journal
Journals Antimicrobial Agents and Chemo...

Antimicrobial Agents and Chemotherapy

https://read.qxmd.com/read/36951566/identification-and-characterization-of-a-novel-major-facilitator-superfamily-efflux-pump-sa09310-mediating-tetracycline-resistance-in-staphylococcus-aureus
#1
JOURNAL ARTICLE
Daiyu Li, Yan Ge, Ning Wang, Yun Shi, Gang Guo, Quanming Zou, Qiang Liu
Drug efflux systems have recently been recognized as an important mechanism of multidrug resistance in bacteria. Here, we described the identification and characterization of a novel chromosomally encoded multidrug efflux pump (SA09310) in Staphylococcus aureus. SA09310 is a 43-kDa protein with 12 transmembrane helices. The conserved amino acid sequence motifs of the major facilitator superfamily (MFS) were identified in the protein SA09310, which indicated that SA09310 belonged to the MFS transporters. Expression of the sa09310 gene was induced by different types of antibiotics, including aminoglycoside, tetracycline, macrolides, and chloramphenicol...
March 23, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/36951560/stimulating-transcription-in-antibiotic-tolerant-escherichia-coli-sensitizes-it-to-fluoroquinolone-and-nonfluoroquinolone-topoisomerase-inhibitors
#2
JOURNAL ARTICLE
Travis J LaGree, Brandon A Byrd, Ryan M Quelle, Stephanie L Schofield, Wendy W K Mok
Antibiotic tolerant bacteria and persistent cells that remain alive after a course of antibiotic treatment can foster the chronicity of infections and the development of antibiotic resistance. Elucidating how bacteria overcome antibiotic action and devising strategies to bolster a new drug's activity can allow us to preserve our antibiotic arsenal. Here, we investigate strategies to potentiate the activities of topoisomerase inhibitors against nongrowing Escherichia coli that are often recalcitrant to existing antibiotics...
March 23, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/36946741/pharmacokinetic-pharmacodynamic-target-attainment-analyses-evaluating-omadacycline-dosing-regimens-for-the-treatment-of-patients-with-community-acquired-bacterial-pneumonia-arising-from-streptococcus-pneumoniae-and-haemophilus-influenzae
#3
JOURNAL ARTICLE
Sujata M Bhavnani, Jeffrey P Hammel, Elizabeth A Lakota, Michael Trang, Justin C Bader, Catharine C Bulik, Brian D VanScoy, Christopher M Rubino, Michael D Huband, Lawrence Friedrich, Judith N Steenbergen, Paul G Ambrose
Omadacycline, a novel aminomethylcycline with in vitro activity against Gram-positive and -negative organisms, including Streptococcus pneumoniae and Haemophilus influenzae, is approved in the United States to treat patients with community-acquired bacterial pneumonia (CABP). Using nonclinical pharmacokinetic-pharmacodynamic (PK-PD) targets for efficacy and in vitro surveillance data for omadacycline against S. pneumoniae and H. influenzae, and a population pharmacokinetic model, PK-PD target attainment analyses were undertaken using total-drug epithelial lining fluid (ELF) and free-drug plasma exposures to evaluate omadacycline 100 mg intravenously (i...
March 22, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/36946729/development-of-modernized-acinetobacter-baumannii-susceptibility-test-interpretive-criteria-for-recommended-antimicrobial-agents-using-pharmacometric-approaches
#4
JOURNAL ARTICLE
A J Lepak, M Trang, J P Hammel, H S Sader, S M Bhavnani, B D VanScoy, J M Pogue, P G Ambrose, D R Andes
Acinetobacter baumannii-Acinetobacter calcoaceticus complex (referred to herein as A. baumannii) treatment guidelines contain numerous older antimicrobial agents with susceptibility test interpretive criteria (STIC, also known as susceptibility breakpoints) set using only epidemiological data. We utilized a combination of in vitro surveillance data, preclinical murine thigh and lung infection models, population pharmacokinetics, simulation, and pharmacokinetic/pharmacodynamic (PK/PD) target attainment analyses to evaluate A...
