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

< 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

Pharmacokinetics of long-acting lenacapavir in participants with hepatic or renal impairment
Antimicrob Agents Chemother. 2024 Mar 8:e0134423. doi: 10.1128/aac.01344-23. Online ahead of print.ABSTRACTLenacapavir is a novel, first-in-class, multistage inhibitor of HIV-1 capsid function approved for the treatment of multidrug-resistant HIV-1 infection in combination with other antiretrovirals for heavily treatment-experienced people with HIV. Two Phase 1, open-label, parallel-group, single-dose studies assessed the pharmacokinetics (PK) of lenacapavir in participants with moderate hepatic impairment [Child-Pugh-Turcotte (CPT) Class B: score 7-9] or severe renal impairment [15 ≤ creatinine clearance (CLcr) ≤29 mL...
Source: Antimicrobial Agents and Chemotherapy - March 8, 2024 Category: Microbiology Authors: Vamshi Jogiraju Elijah Weber Jason Hindman Steve West John Ling Martin Rhee Sandhya Girish Ramesh Palaparthy Renu Singh Source Type: research

Pharmacokinetics of long-acting lenacapavir in participants with hepatic or renal impairment
Antimicrob Agents Chemother. 2024 Mar 8:e0134423. doi: 10.1128/aac.01344-23. Online ahead of print.ABSTRACTLenacapavir is a novel, first-in-class, multistage inhibitor of HIV-1 capsid function approved for the treatment of multidrug-resistant HIV-1 infection in combination with other antiretrovirals for heavily treatment-experienced people with HIV. Two Phase 1, open-label, parallel-group, single-dose studies assessed the pharmacokinetics (PK) of lenacapavir in participants with moderate hepatic impairment [Child-Pugh-Turcotte (CPT) Class B: score 7-9] or severe renal impairment [15 ≤ creatinine clearance (CLcr) ≤29 mL...
Source: Antimicrobial Agents and Chemotherapy - March 8, 2024 Category: Microbiology Authors: Vamshi Jogiraju Elijah Weber Jason Hindman Steve West John Ling Martin Rhee Sandhya Girish Ramesh Palaparthy Renu Singh Source Type: research

Pharmacokinetics of long-acting lenacapavir in participants with hepatic or renal impairment
Antimicrob Agents Chemother. 2024 Mar 8:e0134423. doi: 10.1128/aac.01344-23. Online ahead of print.ABSTRACTLenacapavir is a novel, first-in-class, multistage inhibitor of HIV-1 capsid function approved for the treatment of multidrug-resistant HIV-1 infection in combination with other antiretrovirals for heavily treatment-experienced people with HIV. Two Phase 1, open-label, parallel-group, single-dose studies assessed the pharmacokinetics (PK) of lenacapavir in participants with moderate hepatic impairment [Child-Pugh-Turcotte (CPT) Class B: score 7-9] or severe renal impairment [15 ≤ creatinine clearance (CLcr) ≤29 mL...
Source: Antimicrobial Agents and Chemotherapy - March 8, 2024 Category: Microbiology Authors: Vamshi Jogiraju Elijah Weber Jason Hindman Steve West John Ling Martin Rhee Sandhya Girish Ramesh Palaparthy Renu Singh Source Type: research

Pharmacokinetics of long-acting lenacapavir in participants with hepatic or renal impairment
Antimicrob Agents Chemother. 2024 Mar 8:e0134423. doi: 10.1128/aac.01344-23. Online ahead of print.ABSTRACTLenacapavir is a novel, first-in-class, multistage inhibitor of HIV-1 capsid function approved for the treatment of multidrug-resistant HIV-1 infection in combination with other antiretrovirals for heavily treatment-experienced people with HIV. Two Phase 1, open-label, parallel-group, single-dose studies assessed the pharmacokinetics (PK) of lenacapavir in participants with moderate hepatic impairment [Child-Pugh-Turcotte (CPT) Class B: score 7-9] or severe renal impairment [15 ≤ creatinine clearance (CLcr) ≤29 mL...
Source: Antimicrobial Agents and Chemotherapy - March 8, 2024 Category: Microbiology Authors: Vamshi Jogiraju Elijah Weber Jason Hindman Steve West John Ling Martin Rhee Sandhya Girish Ramesh Palaparthy Renu Singh Source Type: research

