Novel hydrazone compounds with broad-spectrum antiplasmodial activity and synergistic interactions with antimalarial drugs
This study evaluated the antiplasmodial activity of seven novel hydrazone compounds (referred to as CB compounds: CB-27, CB-41, CB-50, CB-53, CB-58, CB-59, and CB-61) against multiple stages of Plasmodium parasites. All CB compounds inhibited blood stage proliferation of drug-resistant or sensitive strains of Plasmodium falciparum in the low micromolar to nanomolar range. Interestingly, CB-41 exhibited prophylactic activity against hypnozoites and liver schizonts in Plasmodium cynomolgi, a primate model for Plasmodium vivax. Four CB compounds (CB-27, CB-41, CB-53, and CB-61) inhibited P. falciparum oocyst formation in mosq...
Source: Antimicrobial Agents and Chemotherapy - April 19, 2024 Category: Microbiology Authors: Ang élica M Rosado-Quiñones Emilee E Col ón-Lorenzo Zarna Rajeshkumar Pala J ürgen Bosch Karl Kudyba Heather Kudyba Susan E Leed Norma Roncal Abel Baerga-Ortiz Abiel Roche-Lima Yamil Gerena David A Fidock Alison Roth Joel Vega-Rodr íguez Adelfa E Ser Source Type: research

Ensuring a sustained workforce to combat antibiotic resistance in the 21st century: the critical need for training the next-gen of scientists at the pre-doctoral level
Antimicrob Agents Chemother. 2024 Apr 19:e0024424. doi: 10.1128/aac.00244-24. Online ahead of print.ABSTRACTAntibiotics revolutionized the treatment of bacterial infection and enhanced modern healthcare. While the current global antibiotic resistance crisis is widely acknowledged, the need for a highly trained cohort of scientists to continue and expand efforts to combat this threat has received less attention. We posit that training of pre-doctoral students in the antibiotic resistance field is critical for future efforts in combating this crisis and urge development of training programs that focus on this need.PMID:38639...
Source: Antimicrobial Agents and Chemotherapy - April 19, 2024 Category: Microbiology Authors: William M Shafer Graeme L Conn Source Type: research

Inactivation of the ribosome assembly factor RimP causes streptomycin resistance and impairs motility in < em > Salmonella < /em >
Antimicrob Agents Chemother. 2024 Apr 17:e0000224. doi: 10.1128/aac.00002-24. Online ahead of print.ABSTRACTThe ribosome is the central hub for protein synthesis and the target of many antibiotics. Although the majority of ribosome-targeting antibiotics inhibit protein synthesis and are bacteriostatic, aminoglycosides promote protein mistranslation and are bactericidal. Understanding the resistance mechanisms of bacteria against aminoglycosides is not only vital for improving the efficacy of this critically important group of antibiotics but also crucial for studying the molecular basis of translational fidelity. In this w...
Source: Antimicrobial Agents and Chemotherapy - April 17, 2024 Category: Microbiology Authors: Zhihui Lyu Yunyi Ling Ambro van Hoof Jiqiang Ling Source Type: research

Possibility of hypoalbuminemia itself as a risk for clinical failure
Antimicrob Agents Chemother. 2024 Apr 17:e0036724. doi: 10.1128/aac.00367-24. Online ahead of print.NO ABSTRACTPMID:38629859 | DOI:10.1128/aac.00367-24 (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - April 17, 2024 Category: Microbiology Authors: Shougen Sumiyoshi Shungo Yamamoto Source Type: research

Inactivation of the ribosome assembly factor RimP causes streptomycin resistance and impairs motility in < em > Salmonella < /em >
Antimicrob Agents Chemother. 2024 Apr 17:e0000224. doi: 10.1128/aac.00002-24. Online ahead of print.ABSTRACTThe ribosome is the central hub for protein synthesis and the target of many antibiotics. Although the majority of ribosome-targeting antibiotics inhibit protein synthesis and are bacteriostatic, aminoglycosides promote protein mistranslation and are bactericidal. Understanding the resistance mechanisms of bacteria against aminoglycosides is not only vital for improving the efficacy of this critically important group of antibiotics but also crucial for studying the molecular basis of translational fidelity. In this w...
Source: Antimicrobial Agents and Chemotherapy - April 17, 2024 Category: Microbiology Authors: Zhihui Lyu Yunyi Ling Ambro van Hoof Jiqiang Ling Source Type: research

