A phase 1 study in healthy volunteers to investigate the safety, tolerability, and pharmacokinetics of VIR-2482: a monoclonal antibody for the prevention of severe influenza A illness
This study has been registered at ClinicalTrials.gov under identifier NCT04033406.PMID:38376227 | DOI:10.1128/aac.01273-23 (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - February 20, 2024 Category: Microbiology Authors: David Plotnik Jennifer E Sager Madhukar Aryal Marie C Fanget Alessia Peter Michael A Schmid Deborah Cebrik Erik Mogalian Keith Boundy Wendy W Yeh Paul Griffin Maribel Reyes Source Type: research

Bactericidal and sterilizing activity of novel regimens combining bedaquiline or TBAJ-587 with GSK2556286 and TBA-7371 in a mouse model of tuberculosis
Antimicrob Agents Chemother. 2024 Feb 20:e0156223. doi: 10.1128/aac.01562-23. Online ahead of print.ABSTRACTThe combination of bedaquiline, pretomanid, and linezolid (BPaL) has become a preferred regimen for treating multidrug- and extensively drug-resistant tuberculosis (TB). However, treatment-limiting toxicities of linezolid and reports of emerging bedaquiline and pretomanid resistance necessitate efforts to develop new short-course oral regimens. We recently found that the addition of GSK2556286 increases the bactericidal and sterilizing activity of BPa-containing regimens in a well-established BALB/c mouse model of tu...
Source: Antimicrobial Agents and Chemotherapy - February 20, 2024 Category: Microbiology Authors: Si-Yang Li Sandeep Tyagi Heena Soni Fabrice Betoudji Paul J Converse Khisimuzi Mdluli Anna M Upton Nader Fotouhi David Barros-Aguirre Llu ís Ballell Elena Jimenez-Navarro Eric L Nuermberger Source Type: research

A population pharmacokinetic model for posaconazole intravenous solution and oral powder for suspension formulations in pediatric patients with neutropenia
The objective of this study was to support posaconazole dose regimens in pediatric patients aged ≥2 years, using a population pharmacokinetic (PK) approach with data from a phase 1b study (NCT02452034). A one-compartment model with first-order absorption was fit to pharmacokinetic data from 144 participants aged 2 to 17 years, who were administered posaconazole as intravenous (IV) and powder for oral suspension (PFS) formulations, or IV only, at dosing regimens of 3.5, 4.5, and 6 mg/kg. The influence of demographic and clinical factors on pharmacokinetic parameters was evaluated using a stepwise forward inclusion/backwar...
Source: Antimicrobial Agents and Chemotherapy - February 20, 2024 Category: Microbiology Authors: Gregory Winchell Rik de Greef Aziz Ouerdani Floris Fauchet Rebecca E Wrishko Eric Mangin Christopher Bruno Hetty Waskin Source Type: research

Interspecies variability in protein binding of antibiotics basis for translational PK/PD studies-a case study using cefazolin
Antimicrob Agents Chemother. 2024 Feb 20:e0164723. doi: 10.1128/aac.01647-23. Online ahead of print.ABSTRACTFor antimicrobial agents in particular, plasma protein binding (PPB) plays a pivotal role in deciphering key properties of drug candidates. Animal models are generally used in the preclinical development of new drugs to predict their effects in humans using translational pharmacokinetics/pharmacodynamics (PK/PD). Thus, we compared the protein binding (PB) of cefazolin as well as bacterial growth under various conditions in vitro. The PB extent of cefazolin was studied in human, bovine, and rat plasmas at different an...
Source: Antimicrobial Agents and Chemotherapy - February 20, 2024 Category: Microbiology Authors: Hifza Ahmed Michaela B öhmdorfer Sabine Eberl Walter J äger Markus Zeitlinger Source Type: research

Phage-antibiotic synergy against daptomycin-nonsusceptible MRSA in an < em > ex vivo < /em > simulated endocardial pharmacokinetic/pharmacodynamic model
We examined PAC activity against two well-characterized DNS MRSA strains (C4 and C37) in vitro and ex vivo. PACs comprising daptomycin (DAP) ± ceftaroline (CPT) and a two-phage cocktail (Intesti13 + Sb-1) were evaluated for phage-antibiotic synergy (PAS) against high MRSA inoculum (109 CFU/mL) using (i) modified checkerboards (CB), (ii) 24-h time-kill assays (TKA), and (iii) 168-h ex vivo simulated endocardial vegetation (SEV) models. PAS was defined as a fractional inhibitory concentration ≤0.5 in CB minimum inhibitory concentration (MIC) or a ≥2 log10 CFU/mL reduction compared to the next best regimen in time-kill a...
Source: Antimicrobial Agents and Chemotherapy - February 20, 2024 Category: Microbiology Authors: Ashlan J Kunz Coyne Callan Bleick Kyle Stamper Razieh Kebriaei Arnold S Bayer Susan M Lehman Michael J Rybak Source Type: research

