Promising aryl selenoate derivatives as antileishmanial agents and their effects on gene expression
Antimicrob Agents Chemother. 2024 Mar 18:e0155923. doi: 10.1128/aac.01559-23. Online ahead of print.ABSTRACTLeishmaniasis remains one of the main public health problems worldwide, with special incidence in the poorest populations. Selenium and its derivatives can be potent therapeutic options against protozoan parasites. In this work, 17 aryl selenoates were synthesized and screened against three species of Leishmania (Leishmania major, Leishmania amazonensis, and Leishmania infantum). Initial screening in promastigotes showed L. infantum species was more sensitive to selenoderivatives than the others. The lead Se-(2-selen...
Source: Antimicrobial Agents and Chemotherapy - March 18, 2024 Category: Microbiology Authors: Celia Fern ández-Rubio Mercedes Rubio-Hern ández Ver ónica Alcolea Aroia Burguete-Mikeo Paul A Nguewa Silvia P érez-Silanes Source Type: research

Efficacy and effect on lipid profiles of switching to ainuovirine-based regimen versus continuing efavirenz-based regimen in people with HIV-1: 24-week results from a real-world, retrospective, multi-center cohort study
In conclusion, we observed good efficacy and favorable changes in lipids in switching to ANV from EFV in treatment-experienced PWH in real world, indicating a promising switching option for PWH who may be more prone to metabolic or cardiovascular diseases.PMID:38483175 | DOI:10.1128/aac.01668-23 (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - March 14, 2024 Category: Microbiology Authors: Chunmei Wang Xiaoli Yu Yingchun Ke Yanhua Fu Yanhe Luo Ying Li Yanmei Bi Xingqiong Chen Linghua Li Xiuhong Zhao Zhong Chen Source Type: research

Efficacy and effect on lipid profiles of switching to ainuovirine-based regimen versus continuing efavirenz-based regimen in people with HIV-1: 24-week results from a real-world, retrospective, multi-center cohort study
In conclusion, we observed good efficacy and favorable changes in lipids in switching to ANV from EFV in treatment-experienced PWH in real world, indicating a promising switching option for PWH who may be more prone to metabolic or cardiovascular diseases.PMID:38483175 | DOI:10.1128/aac.01668-23 (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - March 14, 2024 Category: Microbiology Authors: Chunmei Wang Xiaoli Yu Yingchun Ke Yanhua Fu Yanhe Luo Ying Li Yanmei Bi Xingqiong Chen Linghua Li Xiuhong Zhao Zhong Chen Source Type: research

Efficacy and effect on lipid profiles of switching to ainuovirine-based regimen versus continuing efavirenz-based regimen in people with HIV-1: 24-week results from a real-world, retrospective, multi-center cohort study
In conclusion, we observed good efficacy and favorable changes in lipids in switching to ANV from EFV in treatment-experienced PWH in real world, indicating a promising switching option for PWH who may be more prone to metabolic or cardiovascular diseases.PMID:38483175 | DOI:10.1128/aac.01668-23 (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - March 14, 2024 Category: Microbiology Authors: Chunmei Wang Xiaoli Yu Yingchun Ke Yanhua Fu Yanhe Luo Ying Li Yanmei Bi Xingqiong Chen Linghua Li Xiuhong Zhao Zhong Chen Source Type: research

Deciphering the molecular and functional basis of TMexCD1: the plasmid-encoded efflux pump of resistance-nodulation-division superfamily
In this study, we focused on the differences in the inner membrane pump of these two systems and identified some key residues that contribute to the robust efflux activity of the TMexCD1 system. With the aid of homologous modeling and molecular docking, eight residues from the proximal binding pocket (PBP) and nine from the distal binding pocket (DBP) were selected and subjected to site-directed mutagenesis. Several of them, such as S134, I139, D181, and A290, were shown to be important for substrate binding in the DBP region, and all residues in PBP and DBP showed certain substrate preferences. Apart from the conservative...
Source: Antimicrobial Agents and Chemotherapy - March 13, 2024 Category: Microbiology Authors: Yan Shang Ye Zhang Ruimin Wang Yishu Peng Bo Ding Yuanxiang Liu Chongzhou Li Luhua Feng Honglei Liu Chunyu Yang Yajie Tang Source Type: research

Opportunistic dried blood spot sampling validates and optimizes a pediatric population pharmacokinetic model of metronidazole
Antimicrob Agents Chemother. 2024 Mar 13:e0153323. doi: 10.1128/aac.01533-23. Online ahead of print.ABSTRACTPharmacokinetic models rarely undergo external validation in vulnerable populations such as critically ill infants, thereby limiting the accuracy, efficacy, and safety of model-informed dosing in real-world settings. Here, we describe an opportunistic approach using dried blood spots (DBS) to evaluate a population pharmacokinetic model of metronidazole in critically ill preterm infants of gestational age (GA) ≤31 weeks from the Metronidazole Pharmacokinetics in Premature Infants (PTN_METRO, NCT01222585) study. Firs...
Source: Antimicrobial Agents and Chemotherapy - March 13, 2024 Category: Microbiology Authors: Rachel L Randell Stephen J Balevic Rachel G Greenberg Michael Cohen-Wolkowiez Elizabeth J Thompson Saranya Venkatachalam Michael J Smith Catherine Bendel Joseph M Bliss Hala Chaaban Rakesh Chhabra Christiane E L Dammann L Corbin Downey Chi Hornik Naveed H Source Type: research

