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Pharmacogenetics of aminoglycoside-related ototoxicity: a systematic review J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-04-17 D Gaafar, N Baxter, N Cranswick, J Christodoulou, A Gwee
Background Aminoglycosides (AGs) are important antibiotics in the treatment of Gram-negative sepsis. However, they are associated with the risk of irreversible sensorineural hearing loss (SNHL). Several genetic variants have been implicated in the development of ototoxicity. Objectives To evaluate the pharmacogenetic determinants of AG-related ototoxicity. Methods This study followed the Preferred
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Iron efflux by IetA enhances β-lactam aztreonam resistance and is linked to oxidative stress through cellular respiration in Riemerella anatipestifer J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-04-17 Mafeng Liu, Mengying Wang, Mi Huang, Qun Gao, Dekang Zhu, Mingshu Wang, Renyong Jia, Shun Chen, Xinxin Zhao, Qiao Yang, Ying Wu, Shaqiu Zhang, Juan Huang, Xumin Ou, Sai Mao, Bin Tian, Di Sun, Anchun Cheng
Background Riemerella anatipestifer encodes an iron acquisition system, but whether it encodes the iron efflux pump and its role in antibiotic resistance are largely unknown. Objectives To screen and identify an iron efflux gene in R. anatipestifer and determine whether and how the iron efflux gene is involved in antibiotic resistance. Methods In this study, gene knockout, streptonigrin susceptibility
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Occurrence and characterization of rmtB-harbouring Salmonella and Escherichia coli isolates from a pig farm in the UK J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-04-17 Indre Navickaite, Harry Holmes, Letizia Dondi, Luke Randall, Catherine Fearnley, Emma Taylor, Edward Fullick, Robert Horton, Susanna Williamson, Manal AbuOun, Christopher Teale, Muna F Anjum
Objectives To characterize and elucidate the spread of amikacin-resistant Enterobacteriaceae isolates from environmental samples on a pig farm in the UK, following the previous identification of index Salmonella isolates harbouring the rmtB gene, a 16S rRNA methylase. Methods Environmental samples were collected during two visits to a pig farm in the UK. Isolates were recovered using selective media
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Triazole antifungal drug interactions—practical considerations for excellent prescribing J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-04-17 Russell Lewis, Saarah Niazi-Ali, Andrew McIvor, Souha S Kanj, Johan Maertens, Matteo Bassetti, Deborah Levine, Andreas H Groll, David W Denning
Systemic antifungal therapy is critical for reducing the mortality from many invasive and chronic fungal infections. Triazole antifungals are the most frequently prescribed antifungals but require attention to dosing and drug interactions. Nearly 600 severe drug–drug interactions and over 1100 moderate interactions requiring dose modifications are described or anticipated with systemic antifungal agents
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Extrapolation of lung pharmacokinetics of antitubercular drugs from preclinical species to humans using PBPK modelling J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-04-10 Evangelos Karakitsios, Aristides Dokoumetzidis
Objectives To develop physiologically based pharmacokinetic (PBPK) models for widely used anti-TB drugs, namely rifampicin, pyrazinamide, isoniazid, ethambutol and moxifloxacin lung pharmacokinetics (PK)—regarding both healthy and TB-infected tissue (cellular lesion and caseum)—in preclinical species and to extrapolate to humans. Methods Empirical models were used for the plasma PK of each species
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A comparison of strategies for identifying patients at risk for carbapenem-resistant or extended β-lactam-resistant Pseudomonas aeruginosa J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-04-06 Walaiporn Wangchinda, Keith S Kaye, Twisha S Patel, Owen R Albin, Louis Saravolatz, Joshua G Petrie, Jason M Pogue
Objectives To assess risk factors for carbapenem-resistant Pseudomonas aeruginosa (CR) and extended-β-lactam-resistant P. aeruginosa (EBR) infection/colonization, and to develop and compare tools for predicting isolation of CR and EBR from clinical cultures. Methods This retrospective study analysed hospitalized patients with positive P. aeruginosa cultures between 2015 and 2021. Two case–control analyses
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Ten-year results of an international external quality control programme for measurement of anti-tuberculosis drug concentrations J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-04-06 Ralf Stemkens, Chaima Mouhdad, Eric J F Franssen, Daniel Touw, Jan-Willem Alffenaar, Lindsey H M Te Brake, Marieke G G Sturkenboom, Rob E Aarnoutse
Objectives Participation in an external (interlaboratory) quality control (QC) programme is an essential part of quality assurance as it provides laboratories with valuable insights into their analytical performance. We describe the 10 year results of an international QC programme for the measurement of anti-tuberculosis (TB) drugs. Methods Each year, two rounds were organized in which serum (or plasma)
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Tandem amplification of a plasmid-borne tet(A) variant gene confers tigecycline resistance in Escherichia coli J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-04-04 Chenhui Zou, Chunyan Xu, Runhao Yu, Xinxin Shan, Stefan Schwarz, Dexi Li, Xiang-Dang Du
Objectives To elucidate the mechanism of tigecycline resistance in Escherichia coli that is mediated by the tet(A) variant gene. Methods E. coli strain 573 carried a plasmid-borne tet(A) variant gene, tentatively designated tet(A)TIG, that conferred decreased tigecycline susceptibility (MIC 0.5 mg/L). When exposed to increasing concentrations of tigecycline (0.25–8 mg/L), mutants growing at 2, 4 and
