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Antimicrobial Agents and Chemotherapy

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https://www.readbyqxmd.com/read/28630206/rapid-and-consistent-evolution-of-colistin-resistance-in-xdr-pseudomonas-aeruginosa-during-morbidostat-culture
#1
Bianca Regenbogen, Matthias Willmann, Matthias Steglich, Boyke Bunk, Ulrich Nübel, Silke Peter, Richard A Neher
Colistin is a last resort antibiotic commonly used against multidrug-resistant strains of Pseudomonas aeruginosa To investigate the potential for in-situ evolution of resistance against colistin and to map the molecular targets of colistin resistance, we exposed two P. aeruginosa isolates to colistin using a continuous culture device known as morbidostat. As a result, colistin resistance reproducibly increased 10-fold within ten days, and 100-fold within 20 days, along with highly stereotypic, yet strain specific mutation patterns...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28630205/the-impact-of-gyrb-and-eis-mutations-in-improving-second-line-drug-resistance-detection-among-mycobacterium-tuberculosis-isolates-from-georgia
#2
N Bablishvili, N Tukvadze, E Shashkina, B Mathema, N R Gandhi, H M Blumberg, R R Kempker
SETTING: The country of Georgia has a high burden of multi- and extensively drug-resistant tuberculosis (XDR-TB).OBJECTIVE: To evaluate whether the detection of mutations in gyrB and eis genes increased the sensitivity of detecting phenotypic resistance to ofloxacin and kanamycin or capreomycin as compared to use of the first generation MTBDRsl assay alone which evaluates for mutations in gyrA and rrs genes.DESIGN: A retrospective study of storedMycobacterium tuberculosis isolates. All isolates underwent DNA sequencing of resistance determining regions...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28630204/a-low-molecular-weight-alginate-oligosaccharide-disrupts-pseudomonal-microcolony-formation-and-enhances-antibiotic-effectiveness
#3
Manon F Pritchard, Lydia C Powell, Alison A Jack, Kate Powell, Konrad Beck, Hannah Florance, Julian Forton, Philip D Rye, Arne Dessen, Katja E Hill, David W Thomas
In chronic respiratory disease the formation of dense, 3-dimensional 'micro colonies' by Pseudomonas aeruginosa within the airway plays an important role in contributing to resistance to treatment. An in vitro biofilm model of pseudomonal microcolony formation using artificial sputum (AS) medium was established to study the effects of low molecular weight alginate oligomers (OligoG CF-5/20) on pseudomonal growth, microcolony formation and the efficacy of colistin. The studies employed clinical cystic fibrosis (CF) isolates (n=3) and reference non-mucoid and mucoid multi-drug resistant (MDR) CF isolates (n=7)...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28630203/bactericidal-and-sterilizing-activity-of-a-novel-regimen-with-bedaquiline-pretomanid-moxifloxacin-and-pyrazinamide-in-a-murine-model-of-tuberculosis
#4
Si-Yang Li, Rokeya Tasneen, Sandeep Tyagi, Heena Soni, Paul J Converse, Khisimuzi Mdluli, Eric L Nuermberger
New regimens based on two or more novel agents are sought to shorten or simplify treatment of tuberculosis (TB), including drug-resistant forms. Prior studies showed that the novel combinations of bedaquiline (BDQ) + pretomanid (PMD) + pyrazinamide (PZA) and of PMD + moxifloxacin (MXF) + PZA shorten the treatment duration necessary to prevent relapse by 2-3 and 1-2 months, respectively, compared with the current first-line regimen in a murine TB model. These 3-drug combinations are now being studied in clinical trials...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28630202/identifying-spectra-of-activity-and-therapeutic-niches-for-ceftazidime-avibactam-and-imipenem-relebactam-against-carbapenem-resistant-enterobacteriaceae
#5
Ghady Haidar, Cornelius J Clancy, Liang Chen, Palash Samanta, Ryan K Shields, Barry N Kreiswirth, M Hong Nguyen
