Plasma and Breast Milk Pharmacokinetics of Tenofovir Disoproxil Fumarate in Nursing Mother with Chronic Hepatitis B-Infant Pairs
In this study, we aimed to determine of tenofovir concentration in plasma of mother-infant pairs along with breast milk in chronic hepatitis B patients during lactation period. Patients and Method: A total of eleven mother-infant pairs were enrolled in the study. All the mothers received tenofovir disoproxil fumarate (TDF) 245 mg/day for at least one month because of chronic hepatitis B infection. Maternal blood, breast milk and infant blood samples were obtained concomitantly. Tenofovir concentrations were determined by liquid chromatography tandem mass spectrometry method. Results: The median concentrations of tenofovir ...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: U S Erturk B Mete R Ozaras N Saltoglu I I Balkan A Mert B Kacmaz O Saglam B Guney O A Sayman F Tabak Source Type: research

< em > In vitro < /em > activity of APX2041, a new GWT1-inhibitor and < em > in vivo < /em > efficacy of the prodrug APX2104 against < em > Aspergillus fumigatus < /em >
Antimicrob Agents Chemother. 2021 Jul 26:AAC0068221. doi: 10.1128/AAC.00682-21. Online ahead of print.ABSTRACTInvasive aspergillosis (IA) due to Aspergillus fumigatus is a deadly infection for which new antifungal therapies are needed. Here we demonstrate the efficacy of a Gwt1 inhibitor, APX2041, and its prodrug, APX2104, against A. fumigatus. The wild-type, azole-resistant and echinocandin-resistant A. fumigatus strains were equally susceptible to APX2041 in vitro. APX2104 treatment in vivo significantly prolonged survival of neutropenic mice challenged with the wild-type and azole-resistant strains, revealing APX2104 as...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Shareef K Shaheen Praveen R Juvvadi John Allen Iv E Keats Shwab D Christopher Cole Yohannes G Asfaw Mili Kapoor Karen Joy Shaw William J Steinbach Source Type: research

The Phenotypic/Genotypic Profile of OXA-10-like harboring, Carbapenem-Resistant < em > Pseudomonas aeruginosa < /em > : Using Validated Pharmacokinetic/Pharmacodynamic < em > in vivo < /em > Models to Further Evaluate Enzyme Functionality and Clinical Implications
Antimicrob Agents Chemother. 2021 Jul 26:AAC0127421. doi: 10.1128/AAC.01274-21. Online ahead of print.ABSTRACTIn vitro MICs and in vivo pharmacodynamics of ceftazidime and cefepime human-simulated regimens (HSR) against mCIM-positive P. aeruginosa harboring different OXA-10-like subtypes were described. The murine thigh model assessed ceftazidime (2g q8h HSR) and cefepime (2g and 1g q8h HSR). Phenotypes were similar despite possessing OXA-10-like subtypes with differing spectra. Ceftazidime produced ≥1-log10 kill in all isolates. Cefepime activity was dose-dependent and MIC driven. This approach may be useful in assessi...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Christian M Gill Adrian Brink Chun Yat Chu Jennifer Coetzee George Dimopoulos Clinton Moodley Christoffel Johannes Opperman Spyros Pournaras Fred C Tenover Isabella A Tickler Hafsah Deepa Tootla Sophia Vourli David P Nicolau Source Type: research

Kinetic and Structural Characterization of the First B3 Metallo- β-Lactamase with an Active Site Glutamic Acid
Antimicrob Agents Chemother. 2021 Jul 26:AAC0093621. doi: 10.1128/AAC.00936-21. Online ahead of print.ABSTRACTThe structural diversity in metallo-β-lactamases (MBLs), especially in the vicinity of the active site, has been a major hurdle in the development of clinically effective inhibitors. Representatives from three variants of the B3 MBL subclass, containing either the canonical HHH/DHH active site motif (present in the majority of MBLs in this subclass) or the QHH/DHH (B3-Q) or HRH/DQK (B3-RQK) variations were reported previously. Here, we describe the structure and kinetic properties of the first example (SIE-1) ...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Liam A Wilson Esm ée G Knaven Marc T Morris Marcelo Monteiro Pedroso Christopher J Schofield Thomas Br ück Mikael Boden David W Waite Philip Hugenholtz Luke Guddat Gerhard Schenk Source Type: research

Point mutation or overexpression of < em > A. fumigatus < /em > < em > cyp51B, < /em > encoding lanosterol 14 α-sterol demethylase, leads to triazole resistance
Antimicrob Agents Chemother. 2021 Jul 26:AAC0125221. doi: 10.1128/AAC.01252-21. Online ahead of print.ABSTRACTAspergillus fumigatus is the most common cause of invasive fungal mold infections in immunocompromised individuals. Current antifungal treatment relies heavily on the triazole antifungals which inhibit fungal Erg11/Cyp51 activity and subsequent ergosterol biosynthesis. However, resistance, due primarily to cyp51 mutation, is rapidly increasing. A. fumigatus contains two Cyp51 isoenzymes, Cyp51A and Cyp51B. Overexpression and mutation of Cyp51A is a major cause of triazole resistance in A. fumigatus. The role of Cyp...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Mariana Handelman Zohar Meir Jennifer Scott Yona Shadkchan Wei Liu Ronen Ben-Ami Jorge Amich Nir Osherov Source Type: research

Core oligosaccharide portion of lipopolysaccharide plays important roles on multiple antibiotic resistance in < em > Escherichia coli < /em >
In this study, a series of mutants that lack one or more major components associated with the cell envelope were constructed from Escherichia coli K-12 W3110. WJW02 can only synthesize Kdo2-lipid A which lacks the core oligosaccharide portion of lipopolysaccharide. WJW04, WJW07 and WJW08 were constructed from WJW02 by deleting the gene clusters relevant to the biosynthesis of exopolysaccharide, flagella and fimbria, respectively. WJW09, WJW010 and WJW011 cells cannot synthesize exopolysaccharide, flagella and fimbria, respectively. Comparing to the wild type W3110, mutants WJW02, WJW04, WJW07 and WJW08 cells showed decreas...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Jianli Wang Wenjian Ma Yu Fang Hao Liang Huiting Yang Yiwen Wang Xiaofei Dong Yi Zhan Xiaoyuan Wang Source Type: research