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Continuous evaluation of single-dose moxifloxacin concentrations in brain extracellular fluid, cerebrospinal fluid, and plasma: a novel porcine model J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-04-04 T Mariager, J H Terkelsen, M Bue, K Öbrink-Hansen, R Nau, C R Bjarkam, H Nielsen, J Bodilsen
Background Knowledge regarding CNS pharmacokinetics of moxifloxacin is limited, with unknown consequences for patients with meningitis caused by bacteria resistant to beta-lactams or caused by TB. Objective (i) To develop a novel porcine model for continuous investigation of moxifloxacin concentrations within brain extracellular fluid (ECF), CSF and plasma using microdialysis, and (ii) to compare these
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Influence of ultrafiltration conditions on the measurement of unbound drug concentrations: flucloxacillin as an example J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-04-03 Nynke G L Jager, Eleonora Van Ewijk-Beneken Kolmer, Rob Aarnoutse, Lindsey H M Te Brake
Background When performing therapeutic drug monitoring (TDM) for flucloxacillin, it is advised to measure the unbound, not the total, flucloxacillin concentration. To be able to accurately quantify unbound flucloxacillin concentrations, a reliable analytical method is indispensable. Objective To determine the influence of temperature and pH of the sample during ultrafiltration on the measured unbound
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Methicillin resistance in Staphylococcus pseudintermedius encoded within novel staphylococcal cassette chromosome mec (SCCmec) variants J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-04-02 A C MacFadyen, G K Paterson
Background Staphylococcus pseudintermedius is a common opportunistic pathogen of companion dogs and an occasional human pathogen. Treatment is hampered by antimicrobial resistance including methicillin resistance encoded by mecA within the mobile genetic element SCCmec. Objectives SCCmec elements are diverse, especially in non-Staphyloccocus aureus staphylococci, and novel variants are likely to be
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Performance of disk diffusion method for aztreonam in combination with avibactam against Enterobacteriales J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-04-02 Dandan Yin, Peipei Song, Lan Jiang, Jian Xu, Fupin Hu
Objectives To evaluate the performance of an in-house developed disk diffusion method for aztreonam in combination with avibactam against Enterobacteriales. Methods The in vitro antibacterial activity of aztreonam with avibactam against 204 carbapenemase-producing Enterobacteriales was determined by a disk diffusion method, with a broth microdilution method as a reference. Results The optimal S/R breakpoints
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Assessing the impact of meropenem exposure on ceftolozane/tazobactam-resistance development in Pseudomonas aeruginosa using in vitro serial passage J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-04-02 Aliaa Fouad, Samantha E Nicolau, Pranita D Tamma, Patricia J Simner, David P Nicolau, Christian M Gill
Background Patients infected with difficult-to-treat Pseudomonas aeruginosa are likely to receive meropenem (MEM) empirically before escalation to ceftolozane/tazobactam (C/T). We assessed whether pre-exposure to MEM affected C/T resistance development on C/T exposure. Materials and methods Nine clinical P. aeruginosa isolates were exposed to MEM 16 mg/L for 72 h. Then, isolates were serially passaged
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Integrase strand transfer inhibitor resistance mediated by R263K plus E157Q in a patient with HIV infection treated with bictegravir/tenofovir alafenamide/emtricitabine: case report and review of the literature J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-04-01 Luis Buzon-Martin, Carolina Navarro-San Francisco, María Fernandez-Regueras, Leticia Sanchez-Gomez
Objectives The in vivo selection of E157Q plus R263K has not been reported in patients treated with coformulated bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). To the best of our knowledge, we hereby report the first case of high-grade INSTI resistance associated with the presence of these aminoacidic substitutions in a treatment-experienced HIV patient treated with BIC/FTC/TAF. Methods
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Drug resistance and influencing factors in HIV-1-infected individuals under antiretroviral therapy in Guangxi, China J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-03-29 Xianwu Pang, Qin He, Kailing Tang, Jinghua Huang, Ningye Fang, Haoming Xie, Jie Ma, Qiuying Zhu, Guanghua Lan, Shujia Liang
Objectives To assess the profiles and determinants of drug resistance in HIV-1-infected individuals undergoing ART in Guangxi. Methods Samples and data were collected from HIV-1-infected individuals experiencing virological failure post-ART from 14 cities in Guangxi. Sequencing of the HIV-1 pol gene was conducted, followed by analysis for drug resistance mutations using the Stanford University HIV
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Pharmacokinetics of isavuconazole at different target sites in healthy volunteers after single and multiple intravenous infusions J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-03-28 Felix Bergmann, Michael Wölfl-Duchek, Anselm Jorda, Valentin Al Jalali, Amelie Leutzendorff, Maria Sanz-Codina, Daniela Gompelmann, Karin Trimmel, Maria Weber, Sabine Eberl, Wisse Van Os, Iris K Minichmayr, Birgit Reiter, Thomas Stimpfl, Marco Idzko, Markus Zeitlinger
