Analysis of clinical < em > Candida parapsilosis < /em > isolates reveals copy number variation in key fluconazole resistance genes
We report highly variable copy numbers of the CDR1B region across the collection. Several strains have increased the expansion of the two genes into a tandem array of new chimeric genes. Other strains have experienced a deletion between the two genes creating a single gene with a reciprocal chimerism. We find translocations, duplications, and gene conversion across the CDR gene family in the C. parapsilosis species complex, showing that it is a highly dynamic family.PMID:38712935 | DOI:10.1128/aac.01619-23 (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - May 7, 2024 Category: Microbiology Authors: Sean Bergin Laura A Doorley Jeffrey M Rybak Kenneth H Wolfe Geraldine Butler Christina A Cuomo P David Rogers Source Type: research

Analysis of clinical < em > Candida parapsilosis < /em > isolates reveals copy number variation in key fluconazole resistance genes
We report highly variable copy numbers of the CDR1B region across the collection. Several strains have increased the expansion of the two genes into a tandem array of new chimeric genes. Other strains have experienced a deletion between the two genes creating a single gene with a reciprocal chimerism. We find translocations, duplications, and gene conversion across the CDR gene family in the C. parapsilosis species complex, showing that it is a highly dynamic family.PMID:38712935 | DOI:10.1128/aac.01619-23 (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - May 7, 2024 Category: Microbiology Authors: Sean Bergin Laura A Doorley Jeffrey M Rybak Kenneth H Wolfe Geraldine Butler Christina A Cuomo P David Rogers Source Type: research

< em > In vitro < /em > and < em > in vivo < /em > activities of KSP-1007, a broad-spectrum inhibitor of serine- and metallo- β-lactamases, in combination with meropenem against carbapenem-resistant Gram-negative bacteria
Antimicrob Agents Chemother. 2024 May 6:e0160223. doi: 10.1128/aac.01602-23. Online ahead of print.ABSTRACTKSP-1007 is a novel bicyclic boronate-based broad-spectrum β-lactamase inhibitor and is being developed in combination with meropenem (MEM) for the treatment of infections caused by carbapenem-resistant Gram-negative bacteria, a global health concern, and here, we describe its characteristics. KSP-1007 exhibited low apparent inhibition constant (Ki app) values against all classes of β-lactamase, including imipenemase types and oxacillinase types from Acinetobacter baumannii. Against 207 Enterobacterales and 55 A. ba...
Source: Antimicrobial Agents and Chemotherapy - May 6, 2024 Category: Microbiology Authors: Koji Takemoto Ryo Nakayama Koichi Fujimoto Yumiko Suzuki Yukiko Takarabe Masako Honsho Sachiko Kitahara Yoshihiko Noguchi Hidehito Matsui Tomoyasu Hirose Yukihiro Asami Jun Hidaka Toshiaki Sunazuka Hideaki Hanaki Source Type: research

Long-acting cabotegravir pharmacokinetics with and without oral lead-in for HIV PrEP
This study is registered with ClinicalTrials.gov as NCT02720094.PMID:38709006 | DOI:10.1128/aac.01475-23 (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - May 6, 2024 Category: Microbiology Authors: Kelong Han Parul Patel Scott McCallister Alex R Rinehart Yash Gandhi William Spreen Raphael J Landovitz Sinead Delany-Moretlwe Mark A Marzinke Todd McKeon Piotr Budnik Jean van Wyk Susan L Ford Source Type: research

Could ceftriaxone be a viable alternative to penicillin for the treatment of ocular syphilis?
This study was conducted to compare the effectiveness of ceftriaxone with that of aqueous crystalline penicillin G in treating ocular syphilis. We conducted a retrospective study from 2010 to 2021. Syphilis patients were administered either ceftriaxone (2 g intravenously daily for 14 days) or aqueous crystalline penicillin G [4 million units (MU) intravenously every 4 h for 14 days] as therapeutic interventions. Subsequently, we utilized these two groups to assess the serological results, cerebrospinal fluid analysis, and visual acuity at time intervals spanning 3 to 6 months post-treatment. A total of 205 patients were in...
Source: Antimicrobial Agents and Chemotherapy - May 6, 2024 Category: Microbiology Authors: Xin Gu Haikong Lu Yilan Yang Lin Zhu Mei Shi Zhifang Guan Liyan Ni Ruirui Peng Wei Zhao Juan Wu Tengfei Qi Pingyu Zhou Source Type: research

Bactericidal and sterilizing activity of sudapyridine-clofazimine-TB47 combined with linezolid or pyrazinamide in a murine model of tuberculosis
Antimicrob Agents Chemother. 2024 May 1:e0012424. doi: 10.1128/aac.00124-24. Online ahead of print.ABSTRACTAs an obligate aerobe, Mycobacterium tuberculosis relies on its branched electron transport chain (ETC) for energy production through oxidative phosphorylation. Regimens targeting ETC exhibit promising potential to enhance bactericidal activity against M. tuberculosis and hold the prospect of shortening treatment duration. Our previous research demonstrated that the bacteriostatic drug candidate TB47 (T) inhibited the growth of M. tuberculosis by targeting the cytochrome bc1 complex and exhibited synergistic activity ...
Source: Antimicrobial Agents and Chemotherapy - May 1, 2024 Category: Microbiology Authors: Wei Yu Yanan Ju Xingli Han Xirong Tian Jie Ding Shuai Wang H M Adnan Hameed Yamin Gao Lei Li Yongguo Li Nanshan Zhong Tianyu Zhang Source Type: research