< em > In vitro < /em > , < em > in vivo < /em > , and ADME evaluation of SF < sub > 5 < /sub > -containing < em > N,N' < /em > -diarylureas as antischistosomal agents
Antimicrob Agents Chemother. 2021 Jul 26:AAC0061521. doi: 10.1128/AAC.00615-21. Online ahead of print.ABSTRACTIn recent years, N,N'-diarylureas have emerged as a promising chemotype for the treatment of schistosomiasis, a disease that poses a considerable health burden to millions of people worldwide. Here, we report a novel series of N,N'-diarylureas featuring the scarcely explored pentafluorosulfanyl group. Low IC50 values for Schistosoma mansoni newly transformed schistosomula (0.6 - 7.7 μM) and adult worms (0.1 - 1.6 μM) were observed. Four selected compounds, highly active in presence of albumin (>70% at 10 &...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Alexandra Probst Eug ènia Pujol C écile Häberli Jennifer Keiser Santiago V ázquez Source Type: research

Variability of Beta-Lactam Broth Microdilution for < em > Pseudomonas aeruginosa < /em >
Antimicrob Agents Chemother. 2021 Jul 26:AAC0064021. doi: 10.1128/AAC.00640-21. Online ahead of print.ABSTRACTAntimicrobial susceptibility testing for Pseudomonas aeruginosa is critical to determine suitable treatment options. Commercial susceptibility tests are typically calibrated against the reference method, broth microdilution (BMD). Imprecision of minimum inhibitory concentrations (MICs) obtained by BMD for the same isolate on repeat testing is known to exist. Factors that impact the extent of variability include concentration of the inoculum, operator effects, contents of the media, inherent strain properties, and t...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: A A Bhalodi N Oppermann S A Campeau R M Humphries Source Type: research

A renal and hepatic toxicity analysis of remdesivir formulations: Does what is on the inside really count?
Antimicrob Agents Chemother. 2021 Jul 26:AAC0104521. doi: 10.1128/AAC.01045-21. Online ahead of print.ABSTRACTIt has been postulated that the injectable solution formulation of remdesivir could be more nephrotoxic than the lyophilized powder since it contains twice as much sulfobutylether-β-cyclodextrin (SBECD). Therefore, we evaluated 1000 hospitalized patients with SARS-CoV-2 who received remdesivir lyophilized powder or solution. A logistic regression model accounting for baseline confounders identified that neither the use of the injectable solution (OR = 1.05; 95% CI = 0.49-2.29; P=0.901) nor a Creatinine Clearance
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Sunish Shah Tyler W Ackley Jeffrey E Topal Source Type: research

Mechanisms involved in the active secretion of CTX-M-15 β-lactamase by pathogenic < em > E. coli < /em > ST131
Antimicrob Agents Chemother. 2021 Jul 26:AAC0066321. doi: 10.1128/AAC.00663-21. Online ahead of print.ABSTRACTInfections caused by antimicrobial resistant bacterial pathogens are fast becoming an important global health issue. Strains of Escherichia coli are common causal agents of urinary tract infection and can carry multiple resistance genes. This includes the gene blaCTX-M-15 that encodes for an extended spectrum beta-lactamase (ESBL). While studying antimicrobial resistance (AMR) in the environment we isolated several strains of E. coli ST131 downstream of a waste water treatment plan (WWTP) in a local river. These is...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Severine Rangama Ian D E A Lidbury Jennifer M Holden Chiara Borsetto Andrew R J Murphy Peter M Hawkey Elizabeth M H Wellington Source Type: research

Specific protein-membrane interactions promote packaging of metallo- β-lactamases into outer membrane vesicles
We report that favorable electrostatic protein-membrane interactions are also at work in the soluble enzyme IMP-1, while being absent in VIM-2. These interactions correlate with an enhanced incorporation of IMP-1 compared to VIM-2 into OMVs. Disruption of these interactions in NDM-1 and IMP-1 impairs their inclusion into vesicles, confirming their role in defining the protein cargo in OMVs. These results also indicate that packaging of metallo-β-lactamases into vesicles in their active form is a common phenomenon that involves cargo selection based on specific molecular interactions.PMID:34310214 | DOI:10.1128/AAC.005...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Carolina L ópez Alessio Prunotto Guillermo Bahr Robert A Bonomo Lisandro J Gonz ález Matteo Dal Peraro Alejandro J Vila Source Type: research

The effect of isoniazid intake on ethionamide pharmacokinetics and target attainment in multidrug-resistant tuberculosis patients
Antimicrob Agents Chemother. 2021 Jul 26:AAC0027821. doi: 10.1128/AAC.00278-21. Online ahead of print.ABSTRACTEthionamide is recommended as part of regimens to treat multidrug-resistant and rifampicin-resistant tuberculosis. The study was conducted to (i) describe the distribution of ethionamide minimum inhibitory concentrations (MICs), (ii) describe the pharmacokinetics of ethionamide, and (iii) determine the probability of attaining target AUC0-24/MIC values associated with suppression of resistant subpopulation and microbial kill. Participants received 15-20 mg/kg of ethionamide daily (in 500 or 750 mg doses), as part o...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Maxwell T Chirehwa Richard Court Mariana de Kock Lubbe Wiesner Nihal de Vries Joseph Harding Tawanda Gumbo Gary Maartens Rob Warren Paolo Denti Helen McIlleron Source Type: research