Background Invasive aspergillosis is a severe fungal infection that affects multiple organ systems including the CNS and the lungs. Isavuconazole, a novel triazole antifungal agent, has demonstrated promising activity against Aspergillus spp. However, data on the penetration of isavuconazole into the CNS and ELF and intracellular accumulation remain limited. Materials and methods We conducted a prospective
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Multiomics plasma effects of switching from triple antiretroviral regimens to dolutegravir plus lamivudine J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-03-28 Elisa de Lazzari, Eugenia B Negredo, Pere Domingo, Juan M Tiraboschi, Esteve Ribera, Nadia Abdulghani, Verònica Alba, Salvador Fernández-Arroyo, Consuelo Viladés, Joaquim Peraire, Jose M Gatell, Jose L Blanco, Francesc Vidal, Anna Rull, Esteban Martinez
Introduction The DOLAM trial revealed that switching from triple antiretroviral therapy (three-drug regimen; 3DR) to dolutegravir plus lamivudine (two-drug regimen; 2DR) was virologically non-inferior to continuing 3DR after 48 weeks of follow-up. Weight increased with 2DR relative to 3DR but it did not impact on metabolic parameters. Methods Multiomics plasma profile was performed to gain further
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Ceftazidime/avibactam serum concentration in patients on ECMO J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-03-28 Anaïs Curtiaud, Matthieu Petit, Juliette Chommeloux, Marc Pineton de Chambrun, Guillaume Hekimian, Matthieu Schmidt, Alain Combes, Charles-Edouard Luyt
Objectives The use of extracorporeal membrane oxygenation (ECMO) may alter blood levels of several drugs, including antibiotics, leading to under dosing of these drugs and thus to potential treatment failure. No data exist on pharmacokinetics of new antimicrobial, in particular ceftazidime/avibactam. We therefore perform this study to evaluate ceftazidime/avibactam blood levels in ECMO patients and
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Aminoglycoside resistance genes in early members of the Acinetobacter baumannii ST78A (SMAL, Italian clone) reside in an IS26-bounded island in the chromosome J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-03-26 Christopher J Harmer, Sarah M Cahill, Johanna J Kenyon, Ruth M Hall
Background The Acinetobacter baumannii isolate called SMAL, previously used to determine the structures of capsular polysaccharide and lipooligosaccharide, was recovered in Pavia, Italy in 2002 among the collection of aminoglycoside-resistant isolates designated as SMAL type. This type was later called the Italian clone, then ST78. ST78 isolates are now widely distributed. Objectives To establish the
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Rilpivirine and cabotegravir trough concentrations in people with HIV on long-term treatment with long-acting injectable antiretrovirals J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-03-26 Maria Vittoria Cossu, Dario Cattaneo, Davide Moschese, Andrea Giacomelli, Sara Soloperto, Antonio D’Avolio, Spinello Antinori, Andrea Gori, Giuliano Rizzardini, Cristina Gervasoni
Objective Large inter-individual variability in the pharmacokinetics of rilpivirine and cabotegravir has been reported in the first weeks after starting long-acting injectable (LAI) therapy. Here, we assessed the distribution of rilpivirine and cabotegravir trough concentrations in people with HIV (PWH) on long-term LAI treatment. Methods Adult PWH treated with LAI for at least 32 weeks with an assessment
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Synergistic effects of ceftazidime/avibactam combined with meropenem in a murine model of infection with KPC-producing Klebsiella pneumoniae J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-03-25 Mei Zheng, Fu-Hao Li, Juan Liu, Wen-Jie Li, Ruo-Xi Yin, Da-Tong Cai, Diego O Andrey, Si-Lin Zheng, Ana C Gales, Wan-Jiang Zhang, Jian Sun, Xiao-Ping Liao, Yang Yu
Objectives The emergence and expansion of carbapenem-resistant Klebsiella pneumoniae infections is a concern due to the lack of ‘first-line’ antibiotic treatment options. The ceftazidime/avibactam is an important clinical treatment for carbapenem-resistant K. pneumoniae infections but there is an increasing number of cases of treatment failure and drug resistance. Therefore, a potential solution is
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Imipenem/relebactam pharmacokinetics in critically ill patients supported on extracorporeal membrane oxygenation J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-03-22 Andrew J Fratoni, Abigail K Kois, Jason A Gluck, David P Nicolau, Joseph L Kuti
Background Extracorporeal membrane oxygenation (ECMO) is a life-saving modality but has the potential to alter the pharmacokinetics (PK) of antimicrobials. Imipenem/cilastatin/relebactam is an antibiotic with utility in treating certain multi-drug resistant Gram-negative infections. Herein, we describe the population pharmacokinetics of imipenem and relebactam in critically ill patients supported on
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Investigating the cause of increased tetracycline-resistant Neisseria gonorrhoeae in England, 2016–20 J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-03-22 Rachel Pitt-Kendall, Suzy Sun, Stephen Hughes, Rachel Merrick, Hugo Donaldson, Michael Rayment, Zdravko Ivanov, Michaela Day, Aisha Bari, Monica Rebec, Emma Callan, Hamish Mohammed, Katy Sinka, Michelle Cole, Helen Fifer
Background Antimicrobial resistance in Neisseria gonorrhoeae is a global public health concern. Tetracycline resistance (TetR) increased from 39.4% to 75.2% between 2016 and 2021 in N. gonorrhoeae isolates collected through national surveillance in England, despite the absence of use of tetracyclines for the treatment of gonorrhoea. Objectives We investigated whether there was correlation between bacterial