We determined imipenem, imipenem-relebactam, ceftazidime and ceftazidime-avibactam minimum inhibitory concentrations (MICs) against 100 CRE isolates that underwent whole genome sequencing. KPCs were the most common carbapenemases. Forty-six isolates carried ESBLs. With the addition of relebactam, imipenem susceptibility increased from 8% to 88%. With the addition of avibactam, ceftazidime susceptibility increased from 0% to 85%. Neither imipenem-relebactam nor ceftazidime-avibactam was active against MBL-producers...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28630201/the-combined-effect-of-the-cfr-methyltransferase-and-ribosomal-protein-l3-mutations-on-resistance-to-ribosome-targeting-antibiotics
#6
Kevin K Pakula, Lykke H Hansen, Birte Vester
Several groups of antibiotics inhibit bacterial growth by binding to bacterial ribosomes. Mutations in the ribosomal protein L3 have been associated with resistance to linezolid and tiamulin, which both bind at the peptidyl transferase center in the ribosome. Resistance to these and other antibiotics also occurs through methylation of 23S ribosomal RNA at position A2503 by the methyltransferase Cfr. The mutations in L3 and the cfr gene have been found together in clinical isolates, raising the question whether they provide a combined effect on antibiotic resistance or growth...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28630200/treatment-of-experimental-visceral-leishmaniasis-with-single-dose-liposomal-amphotericin-b-pharmacodynamics-and-biodistribution-at-different-stages-of-disease
#7
Andrew A Voak, Andy Harris, Zeeshan Qaiser, Simon L Croft, Karin Seifert
Visceral leishmaniasis is a neglected tropical disease, which causes significant morbidity and mortality worldwide. Characterising the pharmacokinetics and pharmacodynamics of anti-leishmanial drugs in pre-clinical models is important for drug development and use. Here we investigated the pharmacodynamics and drug distribution of AmBisome® in L. donovani infected BALB/c mice at three different dose levels and two different time points after infection. We additionally compared drug levels in plasma, liver and spleen in infected and uninfected BALB/c mice over time...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28630199/genome-wide-analysis-of-the-antimicrobial-peptides-in-python-bivittatus-and-characterization-of-cathelicidins-with-potent-antimicrobial-activity-and-low-cytotoxicity
#8
Dayeong Kim, Nagasundarapandian Soundrarajan, Juyeon Lee, Hye-Sun Cho, Minkyeung Choi, Se-Yeoun Cha, Byeongyong Ahn, Hyoim Jeon, Minh Thong Le, Hyuk Song, Jin-Hoi Kim, Chankyu Park
In this study, we sought to identify novel antimicrobial peptides (AMPs) in Python bivittatus through bioinformatic analyses of publicly available genome information and experimental validation. In our analysis of the python genome, we identified 29 AMP-related candidate sequences. Of these, we selected five cathelicidin-like sequences and subjected them to further in silico analyses. The results showed that these sequences likely have antimicrobial activity. The sequences were named Pb-CATH1-Pb-CATH5 according to their sequence similarity to previously reported snake cathelicidins...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28630198/genome-evolution-to-penicillin-resistance-in-serotype-3-streptococcus-pneumoniae-by-capsular-switching
#9
Naoko Chiba, Somay Y Murayama, Miyuki Morozumi, Satoshi Iwata, Kimiko Ubukata
Streptococcus pneumoniae of serotype 3 was collected from cases of invasive pneumococcal disease (n = 124) throughout Japan from April 2010 to March 2013. A penicillin-resistant S. pneumoniae (PRSP) isolate from an adult patient, KK0981 of serotype 3, was identified among these strains. Whole-genome analysis characterized this PRSP as a recombinant strain derived from PRSP of serotype 23F with the cps-locus (20.3 kb) replaced by that of a penicillin-susceptible strain of serotype 3.
