior
#18
Michael Muller
Silver has emerged as an important therapeutic option for wound infections in recent years due to its broad spectrum antimicrobial activity. The silver cation (Ag+ ), but not the bulk metal (Ag0 ), is highly toxic for most microorganisms although resistance due to genetic modification or horizontal gene transfer does occur. Pseudomonas aeruginosa , however, achieves silver resistance by producing the redox active metabolite pyocyanin that reduces Ag+ to non-toxic Ag0 Pyocyanin also possess broad spectrum antimicrobial activity...
May 14, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29760147/rifabutin-acts-in-synergy-and-is-bactericidal-with-frontline-mycobacterium-abscessus-antibiotics-clarithromycin-and-tigecycline-suggesting-a-potent-treatment-combination
#19
Mark Pryjma, Ján Burian, Charles J Thompson
Mycobacterium abscessus (MAB ) is a rapidly emerging mycobacterial pathogen causing dangerous pulmonary infections. Because these bacteria are intrinsically multidrug resistant, treatment options are limited and have questionable efficacy. The current treatment regimen relies on a combination of antibiotics including clarithromycin paired with amikacin and either imipenem or cefoxitin. Tigecycline may be added when triple therapy is ineffective. We initially screened a library containing the majority of clinically available antibiotics for anti- MAB activity...
May 14, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29760146/copper-acyl-salicylate-has-potential-as-an-anti-cryptococcus-anti-fungal-agent
#20
Adepemi O Ogundeji, Boitumelo F Porotloane, Carolina H Pohl, Pravin S Kendrekar, Olihile M Sebolai
The in vitro anti-fungal activity of aspirin against cryptococcal cells has been reported. However, its undesired effects may limit its clinical application. Conceivably, a derivative of aspirin could overcome this challenge. Toward this end, this paper considered the usage of an aspirinate-metal complex viz. copper acyl salicylate (CAS) as an anti- Cryptococcus anti-fungal agent. Additionally, the paper examined the influence of this compound on macrophage function. The in vitro susceptibility results revealed that cryptococcal cells were vulnerable (in a dose-dependent manner) to CAS, which may have effected growth inhibition by damaging cryptococcal cell membranes...
May 14, 2018: Antimicrobial Agents and Chemotherapy
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