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A systematic review of national interventions and policies to optimize antibiotic use in healthcare settings in England J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-03-20 Rebecca Knowles, Clare Chandler, Stephen O’Neill, Mike Sharland, Nicholas Mays
Objectives To identify and assess the effectiveness of national antibiotic optimization interventions in primary and secondary care in England (2013–2022). Methods A systematic scoping review was conducted. Literature databases (Embase and Medline) were used to identify interventions and evaluations. Reports included the UK AMR Strategy (2013–2018), National Action Plan (2019–2024) and English Surveillance
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Towards optimizing cefepime/tazobactam (WCK 4282) exposure to achieve efficacy against piperacillin/tazobactam-resistant ESBL infections: dose recommendations for various renal functions, including intermittent haemodialysis, in healthy individuals J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-03-20 Anouk E Muller, Brenda C M De Winter, Birgit C P Koch
Objectives WCK 4282 is a novel combination of cefepime 2 g and tazobactam 2 g being developed for the treatment of infections caused by piperacillin/tazobactam-resistant ESBL infections. The dosing regimen for cefepime/tazobactam needs to be optimized to generate adequate exposures to treat infections caused by ESBL-producing pathogens resistant to both cefepime and piperacillin/tazobactam. Methods
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PHARE: a bioinformatics pipeline for compositional profiling of multiclonal Plasmodium falciparum infections from long-read Nanopore sequencing data J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-03-19 Salome Hosch, Philipp Wagner, Johanna Nouria Giger, Nina Dubach, Elis Saavedra, Carlo Federico Perno, Jean-Chrysostome Gody, Marilou Sonia Pagonendji, Carine Ngoagouni, Christophe Ndoua, Christian Nsanzabana, Ulrich Vickos, Claudia Daubenberger, Tobias Schindler
Background The emergence of drug-resistant clones of Plasmodium falciparum is a major public health concern, and the ability to detect and track the spread of these clones is crucial for effective malaria control and treatment. However, in endemic settings, malaria infected people often carry multiple P. falciparum clones simultaneously making it likely to miss drug-resistant clones using traditional
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In vitro activity of apramycin (EBL-1003) in combination with colistin, meropenem, minocycline or sulbactam against XDR/PDR Acinetobacter baumannii isolates from Greece J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-03-19 I Galani, M Souli, D Katsala, I Karaiskos, H Giamarellou, A Antoniadou
Objectives To evaluate the in vitro activity of the combination of apramycin with colistin, meropenem, minocycline or sulbactam, against some well-characterized XDR Acinetobacter baumannii clinical isolates from Greece, to understand how apramycin can be best incorporated into clinical practice and optimize effectiveness. Methods In vitro interactions of apramycin (0.5×, 1× and 2× the MIC value) with
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Impact of the phenotypic expression of temocillin resistance in Escherichia coli on temocillin efficacy in a murine peritonitis model J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-03-19 Elise Mallart, François Guerin, Ariane Amoura, Matthieu Le Scouarnec, Antoine Hamon, Imane El Meouche, Françoise Chau, Agnès Lefort, Bruno Fantin, Vincent Cattoir, Victoire de Lastours
Background Temocillin is a narrow spectrum β-lactam active against MDR Enterobacterales. Mechanisms of acquired resistance to temocillin are poorly understood. We analysed resistance mechanisms in clinical isolates of Escherichia coli and evaluated their impact on temocillin efficacy in vitro and in a murine peritonitis model. Methods Two sets of isogenic clinical E. coli strains were studied: a susceptible
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Development of an ultrafast PCR to detect clinically relevant acquired vancomycin-resistance genes from cultured enterococci J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-03-19 Axel Philip, Saoussen Oueslati, Francesco Villa, Christophe Pannetier, Vincent Cattoir, Jacques Duranteau, Samy Figueiredo, Thierry Naas
Background VRE are increasingly described worldwide. Screening of hospitalized patients at risk for VRE carriage is mandatory to control their dissemination. Here, we have developed the Bfast [VRE Panel] PCR kit, a rapid and reliable quantitative PCR assay for detection of vanA, vanB, vanD and vanM genes, from solid and liquid cultures adaptable to classical and ultrafast real-time PCR platforms. Methods
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Novel tetracycline resistance gene tet(65) located on a multi-resistance Corynebacterium plasmid J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-03-18 Sonja Kittl, Isabelle Brodard, Milena Tresch, Vincent Perreten
Background Corynebacterium (C.) sp. 22KM0430 related to C. oculi and isolated from a dog exhibited resistance to tetracycline, and its WGS analysis revealed a putative resistance gene on a 35 562-bp plasmid also harbouring the MLSB resistance gene erm(X). Objectives To characterize the novel tetracycline resistance gene tet(65) and demonstrate its functionality by expression in C. glutamicum and Escherichia