March 22, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/36943065/drug-susceptibility-profiling-of-prototheca-species-isolated-from-cases-of-human-protothecosis
#5
JOURNAL ARTICLE
Angelika Proskurnicka, Kinga Żupnik, Zofia Bakuła, Mateusz Iskra, Uwe Rösler, Tomasz Jagielski
Prototheca are unicellular, achlorophyllous, yeast-like microalgae that occur in a wide range of natural habitats. At least five species have been implicated as the causative agents of opportunistic infections of men. Human protothecosis typically manifests as cutaneous, articular, or systemic disease. Treatment is largely empirical with poorly predictable and often unsuccessful outcomes. This is largely due to the frequently observed resistance of Prototheca species to conventional antimicrobial agents. This work is the first to perform drug susceptibility profiling exclusively on isolates from human cases of protothecosis...
March 21, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/36943064/biological-evaluation-of-the-antibacterial-retinoid-cd437-in-cutibacterium-acnes-infection
#6
JOURNAL ARTICLE
Xiao-Wen Huang, Wen Pan, Mei-Zhen Zhong, Yashpal Singh Chhonker, Andrew D Steele, Colleen E Keohane, Biswajit Mishra, Lewis Oscar Felix Raj Lucas, Daryl J Murry, Frederick M Ausubel, William M Wuest, Chang-Xing Li, Eleftherios Mylonakis
Acne vulgaris is a complex skin disease involving infection by Cutibacterium acnes, inflammation, and hyperkeratinization. We evaluated the activity of the retinoid 6-[3-(adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) and 16 other retinoid analogs as potential anti- C. acnes compounds and found that CD437 displayed the highest antimicrobial activity with an MIC against C. acnes (ATCC 6919 and HM-513) of 1 μg/mL. CD437 demonstrated an MBC of 2 μg/mL compared to up to 64 μg/mL for the retinoid adapalene and up to 16 μg/mL for tetracycline, which are commonly used clinically to treat acne...
March 21, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/36943038/effect-of-an-antacid-aluminum-hydroxide-magnesium-hydroxide-simethicone-or-a-proton-pump-inhibitor-omeprazole-on-the-pharmacokinetics-of-tebipenem-pivoxil-hydrobromide-tbp-pi-hbr-in-healthy-adult-subjects
#7
JOURNAL ARTICLE
Gina Patel, Vipul K Gupta, Leanne Gasink, Floni Bajraktari, Yang Lei, Akash Jain, Praveen Srivastava, Angela K Talley
Tebipenem pivoxil hydrobromide (TBP-PI-HBr) is a novel oral carbapenem prodrug being developed for the treatment of serious bacterial infections. This open-label, 3-period, fixed sequence study evaluated the effect of gastric acid-reducing agents, aluminum hydroxide/magnesium hydroxide/simethicone, and omeprazole on the pharmacokinetics (PK) of tebipenem (TBP), the active moiety, following coadministration with immediate release TBP-PI-HBr during fasting. In Period 1, subjects received a single oral dose of TBP-PI-HBr 600 mg (2 × 300 mg tablets)...
March 21, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/36920244/comparison-of-toxicities-among-different-bumped-kinase-inhibitor-analogs-for-treatment-of-cryptosporidiosis
#8
JOURNAL ARTICLE
Matthew A Hulverson, Ryan Choi, Deborah A Schaefer, Dana P Betzer, Molly C McCloskey, Grant R Whitman, Wenlin Huang, Sangun Lee, Andy Pranata, Malcolm D McLeod, Kennan C Marsh, Dale J Kempf, Bruce E LeRoy, Mark T Zafiratos, Aimee L Bielinski, Robert C Hackman, Kayode K Ojo, Samuel L M Arnold, Lynn K Barrett, Saul Tzipori, Michael W Riggs, Erkang Fan, Wesley C Van Voorhis
Recent advances on the development of bumped kinase inhibitors for treatment of cryptosporidiosis have focused on the 5-aminopyrazole-4-carboxamide scaffold, due to analogs that have less hERG inhibition, superior efficacy, and strong in vitro safety profiles. Three compounds, BKI-1770, -1841, and -1708, showed strong efficacy in C. parvum infected mice. Both BKI-1770 and BKI-1841 had efficacy in the C. parvum newborn calf model, reducing diarrhea and oocyst excretion. However, both compounds caused hyperflexion of the limbs seen as dropped pasterns...
