journal
Journals Antimicrobial Agents and Chemo...

Antimicrobial Agents and Chemotherapy

https://read.qxmd.com/read/38051079/molecular-physiological-characterization-of-the-dynamics-of-persister-formation-in-staphylococcus-aureus
#1
JOURNAL ARTICLE
Shiqi Liu, Yixuan Huang, Sean Jensen, Paul Laman, Gertjan Kramer, Sebastian A J Zaat, Stanley Brul
Bacteria possess the ability to enter a growth-arrested state known as persistence in order to survive antibiotic exposure. Clinically, persisters are regarded as the main causative agents for chronic and recurrent infectious diseases. To combat this antibiotic-tolerant population, a better understanding of the molecular physiology of persisters is required. In this study, we collected samples at different stages of the biphasic kill curve to reveal the dynamics of the cellular molecular changes that occur in the process of persister formation...
December 5, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/38051047/therapeutic-effect-of-iturin-a-on-candida-albicans-oral-infection-and-its-pathogenic-factors
#2
JOURNAL ARTICLE
Di Han, Yulan Ji, Saixue Yang, Pei Song, Yihong Shi, Dongyan Shao, Xianqing Chen, Li Shang, Junling Shi, Chunmei Jiang
Candida albicans is responsible for conditions ranging from superficial infections such as oral or vaginal candidiasis to potentially fatal systemic infections. It produces pathogenic factors contributing to its virulence. Iturin A, a lipopeptide derived from Bacillus sp., exhibits a significant inhibitory effect against C. albicans . However, its exact mechanism in mitigating the pathogenic factors of C. albicans remains to be elucidated. This study aimed to explore the influence of iturin A on several pathogenic attributes of C...
December 5, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/38047751/a-novel-shiga-toxin-2a-neutralizing-antibody-therapeutic-with-low-immunogenicity-and-high-efficacy
#3
JOURNAL ARTICLE
Marina E Kirkland, Stephanie Patfield, Anna C Hughes, Bradley Hernlem, Xiaohua He
Shiga toxin-producing Escherichia coli infections are difficult to treat due to the risk of antibiotic-induced stress upregulating the production of toxins, medical treatment is consequently limited to supportive care to prevent the development of hemolytic uremic syndrome (HUS). Here, we introduce a potentially therapeutic humanized mouse monoclonal antibody (Hu-mAb 2-5) targeting Stx2a, the most common Shiga toxin subtype identified from outbreaks. We demonstrate that Hu-mAb 2-5 has low immunogenicity in healthy adults ex vivo and high neutralizing efficacy in vivo , protecting mice from mortality and HUS-related tissue damage...
December 4, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/38047645/molnupiravir-maintains-antiviral-activity-against-sars-cov-2-variants-and-exhibits-a-high-barrier-to-the-development-of-resistance
#4
JOURNAL ARTICLE
Julie M Strizki, John M Gaspar, John A Howe, Beth Hutchins, Hiroshi Mohri, Manoj S Nair, Keith C Kinek, Philip McKenna, Shih Lin Goh, Nicholas Murgolo
Molnupiravir, an oral prodrug of N-hydroxycytidine (NHC), previously demonstrated broad in vitro antiviral activity against multiple RNA viruses and has shown a high barrier to the development of resistance. Here, we present the antiviral activity of NHC against recent SARS-CoV-2 variants and the results of resistance selection studies to better understand the potential for viral resistance to NHC. NHC activity against SARS-CoV-2 variants omicron (BA.1, BA.1.1, BA.2, BA.4, BA.4.6, BA.5, BQ.1.1, XBB.1, and XBB...