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Pharmacodynamic evaluation of ceftriaxone single-dose therapy (0.125–1 g) to eradicate ceftriaxone-susceptible and ceftriaxone-resistant Neisseria gonorrhoeae strains in a hollow fibre infection model for gonorrhoea J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-03-18 Magnus Unemo, Daniel Golparian, Joakim Oxelbark, Fabian Y S Kong, David Brown, Arnold Louie, George Drusano, Susanne Jacobsson
Background Antimicrobial resistance in Neisseria gonorrhoeae is threatening the gonorrhoea treatment, and optimizations of the current ceftriaxone-treatment regimens are crucial. We evaluated the pharmacodynamics of ceftriaxone single-dose therapy (0.125–1 g) against ceftriaxone-susceptible and ceftriaxone-resistant gonococcal strains, based on EUCAST ceftriaxone-resistance breakpoint (MIC > 0.125
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Cost-effectiveness of point-of-care diagnostics for AMR: a systematic review J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-03-18 Abraham Tolley, Akhil Bansal, Rebecca Murerwa, James Howard Dicks
Background Antimicrobial resistance (AMR) is a major threat to global health. By 2050, it is forecast that AMR will cause 10 million deaths and cost 100 trillion USD annually. Point-of-care tests (POCTs) may represent a cost-effective approach to reduce AMR. Objectives We systematically reviewed which POCTs addressing AMR have undergone economic evaluation in primary and secondary healthcare globally
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Corynebacterium diphtheriae and Corynebacterium ulcerans: development of EUCAST methods and generation of data on which to determine breakpoints J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-03-18 Anja Berger, Edgar Badell, Jenny Åhman, Erika Matuschek, Nora Zidane, Gunnar Kahlmeter, Andreas Sing, Sylvain Brisse
Background Evidence-based clinical susceptibility breakpoints have been lacking for antimicrobial agents used for diphtheria. Objectives We aimed to evaluate broth microdilution and disc diffusion methods and create a dataset of MIC values and inhibition zone diameters (ZDs) from which breakpoints could be determined. Methods We included 400 recent clinical isolates equally distributed by species (Corynebacterium
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VIM-type metallo-β-lactamase (MBL)-encoding genomic islands in Pseudomonas spp. in Poland: predominance of clc-like integrative and conjugative elements (ICEs) J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-03-15 P Urbanowicz, R Izdebski, M Biedrzycka, M Gniadkowski
Objectives To characterize VIM-type metallo-β-lactamase (MBL)-encoding genomic islands (GIs) in Pseudomonas aeruginosa and P. putida group isolates from Polish hospitals from 2001–2015/16. Methods Twelve P. aeruginosa and 20 P. putida group isolates producing VIM-like MBLs were selected from a large collection of these based on epidemiological and typing data. The organisms represented all major epidemic
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Assessment of risk-adjusted mortality ratio (RAMR) in bloodstream infections using all-patient refined diagnosis-related groups (APR-DRGs) J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-03-13 Guillermo Maestro De La Calle, Jorge Vélez, Javier Mateo Flores, Noelia García Barrio, María Ángeles Orellana, Víctor Quirós-González, Carlos Lumbreras Bermejo, José Luis Bernal
Objectives To calculate a risk-adjusted mortality ratio (RAMR) for bloodstream infections (BSIs) using all-patient refined diagnosis-related groups (APR-DRGs) and compare it with the crude mortality rate (CMR). Methods Retrospective observational study of prevalent BSI at our institution from January 2019 to December 2022. In-hospital mortality was adjusted with a binary logistic regression model adjusting
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Pharmacokinetics and pharmacodynamics of high-dose isoniazid for the treatment of rifampicin- or multidrug-resistant tuberculosis in Indonesia J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-03-09 Vycke Yunivita, Fajri Gafar, Prayudi Santoso, Lidya Chaidir, Arto Y Soeroto, Triana N Meirina, Lindsey Te Brake, Dick Menzies, Rob E Aarnoutse, Rovina Ruslami
Background Pharmacokinetic data on high-dose isoniazid for the treatment of rifampicin-/multidrug-resistant tuberculosis (RR/MDR-TB) are limited. We aimed to describe the pharmacokinetics of high-dose isoniazid, estimate exposure target attainment, identify predictors of exposures, and explore exposure–response relationships in RR/MDR-TB patients. Methods We performed an observational pharmacokinetic
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What are the optimal pharmacokinetic/pharmacodynamic targets for β-lactamase inhibitors? A systematic review J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-03-09 Getnet M Assefa, Jason A Roberts, Solomon A Mohammed, Fekade B Sime
Background Pharmacokinetic/pharmacodynamic (PK/PD) indices are widely used for the selection of optimum antibiotic doses. For β-lactam antibiotics, fT>MIC, best relates antibiotic exposure to efficacy and is widely used to guide the dosing of β-lactam/β-lactamase inhibitor (BLI) combinations, often without considering any PK/PD exposure requirements for BLIs. Objectives This systematic review aimed
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Not surprising: a rebound in antibacterial consumption in Europe, with Cyprus and Greece on the podium J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-03-05 Nikolaos Spernovasilis, Constantinos Tsioutis
Recent European-wide data place Cyprus and Greece in the highest positions of total antimicrobial consumption. While this level of consumption might be partly attributed to the high rates of infections due to MDR bacteria in these countries, several other reasons should be sought to help apply local measures, to decrease inappropriate and excess antimicrobial use. The present viewpoint aims to provide