Functional and Structural Characterization of Acquired Pan-Aminoglycoside Resistance 16S rRNA Methyltransferase NpmB1
Antimicrob Agents Chemother. 2021 Jul 26:AAC0100921. doi: 10.1128/AAC.01009-21. Online ahead of print.ABSTRACTPost-translational methylation of the A site of 16S rRNA at position A1408 leads to pan-aminoglycoside resistance encompassing both 4,5- and 4,6-disubstituted 2-deoxystreptamine (DOS) aminoglycosides. To date, NpmA is the only acquired enzyme with such function. Here, we present function and structure of NpmB1 whose sequence was identified in Escherichia coli genomes registered from the United Kingdom. NpmB1 possesses 40% amino acid identity with NpmA1 and confers resistance to all clinically relevant aminoglycosid...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Akito Kawai Masahiro Suzuki Kentaro Tsukamoto Yusuke Minato Yohei Doi Source Type: research

Rethinking Remdesivir: Synthesis, Antiviral Activity and Pharmacokinetics of Oral Lipid Prodrugs
Antimicrob Agents Chemother. 2021 Jul 26:AAC0115521. doi: 10.1128/AAC.01155-21. Online ahead of print.ABSTRACTRemdesivir (RDV, GS-5734) is currently the only FDA-approved antiviral drug for the treatment of SARS CoV-2 infection. The drug is approved for use in adults or children 12-years or older who are hospitalized for the treatment of COVID-19 on the basis of an acceleration of clinical recovery for inpatients with this disease. Unfortunately, the drug must be administered intravenously, restricting its use to those requiring hospitalization for relatively advanced disease. RDV is also unstable in plasma and has a compl...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Robert T Schooley Aaron F Carlin James R Beadle Nadejda Valiaeva Xing-Quan Zhang Alex E Clark Rachel E McMillan Sandra L Leibel Rachael N McVicar Jialei Xie Aaron F Garretson Victoria I Smith Joyce Murphy Karl Y Hostetler Source Type: research

Population pharmacokinetics of diethylcarbamazine in patients with lymphatic filariasis and healthy individuals
The objective of this study was to develop a population pharmacokinetic model for DEC in subjects infected with lymphatic filariasis (LF) compared to healthy individuals, and to evaluate the effect of covariates on the volume of distribution (V/F) and oral clearance (CL/F) of DEC. This was an open-label cohort study of treatment naïve Wuchereria bancrofti-infected (n=32) and uninfected (n=24) adults residing in the Agboville district of Côte d'Ivoire. The population pharmacokinetic model for DEC was built using Phoenix NLME 8.0 software. The covariates included in the model building process were age, gender, bod...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Veenu Bala Yashpal S Chhonker Abdullah Alshehri Constant Edi Catherine M Bjerum Benjamin G Koudou Christopher L King Daryl J Murry Source Type: research

RexAB promotes the survival of < em > Staphylococcus aureus < /em > exposed to multiple classes of antibiotics
Antimicrob Agents Chemother. 2021 Jul 26:AAC0059421. doi: 10.1128/AAC.00594-21. Online ahead of print.ABSTRACTAntibiotics inhibit essential bacterial processes, resulting in arrest of growth and in some cases cell death. Many antibiotics are also reported to trigger endogenous production of reactive oxygen species (ROS), which damage DNA, leading to induction of the mutagenic SOS response associated with the emergence of drug resistance. However, the type of DNA damage that arises and how this triggers the SOS response is largely unclear. We found that several different classes of antibiotic triggered dose-dependent induct...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Rebecca S Clarke Kam Pou Ha Andrew M Edwards Source Type: research

Plasma and Breast Milk Pharmacokinetics of Tenofovir Disoproxil Fumarate in Nursing Mother with Chronic Hepatitis B-Infant Pairs
In this study, we aimed to determine of tenofovir concentration in plasma of mother-infant pairs along with breast milk in chronic hepatitis B patients during lactation period. Patients and Method: A total of eleven mother-infant pairs were enrolled in the study. All the mothers received tenofovir disoproxil fumarate (TDF) 245 mg/day for at least one month because of chronic hepatitis B infection. Maternal blood, breast milk and infant blood samples were obtained concomitantly. Tenofovir concentrations were determined by liquid chromatography tandem mass spectrometry method. Results: The median concentrations of tenofovir ...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: U S Erturk B Mete R Ozaras N Saltoglu I I Balkan A Mert B Kacmaz O Saglam B Guney O A Sayman F Tabak Source Type: research

< em > In vitro < /em > activity of APX2041, a new GWT1-inhibitor and < em > in vivo < /em > efficacy of the prodrug APX2104 against < em > Aspergillus fumigatus < /em >
Antimicrob Agents Chemother. 2021 Jul 26:AAC0068221. doi: 10.1128/AAC.00682-21. Online ahead of print.ABSTRACTInvasive aspergillosis (IA) due to Aspergillus fumigatus is a deadly infection for which new antifungal therapies are needed. Here we demonstrate the efficacy of a Gwt1 inhibitor, APX2041, and its prodrug, APX2104, against A. fumigatus. The wild-type, azole-resistant and echinocandin-resistant A. fumigatus strains were equally susceptible to APX2041 in vitro. APX2104 treatment in vivo significantly prolonged survival of neutropenic mice challenged with the wild-type and azole-resistant strains, revealing APX2104 as...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Shareef K Shaheen Praveen R Juvvadi John Allen Iv E Keats Shwab D Christopher Cole Yohannes G Asfaw Mili Kapoor Karen Joy Shaw William J Steinbach Source Type: research

The Phenotypic/Genotypic Profile of OXA-10-like harboring, Carbapenem-Resistant < em > Pseudomonas aeruginosa < /em > : Using Validated Pharmacokinetic/Pharmacodynamic < em > in vivo < /em > Models to Further Evaluate Enzyme Functionality and Clinical Implications
Antimicrob Agents Chemother. 2021 Jul 26:AAC0127421. doi: 10.1128/AAC.01274-21. Online ahead of print.ABSTRACTIn vitro MICs and in vivo pharmacodynamics of ceftazidime and cefepime human-simulated regimens (HSR) against mCIM-positive P. aeruginosa harboring different OXA-10-like subtypes were described. The murine thigh model assessed ceftazidime (2g q8h HSR) and cefepime (2g and 1g q8h HSR). Phenotypes were similar despite possessing OXA-10-like subtypes with differing spectra. Ceftazidime produced ≥1-log10 kill in all isolates. Cefepime activity was dose-dependent and MIC driven. This approach may be useful in assessi...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Christian M Gill Adrian Brink Chun Yat Chu Jennifer Coetzee George Dimopoulos Clinton Moodley Christoffel Johannes Opperman Spyros Pournaras Fred C Tenover Isabella A Tickler Hafsah Deepa Tootla Sophia Vourli David P Nicolau Source Type: research