December 4, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/38047644/relative-inhibitory-activities-of-the-broad-spectrum-%C3%AE-lactamase-inhibitor-taniborbactam-against-metallo-%C3%AE-lactamases
#5
JOURNAL ARTICLE
Christophe Le Terrier, Clément Viguier, Patrice Nordmann, Alejandro J Vila, Laurent Poirel
Taniborbactam (TAN) is a novel broad-spectrum β-lactamase inhibitor with significant activity against subclass B1 metallo-β-lactamases (MBLs). Here, we showed that TAN exhibited an overall excellent activity against B1 MBLs including most NDM- and VIM-like as well as SPM-1, GIM-1, and DIM-1 enzymes, but not against SIM-1. Noteworthy, VIM-1-like enzymes (particularly VIM-83) were less inhibited by TAN than VIM-2-like. Like NDM-9, NDM-30 (also differing from NDM-1 by a single amino acid substitution) was resistant to TAN...
December 4, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/38038476/loss-of-function-mutations-in-ndh-do-not-confer-delamanid-ethionamide-isoniazid-or-pretomanid-resistance-in-mycobacterium-tuberculosis
#6
JOURNAL ARTICLE
Sushil Pandey, Catherine Vilchèze, Jim Werngren, Arnold Bainomugisa, Mikael Mansjö, Ramona Groenheit, Paolo Miotto, Daniela M Cirillo, Christopher Coulter, Alain R Baulard, Thomas Schön, William R Jacobs, Kamel Djaout, Claudio U Köser
Results from clinical strains and knockouts of the H37Rv and CDC1551 laboratory strains demonstrated that ndh ( Rv1854c ) is not a resistance-conferring gene for isoniazid, ethionamide, delamanid, or pretomanid in Mycobacterium tuberculosis . This difference in the susceptibility to NAD-adduct-forming drugs compared with other mycobacteria may be driven by differences in the absolute intrabacterial NADH concentration.
December 1, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/38038460/pharmacokinetics-and-tolerability-of-cabotegravir-and-rilpivirine-long-acting-intramuscular-injections-to-the-vastus-lateralis-lateral-thigh-muscles-of-healthy-adult-participants
#7
JOURNAL ARTICLE
Kelong Han, Hakop Gevorkyan, Jafar Sadik Shaik, Herta Crauwels, Claudia Leemereise, Gilda Bontempo, Beta Win, Vasiliki Chounta, Ciara Seal, Rebecca DeMoor, Ronald D'Amico, William R Spreen, Susan L Ford
Cabotegravir + rilpivirine administered via intramuscular gluteal injections is the first complete long-acting (LA) regimen approved for maintaining HIV-1 virologic suppression. The vastus lateralis (lateral) thigh muscle could be a potential alternative site of administration in circumstances such as injection site fatigue, intolerability, or contraindication for gluteal administration. Cabotegravir and rilpivirine pharmacokinetics and participant tolerability were evaluated following single intramuscular injections to the lateral thigh...
December 1, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/38018963/pharmacological-validation-of-dihydrofolate-reductase-as-a-drug-target-in-mycobacterium-abscessus
#8
JOURNAL ARTICLE
Wassihun Wedajo Aragaw, Dereje A Negatu, Christopher J Bungard, Véronique A Dartois, Abdellatif El Marrouni, Elliott B Nickbarg, David B Olsen, Ralf Warrass, Thomas Dick
The Mycobacterium abscessus drug development pipeline is poorly populated, with particularly few validated target-lead couples to initiate de novo drug discovery. Trimethoprim, an inhibitor of dihydrofolate reductase (DHFR) used for the treatment of a range of bacterial infections, is not active against M. abscessus . Thus, evidence that M. abscessus DHFR is vulnerable to pharmacological intervention with a small molecule inhibitor is lacking. Here, we show that the pyrrolo-quinazoline PQD-1, previously identified as a DHFR inhibitor active against Mycobacterium tuberculosis , exerts whole cell activity against M...
