Delayed gametocyte clearance in < em > Plasmodium vivax < /em > malaria is associated with polymorphisms in the cytochrome P450 reductase (CPR)
Antimicrob Agents Chemother. 2024 Feb 27:e0120423. doi: 10.1128/aac.01204-23. Online ahead of print.ABSTRACTPrimaquine (PQ) is the main drug used to eliminate dormant liver stages and prevent relapses in Plasmodium vivax malaria. It also has an effect on the gametocytes of Plasmodium falciparum; however, it is unclear to what extent PQ affects P. vivax gametocytes. PQ metabolism involves multiple enzymes, including the highly polymorphic CYP2D6 and the cytochrome P450 reductase (CPR). Since genetic variability can impact drug metabolism, we conducted an evaluation of the effect of CYP2D6 and CPR variants on PQ gametocytoci...
Source: Antimicrobial Agents and Chemotherapy - February 27, 2024 Category: Microbiology Authors: Yanka Evellyn Alves Rodrigues Salazar Jaime Louzada Maria Carolina Silva de Barros Pu ça Luiz Felipe Ferreira Guimar ães Jos é Luiz Fernandes Vieira Andr é Machado de Siqueira Jos é Pedro Gil Cristiana Ferreira Alves de Brito Tais Nobrega de Sousa Source Type: research

< em > Ex vivo < /em > drug susceptibility and resistance mediating genetic polymorphisms of < em > Plasmodium falciparum < /em > in Bobo-Dioulasso, Burkina Faso
Antimicrob Agents Chemother. 2024 Feb 27:e0153423. doi: 10.1128/aac.01534-23. Online ahead of print.ABSTRACTMalaria remains a leading cause of morbidity and mortality in Burkina Faso, which utilizes artemether-lumefantrine as the principal therapy to treat uncomplicated malaria and seasonal malaria chemoprevention with monthly sulfadoxine-pyrimethamine plus amodiaquine in children during the transmission season. Monitoring the activities of available antimalarial drugs is a high priority. We assessed the ex vivo susceptibility of Plasmodium falciparum to 11 drugs in isolates from patients presenting with uncomplicated mala...
Source: Antimicrobial Agents and Chemotherapy - February 27, 2024 Category: Microbiology Authors: A Fabrice Som é Melissa D Conrad Zachari Kabr é Aminata Fofana R Serge Yerbanga Thomas Bazi é Catherine Neya Myreille Som é Tegawinde Josue Kagambega Jenny Legac Shreeya Garg Jeffrey A Bailey Jean-Bosco Ou édraogo Philip J Rosenthal Roland A Cooper Source Type: research

Ethambutol and meropenem/clavulanate synergy promotes enhanced extracellular and intracellular killing of < em > Mycobacterium tuberculosis < /em >
This study demonstrates that pairing beta-lactams with ethambutol (EMB) significantly improves their efficacy against Mycobacterium tuberculosis (Mtb). The presence of EMB enhances beta-lactam access through the cell wall, which may translate into a prolonged contact between the drug and its targets at a concentration that effectively kills the pathogen. Importantly, we showed that the effects of the EMB and meropenem (MEM)/clavulanate combination were maintained intracellularly. These results are of high significance considering that the time above the minimum inhibitory concentration is the main determinant of beta-lacta...
Source: Antimicrobial Agents and Chemotherapy - February 27, 2024 Category: Microbiology Authors: Francisco Oliven ça David Pires C átia Silveiro Bianca Gama Frederico Holtreman Elsa Anes Maria Jo ão Catalão Source Type: research

Impact of hypoalbuminemia on clinical outcomes among patients with obesity treated with ceftriaxone
Antimicrob Agents Chemother. 2024 Feb 27:e0166323. doi: 10.1128/aac.01663-23. Online ahead of print.ABSTRACTThe use of ceftriaxone, a highly protein-bound drug, in the setting of hypoalbuminemia may result in suboptimal drug exposure. Patients with obesity also exhibit higher absolute drug clearance. We aimed to evaluate the impact of hypoalbuminemia on clinical success among hospitalized adults with obesity who were treated with ceftriaxone. This retrospective review included adult inpatients with weight >100 kg or body mass index >40 kg/m2 who received ceftriaxone 2 g intravenously every 12 hours for at least 72 ho...
Source: Antimicrobial Agents and Chemotherapy - February 27, 2024 Category: Microbiology Authors: Kellie Arensman Hannan Evan Draper Kristin C Cole Jack Mc Hugh Christina G Rivera Omar Abu Saleh Source Type: research