Possibility of hypoalbuminemia itself as a risk for clinical failure
Antimicrob Agents Chemother. 2024 Apr 17:e0036724. doi: 10.1128/aac.00367-24. Online ahead of print.NO ABSTRACTPMID:38629859 | DOI:10.1128/aac.00367-24 (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - April 17, 2024 Category: Microbiology Authors: Shougen Sumiyoshi Shungo Yamamoto Source Type: research

Inactivation of the ribosome assembly factor RimP causes streptomycin resistance and impairs motility in < em > Salmonella < /em >
Antimicrob Agents Chemother. 2024 Apr 17:e0000224. doi: 10.1128/aac.00002-24. Online ahead of print.ABSTRACTThe ribosome is the central hub for protein synthesis and the target of many antibiotics. Although the majority of ribosome-targeting antibiotics inhibit protein synthesis and are bacteriostatic, aminoglycosides promote protein mistranslation and are bactericidal. Understanding the resistance mechanisms of bacteria against aminoglycosides is not only vital for improving the efficacy of this critically important group of antibiotics but also crucial for studying the molecular basis of translational fidelity. In this w...
Source: Antimicrobial Agents and Chemotherapy - April 17, 2024 Category: Microbiology Authors: Zhihui Lyu Yunyi Ling Ambro van Hoof Jiqiang Ling Source Type: research

Possibility of hypoalbuminemia itself as a risk for clinical failure
Antimicrob Agents Chemother. 2024 Apr 17:e0036724. doi: 10.1128/aac.00367-24. Online ahead of print.NO ABSTRACTPMID:38629859 | DOI:10.1128/aac.00367-24 (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - April 17, 2024 Category: Microbiology Authors: Shougen Sumiyoshi Shungo Yamamoto Source Type: research

Correction for Chen et al., "Repurposing a human acetyl-CoA carboxylase inhibitor firsocostat to treat fungal candidiasis alone and in combination"
Antimicrob Agents Chemother. 2024 Apr 16:e0029324. doi: 10.1128/aac.00293-24. Online ahead of print.NO ABSTRACTPMID:38624213 | DOI:10.1128/aac.00293-24 (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - April 16, 2024 Category: Microbiology Authors: Tianyu Chen Jing Yao Keao Quan Jingchen Xu Xudong Hang Qian Tong Genyan Liu Peipei Luo Liping Zeng Ganzhu Feng Hongkai Bi Source Type: research

Precise genome editing underlines the distinct contributions of mutations in < em > ERG11 < /em > , < em > ERG3 < /em > , < em > MRR1 < /em > , and < em > TAC1 < /em > genes to antifungal resistance in < em > Candida parapsilosis < /em >
Antimicrob Agents Chemother. 2024 Apr 16:e0002224. doi: 10.1128/aac.00022-24. Online ahead of print.ABSTRACTCandida parapsilosis has recently emerged as a major threat due to the worldwide emergence of fluconazole-resistant strains causing clonal outbreaks in hospitals and poses a therapeutic challenge due to the limited antifungal armamentarium. Here, we used precise genome editing using CRISPR-Cas9 to gain further insights into the contribution of mutations in ERG11, ERG3, MRR1, and TAC1 genes and the influence of allelic dosage to antifungal resistance in C. parapsilosis. Seven of the most common amino acid substitution...
Source: Antimicrobial Agents and Chemotherapy - April 16, 2024 Category: Microbiology Authors: Sophie Hartuis Isabelle Ourliac-Garnier Estelle Robert Marjorie Albassier L éa Duchesne Clara Beaufils Jos éphine Kuhn Patrice Le Pape Florent Morio Source Type: research

Genomic characterization of ST38 NDM-5-producing < em > Escherichia coli < /em > isolates from an outbreak in the Czech Republic
Antimicrob Agents Chemother. 2024 Apr 16:e0013324. doi: 10.1128/aac.00133-24. Online ahead of print.ABSTRACTA 2-year national genomic screening in the Czech Republic identified a notable prevalence of the New Delhi metallo-β-lactamase 5 (NDM-5)-producing Escherichia coli sequence type 38 (ST38) in the city of Brno. Forty-two ST38 E. coli isolates harbored the blaNDM-5 gene on the chromosome. Virulence factors confirmed the persistence of these isolates through biofilm formation. Single Nucleotide Polymorphisms (SNPs)-based phylogeny and CRISPR assay typing showed minimal genomic variations, implying a clonally driven outb...
Source: Antimicrobial Agents and Chemotherapy - April 16, 2024 Category: Microbiology Authors: Katerina Chudejova Tsolaire Sourenian Jana Palkovicova Katarina Stredanska Lucie Nechutna Katerina Vlkova Vendula Studentova Working Group for Monitoring of Antibiotic Resistance Jaroslav Hrabak Costas C Papagiannitsis Monika Dolejska Ibrahim Bitar Workin Source Type: research