November 29, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/38018962/repurposing-a-human-acetyl-coa-carboxylase-inhibitor-firsocostat-to-treat-fungal-candidiasis-alone-and-in-combination
#9
JOURNAL ARTICLE
Tianyu Chen, Jing Yao, Keao Quan, Jingchen Xu, Xudong Hang, Qian Tong, Genyan Liu, Peipei Luo, Liping Zeng, Ganzhu Feng, Hongkai Bi
Opportunistic fungal infections, particularly caused by Candida albicans , remain a common cause of high morbidity and mortality in immunocompromised patients. The escalating prevalence of antifungal drug resistance necessitates the immediate exploration of alternative treatment strategies to combat these life-threatening fungal diseases. In this study, we investigated the antifungal efficacy of firsocostat, a human acetyl-CoA carboxylase (ACC) inhibitor, against C. albicans . Firsocostat alone displayed moderate antifungal activity, while combining it with voriconazole, itraconazole, or amphotericin B exhibited synergistic effects across almost all drug-sensitive and drug-resistant C...
November 29, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/38014946/successful-addition-of-topical-antibiotic-treatment-after-surgery-in-treatment-refractory-nontuberculous-mycobacterial-skin-and-soft-tissue-infections
#10
JOURNAL ARTICLE
Ralf Stemkens, Maarten Cobussen, Erik de Laat, Wouter Hoefsloot, Reinout van Crevel, Rob E Aarnoutse, Jakko van Ingen
Treatment of skin and soft tissue infections with nontuberculous mycobacteria sometimes fails despite repeated debridements and long-term systemic antibiotic therapy. These treatment-refractory infections can cause significant morbidity and pose a treatment challenge. Following surgery, we treated three patients with negative pressure wound therapy with the instillation and dwell time of topical antibiotics, in addition to systemic antibiotic treatment. Treatment was successful and well tolerated, except for some local irritation...
November 28, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/38014945/population-pharmacokinetic-modeling-and-target-attainment-analyses-of-rezafungin-for-the-treatment-of-candidemia-and-invasive-candidiasis
#11
JOURNAL ARTICLE
Stefan Roepcke, Julie Passarell, Helen Walker, Shawn Flanagan
Rezafungin is a chemically and metabolically stable echinocandin with a longer half-life than other echinocandins, allowing for a once-weekly intravenous infusion versus a daily infusion. Rezafungin is approved in the US for the treatment of candidemia and/or invasive candidiasis and is in development for the prevention of invasive fungal disease caused by Candida , Aspergillus , and Pneumocystis spp. in immunosuppressed patients. A population pharmacokinetic (PPK) model was developed using data from five Phase 1, one Phase 2, and one Phase 3 study...
November 28, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/38014944/-in-vitro-activity-of-cefiderocol-a-siderophore-cephalosporin-against-carbapenem-resistant-hypervirulent-klebsiella-pneumoniae-in-china
#12
JOURNAL ARTICLE
Jiankang Zhao, Danni Pu, Ziyao Li, Xinmeng Liu, Yulin Zhang, Yongli Wu, Feilong Zhang, Chen Li, Xianxia Zhuo, Binghuai Lu, Bin Cao
Cefiderocol is a siderophore cephalosporin that binds ferric iron and utilizes iron transporters to cross the cell membrane. Hypervirulent Klebsiella pneumoniae (hvKp) is known to produce more siderophores; in this case, the uptake of cefiderocol may be decreased. Therefore, the objective of this study was to evaluate the in vitro activity of cefiderocol against hvKp isolates. A total of 320 carbapenem-resistant K. pneumoniae (CRKp) isolates were collected in China between 2014 and 2022, including 171 carbapenem-resistant hvKp (CR-hvKp) and 149 carbapenem-resistant classical K...
November 28, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/38014943/case-commentary-another-prong-of-attack-topical-antibiotic-instillation-with-negative-pressure-wound-therapy-for-nontuberculous-mycobacterial-skin-and-soft-tissue-infections
#13
JOURNAL ARTICLE
David C Nguyen, Angel M Buettner, Khalid M Dousa
Nontuberculous mycobacteria (NTM) skin infections remain therapeutically challenging. Given the diversity in infections, host responses, and antimicrobials, clinical guidelines are often built on case series and observational studies. In this commentary, we respond to a paper by Stemkens et al. that introduces an emerging strategy: adjunctive negative pressure wound therapy with instillation and dwell time combined with topical antibiotics for refractory NTM skin and soft tissue infections. We delve into the primary considerations surrounding this innovative approach...