Balancing the scales: achieving the optimal beta-lactam to beta-lactamase inhibitor ratio with continuous infusion piperacillin/tazobactam against extended spectrum beta-lactamase producing < em > Enterobacterales < /em >
This study included 257 critically ill patients (79.3% male) with intra-abdominal, bloodstream, and hospital-acquired pneumonia infections in 89.5% as the primary indication. The median (min-max range) age, body weight, and estimated glomerular filtration rate (eGFR) were 66 (23-93) years, 75 (39-310) kg, and 79.2 (6.4-234) mL/min, respectively. Doses of up to 22.5 g/day were used to optimize TZP based on TDM. The 2021 chronic kidney disease epidemiology equation in mL/min best modeled TZP CL. The ratio of piperacillin:tazobactam increased from 6:1 to 10:1 between an eGFR of <20 mL/min and >120 mL/min. At conventiona...
Source: Antimicrobial Agents and Chemotherapy - February 27, 2024 Category: Microbiology Authors: Pier Giorgio Cojutti Manjunath P Pai Tommaso Tonetti Antonio Siniscalchi Pierluigi Viale Federico Pea Source Type: research

Amoebicidal effect of synthetic indoles against < em > Acanthamoeba < /em > spp.: a study of cell death
Antimicrob Agents Chemother. 2024 Feb 27:e0165123. doi: 10.1128/aac.01651-23. Online ahead of print.ABSTRACTOrganic and synthetic chemistry plays a crucial role in drug discovery fields. Moreover, chemical modifications of available molecules to enhance their efficacy, selectivity and safety have been considered as an attractive approach for the development of new bioactive agents. Indoles, a versatile group of natural heterocyclic compounds, have been widely used in pharmaceutical industry due to their broad spectrum of activities including antimicrobial, antitumoral and anti-inflammatory among others. Herein, we report t...
Source: Antimicrobial Agents and Chemotherapy - February 27, 2024 Category: Microbiology Authors: Ines Sifaoui Rub én L Rodríguez-Expósito Mar ía Reyes-Batlle Alejandra Dumpi érrez Ramos Raquel Diana-Rivero Fernando Garc ía-Tellado David Tejedor Jos é E Piñero Jacob Lorenzo-Morales Source Type: research

Delayed gametocyte clearance in < em > Plasmodium vivax < /em > malaria is associated with polymorphisms in the cytochrome P450 reductase (CPR)
Antimicrob Agents Chemother. 2024 Feb 27:e0120423. doi: 10.1128/aac.01204-23. Online ahead of print.ABSTRACTPrimaquine (PQ) is the main drug used to eliminate dormant liver stages and prevent relapses in Plasmodium vivax malaria. It also has an effect on the gametocytes of Plasmodium falciparum; however, it is unclear to what extent PQ affects P. vivax gametocytes. PQ metabolism involves multiple enzymes, including the highly polymorphic CYP2D6 and the cytochrome P450 reductase (CPR). Since genetic variability can impact drug metabolism, we conducted an evaluation of the effect of CYP2D6 and CPR variants on PQ gametocytoci...
Source: Antimicrobial Agents and Chemotherapy - February 27, 2024 Category: Microbiology Authors: Yanka Evellyn Alves Rodrigues Salazar Jaime Louzada Maria Carolina Silva de Barros Pu ça Luiz Felipe Ferreira Guimar ães Jos é Luiz Fernandes Vieira Andr é Machado de Siqueira Jos é Pedro Gil Cristiana Ferreira Alves de Brito Tais Nobrega de Sousa Source Type: research