Kinetic and Structural Characterization of the First B3 Metallo- β-Lactamase with an Active Site Glutamic Acid
Antimicrob Agents Chemother. 2021 Jul 26:AAC0093621. doi: 10.1128/AAC.00936-21. Online ahead of print.ABSTRACTThe structural diversity in metallo-β-lactamases (MBLs), especially in the vicinity of the active site, has been a major hurdle in the development of clinically effective inhibitors. Representatives from three variants of the B3 MBL subclass, containing either the canonical HHH/DHH active site motif (present in the majority of MBLs in this subclass) or the QHH/DHH (B3-Q) or HRH/DQK (B3-RQK) variations were reported previously. Here, we describe the structure and kinetic properties of the first example (SIE-1) ...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Liam A Wilson Esm ée G Knaven Marc T Morris Marcelo Monteiro Pedroso Christopher J Schofield Thomas Br ück Mikael Boden David W Waite Philip Hugenholtz Luke Guddat Gerhard Schenk Source Type: research

Point mutation or overexpression of < em > A. fumigatus < /em > < em > cyp51B, < /em > encoding lanosterol 14 α-sterol demethylase, leads to triazole resistance
Antimicrob Agents Chemother. 2021 Jul 26:AAC0125221. doi: 10.1128/AAC.01252-21. Online ahead of print.ABSTRACTAspergillus fumigatus is the most common cause of invasive fungal mold infections in immunocompromised individuals. Current antifungal treatment relies heavily on the triazole antifungals which inhibit fungal Erg11/Cyp51 activity and subsequent ergosterol biosynthesis. However, resistance, due primarily to cyp51 mutation, is rapidly increasing. A. fumigatus contains two Cyp51 isoenzymes, Cyp51A and Cyp51B. Overexpression and mutation of Cyp51A is a major cause of triazole resistance in A. fumigatus. The role of Cyp...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Mariana Handelman Zohar Meir Jennifer Scott Yona Shadkchan Wei Liu Ronen Ben-Ami Jorge Amich Nir Osherov Source Type: research

Core oligosaccharide portion of lipopolysaccharide plays important roles on multiple antibiotic resistance in < em > Escherichia coli < /em >
In this study, a series of mutants that lack one or more major components associated with the cell envelope were constructed from Escherichia coli K-12 W3110. WJW02 can only synthesize Kdo2-lipid A which lacks the core oligosaccharide portion of lipopolysaccharide. WJW04, WJW07 and WJW08 were constructed from WJW02 by deleting the gene clusters relevant to the biosynthesis of exopolysaccharide, flagella and fimbria, respectively. WJW09, WJW010 and WJW011 cells cannot synthesize exopolysaccharide, flagella and fimbria, respectively. Comparing to the wild type W3110, mutants WJW02, WJW04, WJW07 and WJW08 cells showed decreas...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Jianli Wang Wenjian Ma Yu Fang Hao Liang Huiting Yang Yiwen Wang Xiaofei Dong Yi Zhan Xiaoyuan Wang Source Type: research

< em > In vitro < /em > , < em > in vivo < /em > , and ADME evaluation of SF < sub > 5 < /sub > -containing < em > N,N' < /em > -diarylureas as antischistosomal agents
Antimicrob Agents Chemother. 2021 Jul 26:AAC0061521. doi: 10.1128/AAC.00615-21. Online ahead of print.ABSTRACTIn recent years, N,N'-diarylureas have emerged as a promising chemotype for the treatment of schistosomiasis, a disease that poses a considerable health burden to millions of people worldwide. Here, we report a novel series of N,N'-diarylureas featuring the scarcely explored pentafluorosulfanyl group. Low IC50 values for Schistosoma mansoni newly transformed schistosomula (0.6 - 7.7 μM) and adult worms (0.1 - 1.6 μM) were observed. Four selected compounds, highly active in presence of albumin (>70% at 10 &...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Alexandra Probst Eug ènia Pujol C écile Häberli Jennifer Keiser Santiago V ázquez Source Type: research

Variability of Beta-Lactam Broth Microdilution for < em > Pseudomonas aeruginosa < /em >
Antimicrob Agents Chemother. 2021 Jul 26:AAC0064021. doi: 10.1128/AAC.00640-21. Online ahead of print.ABSTRACTAntimicrobial susceptibility testing for Pseudomonas aeruginosa is critical to determine suitable treatment options. Commercial susceptibility tests are typically calibrated against the reference method, broth microdilution (BMD). Imprecision of minimum inhibitory concentrations (MICs) obtained by BMD for the same isolate on repeat testing is known to exist. Factors that impact the extent of variability include concentration of the inoculum, operator effects, contents of the media, inherent strain properties, and t...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: A A Bhalodi N Oppermann S A Campeau R M Humphries Source Type: research

A renal and hepatic toxicity analysis of remdesivir formulations: Does what is on the inside really count?
Antimicrob Agents Chemother. 2021 Jul 26:AAC0104521. doi: 10.1128/AAC.01045-21. Online ahead of print.ABSTRACTIt has been postulated that the injectable solution formulation of remdesivir could be more nephrotoxic than the lyophilized powder since it contains twice as much sulfobutylether-β-cyclodextrin (SBECD). Therefore, we evaluated 1000 hospitalized patients with SARS-CoV-2 who received remdesivir lyophilized powder or solution. A logistic regression model accounting for baseline confounders identified that neither the use of the injectable solution (OR = 1.05; 95% CI = 0.49-2.29; P=0.901) nor a Creatinine Clearance
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Sunish Shah Tyler W Ackley Jeffrey E Topal Source Type: research