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Genomics to detect transmission of livestock-associated methicillin-resistant Staphylococcus aureus from UK pigs in abattoirs during slaughter J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-03-05 Muna F Anjum, Nicholas Duggett, Ewart Sheldon, Meenaxi Sharma, Richard P Smith, Chris J Teale
Background Livestock-associated MRSA (LA-MRSA) transmission/cross-contamination can occur at abattoir through colonized pigs, increasing occupational hazards and health concerns for workers. To assess this risk we used genomics to identify LA-MRSA lineages present in batches of pigs sent to slaughter and distribution of clones. Methods WGS was performed on 85 LA-MRSA previously isolated from six abattoirs
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Development and validation of an UPLC–MS/MS assay for the simultaneous quantification of seven commonly used antibiotics in human plasma and its application in therapeutic drug monitoring J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-02-28 Xin Meng Mekking, Kirsten Velthoven-Graafland, Marga J A Teulen, Roger J M Brüggemann, Lindsey H M te Brake, Nynke G L Jager
Objective To develop and validate an UPLC–MS/MS assay for simultaneous determination of the total concentration of ceftazidime, ciprofloxacin, flucloxacillin, piperacillin, tazobactam, sulfamethoxazole, N-acetyl sulfamethoxazole and trimethoprim, and the protein-unbound concentration of flucloxacillin, in human plasma to be used for research and clinical practice. Methods Sample pretreatment included
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Temocillin for febrile urinary tract infections caused by ESBL-producing Enterobacteriaceae in children: a monocentric exposed/non-exposed study J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-02-27 Jules Bayart, Juliette Drouet, Matthieu Peycelon, Patricia Mariani, Enora Le Roux, Maya Husain, Julien Agar, Stéphane Bonacorsi, Marion Caseris
Objectives To compare the efficacy of temocillin with standard of care (SOC) for treatment of ESBL-producing Enterobacteriaceae (ESBL-E) febrile urinary tract infection (ESBL-E FUTI) in children. Methods A monocentric retrospective study of children hospitalized with confirmed ESBL-E FUTI from January 2015 to May 2022 was conducted, comparing clinical cure and a 3 month relapse between two groups of
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Unravelling the complex interplay between antibiotic consumption and adaptive changes in methicillin-resistant Staphylococcus aureus J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-02-27 Sebastiaan J van Hal, Slade O Jensen, Stephen Y C Tong, Stephen Bentley, Matthew T Holden
Objectives This study aims to elucidate the genomic dynamics driving the emergence of antimicrobial resistance (AMR), with a specific focus on the interplay between AMR and antimicrobial usage. Methods We conducted a comprehensive analysis using a ST239 methicillin-resistant Staphylococcus aureus (MRSA) dataset over a continuous 12-year period from a single hospital. Genomic analyses were performed
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Repurposing cinacalcet suppresses multidrug-resistant Staphylococcus aureus by disruption of cell membrane and inhibits biofilm by targeting IcaR J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-02-27 Zu-Ye Fang, Zi-Yuan Zhang, Yun-Dan Zheng, Dan Lei, Jianpeng Zhuang, Nan Li, Qing-Yu He, Xuesong Sun
Background MDR Staphylococcus aureus infections, along with the severity of biofilm-associated infections, continue to threaten human health to a great extent. It necessitates the urgent development of novel antimicrobial and antibiofilm agents. Objectives To reveal the mechanism and target of cinacalcet as an antibacterial and antimicrobial agent for S. aureus. Methods Screening of non-antibiotic
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Antimicrobial susceptibility profile of clinically relevant Bacteroides, Phocaeicola, Parabacteroides and Prevotella species, isolated by eight laboratories in the Netherlands J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-02-23 K E Boiten, D W Notermans, R J Rentenaar, J van Prehn, L G M Bode, I Maat, W van der Zwet, A Jansz, T J H Siebers, J W A Rossen, S C de Greeff, A P A Hendrickx, E J Kuijper, A C M Veloo
Objectives Recently, reports on antimicrobial-resistant Bacteroides and Prevotella isolates have increased in the Netherlands. This urged the need for a surveillance study on the antimicrobial susceptibility profile of Bacteroides, Phocaeicola, Parabacteroides and Prevotella isolates consecutively isolated from human clinical specimens at eight different Dutch laboratories. Methods Each laboratory
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The relationship between viral clearance rates and disease progression in early symptomatic COVID-19: a systematic review and meta-regression analysis J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-02-22 Shivani Singh, Simon Boyd, William H K Schilling, James A Watson, Mavuto Mukaka, Nicholas J White
Background Effective antiviral drugs accelerate viral clearance in acute COVID-19 infections; the relationship between accelerating viral clearance and reducing severe clinical outcomes is unclear. Methods A systematic review was conducted of randomized controlled trials (RCTs) of antiviral therapies in early symptomatic COVID-19, where viral clearance data were available. Treatment benefit was defined
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Why do we use 100 mg of clofazimine in TB and NTM treatment? J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-02-22 Jakko van Ingen