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28630197/pharmacodynamics-of-cefepime-combined-with-tazobactam-against-clinically-relevant-enterobactereaceae-in-a-neutropenic-mouse-thigh-model
#10
Maria J Melchers, Anita C van Mil, Claudia Lagarde, Jan den Hartigh, Johan W Mouton
The lack of new antibiotics prompted the investigation of the combination of two existing agents cefepime, a broad-spectrum cephalosporin and tazobactam to broaden its efficacy against extended-spectrum beta-lactamase producing Enterobacteriaceae. We determined the pharmacokinetic and pharmacodynamic properties of the combination in a murine neutropenic thigh model in order to establishing its exposure- response relationships (ERR). The PK of cefepime was determined for five doses; that of tazobactam was determined in earlier studies (Melchers et al Antimicrob...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28630196/antimicrobial-susceptibility-trends-among-staphylococcus-aureus-from-united-states-hospitals-results-from-7-years-of-the-ceftaroline-aware-surveillance-program-2010-2016
#11
Helio S Sader, Rodrigo E Mendes, Jennifer M Streit, Robert K Flamm
We evaluated trends in Staphylococcus aureus antimicrobial susceptibility in United States hospitals in the 2010-2016 period. A total of 21,056 clinical isolates from 42 medical centers were tested for susceptibility by broth microdilution methods. MRSA rates decreased from 50.0% (2010) to 42.2% (2016). Susceptibility to erythromycin, levofloxacin, and clindamycin increased slightly, whereas susceptibility to ceftaroline, trimethoprim-sulfamethoxazole, and tetracycline remained stable. Ceftaroline retained potent activity against MSSA and MRSA (97...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28630195/topical-antimicrobial-treatments-can-elicit-shifts-to-resident-skin-bacterial-communities-and-reduce-colonization-by-staphylococcus-aureus-competitors
#12
Adam J SanMiguel, Jacquelyn S Meisel, Joseph Horwinski, Qi Zheng, Elizabeth A Grice
The skin microbiome is a complex ecosystem with important implications for cutaneous health and disease. Topical antibiotics and antiseptics are often employed to preserve the balance of this population, and inhibit colonization by more pathogenic bacteria. Despite their widespread use, however, the impact of these interventions on broader microbial communities remains poorly understood. Here we report the longitudinal effects of topical antibiotics and antiseptics on skin bacterial communities and their role in Staphylococcus aureus colonization resistance...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28630194/pharmacokinetics-safety-and-tolerability-of-single-dose-intravenous-zti-01-and-oral-fosfomycin-in-healthy-volunteers
#13
E Wenzler, E J Ellis-Grosse, K A Rodvold
The pharmacokinetics, safety, and tolerability of intravenous (IV) fosfomycin disodium (ZTI-01) and oral fosfomycin tromethamine were evaluated after a single dose in 28 healthy adult subjects. Subjects received a single 1 hour IV infusion of 1 g and 8 g fosfomycin disodium and a single dose of 3 g oral fosfomycin tromethamine in a phase I, randomized, open-label, three-period crossover study. Serial blood and urine samples were collected before and up to 48 hours after dosing. The mean pharmacokinetic parameters ± standard deviations of fosfomycin in plasma after 1 g and 8 g IV were: Cmax= 44...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28630193/pyrazinamide-susceptibility-and-pnca-mutation-profile-of-mycobacterium-tuberculosis-among-multi-drug-resistant-tuberculosis-patients-in-bangladesh
#14
Arfatur Rahman, Sara Sabrina Ferdous, Shahriar Ahmed, S M Mazidur Rahman, Mohammad Khaja Mafij Uddin, Suporn Pholwat, Jean Gratz, Eric Houpt, Sayera Banu
Pyrazinamide (PZA) is a front line anti-tuberculosis (anti-TB) drug used in both first and second line treatment regimen. However, due to complex laboratory requirements, the PZA susceptibility test is rarely performed leading to the scarcity of data. Bangladesh is both a high TB and multi-drug resistant (MDR-TB) burden country but to our knowledge the published data on PZA susceptibility is limited, especially among MDR-TB patients. We aimed to analyze the PZA susceptibility pattern of Mycobacterium tuberculosis (MTB) isolates from MDR-TB patients and to correlate pncA mutation with PZA resistance in Bangladesh...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28630192/in-vitro-activity-of-aztreonam-avibactam-against-enterobacteriaceae-and-pseudomonas-aeruginosa-isolated-by-clinical-laboratories-in-40-countries-from-2012-to-2015
#15
James A Karlowsky, Krystyna M Kazmierczak, Boudewijn L M de Jonge, Meredith A Hackel, Daniel F Sahm, Patricia A Bradford
The combination of the monobactam, aztreonam, and the non-β-lactam β-lactamase inhibitor, avibactam, is currently in clinical development for the treatment of serious infections caused by metallo-β-lactamase (MBL)-producing Enterobacteriaceae, a difficult to treat subtype of carbapenem-resistant Enterobacteriaceae for which therapeutic options are currently very limited. The present study tested clinically significant isolates of Enterobacteriaceae (n=51,352) and Pseudomonas aeruginosa (n=11,842) collected from hospitalized patients in 208 medical center laboratories from 40 countries from 2012 to 2015 for in vitro susceptibility to aztreonam-avibactam, aztreonam, and comparator antimicrobial agents using standard broth microdilution methodology...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28630191/ceftazidime-avibactam-and-aztreonam-an-interesting-strategy-to-overcome-%C3%AE-lactam-resistance-conferred-by-metallo-%C3%AE-lactamases-in-enterobacteriaceae-and-pseudomonas-aeruginosa
#16
Benjamin Davido, Lesly Fellous, Christine Lawrence, Virginie Maxime, Martin Rottman, Aurélien Dinh
We have read with great interest Marshal S. et al. regarding the efficacy of the ceftazidime-avibactam (CAZ-AVI) and aztreonam (ATM) combination on metallo- β -lactamases producing Enterobacteriaceae (1).….