Deciphering the molecular and functional basis of TMexCD1: the plasmid-encoded efflux pump of resistance-nodulation-division superfamily
In this study, we focused on the differences in the inner membrane pump of these two systems and identified some key residues that contribute to the robust efflux activity of the TMexCD1 system. With the aid of homologous modeling and molecular docking, eight residues from the proximal binding pocket (PBP) and nine from the distal binding pocket (DBP) were selected and subjected to site-directed mutagenesis. Several of them, such as S134, I139, D181, and A290, were shown to be important for substrate binding in the DBP region, and all residues in PBP and DBP showed certain substrate preferences. Apart from the conservative...
Source: Antimicrobial Agents and Chemotherapy - March 13, 2024 Category: Microbiology Authors: Yan Shang Ye Zhang Ruimin Wang Yishu Peng Bo Ding Yuanxiang Liu Chongzhou Li Luhua Feng Honglei Liu Chunyu Yang Yajie Tang Source Type: research

Opportunistic dried blood spot sampling validates and optimizes a pediatric population pharmacokinetic model of metronidazole
Antimicrob Agents Chemother. 2024 Mar 13:e0153323. doi: 10.1128/aac.01533-23. Online ahead of print.ABSTRACTPharmacokinetic models rarely undergo external validation in vulnerable populations such as critically ill infants, thereby limiting the accuracy, efficacy, and safety of model-informed dosing in real-world settings. Here, we describe an opportunistic approach using dried blood spots (DBS) to evaluate a population pharmacokinetic model of metronidazole in critically ill preterm infants of gestational age (GA) ≤31 weeks from the Metronidazole Pharmacokinetics in Premature Infants (PTN_METRO, NCT01222585) study. Firs...
Source: Antimicrobial Agents and Chemotherapy - March 13, 2024 Category: Microbiology Authors: Rachel L Randell Stephen J Balevic Rachel G Greenberg Michael Cohen-Wolkowiez Elizabeth J Thompson Saranya Venkatachalam Michael J Smith Catherine Bendel Joseph M Bliss Hala Chaaban Rakesh Chhabra Christiane E L Dammann L Corbin Downey Chi Hornik Naveed H Source Type: research

A panel of janus kinase inhibitors identified with anti-inflammatory effects protect mice from lethal influenza virus infection
In this study, 15 JAK inhibitors were identified through a screening process based on their anti-inflammatory activity against influenza virus infection in vitro. Remarkably, 7 of the 10 selected inhibitors exhibited protective effects against lethal influenza virus infection in mice, thereby highlighting the potential therapeutic value of JAK inhibitors for treating influenza.PMID:38470034 | DOI:10.1128/aac.01350-23 (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - March 12, 2024 Category: Microbiology Authors: Yang Yu Si Chen Haonan Zhang Yuanyuan Duan Zhuogang Li Lefang Jiang Weihua Cao Qun Peng Xulin Chen Source Type: research

Two-way pharmacodynamic modeling of drug combinations and its application to pairs of repurposed Ebola and SARS-CoV-2 agents
Antimicrob Agents Chemother. 2024 Mar 12:e0101523. doi: 10.1128/aac.01015-23. Online ahead of print.ABSTRACTExisting pharmacodynamic (PD) mathematical models for drug combinations discriminate antagonistic, additive, multiplicative, and synergistic effects, but fail to consider how concentration-dependent drug interaction effects may vary across an entire dose-response matrix. We developed a two-way pharmacodynamic (TWPD) model to capture the PD of two-drug combinations. TWPD captures interactions between upstream and downstream drugs that act on different stages of viral replication, by quantifying upstream drug efficacy ...
Source: Antimicrobial Agents and Chemotherapy - March 12, 2024 Category: Microbiology Authors: Shuang Xu Shadisadat Esmaeili E Fabian Cardozo-Ojeda Ashish Goyal Judith M White Stephen J Polyak Joshua T Schiffer Source Type: research