< em > Ex vivo < /em > drug susceptibility and resistance mediating genetic polymorphisms of < em > Plasmodium falciparum < /em > in Bobo-Dioulasso, Burkina Faso
Antimicrob Agents Chemother. 2024 Feb 27:e0153423. doi: 10.1128/aac.01534-23. Online ahead of print.ABSTRACTMalaria remains a leading cause of morbidity and mortality in Burkina Faso, which utilizes artemether-lumefantrine as the principal therapy to treat uncomplicated malaria and seasonal malaria chemoprevention with monthly sulfadoxine-pyrimethamine plus amodiaquine in children during the transmission season. Monitoring the activities of available antimalarial drugs is a high priority. We assessed the ex vivo susceptibility of Plasmodium falciparum to 11 drugs in isolates from patients presenting with uncomplicated mala...
Source: Antimicrobial Agents and Chemotherapy - February 27, 2024 Category: Microbiology Authors: A Fabrice Som é Melissa D Conrad Zachari Kabr é Aminata Fofana R Serge Yerbanga Thomas Bazi é Catherine Neya Myreille Som é Tegawinde Josue Kagambega Jenny Legac Shreeya Garg Jeffrey A Bailey Jean-Bosco Ou édraogo Philip J Rosenthal Roland A Cooper Source Type: research

Ethambutol and meropenem/clavulanate synergy promotes enhanced extracellular and intracellular killing of < em > Mycobacterium tuberculosis < /em >
This study demonstrates that pairing beta-lactams with ethambutol (EMB) significantly improves their efficacy against Mycobacterium tuberculosis (Mtb). The presence of EMB enhances beta-lactam access through the cell wall, which may translate into a prolonged contact between the drug and its targets at a concentration that effectively kills the pathogen. Importantly, we showed that the effects of the EMB and meropenem (MEM)/clavulanate combination were maintained intracellularly. These results are of high significance considering that the time above the minimum inhibitory concentration is the main determinant of beta-lacta...
Source: Antimicrobial Agents and Chemotherapy - February 27, 2024 Category: Microbiology Authors: Francisco Oliven ça David Pires C átia Silveiro Bianca Gama Frederico Holtreman Elsa Anes Maria Jo ão Catalão Source Type: research

Impact of hypoalbuminemia on clinical outcomes among patients with obesity treated with ceftriaxone
Antimicrob Agents Chemother. 2024 Feb 27:e0166323. doi: 10.1128/aac.01663-23. Online ahead of print.ABSTRACTThe use of ceftriaxone, a highly protein-bound drug, in the setting of hypoalbuminemia may result in suboptimal drug exposure. Patients with obesity also exhibit higher absolute drug clearance. We aimed to evaluate the impact of hypoalbuminemia on clinical success among hospitalized adults with obesity who were treated with ceftriaxone. This retrospective review included adult inpatients with weight >100 kg or body mass index >40 kg/m2 who received ceftriaxone 2 g intravenously every 12 hours for at least 72 ho...
Source: Antimicrobial Agents and Chemotherapy - February 27, 2024 Category: Microbiology Authors: Kellie Arensman Hannan Evan Draper Kristin C Cole Jack Mc Hugh Christina G Rivera Omar Abu Saleh Source Type: research

Balancing the scales: achieving the optimal beta-lactam to beta-lactamase inhibitor ratio with continuous infusion piperacillin/tazobactam against extended spectrum beta-lactamase producing < em > Enterobacterales < /em >
This study included 257 critically ill patients (79.3% male) with intra-abdominal, bloodstream, and hospital-acquired pneumonia infections in 89.5% as the primary indication. The median (min-max range) age, body weight, and estimated glomerular filtration rate (eGFR) were 66 (23-93) years, 75 (39-310) kg, and 79.2 (6.4-234) mL/min, respectively. Doses of up to 22.5 g/day were used to optimize TZP based on TDM. The 2021 chronic kidney disease epidemiology equation in mL/min best modeled TZP CL. The ratio of piperacillin:tazobactam increased from 6:1 to 10:1 between an eGFR of <20 mL/min and >120 mL/min. At conventiona...
Source: Antimicrobial Agents and Chemotherapy - February 27, 2024 Category: Microbiology Authors: Pier Giorgio Cojutti Manjunath P Pai Tommaso Tonetti Antonio Siniscalchi Pierluigi Viale Federico Pea Source Type: research