The Spx stress regulator confers high-level β-lactam resistance and decreases susceptibility to last-line antibiotics in methicillin-resistant < em > Staphylococcus aureus < /em >
Antimicrob Agents Chemother. 2024 May 1:e0033524. doi: 10.1128/aac.00335-24. Online ahead of print.ABSTRACTInfections caused by methicillin-resistant Staphylococcus aureus (MRSA) are a leading cause of mortality worldwide. MRSA has acquired resistance to next-generation β-lactam antibiotics through the horizontal acquisition of the mecA resistance gene. Development of high resistance is, however, often associated with additional mutations in a set of chromosomal core genes, known as potentiators, which, through poorly described mechanisms, enhance resistance. The yjbH gene was recently identified as a hot spot for adaptiv...
Source: Antimicrobial Agents and Chemotherapy - May 1, 2024 Category: Microbiology Authors: Tobias Krogh Nielsen Ida Birkj ær Petersen Lijuan Xu Maria Disen Barbuti Viktor Mebus Anni Justh Abdulelah Ahmed Alqarzaee Nicolas Jacques C écile Oury Vinai Thomas Morten Kjos Camilla Henriksen Dorte Frees Source Type: research

Insights into the activity of cefiderocol against PER-2 producing Enterobacterales
In this study, we explored the stability of cefiderocol (FDC) against PER-2 β-lactamase to gain insights into structure activity relationships (SAR) of this synthetic siderophore-conjugated antibiotic. Herein, we show that the MICs of FDC for PER-2 producing isolates and transformants ranged between 0.125 and 64 µg/mL; diazabicyclooctanes (DBOs) reduced the MIC values. In PER-2 mutants, MIC values decreased up to 10-12 dilutions in agreement with previous observations especially in the case of Arg220 substitutions. Catalytic efficiency for PER-2 was 0.072 µM-1 s-1, comparable with PER-1 (0.046 µM-1 s-1) and NDM-1 (0.06...
Source: Antimicrobial Agents and Chemotherapy - May 1, 2024 Category: Microbiology Authors: Melina Ruggiero Ivan Brice ño Muñoz Gabriel Gutkind Andrea M Hujer Robert A Bonomo Pablo Power Source Type: research

A pairwise approach to revitalize β-lactams for the treatment of TB
Antimicrob Agents Chemother. 2024 May 1:e0003424. doi: 10.1128/aac.00034-24. Online ahead of print.ABSTRACTThe dual β-lactam approach has been successfully applied to overcome target redundancy in nontuberculous mycobacteria. Surprisingly, this approach has not been leveraged for Mycobacterium tuberculosis, despite the high conservation of peptidoglycan synthesis. Through a comprehensive screen of oral β-lactam pairs, we have discovered that cefuroxime strongly potentiates the bactericidal activity of tebipenem and sulopenem-advanced clinical candidates-and amoxicillin, at concentrations achieved clinically. β-lactam pa...
Source: Antimicrobial Agents and Chemotherapy - May 1, 2024 Category: Microbiology Authors: Dereje A Negatu Wassihun Wedajo Aragaw V éronique Dartois Thomas Dick Source Type: research

Bactericidal and sterilizing activity of sudapyridine-clofazimine-TB47 combined with linezolid or pyrazinamide in a murine model of tuberculosis
Antimicrob Agents Chemother. 2024 May 1:e0012424. doi: 10.1128/aac.00124-24. Online ahead of print.ABSTRACTAs an obligate aerobe, Mycobacterium tuberculosis relies on its branched electron transport chain (ETC) for energy production through oxidative phosphorylation. Regimens targeting ETC exhibit promising potential to enhance bactericidal activity against M. tuberculosis and hold the prospect of shortening treatment duration. Our previous research demonstrated that the bacteriostatic drug candidate TB47 (T) inhibited the growth of M. tuberculosis by targeting the cytochrome bc1 complex and exhibited synergistic activity ...
Source: Antimicrobial Agents and Chemotherapy - May 1, 2024 Category: Microbiology Authors: Wei Yu Yanan Ju Xingli Han Xirong Tian Jie Ding Shuai Wang H M Adnan Hameed Yamin Gao Lei Li Yongguo Li Nanshan Zhong Tianyu Zhang Source Type: research