March 15, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/36920237/echinocandin-resistance-in-candida-auris-occurs-in-the-murine-gastrointestinal-tract-due-to-fks1-mutations
#9
JOURNAL ARTICLE
Tatsuro Hirayama, Taiga Miyazaki, Makoto Sumiyoshi, Yuya Ito, Nobuyuki Ashizawa, Kazuaki Takeda, Naoki Iwanaga, Takahiro Takazono, Kazuko Yamamoto, Koichi Izumikawa, Katsunori Yanagihara, Koichi Makimura, Kazuhiro Tsukamoto, Shigeru Kohno, Hiroshi Mukae
Candida auris is resistant to multiple antifungal agents. This study investigated its antifungal susceptibility and explored FKS1 mutations across the isolates from mice enterically colonized with wild-type C. auris and treated with echinocandin. Resistant C. auris with FKS1 mutations, including S639F, S639Y, D642Y, R1354H, or R1354Y, were isolated and found to be micafungin- and caspofungin-resistant in vivo ; however, the MICs of isolates with mutation in R1354 remained below the micafungin breakpoint in vitro ...
March 15, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/36920230/model-informed-clinical-practice-determining-an-appropriate-ampicillin-sulbactam-redosing-regimen-in-surgical-patients-by-utilizing-population-pharmacokinetics-and-target-attainment-analysis
#10
JOURNAL ARTICLE
Joshua A Reeder, Cormac T O'Sullivan, Min Xu, Nan Wu, Dilek Ince, William K Rogers, Guohua An
In the current study, population pharmacokinetic (PK) of ampicillin-sulbactam was performed based on the clinical pharmacokinetics data collected from a prospective study conducted in 40 surgical patients undergoing prolonged surgery where antibiotic redosing was implemented. A population PK model was successfully developed to characterize the disposition of ampicillin and sulbactam. The final models were two-compartment models for both drugs, with creatinine clearance and heart failure affecting clearance and body surface area having an impact on the central volume of distribution of both ampicillin and sulbactam...
March 15, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/36920217/next-generation-diarylquinolines-improve-sterilizing-activity-of-regimens-with-pretomanid-and-the-novel-oxazolidinone-tbi-223-in-a-mouse-tuberculosis-model
#11
JOURNAL ARTICLE
Si-Yang Li, Paul J Converse, Fabrice Betoudji, Jin Lee, Khisimuzi Mdluli, Anna Upton, Nader Fotouhi, Eric L Nuermberger
A regimen comprised of bedaquiline (BDQ, or B), pretomanid, and linezolid (BPaL) is the first oral 6-month regimen approved by the U.S. Food and Drug Administration and recommended by the World Health Organization for the treatment of extensively drug-resistant tuberculosis. We used a well-established BALB/c mouse model of tuberculosis to evaluate the treatment-shortening potential of replacing bedaquiline with either of two new, more potent diarylquinolines, TBAJ-587 and TBAJ-876, in early clinical trials...
March 15, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/36920213/phenotypic-and-genomic-characterization-of-st133-siderophore-encoding-extensively-drug-resistant-enterobacter-hormaechei
#12
JOURNAL ARTICLE
Yonglu Huang, Yuchen Wu, Chang Cai, Rong Zhang, Gongxiang Chen, Ning Dong
We identified an ST133 extensively drug-resistant Enterobacter hormaechei, C210017, with increased virulence in the Galleria mellonella infection model. Genomic analysis suggested it carried antibiotic resistance genes bla KPC-2 and mcr-9.1 , and genes iutAiucABCD and iroBCDEN encoding the virulence factor, siderophores. Comparative genomics of C210017 and the 178 ST133 E. hormaechei strains in the database suggested they all belonged to serotype O3 and most strains (77.5%) carried the IncHI2 superplasmids associated with the resistance, virulence, and adaptation of the host strain...