Current tuberculosis and non-tuberculous mycobacterial disease guidelines recommend the use of clofazimine in a 100 mg once-daily dose. The rationale behind this exact dose is not provided. I performed a literature review to determine the reasoning behind the current dosing regimen. The current 100 mg once-daily dose of clofazimine stems from a deliberate attempt to find the minimum effective daily
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Identification and evolution of ICE-PmuST394: a novel integrative conjugative element in Pasteurella multocida ST394 J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-02-21 Piklu Roy Chowdhury, Tamara Alhamami, Henrietta Venter, Tania Veltman, Mandi Carr, Joanne Mollinger, Darren J Trott, Steven P Djordjevic
Background The emergence of macrolide and tetracycline resistance within Pasteurella multocida isolated from feedlot cattle and the dominance of ST394 in Australia was reported recently. Objectives To establish the genetic context of the resistance genes in P. multocida 17BRD-035, the ST394 reference genome, and conduct a molecular risk assessment of their ability to disperse laterally. Methods A bioinformatic
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COVID-19 hospitalization risk after outpatient nirmatrelvir/ritonavir use, January to August 2022, North Carolina J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-02-21 Heather I Henderson, David A Wohl, William A Fischer, Luther A Bartelt, David van Duin, Deana M Agil, Lindsay E Browne, Kuo-Ping Li, Amanda Moy, Joseph J Eron, Sonia Napravnik
Background In the USA, nirmatrelvir/ritonavir is authorized for the treatment of mild-to-moderate COVID-19 in patients at least 12 years of age, at high risk for progression to severe COVID-19. Objectives To estimate the impact of outpatient nirmatrelvir/ritonavir on COVID-19 hospitalization risk in a US healthcare system. Methods We conducted a cohort study using electronic health records among outpatients
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Lower blood levels of isavuconazole in critically ill patients compared with other populations: possible need for therapeutic drug monitoring J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-02-17 Malgorzata Mikulska, Monica Melchio, Alessio Signori, Nadir Ullah, Franca Miletich, Chiara Sepulcri, Alessandro Limongelli, Daniele Roberto Giacobbe, Elisa Balletto, Chiara Russo, Laura Magnasco, Antonio Vena, Carmen Di Grazia, Anna Maria Raiola, Federica Portunato, Chiara Dentone, Denise Battaglini, Lorenzo Ball, Chiara Robba, Emanuele Angelucci, Iole Brunetti, Matteo Bassetti
Background Isavuconazole is first-line treatment of invasive aspergillosis. Therapeutic drug monitoring (TDM) is deemed not necessary, since most patients reached therapeutic levels (>1 mg/L) in large studies. Low levels were reported in some critically ill patients admitted to the ICU. The aim was to compare isavuconazole levels between critically ill and non-critically ill patients. Materials and
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Phenotypic and genetic characterization of antimicrobial resistance in Salmonella enterica serovar Choleraesuis isolates from humans and animals in Spain from 2006 to 2021 J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-02-17 Camille Jacqueline, Clara Samper-Cativiela, Sara Monzon Fernandez, María Ugarte-Ruiz, Isabel Cuesta de la Plaza, Julio Alvarez, Silvia Herrera-Leon
Objectives While an increase in the levels of MDR in Salmonella enterica sevorar Choleraesuis has been reported in Europe, little is known about the situation in Spain. Therefore, we first aimed to assess the phenotypic resistance profile and to determine the presence of genetic determinants of resistance of S. Choleraesuis isolates collected in animal and human. Our second objective was to identify
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The pharmacokinetics/pharmacodynamics of ceftazidime/avibactam for central nervous system infections caused by carbapenem-resistant Gram-negatives: a prospective study J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-02-17 Ying Xu, Xuemei Luo, Binbin Yuan, Pei Liang, Ning Liu, Danjiang Dong, Weihong Ge, Qin Gu
Objectives To describe the pharmacokinetics/pharmacodynamics (PK/PD) of ceftazidime/avibactam in critically ill patients with CNS infections. Methods A prospective study of critically ill patients with CNS infections who were treated with ceftazidime/avibactam and the steady-state concentration (Css) of ceftazidime/avibactam in serum and/or CSF was conducted between August 2020 and May 2023. The relationship
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Global spread of the linezolid-resistant Enterococcus faecalis ST476 clonal lineage carrying optrA J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-02-17 Andrea Brenciani, Marzia Cinthi, Sonia Nina Coccitto, Francesca Romana Massacci, Elisa Albini, Lucilla Cucco, Marta Paniccià, Ana R Freitas, Stefan Schwarz, Eleonora Giovanetti, Chiara Francesca Magistrali
Objectives To investigate the global distribution of an optrA-harbouring linezolid-resistant Enterococcus faecalis ST476 clonal lineage. Methods Comprehensive searches of the NCBI database were performed to identify published peer-reviewed articles and genomes of E. faecalis ST476. Each genome was analysed for resistome, virulome, OptrA variant and optrA genetic contexts. A phylogenetic comparison
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Identification of a CTX-M-255 β-lactamase containing a G239S substitution selectively conferring resistance to penicillin/β-lactamase inhibitor combinations J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-02-17 Minna Rud Andreasen, Tim Rick, Nicolai Riff Alexandersen, Katrine Hartung Hansen, Martin Schou Pedersen, Jakob K Warweitzky, Carolina Mastella Botelho, Susanne Häussler, Lotte Jelsbak, Kristian Schønning