The Spx stress regulator confers high-level β-lactam resistance and decreases susceptibility to last-line antibiotics in methicillin-resistant < em > Staphylococcus aureus < /em >
Antimicrob Agents Chemother. 2024 May 1:e0033524. doi: 10.1128/aac.00335-24. Online ahead of print.ABSTRACTInfections caused by methicillin-resistant Staphylococcus aureus (MRSA) are a leading cause of mortality worldwide. MRSA has acquired resistance to next-generation β-lactam antibiotics through the horizontal acquisition of the mecA resistance gene. Development of high resistance is, however, often associated with additional mutations in a set of chromosomal core genes, known as potentiators, which, through poorly described mechanisms, enhance resistance. The yjbH gene was recently identified as a hot spot for adaptiv...
Source: Antimicrobial Agents and Chemotherapy - May 1, 2024 Category: Microbiology Authors: Tobias Krogh Nielsen Ida Birkj ær Petersen Lijuan Xu Maria Disen Barbuti Viktor Mebus Anni Justh Abdulelah Ahmed Alqarzaee Nicolas Jacques C écile Oury Vinai Thomas Morten Kjos Camilla Henriksen Dorte Frees Source Type: research

Insights into the activity of cefiderocol against PER-2 producing Enterobacterales
In this study, we explored the stability of cefiderocol (FDC) against PER-2 β-lactamase to gain insights into structure activity relationships (SAR) of this synthetic siderophore-conjugated antibiotic. Herein, we show that the MICs of FDC for PER-2 producing isolates and transformants ranged between 0.125 and 64 µg/mL; diazabicyclooctanes (DBOs) reduced the MIC values. In PER-2 mutants, MIC values decreased up to 10-12 dilutions in agreement with previous observations especially in the case of Arg220 substitutions. Catalytic efficiency for PER-2 was 0.072 µM-1 s-1, comparable with PER-1 (0.046 µM-1 s-1) and NDM-1 (0.06...
Source: Antimicrobial Agents and Chemotherapy - May 1, 2024 Category: Microbiology Authors: Melina Ruggiero Ivan Brice ño Muñoz Gabriel Gutkind Andrea M Hujer Robert A Bonomo Pablo Power Source Type: research

A pairwise approach to revitalize β-lactams for the treatment of TB
Antimicrob Agents Chemother. 2024 May 1:e0003424. doi: 10.1128/aac.00034-24. Online ahead of print.ABSTRACTThe dual β-lactam approach has been successfully applied to overcome target redundancy in nontuberculous mycobacteria. Surprisingly, this approach has not been leveraged for Mycobacterium tuberculosis, despite the high conservation of peptidoglycan synthesis. Through a comprehensive screen of oral β-lactam pairs, we have discovered that cefuroxime strongly potentiates the bactericidal activity of tebipenem and sulopenem-advanced clinical candidates-and amoxicillin, at concentrations achieved clinically. β-lactam pa...
Source: Antimicrobial Agents and Chemotherapy - May 1, 2024 Category: Microbiology Authors: Dereje A Negatu Wassihun Wedajo Aragaw V éronique Dartois Thomas Dick Source Type: research

Bactericidal and sterilizing activity of sudapyridine-clofazimine-TB47 combined with linezolid or pyrazinamide in a murine model of tuberculosis
Antimicrob Agents Chemother. 2024 May 1:e0012424. doi: 10.1128/aac.00124-24. Online ahead of print.ABSTRACTAs an obligate aerobe, Mycobacterium tuberculosis relies on its branched electron transport chain (ETC) for energy production through oxidative phosphorylation. Regimens targeting ETC exhibit promising potential to enhance bactericidal activity against M. tuberculosis and hold the prospect of shortening treatment duration. Our previous research demonstrated that the bacteriostatic drug candidate TB47 (T) inhibited the growth of M. tuberculosis by targeting the cytochrome bc1 complex and exhibited synergistic activity ...
Source: Antimicrobial Agents and Chemotherapy - May 1, 2024 Category: Microbiology Authors: Wei Yu Yanan Ju Xingli Han Xirong Tian Jie Ding Shuai Wang H M Adnan Hameed Yamin Gao Lei Li Yongguo Li Nanshan Zhong Tianyu Zhang Source Type: research

The Spx stress regulator confers high-level β-lactam resistance and decreases susceptibility to last-line antibiotics in methicillin-resistant < em > Staphylococcus aureus < /em >
Antimicrob Agents Chemother. 2024 May 1:e0033524. doi: 10.1128/aac.00335-24. Online ahead of print.ABSTRACTInfections caused by methicillin-resistant Staphylococcus aureus (MRSA) are a leading cause of mortality worldwide. MRSA has acquired resistance to next-generation β-lactam antibiotics through the horizontal acquisition of the mecA resistance gene. Development of high resistance is, however, often associated with additional mutations in a set of chromosomal core genes, known as potentiators, which, through poorly described mechanisms, enhance resistance. The yjbH gene was recently identified as a hot spot for adaptiv...
Source: Antimicrobial Agents and Chemotherapy - May 1, 2024 Category: Microbiology Authors: Tobias Krogh Nielsen Ida Birkj ær Petersen Lijuan Xu Maria Disen Barbuti Viktor Mebus Anni Justh Abdulelah Ahmed Alqarzaee Nicolas Jacques C écile Oury Vinai Thomas Morten Kjos Camilla Henriksen Dorte Frees Source Type: research