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28630190/%C3%AE-lactam-antibiotics-with-a-high-affinity-for-pbp2-act-synergistically-with-the-ftsz-targeting-agent-txa707-against-methicillin-resistant-staphylococcus-aureus
#17
Edgar Ferrer-González, Malvika Kaul, Ajit K Parhi, Edmond J LaVoie, Daniel S Pilch
Methicillin-resistant Staphylococcus aureus (MRSA) is a multi-drug resistant pathogen that poses a significant risk to global health today. We have developed a promising new FtsZ-targeting agent (TXA707) with potent activity against MRSA isolates resistant to current standard-of-care antibiotics. Here we present results that demonstrate differing extents of synergy between TXA707 and a broad range of β-lactam antibiotics (including six cephalosporins, two penicillins, and two carbapenems) against MRSA. To explore whether there is a correlation between the extent of synergy and the preferential antibacterial target of each β-lactam, we determined the binding affinities of the β-lactam antibiotics for each of the four native penicillin binding proteins (PBPs) of S...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28630189/in-vitro-activity-of-delafloxacin-and-microbiological-response-against-fluoroquinolone-susceptible-and-non-susceptible-s-aureus-isolates-from-two-phase-3-studies-of-acute-bacterial-skin-and-skin-structure-infections-absssi
#18
S McCurdy, L Lawrence, M Quintas, L Woosley, R Flamm, C Tseng, S Cammarata
Delafloxacin is an investigational anionic fluoroquinolone antibiotic with broad spectrum in vitro activity, including Gram-positive organisms, Gram-negative organisms, atypical organisms, and anaerobes. The in vitro activity of delafloxacin and percent microbiological response in subjects infected with fluoroquinolone susceptible and non-susceptible S. aureus isolates was determined from two global Phase 3 studies of delafloxacin versus vancomycin plus aztreonam in ABSSSI. Patients were enrolled in 23 countries predominately in the US but also Eastern Europe, South America and Asia...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28630188/identification-of-a-novel-antibacterial-compound-1-2-4-dichlorophenethyl-amino-3-phenoxypropan-2-ol-active-against-persisters-of-pseudomonas-aeruginosa
#19
Veerle Liebens, Valerie Defraine, Wouter Knapen, Toon Swings, Serge Beullens, Romu Corbau, Arnaud Marchand, Patrick Chaltin, Maarten Fauvart, Jan Michiels
Antibiotics typically fail to completely eradicate a bacterial population, leaving a small fraction of transiently antibiotic-tolerant persister cells intact. Persisters are therefore seen as a major cause of treatment failure and greatly contribute to the recalcitrant nature of chronic infections. The current report is focused on Pseudomonas aeruginosa, a Gram-negative pathogen belonging to the notorious ESKAPE group and, due to an increasing resistance against most conventional antibiotics, posing a serious threat to human health...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28630187/cumulative-effect-of-an-antimicrobial-stewardship-and-rapid-diagnostic-testing-bundle-on-early-streamlining-of-antimicrobial-therapy-in-gram-negative-bloodstream-infections
#20
P B Bookstaver, E B Nimmich, T J Smith, J A Justo, J Kohn, K L Hammer, C Troficanto, H A Albrecht, M N Al-Hasan
OBJECTIVES: The use of rapid diagnostic tests (RDT) enhances antimicrobial stewardship programs (ASP) interventions in optimization of antimicrobial therapy. This quasi-experimental cohort study evaluates the combined impact of an ASP/RDT bundle on appropriateness of empirical antimicrobial therapy (EAT) and time to de-escalation of broad-spectrum agents (BSAA) in gram-negative bloodstream infections (GNBSI). METHODS: ASP/RDT bundle consisted of a system-wide GNBSI treatment guidelines, prospective stewardship monitoring, and sequential introduction of two RDTs, Matrix Assisted Laser Desorption Ionization Time-of-Flight (MALDI-TOF) and FilmArray® Blood Culture Identification (BCID) panel...
June 19, 2017: Antimicrobial Agents and Chemotherapy
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