A multi-species outbreak of VIM-producing carbapenem-resistant bacteria in a burn unit and subsequent investigation of rapid development of cefiderocol resistance
We describe a case series of bacterial infections in a tertiary care hospital due to multi-species acquisition of a VIM gene along with our experience using novel β-lactam antibiotics and antibiotic combinations to treat these infections. Four patients were treated with the combination of ceftazidime-avibactam and aztreonam, with no resistance to the combination detected. However, cefiderocol-resistant Klebsiella pneumoniae isolates were detected in two out of the five patients who received cefiderocol within 3 weeks of having started the antibiotic. Strain pairs of sequential susceptible and resistant isolates from both ...
Source: Antimicrobial Agents and Chemotherapy - February 20, 2024 Category: Microbiology Authors: Jeffrey A Freiberg Lili Tao Carmila Manuel Laura A Mike George E Nelson Bryan D Harris Amy J Mathers Thomas R Talbot Eric P Skaar Romney M Humphries Source Type: research

Identifying and mathematically modeling the time-course of extracellular metabolic markers associated with resistance to ceftolozane/tazobactam in < em > Pseudomonas aeruginosa < /em >
Antimicrob Agents Chemother. 2024 Feb 20:e0108123. doi: 10.1128/aac.01081-23. Online ahead of print.ABSTRACTExtracellular bacterial metabolites have potential as markers of bacterial growth and resistance emergence but have not been evaluated in dynamic in vitro studies. We investigated the dynamic metabolomic footprint of a multidrug-resistant hypermutable Pseudomonas aeruginosa isolate exposed to ceftolozane/tazobactam as continuous infusion (4.5 g/day, 9 g/day) in a hollow-fiber infection model over 7-9 days in biological replicates (n = 5). Bacterial samples were collected at 0, 7, 23, 47, 71, 95, 143, 167, 191, and 21...
Source: Antimicrobial Agents and Chemotherapy - February 20, 2024 Category: Microbiology Authors: Jessica R Tait Dovile Anderson Roger L Nation Darren J Creek Cornelia B Landersdorfer Source Type: research

A phase 1 study in healthy volunteers to investigate the safety, tolerability, and pharmacokinetics of VIR-2482: a monoclonal antibody for the prevention of severe influenza A illness
This study has been registered at ClinicalTrials.gov under identifier NCT04033406.PMID:38376227 | DOI:10.1128/aac.01273-23 (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - February 20, 2024 Category: Microbiology Authors: David Plotnik Jennifer E Sager Madhukar Aryal Marie C Fanget Alessia Peter Michael A Schmid Deborah Cebrik Erik Mogalian Keith Boundy Wendy W Yeh Paul Griffin Maribel Reyes Source Type: research

Bactericidal and sterilizing activity of novel regimens combining bedaquiline or TBAJ-587 with GSK2556286 and TBA-7371 in a mouse model of tuberculosis
Antimicrob Agents Chemother. 2024 Feb 20:e0156223. doi: 10.1128/aac.01562-23. Online ahead of print.ABSTRACTThe combination of bedaquiline, pretomanid, and linezolid (BPaL) has become a preferred regimen for treating multidrug- and extensively drug-resistant tuberculosis (TB). However, treatment-limiting toxicities of linezolid and reports of emerging bedaquiline and pretomanid resistance necessitate efforts to develop new short-course oral regimens. We recently found that the addition of GSK2556286 increases the bactericidal and sterilizing activity of BPa-containing regimens in a well-established BALB/c mouse model of tu...
Source: Antimicrobial Agents and Chemotherapy - February 20, 2024 Category: Microbiology Authors: Si-Yang Li Sandeep Tyagi Heena Soni Fabrice Betoudji Paul J Converse Khisimuzi Mdluli Anna M Upton Nader Fotouhi David Barros-Aguirre Llu ís Ballell Elena Jimenez-Navarro Eric L Nuermberger Source Type: research

A population pharmacokinetic model for posaconazole intravenous solution and oral powder for suspension formulations in pediatric patients with neutropenia
The objective of this study was to support posaconazole dose regimens in pediatric patients aged ≥2 years, using a population pharmacokinetic (PK) approach with data from a phase 1b study (NCT02452034). A one-compartment model with first-order absorption was fit to pharmacokinetic data from 144 participants aged 2 to 17 years, who were administered posaconazole as intravenous (IV) and powder for oral suspension (PFS) formulations, or IV only, at dosing regimens of 3.5, 4.5, and 6 mg/kg. The influence of demographic and clinical factors on pharmacokinetic parameters was evaluated using a stepwise forward inclusion/backwar...
Source: Antimicrobial Agents and Chemotherapy - February 20, 2024 Category: Microbiology Authors: Gregory Winchell Rik de Greef Aziz Ouerdani Floris Fauchet Rebecca E Wrishko Eric Mangin Christopher Bruno Hetty Waskin Source Type: research