Combination of ganciclovir and trifluridine prevents drug-resistance emergence in HSV-1
Antimicrob Agents Chemother. 2024 Apr 15:e0011024. doi: 10.1128/aac.00110-24. Online ahead of print.ABSTRACTOcular herpes simplex virus 1 (HSV-1) infections can lead to visual impairment. Long-term acyclovir (ACV) prophylaxis reduces the frequency of recurrences but is associated with drug resistance. Novel therapies are needed to treat drug-resistant HSV-1 infections. Here, we describe the effects of trifluridine (TFT) in combination with ACV or ganciclovir (GCV) on HSV-1 replication and drug-resistance emergence. Wild-type HSV-1 was grown under increasing doses of one antiviral (ACV, GCV, or TFT) or combinations thereof ...
Source: Antimicrobial Agents and Chemotherapy - April 15, 2024 Category: Microbiology Authors: Hanna Helena Schalkwijk Neesha Rajesh Shewakramani Kalyan Das Graciela Andrei Robert Snoeck Source Type: research

Combination of ganciclovir and trifluridine prevents drug-resistance emergence in HSV-1
Antimicrob Agents Chemother. 2024 Apr 15:e0011024. doi: 10.1128/aac.00110-24. Online ahead of print.ABSTRACTOcular herpes simplex virus 1 (HSV-1) infections can lead to visual impairment. Long-term acyclovir (ACV) prophylaxis reduces the frequency of recurrences but is associated with drug resistance. Novel therapies are needed to treat drug-resistant HSV-1 infections. Here, we describe the effects of trifluridine (TFT) in combination with ACV or ganciclovir (GCV) on HSV-1 replication and drug-resistance emergence. Wild-type HSV-1 was grown under increasing doses of one antiviral (ACV, GCV, or TFT) or combinations thereof ...
Source: Antimicrobial Agents and Chemotherapy - April 15, 2024 Category: Microbiology Authors: Hanna Helena Schalkwijk Neesha Rajesh Shewakramani Kalyan Das Graciela Andrei Robert Snoeck Source Type: research

Effect modification of dosing strategy (AUC or trough) on AKI associated with vancomycin in combination with piperacillin/tazobactam or cefepime and meropenem
Antimicrob Agents Chemother. 2024 Apr 12:e0108523. doi: 10.1128/aac.01085-23. Online ahead of print.ABSTRACTPiperacillin-tazobactam (TZP), cefepime (FEP), or meropenem (MEM) and vancomycin (VAN) are commonly used in combination for sepsis. Studies have shown an increased risk of acute kidney injury (AKI) with TZP and VAN compared to FEP or MEM. VAN guidelines recommend area under the curve (AUC) monitoring over trough (Tr) to minimize the risk of AKI. We investigated the association of AKI and MAKE-30 with the two VAN monitoring strategies when used in combination with TZP or FEP/MEM. Adult patients between 2015 and 2019 w...
Source: Antimicrobial Agents and Chemotherapy - April 12, 2024 Category: Microbiology Authors: Breanne Mefford Katie L Wallace J Chris Donaldson Brittany D Bissell Turpin Parijat Sen Aric D Schadler Lucas J Liu Melissa L Thompson Bastin Source Type: research

Effect modification of dosing strategy (AUC or trough) on AKI associated with vancomycin in combination with piperacillin/tazobactam or cefepime and meropenem
Antimicrob Agents Chemother. 2024 Apr 12:e0108523. doi: 10.1128/aac.01085-23. Online ahead of print.ABSTRACTPiperacillin-tazobactam (TZP), cefepime (FEP), or meropenem (MEM) and vancomycin (VAN) are commonly used in combination for sepsis. Studies have shown an increased risk of acute kidney injury (AKI) with TZP and VAN compared to FEP or MEM. VAN guidelines recommend area under the curve (AUC) monitoring over trough (Tr) to minimize the risk of AKI. We investigated the association of AKI and MAKE-30 with the two VAN monitoring strategies when used in combination with TZP or FEP/MEM. Adult patients between 2015 and 2019 w...
Source: Antimicrobial Agents and Chemotherapy - April 12, 2024 Category: Microbiology Authors: Breanne Mefford Katie L Wallace J Chris Donaldson Brittany D Bissell Turpin Parijat Sen Aric D Schadler Lucas J Liu Melissa L Thompson Bastin Source Type: research