March 15, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/36920206/pharmacological-elevation-of-cellular-dihydrosphingomyelin-provides-a-novel-antiviral-strategy-against-west-nile-virus-infection
#13
JOURNAL ARTICLE
Nereida Jiménez de Oya, Ana San-Félix, Mireia Casasampere, Ana-Belén Blázquez, Patricia Mingo-Casas, Estela Escribano-Romero, Eva Calvo-Pinilla, Teresa Poderoso, Josefina Casas, Juan-Carlos Saiz, María-Jesús Pérez-Pérez, Miguel A Martín-Acebes
The flavivirus life cycle is strictly dependent on cellular lipid metabolism. Polyphenols like gallic acid and its derivatives are promising lead compounds for new therapeutic agents as they can exert multiple pharmacological activities, including the alteration of lipid metabolism. The evaluation of our collection of polyphenols against West Nile virus (WNV), a representative medically relevant flavivirus, led to the identification of N , N '-(dodecane-1,12-diyl)bis(3,4,5-trihydroxybenzamide) and its 2,3,4-trihydroxybenzamide regioisomer as selective antivirals with low cytotoxicity and high antiviral activity (half-maximal effective concentrations [EC50 s] of 2...
March 15, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/36920191/side-by-side-profiling-of-oxazolidinones-to-estimate-the-therapeutic-window-against-mycobacterial-infections
#14
JOURNAL ARTICLE
Dereje A Negatu, Wassihun Wedajo Aragaw, Julianna Cangialosi, Véronique Dartois, Thomas Dick
New oxazolidinones are in clinical development for the treatment of tuberculosis and nontuberculous mycobacterial (NTM) infections, as a replacement for linezolid and tedizolid, which cause mitochondrial toxicity after prolonged treatment. Here, we carried out side-by-side measurements of mitochondrial protein synthesis inhibition and activity against clinically relevant mycobacterial pathogens of approved and novel oxazolidinones. We found a large range of selectivity indices suggesting TBI-223 and sutezolid as promising candidates against tuberculosis and NTM lung disease caused by Mycobacterium kansasii...
March 15, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/36920188/-in-vitro-and-in-vivo-efficacy-of-nitd-916-against-mycobacterium-fortuitum
#15
JOURNAL ARTICLE
Françoise Roquet-Banères, Matthéo Alcaraz, Claire Hamela, Jan Abendroth, Thomas E Edwards, Laurent Kremer
Mycobacterium fortuitum represents one of the most clinically relevant rapid-growing mycobacterial species. Treatments are complex due to antibiotic resistance and to severe side effects of effective drugs, prolonged time of treatment, and co-infection with other pathogens. Herein, we explored the activity of NITD-916, a direct inhibitor of the enoyl-ACP reductase InhA of the type II fatty acid synthase in Mycobacterium tuberculosis. We found that this compound displayed very low MIC values against a panel of M...
March 15, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/36916956/evaluation-of-the-impact-of-comorbidities-on-omadacycline-pharmacokinetics
#16
JOURNAL ARTICLE
M Trang, E A Lakota, M C Safir, S M Bhavnani, L Friedrich, J N Steenbergen, P C McGovern, E Tzanis, C M Rubino
Omadacycline is approved in the United States for the treatment of patients with community-acquired bacterial pneumonia or acute bacterial skin and skin structure infections. Analyses were undertaken to evaluate pharmacokinetic differences among subjects or patients stratified by comorbidities. Differences in clearance by smoking status, history of diabetes mellitus, chronic lung disease, hypertension, heart failure, or coronary artery disease were evaluated using a Welch two-sample t test. Smoking was the only significant comorbidity after correction for sex, with a clinically insignificant difference of 13%...