Mechanisms involved in the active secretion of CTX-M-15 β-lactamase by pathogenic < em > E. coli < /em > ST131
Antimicrob Agents Chemother. 2021 Jul 26:AAC0066321. doi: 10.1128/AAC.00663-21. Online ahead of print.ABSTRACTInfections caused by antimicrobial resistant bacterial pathogens are fast becoming an important global health issue. Strains of Escherichia coli are common causal agents of urinary tract infection and can carry multiple resistance genes. This includes the gene blaCTX-M-15 that encodes for an extended spectrum beta-lactamase (ESBL). While studying antimicrobial resistance (AMR) in the environment we isolated several strains of E. coli ST131 downstream of a waste water treatment plan (WWTP) in a local river. These is...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Severine Rangama Ian D E A Lidbury Jennifer M Holden Chiara Borsetto Andrew R J Murphy Peter M Hawkey Elizabeth M H Wellington Source Type: research

Specific protein-membrane interactions promote packaging of metallo- β-lactamases into outer membrane vesicles
We report that favorable electrostatic protein-membrane interactions are also at work in the soluble enzyme IMP-1, while being absent in VIM-2. These interactions correlate with an enhanced incorporation of IMP-1 compared to VIM-2 into OMVs. Disruption of these interactions in NDM-1 and IMP-1 impairs their inclusion into vesicles, confirming their role in defining the protein cargo in OMVs. These results also indicate that packaging of metallo-β-lactamases into vesicles in their active form is a common phenomenon that involves cargo selection based on specific molecular interactions.PMID:34310214 | DOI:10.1128/AAC.005...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Carolina L ópez Alessio Prunotto Guillermo Bahr Robert A Bonomo Lisandro J Gonz ález Matteo Dal Peraro Alejandro J Vila Source Type: research

The effect of isoniazid intake on ethionamide pharmacokinetics and target attainment in multidrug-resistant tuberculosis patients
Antimicrob Agents Chemother. 2021 Jul 26:AAC0027821. doi: 10.1128/AAC.00278-21. Online ahead of print.ABSTRACTEthionamide is recommended as part of regimens to treat multidrug-resistant and rifampicin-resistant tuberculosis. The study was conducted to (i) describe the distribution of ethionamide minimum inhibitory concentrations (MICs), (ii) describe the pharmacokinetics of ethionamide, and (iii) determine the probability of attaining target AUC0-24/MIC values associated with suppression of resistant subpopulation and microbial kill. Participants received 15-20 mg/kg of ethionamide daily (in 500 or 750 mg doses), as part o...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Maxwell T Chirehwa Richard Court Mariana de Kock Lubbe Wiesner Nihal de Vries Joseph Harding Tawanda Gumbo Gary Maartens Rob Warren Paolo Denti Helen McIlleron Source Type: research

Functional and Structural Characterization of Acquired Pan-Aminoglycoside Resistance 16S rRNA Methyltransferase NpmB1
Antimicrob Agents Chemother. 2021 Jul 26:AAC0100921. doi: 10.1128/AAC.01009-21. Online ahead of print.ABSTRACTPost-translational methylation of the A site of 16S rRNA at position A1408 leads to pan-aminoglycoside resistance encompassing both 4,5- and 4,6-disubstituted 2-deoxystreptamine (DOS) aminoglycosides. To date, NpmA is the only acquired enzyme with such function. Here, we present function and structure of NpmB1 whose sequence was identified in Escherichia coli genomes registered from the United Kingdom. NpmB1 possesses 40% amino acid identity with NpmA1 and confers resistance to all clinically relevant aminoglycosid...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Akito Kawai Masahiro Suzuki Kentaro Tsukamoto Yusuke Minato Yohei Doi Source Type: research

Rethinking Remdesivir: Synthesis, Antiviral Activity and Pharmacokinetics of Oral Lipid Prodrugs
Antimicrob Agents Chemother. 2021 Jul 26:AAC0115521. doi: 10.1128/AAC.01155-21. Online ahead of print.ABSTRACTRemdesivir (RDV, GS-5734) is currently the only FDA-approved antiviral drug for the treatment of SARS CoV-2 infection. The drug is approved for use in adults or children 12-years or older who are hospitalized for the treatment of COVID-19 on the basis of an acceleration of clinical recovery for inpatients with this disease. Unfortunately, the drug must be administered intravenously, restricting its use to those requiring hospitalization for relatively advanced disease. RDV is also unstable in plasma and has a compl...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Robert T Schooley Aaron F Carlin James R Beadle Nadejda Valiaeva Xing-Quan Zhang Alex E Clark Rachel E McMillan Sandra L Leibel Rachael N McVicar Jialei Xie Aaron F Garretson Victoria I Smith Joyce Murphy Karl Y Hostetler Source Type: research

Population pharmacokinetics of diethylcarbamazine in patients with lymphatic filariasis and healthy individuals
The objective of this study was to develop a population pharmacokinetic model for DEC in subjects infected with lymphatic filariasis (LF) compared to healthy individuals, and to evaluate the effect of covariates on the volume of distribution (V/F) and oral clearance (CL/F) of DEC. This was an open-label cohort study of treatment naïve Wuchereria bancrofti-infected (n=32) and uninfected (n=24) adults residing in the Agboville district of Côte d'Ivoire. The population pharmacokinetic model for DEC was built using Phoenix NLME 8.0 software. The covariates included in the model building process were age, gender, bod...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Veenu Bala Yashpal S Chhonker Abdullah Alshehri Constant Edi Catherine M Bjerum Benjamin G Koudou Christopher L King Daryl J Murry Source Type: research