Amoebicidal effect of synthetic indoles against < em > Acanthamoeba < /em > spp.: a study of cell death
Antimicrob Agents Chemother. 2024 Feb 27:e0165123. doi: 10.1128/aac.01651-23. Online ahead of print.ABSTRACTOrganic and synthetic chemistry plays a crucial role in drug discovery fields. Moreover, chemical modifications of available molecules to enhance their efficacy, selectivity and safety have been considered as an attractive approach for the development of new bioactive agents. Indoles, a versatile group of natural heterocyclic compounds, have been widely used in pharmaceutical industry due to their broad spectrum of activities including antimicrobial, antitumoral and anti-inflammatory among others. Herein, we report t...
Source: Antimicrobial Agents and Chemotherapy - February 27, 2024 Category: Microbiology Authors: Ines Sifaoui Rub én L Rodríguez-Expósito Mar ía Reyes-Batlle Alejandra Dumpi érrez Ramos Raquel Diana-Rivero Fernando Garc ía-Tellado David Tejedor Jos é E Piñero Jacob Lorenzo-Morales Source Type: research

Proactive therapeutic monitoring of dalbavancin concentrations in the long-term management of chronic osteoarticular/periprosthetic joint infections
Antimicrob Agents Chemother. 2024 Feb 22:e0002324. doi: 10.1128/aac.00023-24. Online ahead of print.ABSTRACTHere, we describe the use of proactive therapeutic drug monitoring (TDM) to individualize the optimal timing of drug injections in 16 adult patients with chronic osteoarticular infections receiving a median of 7 injections of dalbavancin (up to 12 injections in 15 months). Dalbavancin injections were repeated at medians of 39-47 days, with infusion intervals ranging from 26 to 69 days. TDM can facilitates a precise, targeted use of dalbavancin for infections requiring prolonged treatments.PMID:38385700 | DOI:10.1128/...
Source: Antimicrobial Agents and Chemotherapy - February 22, 2024 Category: Microbiology Authors: Dario Cattaneo Marta Fusi Lucia Galli Camilla Genovese Riccardo Giorgi Maddalena Matone Stefania Merli Marta Colaneri Andrea Gori Source Type: research

Bimodal distribution of azole susceptibility in < em > Sporothrix brasiliensis < /em > isolates in Brazil
Antimicrob Agents Chemother. 2024 Feb 22:e0162023. doi: 10.1128/aac.01620-23. Online ahead of print.ABSTRACTSporothrix brasiliensis is an emerging zoonotic fungal pathogen that can be difficult to treat. Antifungal susceptibility testing was performed on the mold phase of a convenience sample of 61 Sporothrix spp. isolates from human and cat sporotrichosis cases in Brazil using the Clinical and Laboratory Standards Institute standard M38. A bimodal distribution of azole susceptibility was observed with 50% (28/56) of S. brasiliensis isolates showing elevated itraconazole minimum inhibitory concentrations ≥16 µg/mL. Phyl...
Source: Antimicrobial Agents and Chemotherapy - February 22, 2024 Category: Microbiology Authors: Amanda Ribeiro Dos Santos Lalitha Gade Elizabeth Misas Anastasia P Litvintseva Natalie S Nunnally Lindsay A Parnell Malavika Rajeev Marcia de Souza Carvalho Melhem Juliana Possato Fernandes Takahashi Gabriel Manzi Oliboni Lucas Xavier Bonfieti Lisandra Si Source Type: research

Antibiotic-induced ROS-mediated Fur allosterism contributes to < em > Helicobacter pylori < /em > resistance by inhibiting < em > arsR < /em > activation of < em > mutS < /em > and < em > mutY < /em >
This study unveils a novel mechanism of antibiotic-induced resistance in H. pylori, providing crucial insights for the prevention and control of antibiotic resistance in H. pylori.PMID:38386782 | DOI:10.1128/aac.01679-23 (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - February 22, 2024 Category: Microbiology Authors: Junyuan Xue Wen Li Yican Zhao Liyuan Wang Peiyuan Cheng Lu Zhang Yantong Zheng Wenxin Zhang Yakun Bi Zhenghong Chen Ting Jiang Yundong Sun Source Type: research