March 14, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/36916944/efavirenz-based-antiretroviral-therapy-but-not-pregnancy-increased-unbound-piperaquine-exposure-in-women-during-malaria-chemoprevention
#17
JOURNAL ARTICLE
Howard Hong, Usman Aslam-Mir, Richard Kajubi, Erika Wallender, Norah Mwebaza, Grant Dorsey, Philip J Rosenthal, Francesca T Aweeka, Liusheng Huang
Dihydroartemisinin-piperaquine (DP) is highly effective for malaria chemoprevention during pregnancy, but the standard dosing of DP that is used for nonpregnant adults may not be optimal for pregnant women. We previously reported that the pharmacokinetic exposure of total piperaquine (PQ; both bound and unbound to plasma proteins) is reduced significantly in the context of pregnancy or efavirenz (EFV)-based antiretroviral therapy (ART). However, as PQ is >99% protein-bound, reduced protein binding during pregnancy may lead to an increase in the pharmacologically active unbound drug fraction (fu ), relative to the total PQ...
March 14, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/36916920/molecular-markers-of-sulfadoxine-pyrimethamine-resistance-in-samples-from-children-with-uncomplicated-plasmodium-falciparum-at-three-sites-in-angola-in-2019
#18
JOURNAL ARTICLE
Stefano R Rosillo, Pedro Rafael Dimbu, Ana Luisa M Cândido, Je-Hoon Michael Oh, Carolina Miguel Ferreira, Benjamin Nieto Andrade, Sarah Labuda, Roberta Horth, Julia Kelley, Joana F M Morais, Filomeno Fortes, José Franco Martins, Eldin Talundzic, Mateusz M Pluciński
Sulfadoxine-pyrimethamine (SP) is used for prevention of malaria in pregnant women in Angola. We sequenced the Plasmodium falciparum dihydrofolate reductase ( pfdhfr ) and dihydropteroate synthase ( pfdhps ) genes, implicated in SP resistance, in samples collected during a 2019 study of artemisinin-based combination therapy efficacy in Benguela, Lunda Sul, and Zaire provinces. A total of 90 day 0 and day of failure samples were individually sequenced, while 508 day 0 samples from participants without recurrent parasitemia were pooled after DNA extraction into 61 pools...
March 14, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/36912665/the-capsule-increases-susceptibility-to-last-resort-polymyxins-but-not-to-other-antibiotics-in-klebsiella-pneumoniae
#19
JOURNAL ARTICLE
Francesca D'Angelo, Eduardo P C Rocha, Olaya Rendueles
The extracellular capsule is a virulence factor present in many facultative pathogens, but its role in antimicrobial resistance remains controversial. To shed light on this debate, we tested six antibiotics on four Klebsiella pneumoniae species complex strains. Noncapsulated strains exhibited increased tolerance to polymyxins, but not to other antibiotics, as measured using the MIC. Our results urge caution on the use of therapeutic agents that target the capsule and may result in selection for its inactivation...
March 13, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/36912655/elucidating-the-mechanism-of-action-of-the-gram-negative-pathogen-selective-cyclic-antimicrobial-lipopeptide-brevicidine
#20
JOURNAL ARTICLE
Xinghong Zhao, Xinyi Zhong, Shinong Yang, Kai Deng, Lu Liu, Xu Song, Yuanfeng Zou, Lixia Li, Xun Zhou, Renyong Jia, Juchun Lin, Huaqiao Tang, Gang Ye, Jianqing Yang, Shan Zhao, Yifei Lang, Hongping Wan, Zhongqiong Yin, Oscar P Kuipers
Due to the accelerated appearance of antimicrobial-resistant (AMR) pathogens in clinical infections, new first-in-class antibiotics, operating via novel modes of action, are desperately needed. Brevicidine, a bacterial nonribosomally produced cyclic lipopeptide, has shown potent and selective antimicrobial activity against Gram-negative pathogens. However, before our investigations, little was known about how brevicidine exerts its potent bactericidal effect against Gram-negative pathogens. In this study, we find that brevicidine has potent antimicrobial activity against AMR Enterobacteriaceae pathogens, with MIC values ranging between 0...
March 13, 2023: Antimicrobial Agents and Chemotherapy
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