< em > Staphylococcus aureus < /em > AbcA transporter enhances persister formation under β-lactam exposure
Antimicrob Agents Chemother. 2024 Feb 16:e0134023. doi: 10.1128/aac.01340-23. Online ahead of print.ABSTRACTWe evaluated the role of Staphylococcus aureus AbcA transporter in bacterial persistence and survival following exposure to the bactericidal agents nafcillin and oxacillin at both the population and single-cell levels. We show that AbcA overexpression resulted in resistance to nafcillin but not oxacillin. Using distinct fluorescent reporters of cell viability and AbcA expression, we found that over 6-14 hours of persistence formation, the proportion of AbcA reporter-expressing cells assessed by confocal microscopy in...
Source: Antimicrobial Agents and Chemotherapy - February 16, 2024 Category: Microbiology Authors: Q C Truong-Bolduc Y Wang R Ferrer-Espada J L Reedy A T Martens Y Goulev J Paulsson J M Vyas D C Hooper Source Type: research

Antibacterial activity of ibezapolstat against antimicrobial-resistant clinical strains of < em > Clostridioides difficile < /em >
This study demonstrated the potent antibacterial activity of IBZ against a large collection of C. difficile strains including multidrug-resistant strains. This study highlights the therapeutic potential of IBZ against multidrug-resistant strains of C. difficile.PMID:38364016 | DOI:10.1128/aac.01621-23 (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - February 16, 2024 Category: Microbiology Authors: Eug énie Bassères Taryn A Eubank Khurshida Begum M Jahangir Alam Jinhee Jo Thanh M Le Chris K Lancaster Anne J Gonzales-Luna Kevin W Garey Source Type: research

< em > Staphylococcus aureus < /em > AbcA transporter enhances persister formation under β-lactam exposure
Antimicrob Agents Chemother. 2024 Feb 16:e0134023. doi: 10.1128/aac.01340-23. Online ahead of print.ABSTRACTWe evaluated the role of Staphylococcus aureus AbcA transporter in bacterial persistence and survival following exposure to the bactericidal agents nafcillin and oxacillin at both the population and single-cell levels. We show that AbcA overexpression resulted in resistance to nafcillin but not oxacillin. Using distinct fluorescent reporters of cell viability and AbcA expression, we found that over 6-14 hours of persistence formation, the proportion of AbcA reporter-expressing cells assessed by confocal microscopy in...
Source: Antimicrobial Agents and Chemotherapy - February 16, 2024 Category: Microbiology Authors: Q C Truong-Bolduc Y Wang R Ferrer-Espada J L Reedy A T Martens Y Goulev J Paulsson J M Vyas D C Hooper Source Type: research

Antibacterial activity of ibezapolstat against antimicrobial-resistant clinical strains of < em > Clostridioides difficile < /em >
This study demonstrated the potent antibacterial activity of IBZ against a large collection of C. difficile strains including multidrug-resistant strains. This study highlights the therapeutic potential of IBZ against multidrug-resistant strains of C. difficile.PMID:38364016 | DOI:10.1128/aac.01621-23 (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - February 16, 2024 Category: Microbiology Authors: Eug énie Bassères Taryn A Eubank Khurshida Begum M Jahangir Alam Jinhee Jo Thanh M Le Chris K Lancaster Anne J Gonzales-Luna Kevin W Garey Source Type: research

< em > Staphylococcus aureus < /em > AbcA transporter enhances persister formation under β-lactam exposure
Antimicrob Agents Chemother. 2024 Feb 16:e0134023. doi: 10.1128/aac.01340-23. Online ahead of print.ABSTRACTWe evaluated the role of Staphylococcus aureus AbcA transporter in bacterial persistence and survival following exposure to the bactericidal agents nafcillin and oxacillin at both the population and single-cell levels. We show that AbcA overexpression resulted in resistance to nafcillin but not oxacillin. Using distinct fluorescent reporters of cell viability and AbcA expression, we found that over 6-14 hours of persistence formation, the proportion of AbcA reporter-expressing cells assessed by confocal microscopy in...
Source: Antimicrobial Agents and Chemotherapy - February 16, 2024 Category: Microbiology Authors: Q C Truong-Bolduc Y Wang R Ferrer-Espada J L Reedy A T Martens Y Goulev J Paulsson J M Vyas D C Hooper Source Type: research