RexAB promotes the survival of < em > Staphylococcus aureus < /em > exposed to multiple classes of antibiotics
Antimicrob Agents Chemother. 2021 Jul 26:AAC0059421. doi: 10.1128/AAC.00594-21. Online ahead of print.ABSTRACTAntibiotics inhibit essential bacterial processes, resulting in arrest of growth and in some cases cell death. Many antibiotics are also reported to trigger endogenous production of reactive oxygen species (ROS), which damage DNA, leading to induction of the mutagenic SOS response associated with the emergence of drug resistance. However, the type of DNA damage that arises and how this triggers the SOS response is largely unclear. We found that several different classes of antibiotic triggered dose-dependent induct...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Rebecca S Clarke Kam Pou Ha Andrew M Edwards Source Type: research

Plasma and Breast Milk Pharmacokinetics of Tenofovir Disoproxil Fumarate in Nursing Mother with Chronic Hepatitis B-Infant Pairs
In this study, we aimed to determine of tenofovir concentration in plasma of mother-infant pairs along with breast milk in chronic hepatitis B patients during lactation period. Patients and Method: A total of eleven mother-infant pairs were enrolled in the study. All the mothers received tenofovir disoproxil fumarate (TDF) 245 mg/day for at least one month because of chronic hepatitis B infection. Maternal blood, breast milk and infant blood samples were obtained concomitantly. Tenofovir concentrations were determined by liquid chromatography tandem mass spectrometry method. Results: The median concentrations of tenofovir ...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: U S Erturk B Mete R Ozaras N Saltoglu I I Balkan A Mert B Kacmaz O Saglam B Guney O A Sayman F Tabak Source Type: research

< em > In vitro < /em > activity of APX2041, a new GWT1-inhibitor and < em > in vivo < /em > efficacy of the prodrug APX2104 against < em > Aspergillus fumigatus < /em >
Antimicrob Agents Chemother. 2021 Jul 26:AAC0068221. doi: 10.1128/AAC.00682-21. Online ahead of print.ABSTRACTInvasive aspergillosis (IA) due to Aspergillus fumigatus is a deadly infection for which new antifungal therapies are needed. Here we demonstrate the efficacy of a Gwt1 inhibitor, APX2041, and its prodrug, APX2104, against A. fumigatus. The wild-type, azole-resistant and echinocandin-resistant A. fumigatus strains were equally susceptible to APX2041 in vitro. APX2104 treatment in vivo significantly prolonged survival of neutropenic mice challenged with the wild-type and azole-resistant strains, revealing APX2104 as...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Shareef K Shaheen Praveen R Juvvadi John Allen Iv E Keats Shwab D Christopher Cole Yohannes G Asfaw Mili Kapoor Karen Joy Shaw William J Steinbach Source Type: research

The Phenotypic/Genotypic Profile of OXA-10-like harboring, Carbapenem-Resistant < em > Pseudomonas aeruginosa < /em > : Using Validated Pharmacokinetic/Pharmacodynamic < em > in vivo < /em > Models to Further Evaluate Enzyme Functionality and Clinical Implications
Antimicrob Agents Chemother. 2021 Jul 26:AAC0127421. doi: 10.1128/AAC.01274-21. Online ahead of print.ABSTRACTIn vitro MICs and in vivo pharmacodynamics of ceftazidime and cefepime human-simulated regimens (HSR) against mCIM-positive P. aeruginosa harboring different OXA-10-like subtypes were described. The murine thigh model assessed ceftazidime (2g q8h HSR) and cefepime (2g and 1g q8h HSR). Phenotypes were similar despite possessing OXA-10-like subtypes with differing spectra. Ceftazidime produced ≥1-log10 kill in all isolates. Cefepime activity was dose-dependent and MIC driven. This approach may be useful in assessi...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Christian M Gill Adrian Brink Chun Yat Chu Jennifer Coetzee George Dimopoulos Clinton Moodley Christoffel Johannes Opperman Spyros Pournaras Fred C Tenover Isabella A Tickler Hafsah Deepa Tootla Sophia Vourli David P Nicolau Source Type: research

Kinetic and Structural Characterization of the First B3 Metallo- β-Lactamase with an Active Site Glutamic Acid
Antimicrob Agents Chemother. 2021 Jul 26:AAC0093621. doi: 10.1128/AAC.00936-21. Online ahead of print.ABSTRACTThe structural diversity in metallo-β-lactamases (MBLs), especially in the vicinity of the active site, has been a major hurdle in the development of clinically effective inhibitors. Representatives from three variants of the B3 MBL subclass, containing either the canonical HHH/DHH active site motif (present in the majority of MBLs in this subclass) or the QHH/DHH (B3-Q) or HRH/DQK (B3-RQK) variations were reported previously. Here, we describe the structure and kinetic properties of the first example (SIE-1) ...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Liam A Wilson Esm ée G Knaven Marc T Morris Marcelo Monteiro Pedroso Christopher J Schofield Thomas Br ück Mikael Boden David W Waite Philip Hugenholtz Luke Guddat Gerhard Schenk Source Type: research

Point mutation or overexpression of < em > A. fumigatus < /em > < em > cyp51B, < /em > encoding lanosterol 14 α-sterol demethylase, leads to triazole resistance
Antimicrob Agents Chemother. 2021 Jul 26:AAC0125221. doi: 10.1128/AAC.01252-21. Online ahead of print.ABSTRACTAspergillus fumigatus is the most common cause of invasive fungal mold infections in immunocompromised individuals. Current antifungal treatment relies heavily on the triazole antifungals which inhibit fungal Erg11/Cyp51 activity and subsequent ergosterol biosynthesis. However, resistance, due primarily to cyp51 mutation, is rapidly increasing. A. fumigatus contains two Cyp51 isoenzymes, Cyp51A and Cyp51B. Overexpression and mutation of Cyp51A is a major cause of triazole resistance in A. fumigatus. The role of Cyp...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Mariana Handelman Zohar Meir Jennifer Scott Yona Shadkchan Wei Liu Ronen Ben-Ami Jorge Amich Nir Osherov Source Type: research