Hydrogen sulfide production does not affect antibiotic resistance in < em > Pseudomonas aeruginosa < /em >
Antimicrob Agents Chemother. 2024 Mar 6:e0007524. doi: 10.1128/aac.00075-24. Online ahead of print.ABSTRACTHydrogen sulfide (H2S) has been proposed to protect bacteria from antibiotics, pointing to H2S-producing enzymes as possible targets for the development of antibiotic adjuvants. Here, MIC assays performed with Pseudomonas aeruginosa mutants producing altered H2S levels demonstrate that H2S does not affect antibiotic resistance in this bacterium. Moreover, correlation analyses in a large collection of P. aeruginosa cystic fibrosis isolates argue against the protective role of H2S from antibiotic activity during chronic...
Source: Antimicrobial Agents and Chemotherapy - March 6, 2024 Category: Microbiology Authors: Lorenzo Caruso Marta Mellini Ortensia Catalano Gonzaga Alessandra Astegno Elena Forte Adele Di Matteo Alessandro Giuffr è Paolo Visca Francesco Imperi Livia Leoni Giordano Rampioni Source Type: research

BPR3P0128, a non-nucleoside RNA-dependent RNA polymerase inhibitor, inhibits SARS-CoV-2 variants of concern and exerts synergistic antiviral activity in combination with remdesivir
Antimicrob Agents Chemother. 2024 Mar 6:e0095623. doi: 10.1128/aac.00956-23. Online ahead of print.ABSTRACTViral RNA-dependent RNA polymerase (RdRp), a highly conserved molecule in RNA viruses, has recently emerged as a promising drug target for broad-acting inhibitors. Through a Vero E6-based anti-cytopathic effect assay, we found that BPR3P0128, which incorporates a quinoline core similar to hydroxychloroquine, outperformed the adenosine analog remdesivir in inhibiting RdRp activity (EC50 = 0.66 µM and 3 µM, respectively). BPR3P0128 demonstrated broad-spectrum activity against various severe acute respiratory syndrome ...
Source: Antimicrobial Agents and Chemotherapy - March 6, 2024 Category: Microbiology Authors: Wen-Fang Tang Yu-Hsiu Chang Cheng-Chin Lin Jia-Rong Jheng Chung-Fan Hsieh Yuan-Fan Chin Tein-Yao Chang Jin-Ching Lee Po-Huang Liang Chia-Yi Lin Guan-Hua Lin Jie-Yun Cai Yu-Li Chen Yuan-Siao Chen Shan-Ko Tsai Ping-Cheng Liu Chuen-Mi Yang Tolou Shadbahr Jin Source Type: research

Hydrogen sulfide production does not affect antibiotic resistance in < em > Pseudomonas aeruginosa < /em >
Antimicrob Agents Chemother. 2024 Mar 6:e0007524. doi: 10.1128/aac.00075-24. Online ahead of print.ABSTRACTHydrogen sulfide (H2S) has been proposed to protect bacteria from antibiotics, pointing to H2S-producing enzymes as possible targets for the development of antibiotic adjuvants. Here, MIC assays performed with Pseudomonas aeruginosa mutants producing altered H2S levels demonstrate that H2S does not affect antibiotic resistance in this bacterium. Moreover, correlation analyses in a large collection of P. aeruginosa cystic fibrosis isolates argue against the protective role of H2S from antibiotic activity during chronic...
Source: Antimicrobial Agents and Chemotherapy - March 6, 2024 Category: Microbiology Authors: Lorenzo Caruso Marta Mellini Ortensia Catalano Gonzaga Alessandra Astegno Elena Forte Adele Di Matteo Alessandro Giuffr è Paolo Visca Francesco Imperi Livia Leoni Giordano Rampioni Source Type: research

BPR3P0128, a non-nucleoside RNA-dependent RNA polymerase inhibitor, inhibits SARS-CoV-2 variants of concern and exerts synergistic antiviral activity in combination with remdesivir
Antimicrob Agents Chemother. 2024 Mar 6:e0095623. doi: 10.1128/aac.00956-23. Online ahead of print.ABSTRACTViral RNA-dependent RNA polymerase (RdRp), a highly conserved molecule in RNA viruses, has recently emerged as a promising drug target for broad-acting inhibitors. Through a Vero E6-based anti-cytopathic effect assay, we found that BPR3P0128, which incorporates a quinoline core similar to hydroxychloroquine, outperformed the adenosine analog remdesivir in inhibiting RdRp activity (EC50 = 0.66 µM and 3 µM, respectively). BPR3P0128 demonstrated broad-spectrum activity against various severe acute respiratory syndrome ...
Source: Antimicrobial Agents and Chemotherapy - March 6, 2024 Category: Microbiology Authors: Wen-Fang Tang Yu-Hsiu Chang Cheng-Chin Lin Jia-Rong Jheng Chung-Fan Hsieh Yuan-Fan Chin Tein-Yao Chang Jin-Ching Lee Po-Huang Liang Chia-Yi Lin Guan-Hua Lin Jie-Yun Cai Yu-Li Chen Yuan-Siao Chen Shan-Ko Tsai Ping-Cheng Liu Chuen-Mi Yang Tolou Shadbahr Jin Source Type: research