Objectives An Escherichia coli isolate, WGS1363, showed resistance to piperacillin/tazobactam but susceptibility to cephalosporins and contained a previously unrecognized β-lactamase, CTX-M-255, as the only acquired β-lactamase. CTX-M-255 was identical to CTX-M-27 except for a G239S substitution. Here, we characterize the hydrolytic spectrum of CTX-M-255 and a previously reported β-lactamase, CTX-M-178
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Differences in antibiotic use between COPD and non-COPD residents based on the health information system J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-02-10 Xin Yin, Yonggen Jiang, Yiling Wu, Xuyan Su, Shanshan Hou, Jing Li, Wei Luo, Minjun Yu, Jinxin Zang, Wei Wang, Qi Zhao, Yinfeng Zhu, Genming Zhao, Qingwu Jiang, Na Wang
Objectives To compare the differences in antibiotic use between COPD and non-COPD residents, and to explore the effect of COPD on antibiotic use. Methods Participants aged 40 years old or over from the Songjiang Adult Cohort were included. Information on prescription and baseline survey was collected based on the health information system. A logit-negative binomial Hurdle model was used to explore
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Do dietary interventions exert clinically important effects on the bioavailability of β-lactam antibiotics? A systematic review with meta-analyses J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-02-09 Agnieszka Wiesner, Paweł Zagrodzki, Paweł Paśko
Background Managing drug–food interactions may help to achieve the optimal action and safety profile of β-lactam antibiotics. Methods We conducted a systematic review with meta-analyses in adherence to PRISMA guidelines for 32 β-lactams. We included 166 studies assessing the impact of food, beverages, antacids or mineral supplements on the pharmacokinetic (PK) parameters or PK/pharmacodynamic (PK/PD)
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Detection of antimicrobial resistance in <5 h in Neisseria gonorrhoeae isolates using flow cytometry—proof of concept for seven clinically relevant antimicrobials J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-02-09 Sofia Somajo, Frida Nilsson, Oskar Ekelund, Magnus Unemo
Introduction Antimicrobial resistance in Neisseria gonorrhoeae compromises gonorrhoea treatment and rapid antimicrobial susceptibility testing (AST) would be valuable. We have developed a rapid and accurate flow cytometry method (FCM) for AST of gonococci. Methods The 2016 WHO gonococcal reference strains, and WHO Q, R and S (n = 17) were tested against seven clinically relevant antibiotics (ceftriaxone
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Novel sequence type of carbapenem-resistant Acinetobacter pittii ST1451 with enhanced virulence isolated from septicaemic neonates in India J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-02-09 Subhasree Roy, Daichi Morita, Sushmita Bhattacharya, Shanta Dutta, Sulagna Basu
Background The clinical relevance of Acinetobacter pittii is increasing, but reports of this organism causing neonatal sepsis are rare. Objectives To understand the mechanisms of resistance and virulence of A. pittii isolated from neonatal blood belonging to a novel sequence type. Materials and methods Antibiotic susceptibility, MLST, WGS, phylogenomic comparison with a global collection of carbapenemase-harbouring
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Carriage of methicillin-resistant Staphylococcus aureus in children <6 years old: a retrospective follow-up study of the natural course and effectiveness of decolonization treatment J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-02-09 Thomas Helbo, Jonas Bredtoft Boel, Mette Damkjær Bartels, Magnus Glindvad Ahlström, Barbara Juliane Holzknecht, Helle Brander Eriksen
Background Decolonization treatment of MRSA carriers is recommended in Denmark, except in households with MRSA-positive children <2 years old (wait-and-see approach). Objectives To investigate a wait-and-see approach in children 2–5 years old, and the effect of decolonization treatment of MRSA carriage in all children <6 years old. Patients and methods In this retrospective follow-up study, we included
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Effect of different strategies for excluding duplicate cultures on the correlation between hospital resistance rates and antibiotic consumption J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-02-09 Tomás Reyes Barros, Waldo Gutiérrez Torres, Patricia García Cañete, Jaime Cerda Lorca
Introduction Studies may underestimate the impact of antibiotics on bacterial resistance when correlating hospital antibiotic use with resistance rates (RRs) that exclude duplicate cultures as duplicates usually include more resistant isolates. Comparing correlations between antibiotic consumption and RRs resulting from different strategies for excluding duplicates could help explore how their exclusion
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Differential in vitro susceptibility to ampicillin/ceftriaxone combination therapy among Enterococcus faecalis infective endocarditis clinical isolates J. Antimicrob. Chemother. (IF 5.2) Pub Date : 2024-02-09 Kevin J Westbrook, Gayatri Shankar Chilambi, Madison E Stellfox, Hayley R Nordstrom, Yanhong Li, Alina Iovleva, Niyati H Shah, Chelsea E Jones, Ellen G Kline, Kevin M Squires, William R Miller, Truc T Tran, Cesar A Arias, Yohei Doi, Ryan K Shields, Daria Van Tyne
Objectives To investigate the genomic diversity and β-lactam susceptibilities of Enterococcus faecalis collected from patients with infective endocarditis (IE). Methods We collected 60 contemporary E. faecalis isolates from definite or probable IE cases identified between 2018 and 2021 at the University of Pittsburgh Medical Center. We used whole-genome sequencing to study bacterial genomic diversity