Core oligosaccharide portion of lipopolysaccharide plays important roles on multiple antibiotic resistance in < em > Escherichia coli < /em >
In this study, a series of mutants that lack one or more major components associated with the cell envelope were constructed from Escherichia coli K-12 W3110. WJW02 can only synthesize Kdo2-lipid A which lacks the core oligosaccharide portion of lipopolysaccharide. WJW04, WJW07 and WJW08 were constructed from WJW02 by deleting the gene clusters relevant to the biosynthesis of exopolysaccharide, flagella and fimbria, respectively. WJW09, WJW010 and WJW011 cells cannot synthesize exopolysaccharide, flagella and fimbria, respectively. Comparing to the wild type W3110, mutants WJW02, WJW04, WJW07 and WJW08 cells showed decreas...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Jianli Wang Wenjian Ma Yu Fang Hao Liang Huiting Yang Yiwen Wang Xiaofei Dong Yi Zhan Xiaoyuan Wang Source Type: research

< em > In vitro < /em > , < em > in vivo < /em > , and ADME evaluation of SF < sub > 5 < /sub > -containing < em > N,N' < /em > -diarylureas as antischistosomal agents
Antimicrob Agents Chemother. 2021 Jul 26:AAC0061521. doi: 10.1128/AAC.00615-21. Online ahead of print.ABSTRACTIn recent years, N,N'-diarylureas have emerged as a promising chemotype for the treatment of schistosomiasis, a disease that poses a considerable health burden to millions of people worldwide. Here, we report a novel series of N,N'-diarylureas featuring the scarcely explored pentafluorosulfanyl group. Low IC50 values for Schistosoma mansoni newly transformed schistosomula (0.6 - 7.7 μM) and adult worms (0.1 - 1.6 μM) were observed. Four selected compounds, highly active in presence of albumin (>70% at 10 &...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Alexandra Probst Eug ènia Pujol C écile Häberli Jennifer Keiser Santiago V ázquez Source Type: research

Variability of Beta-Lactam Broth Microdilution for < em > Pseudomonas aeruginosa < /em >
Antimicrob Agents Chemother. 2021 Jul 26:AAC0064021. doi: 10.1128/AAC.00640-21. Online ahead of print.ABSTRACTAntimicrobial susceptibility testing for Pseudomonas aeruginosa is critical to determine suitable treatment options. Commercial susceptibility tests are typically calibrated against the reference method, broth microdilution (BMD). Imprecision of minimum inhibitory concentrations (MICs) obtained by BMD for the same isolate on repeat testing is known to exist. Factors that impact the extent of variability include concentration of the inoculum, operator effects, contents of the media, inherent strain properties, and t...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: A A Bhalodi N Oppermann S A Campeau R M Humphries Source Type: research

A renal and hepatic toxicity analysis of remdesivir formulations: Does what is on the inside really count?
Antimicrob Agents Chemother. 2021 Jul 26:AAC0104521. doi: 10.1128/AAC.01045-21. Online ahead of print.ABSTRACTIt has been postulated that the injectable solution formulation of remdesivir could be more nephrotoxic than the lyophilized powder since it contains twice as much sulfobutylether-β-cyclodextrin (SBECD). Therefore, we evaluated 1000 hospitalized patients with SARS-CoV-2 who received remdesivir lyophilized powder or solution. A logistic regression model accounting for baseline confounders identified that neither the use of the injectable solution (OR = 1.05; 95% CI = 0.49-2.29; P=0.901) nor a Creatinine Clearance
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Sunish Shah Tyler W Ackley Jeffrey E Topal Source Type: research

Mechanisms involved in the active secretion of CTX-M-15 β-lactamase by pathogenic < em > E. coli < /em > ST131
Antimicrob Agents Chemother. 2021 Jul 26:AAC0066321. doi: 10.1128/AAC.00663-21. Online ahead of print.ABSTRACTInfections caused by antimicrobial resistant bacterial pathogens are fast becoming an important global health issue. Strains of Escherichia coli are common causal agents of urinary tract infection and can carry multiple resistance genes. This includes the gene blaCTX-M-15 that encodes for an extended spectrum beta-lactamase (ESBL). While studying antimicrobial resistance (AMR) in the environment we isolated several strains of E. coli ST131 downstream of a waste water treatment plan (WWTP) in a local river. These is...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Severine Rangama Ian D E A Lidbury Jennifer M Holden Chiara Borsetto Andrew R J Murphy Peter M Hawkey Elizabeth M H Wellington Source Type: research

Specific protein-membrane interactions promote packaging of metallo- β-lactamases into outer membrane vesicles
We report that favorable electrostatic protein-membrane interactions are also at work in the soluble enzyme IMP-1, while being absent in VIM-2. These interactions correlate with an enhanced incorporation of IMP-1 compared to VIM-2 into OMVs. Disruption of these interactions in NDM-1 and IMP-1 impairs their inclusion into vesicles, confirming their role in defining the protein cargo in OMVs. These results also indicate that packaging of metallo-β-lactamases into vesicles in their active form is a common phenomenon that involves cargo selection based on specific molecular interactions.PMID:34310214 | DOI:10.1128/AAC.005...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Carolina L ópez Alessio Prunotto Guillermo Bahr Robert A Bonomo Lisandro J Gonz ález Matteo Dal Peraro Alejandro J Vila Source Type: research

The effect of isoniazid intake on ethionamide pharmacokinetics and target attainment in multidrug-resistant tuberculosis patients
Antimicrob Agents Chemother. 2021 Jul 26:AAC0027821. doi: 10.1128/AAC.00278-21. Online ahead of print.ABSTRACTEthionamide is recommended as part of regimens to treat multidrug-resistant and rifampicin-resistant tuberculosis. The study was conducted to (i) describe the distribution of ethionamide minimum inhibitory concentrations (MICs), (ii) describe the pharmacokinetics of ethionamide, and (iii) determine the probability of attaining target AUC0-24/MIC values associated with suppression of resistant subpopulation and microbial kill. Participants received 15-20 mg/kg of ethionamide daily (in 500 or 750 mg doses), as part o...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Maxwell T Chirehwa Richard Court Mariana de Kock Lubbe Wiesner Nihal de Vries Joseph Harding Tawanda Gumbo Gary Maartens Rob Warren Paolo Denti Helen McIlleron Source Type: research