< em > Pseudomonas aeruginosa < /em > ventricular assist device infections: findings from ineffective phage therapies in five cases
Antimicrob Agents Chemother. 2024 Mar 12:e0172823. doi: 10.1128/aac.01728-23. Online ahead of print.ABSTRACTLeft ventricular assist devices (LVAD) are increasingly used for management of heart failure; infection remains a frequent complication. Phage therapy has been successful in a variety of antibiotic refractory infections and is of interest in treating LVAD infections. We performed a retrospective review of four patients that underwent five separate courses of intravenous (IV) phage therapy with concomitant antibiotic for treatment of endovascular Pseudomonas aeruginosa LVAD infection. We assessed phage susceptibility,...
Source: Antimicrobial Agents and Chemotherapy - March 12, 2024 Category: Microbiology Authors: Saima Aslam Dwayne Roach Mikeljon P Nikolich Biswajit Biswas Robert T Schooley Kimberley A Lilly-Bishop Gregory K Rice Regina Z Cer Theron Hamilton Matthew Henry Tiffany Luong Ann-Charlott Salabarria Laura Sisk-Hackworth Andrey A Filippov Francois Lebreto Source Type: research

Sub-MIC levels of bedaquiline and clofazimine can select < em > Mycobacterium tuberculosis < /em > mutants with increased MIC
Antimicrob Agents Chemother. 2024 Mar 12:e0127523. doi: 10.1128/aac.01275-23. Online ahead of print.ABSTRACTMultidrug-resistant tuberculosis (MDR-TB) patients not cured at the time of stopping treatment are exposed to Minimum Inhibitory Concentration (MIC) and sub-MIC levels for many months after discontinuing bedaquiline (BDQ) or clofazimine (CFZ) treatment. In vitro cultures treated with BDQ and CFZ sub-MIC concentrations clearly showed enrichment in the Rv0678 mutant population, demonstrating that pre-existing Rv0678 mutants can be selected by sub-MIC concentrations of BDQ and CFZ if not protected by an alternative MDR-...
Source: Antimicrobial Agents and Chemotherapy - March 12, 2024 Category: Microbiology Authors: Cristina Villellas Frederik Stevenaert Bart Remmerie Koen Andries Source Type: research

Murepavadin promotes the killing efficacies of aminoglycoside antibiotics against < em > Pseudomonas aeruginosa < /em > by enhancing membrane potential
Antimicrob Agents Chemother. 2024 Mar 12:e0153923. doi: 10.1128/aac.01539-23. Online ahead of print.ABSTRACTMurepavadin is a peptidomimetic that specifically targets the lipopolysaccharide transport protein LptD of Pseudomonas aeruginosa. Here, we found that murepavadin enhances the bactericidal efficacies of tobramycin and amikacin. We further demonstrated that murepavadin enhances bacterial respiration activity and subsequent membrane potential, which promotes intracellular uptake of aminoglycoside antibiotics. In addition, the murepavadin-amikacin combination displayed a synergistic bactericidal effect in a murine pneum...
Source: Antimicrobial Agents and Chemotherapy - March 12, 2024 Category: Microbiology Authors: Xiaoya Wei Jiacong Gao Dandan Zhou Congjuan Xu Ping Chen Shuiping Chen Yanhong Zhang Xuehua Liu Guanxian Li Guangbo Zhu Huimin Liu Jinjin Li Bin Geng Linlin Gao Zhihui Cheng Iain L Lamont Daniel Pletzer Yongxin Jin Shouguang Jin Weihui Wu Source Type: research

A panel of janus kinase inhibitors identified with anti-inflammatory effects protect mice from lethal influenza virus infection
In this study, 15 JAK inhibitors were identified through a screening process based on their anti-inflammatory activity against influenza virus infection in vitro. Remarkably, 7 of the 10 selected inhibitors exhibited protective effects against lethal influenza virus infection in mice, thereby highlighting the potential therapeutic value of JAK inhibitors for treating influenza.PMID:38470034 | DOI:10.1128/aac.01350-23 (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - March 12, 2024 Category: Microbiology Authors: Yang Yu Si Chen Haonan Zhang Yuanyuan Duan Zhuogang Li Lefang Jiang Weihua Cao Qun Peng Xulin Chen Source Type: research

Two-way pharmacodynamic modeling of drug combinations and its application to pairs of repurposed Ebola and SARS-CoV-2 agents
Antimicrob Agents Chemother. 2024 Mar 12:e0101523. doi: 10.1128/aac.01015-23. Online ahead of print.ABSTRACTExisting pharmacodynamic (PD) mathematical models for drug combinations discriminate antagonistic, additive, multiplicative, and synergistic effects, but fail to consider how concentration-dependent drug interaction effects may vary across an entire dose-response matrix. We developed a two-way pharmacodynamic (TWPD) model to capture the PD of two-drug combinations. TWPD captures interactions between upstream and downstream drugs that act on different stages of viral replication, by quantifying upstream drug efficacy ...
Source: Antimicrobial Agents and Chemotherapy - March 12, 2024 Category: Microbiology Authors: Shuang Xu Shadisadat Esmaeili E Fabian Cardozo-Ojeda Ashish Goyal Judith M White Stephen J Polyak Joshua T Schiffer Source Type: research