November 28, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/37975660/individual-meropenem-epithelial-lining-fluid-and-plasma-pk-pd-target-attainment
#14
JOURNAL ARTICLE
Roxane Rohani, Paul R Yarnold, Marc H Scheetz, Michael N Neely, Mengjia Kang, Helen K Donnelly, Kay Dedicatoria, Sophie H Nozick, Rachel L Medernach, Alan R Hauser, Egon A Ozer, Estefani Diaz, Alexander V Misharin, Richard G Wunderink, Nathaniel J Rhodes
It is unclear whether plasma is a reliable surrogate for target attainment in the epithelial lining fluid (ELF). The objective of this study was to characterize meropenem target attainment in plasma and ELF using prospective samples. The first 24-hour T>MIC was evaluated vs 1xMIC and 4xMIC targets at the patient (i.e., fixed MIC of 2 mg/L) and population [i.e., cumulative fraction of response (CFR) according to EUCAST MIC distributions] levels for both plasma and ELF. Among 65 patients receiving ≥24 hours of treatment, 40% of patients failed to achieve >50% T>4xMIC in plasma and ELF, and 30% of patients who achieved >50% T>4xMIC in plasma had <50% T>4xMIC in ELF...
November 17, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/37971260/cytochrome-p450-2d6-profiles-and-anti-relapse-efficacy-of-tafenoquine-against-plasmodium-vivax-in-australian-defence-force-personnel
#15
JOURNAL ARTICLE
Simone Dowd, Nanhua Chen, Michelle L Gatton, Michael D Edstein, Qin Cheng
Plasmodium vivax infections and relapses remain a major health problem for malaria-endemic countries, deployed military personnel, and travelers. Presumptive anti-relapse therapy and radical cure using the 8-aminoquinoline drugs primaquine and tafenoquine are necessary to prevent relapses. Although it has been demonstrated that the efficacy of primaquine is associated with Cytochrome P450 2D6 (CYP2D6) activity, there is insufficient data on the role of CYP2D6 in the anti-relapse efficacy of tafenoquine. We investigated the relationship between CYP2D6 activity status and tafenoquine efficacy in preventing P...
November 16, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/37971244/subcutaneous-infusion-of-high-dose-benzathine-penicillin-g-is-safe-tolerable-and-suitable-for-less-frequent-dosing-for-rheumatic-heart-disease-secondary-prophylaxis-a-phase-1-open-label-population-pharmacokinetic-study
#16
JOURNAL ARTICLE
Joseph Kado, Sam Salman, Thel K Hla, Stephanie Enkel, Robert Henderson, Robert M Hand, Adam Hort, Madhu Page-Sharp, Kevin Batty, Brioni R Moore, Julie Bennett, Anneka Anderson, Jonathan Carapetis, Laurens Manning
Since 1955, the recommended strategy for rheumatic heart disease (RHD) secondary prophylaxis has been benzathine penicillin G [BPG; 1.2 MU (900 mg)] injections administered intramuscularly every 4 weeks. Due to dosing frequency, pain, and programmatic challenges, adherence is suboptimal. It has previously been demonstrated that BPG delivered subcutaneously at a standard dose is safe and tolerable and has favorable pharmacokinetics, setting the scene for improved regimens with less frequent administration. The safety, tolerability, and pharmacokinetics of subcutaneous infusions of high-dose BPG were assessed in 24 healthy adult volunteers assigned to receive either 3...
November 16, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/37971243/safety-tolerability-and-pharmacokinetics-of-ibrexafungerp-in-healthy-chinese-subjects-a-randomized-double-blind-placebo-controlled-phase-1-trial
#17
JOURNAL ARTICLE
Xiaoyan Liu, Rui Zhang, Rong Li, Qiong Wu, Chao Pan, Xiangqing Yu, Yuhui Liu, Benjie Wang, Shuwen Yu
Ibrexafungerp (code name in China: HS-10366) is a first-in-class and orally active triterpenoid antifungal agent with broad antifungal activity against Candida spp., Aspergillus spp., and other fungal pathogens. It was approved by the U.S. Food and Drug Administration for the treatment of vulvovaginal candidiasis. The study aimed to evaluate the safety, tolerability, and pharmacokinetic (PK) characteristics of oral ibrexafungerp in healthy Chinese adults. A single-center, randomized, double-blind, placebo-controlled single ascending dose (SAD, n = 42), and multiple ascending dose (MAD, n = 28) study was conducted in healthy Chinese subjects from March to October 2022...