Functional and Structural Characterization of Acquired Pan-Aminoglycoside Resistance 16S rRNA Methyltransferase NpmB1
Antimicrob Agents Chemother. 2021 Jul 26:AAC0100921. doi: 10.1128/AAC.01009-21. Online ahead of print.ABSTRACTPost-translational methylation of the A site of 16S rRNA at position A1408 leads to pan-aminoglycoside resistance encompassing both 4,5- and 4,6-disubstituted 2-deoxystreptamine (DOS) aminoglycosides. To date, NpmA is the only acquired enzyme with such function. Here, we present function and structure of NpmB1 whose sequence was identified in Escherichia coli genomes registered from the United Kingdom. NpmB1 possesses 40% amino acid identity with NpmA1 and confers resistance to all clinically relevant aminoglycosid...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Akito Kawai Masahiro Suzuki Kentaro Tsukamoto Yusuke Minato Yohei Doi Source Type: research

Rethinking Remdesivir: Synthesis, Antiviral Activity and Pharmacokinetics of Oral Lipid Prodrugs
Antimicrob Agents Chemother. 2021 Jul 26:AAC0115521. doi: 10.1128/AAC.01155-21. Online ahead of print.ABSTRACTRemdesivir (RDV, GS-5734) is currently the only FDA-approved antiviral drug for the treatment of SARS CoV-2 infection. The drug is approved for use in adults or children 12-years or older who are hospitalized for the treatment of COVID-19 on the basis of an acceleration of clinical recovery for inpatients with this disease. Unfortunately, the drug must be administered intravenously, restricting its use to those requiring hospitalization for relatively advanced disease. RDV is also unstable in plasma and has a compl...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Robert T Schooley Aaron F Carlin James R Beadle Nadejda Valiaeva Xing-Quan Zhang Alex E Clark Rachel E McMillan Sandra L Leibel Rachael N McVicar Jialei Xie Aaron F Garretson Victoria I Smith Joyce Murphy Karl Y Hostetler Source Type: research

Population pharmacokinetics of diethylcarbamazine in patients with lymphatic filariasis and healthy individuals
The objective of this study was to develop a population pharmacokinetic model for DEC in subjects infected with lymphatic filariasis (LF) compared to healthy individuals, and to evaluate the effect of covariates on the volume of distribution (V/F) and oral clearance (CL/F) of DEC. This was an open-label cohort study of treatment naïve Wuchereria bancrofti-infected (n=32) and uninfected (n=24) adults residing in the Agboville district of Côte d'Ivoire. The population pharmacokinetic model for DEC was built using Phoenix NLME 8.0 software. The covariates included in the model building process were age, gender, bod...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Veenu Bala Yashpal S Chhonker Abdullah Alshehri Constant Edi Catherine M Bjerum Benjamin G Koudou Christopher L King Daryl J Murry Source Type: research

RexAB promotes the survival of < em > Staphylococcus aureus < /em > exposed to multiple classes of antibiotics
Antimicrob Agents Chemother. 2021 Jul 26:AAC0059421. doi: 10.1128/AAC.00594-21. Online ahead of print.ABSTRACTAntibiotics inhibit essential bacterial processes, resulting in arrest of growth and in some cases cell death. Many antibiotics are also reported to trigger endogenous production of reactive oxygen species (ROS), which damage DNA, leading to induction of the mutagenic SOS response associated with the emergence of drug resistance. However, the type of DNA damage that arises and how this triggers the SOS response is largely unclear. We found that several different classes of antibiotic triggered dose-dependent induct...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Rebecca S Clarke Kam Pou Ha Andrew M Edwards Source Type: research

Plasma and Breast Milk Pharmacokinetics of Tenofovir Disoproxil Fumarate in Nursing Mother with Chronic Hepatitis B-Infant Pairs
In this study, we aimed to determine of tenofovir concentration in plasma of mother-infant pairs along with breast milk in chronic hepatitis B patients during lactation period. Patients and Method: A total of eleven mother-infant pairs were enrolled in the study. All the mothers received tenofovir disoproxil fumarate (TDF) 245 mg/day for at least one month because of chronic hepatitis B infection. Maternal blood, breast milk and infant blood samples were obtained concomitantly. Tenofovir concentrations were determined by liquid chromatography tandem mass spectrometry method. Results: The median concentrations of tenofovir ...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: U S Erturk B Mete R Ozaras N Saltoglu I I Balkan A Mert B Kacmaz O Saglam B Guney O A Sayman F Tabak Source Type: research

< em > In vitro < /em > activity of APX2041, a new GWT1-inhibitor and < em > in vivo < /em > efficacy of the prodrug APX2104 against < em > Aspergillus fumigatus < /em >
Antimicrob Agents Chemother. 2021 Jul 26:AAC0068221. doi: 10.1128/AAC.00682-21. Online ahead of print.ABSTRACTInvasive aspergillosis (IA) due to Aspergillus fumigatus is a deadly infection for which new antifungal therapies are needed. Here we demonstrate the efficacy of a Gwt1 inhibitor, APX2041, and its prodrug, APX2104, against A. fumigatus. The wild-type, azole-resistant and echinocandin-resistant A. fumigatus strains were equally susceptible to APX2041 in vitro. APX2104 treatment in vivo significantly prolonged survival of neutropenic mice challenged with the wild-type and azole-resistant strains, revealing APX2104 as...
Source: Antimicrobial Agents and Chemotherapy - July 26, 2021 Category: Microbiology Authors: Shareef K Shaheen Praveen R Juvvadi John Allen Iv E Keats Shwab D Christopher Cole Yohannes G Asfaw Mili Kapoor Karen Joy Shaw William J Steinbach Source Type: research