November 16, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/37971242/plasmid-genomic-epidemiology-of-bla-kpc-carbapenemase-producing-enterobacterales-in-canada-2010-2021
#18
JOURNAL ARTICLE
Nicole Lerminiaux, Robyn Mitchell, Jessica Bartoszko, Ian Davis, Chelsey Ellis, Ken Fakharuddin, Susy S Hota, Kevin Katz, Pamela Kibsey, Jerome A Leis, Yves Longtin, Allison McGeer, Jessica Minion, Michael Mulvey, Sonja Musto, Ewa Rajda, Stephanie W Smith, Jocelyn A Srigley, Kathryn N Suh, Nisha Thampi, Jen Tomlinson, Titus Wong, Laura Mataseje
Carbapenems are considered last-resort antibiotics for the treatment of infections caused by multidrug-resistant Enterobacterales , but carbapenem resistance due to acquisition of carbapenemase genes is a growing threat that has been reported worldwide. Klebsiella pneumoniae carbapenemase ( bla KPC ) is the most common type of carbapenemase in Canada and elsewhere; it can hydrolyze penicillins, cephalosporins, aztreonam, and carbapenems and is frequently found on mobile plasmids in the Tn 4401 transposon. This means that alongside clonal expansion, bla KPC can disseminate through plasmid- and transposon-mediated horizontal gene transfer...
November 16, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/37971241/unraveling-the-mechanism-of-ceftaroline-induced-allosteric-regulation-in-penicillin-binding-protein-2a-insights-for-novel-antibiotic-development-against-methicillin-resistant-staphylococcus-aureus
#19
JOURNAL ARTICLE
Fangfang Jiao, Yiqiong Bao, Mengrong Li, Yan Zhang, Feng Zhang, Pinkai Wang, Jun Tao, Henry H Y Tong, Jingjing Guo
Methicillin-resistant Staphylococcus aureus (MRSA) acquires high-level resistance against β-lactam antibiotics by expressing penicillin-binding protein 2a (PBP2a). PBP2a is a cell wall-synthesizing protein whose closed active site exhibits a reduced binding affinity toward β-lactam antibiotics. Ceftaroline (CFT), a fifth-generation cephalosporin, can effectively inhibit the PBP2a activity by binding to an allosteric site to trigger the active site opening, allowing a second CFT to access the active site...
November 16, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/37971240/-in-vitro-and-in-vivo-activity-of-cefiderocol-against-achromobacter-spp-and-burkholderia-cepacia-complex-including-carbapenem-non-susceptible-isolates
#20
JOURNAL ARTICLE
Miki Takemura, Rio Nakamura, Merime Ota, Ryuichiro Nakai, Daniel F Sahm, Meredith A Hackel, Yoshinori Yamano
Achromobacter spp. and Burkholderia cepacia complex (Bcc) are rare but diverse opportunistic pathogens associated with serious infections, which are often multidrug resistant. This study compared the in vitro antibacterial activity of the siderophore antibiotic cefiderocol against Achromobacter spp. and Bcc isolates with that of other approved antibacterial drugs, including ceftazidime-avibactam, ciprofloxacin, colistin, imipenem-relebactam, and meropenem-vaborbactam. Isolates were collected in the SIDERO multinational surveillance program...
November 16, 2023: Antimicrobial Agents and Chemotherapy
journal
journal
22731
1
2
Fetch more papers »
Fetching more papers... Fetching...
Remove bar
Read by QxMD icon Read
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"

We want to hear from doctors like you!

Take a second to answer a survey question.