Journal of Antimicrobial Chemotherapy

BACKGROUND: Vancomycin-resistant enterococci (VRE) represent a public health threat due to the few available treatments. Such alarm has triggered worldwide initiatives to develop effective antimicrobial compounds and novel delivery and therapeutic strategies. vanA operon is responsible for most cases of acquired vancomycin resistance in enterococci. OBJECTIVES: Development of a transcription factor decoy (TFD) system as a vanA gene transcription-inhibitor. METHODS: Vancomycin MIC was determined in the presence of TFD-lipoplexes...

OBJECTIVES: To describe the population pharmacokinetics of cefazolin in infected hospitalized patients requiring intermittent haemodialysis (IHD). METHODS: This prospective population pharmacokinetic study was conducted in IHD patients prescribed cefazolin 2 g three times weekly. Plasma samples were collected at prespecified timepoints and assayed for total and unbound concentrations using validated LC. Pharmacokinetic modelling and dosing simulations were performed using Pmetrics®...

BACKGROUND: Effective management of drug-food interactions is crucial for enhancing antibiotics' efficacy/safety. Adhering to PRISMA guidelines, we conducted a systematic review to assess the impact of dietary interventions on the bioavailability of 15 macrolides and 10 tetracyclines. METHODS: We included studies examining the influence of food, beverages, antacids, and mineral supplements on the pharmacokinetic parameters of orally administered macrolides and tetracyclines...

BACKGROUND: Procalcitonin (PCT) is a blood marker used to help diagnose bacterial infections and guide antibiotic treatment. PCT testing was widely used/adopted during the COVID-19 pandemic in the UK. OBJECTIVES: Primary: to measure the difference in length of early (during first 7 days) antibiotic prescribing between patients with COVID-19 who did/did not have baseline PCT testing during the first wave of the pandemic. Secondary: to measure differences in length of hospital/ICU stay, mortality, total days of antibiotic prescribing and resistant bacterial infections between these groups...

BACKGROUND: There are limited treatment options for prosthetic joint infections (PJI) due to multidrug-resistant Staphylococcus epidermidis (MDRSE). Fosfomycin (FOF) has gained attention as a potential therapy, but there is a paucity of information on the phenotypic and genotypic susceptibility amongst S. epidermidis, including MDRSE. OBJECTIVES: To investigate phenotypical and genotypical susceptibility to FOF in S. epidermidis isolates prospectively collected from PJIs in Sweden...

BACKGROUND: The antiviral efficacy of Evusheld (AZD7442) in patients hospitalized for SARS-CoV-2 is unknown. METHODS: We analysed the evolution of both the nasopharyngeal viral load and the serum neutralization activity against the variant of infection in 199 hospitalized patients (109 treated with Evusheld, 90 treated with placebo) infected with the SARS-CoV-2 virus and included in the randomized, double-blind, trial DisCoVeRy (NCT04315948). Using a mechanistic mathematical model, we reconstructed the trajectories of viral kinetics and how they are modulated by the increase in serum neutralization activity during Evusheld treatment...

BACKGROUND: The CDC reported a 35% increase in hospital-onset (HO) carbapenem-resistant Enterobacterales (CRE) infections during the COVID-19 pandemic. We evaluated patient outcomes following HO and community-onset (CO) CRE bloodstream infections (BSI). METHODS: Patients prospectively enrolled in CRACKLE-2 from 56 hospitals in 10 countries between 30 April 2016 and 30 November 2019 with a CRE BSI were eligible. Infections were defined as CO or HO by CDC guidelines, and clinical characteristics and outcomes were compared...

OBJECTIVES: Bacterial persistence is a significant cause of the intractability of chronic and relapsing infections. Despite its importance, many of the underlying mechanisms are still not well understood. METHODS: Antibiotic-tolerant mutants of Burkholderia thailandensis were isolated through exposure to lethal doses of AMP or MEM, followed by whole-genome sequencing to identify mutations. Subsequently, these mutants underwent comprehensive characterization via killing curves, growth curves, and persistence-fraction plots...

BACKGROUND: Despite improvements in treatment and oral pre-exposure prophylaxis (PrEP) access, 1.3 million people acquired HIV in 2022. Six-monthly lenacapavir PrEP could benefit tens of millions of people at high risk of infection. However, prices are currently up to $44 819 per person per year (pppy). OBJECTIVES: We projected minimum lenacapavir pricing based on generic mass production and a Cost-Plus (Cost+) model. METHODS: Current active pharmaceutical ingredient (API) and key starting materials (KSMs) costs were obtained from export databases...

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The similarity of current definitions of 'cross-resistance' and 'co-resistance' continues to cause confusion both in the scientific community as well as in understanding policies and in particular when looking at resistance from a risk assessment perspective. Further, lack of harmonized definitions of these terms in the regulatory space is challenging for interpretation. The purpose of this article is to: (i) provide an overview of the ambiguity in existing terminology related to cross-resistance, co-resistance and co-selection; (ii) emphasize the challenges created by the use of poor terminology in research and scientific literature; and (iii) propose a clear set of harmonized definitions that could be put into use through international regulatory agencies and institutions, such as the World Health Organization, Food and Drug Administration, European Medicines Agency, Center for Disease Control, Committee for Veterinary Medicinal Products, World Organization for Animal Health/Office International des Epizooties and the Food and Agriculture Organization of the United Nations...

BACKGROUND: Burkholderia cepacia complex (Bcc) is a collection of intrinsically drug-resistant Gram-negative bacteria that cause life-threatening disease in people with cystic fibrosis (CF). Standard antimicrobial susceptibility testing methods have poor predictive value for clinical outcomes in Bcc infections, probably due in part to differences between in vitro testing conditions and the environment in which Bcc grow in the lungs of people with CF. OBJECTIVES: To compare the activity of commonly used antibiotics under standard in vitro testing conditions with activity in conditions mimicking those found in vivo...

OBJECTIVES: To determine the association of adequate empirical combination therapy (AECT) with 30-day all-cause mortality in patients with septic shock due to Pseudomonas aeruginosa bloodstream infections (BSI). METHODS: This multicentre, retrospective cohort study analysed data from 14 public hospitals in Italy, including all consecutive adult patients admitted during 2021-2022 with septic shock due to P. aeruginosa BSI. We compared the outcomes of patients receiving AECT to those on adequate empirical monotherapy (AEMT) using Cox regression analyses...

Treatment of patients with serious infections due to resistant Gram-negative bacteria remains highly problematic and has prompted clinicians to use existing antimicrobial agents in innovative ways. One approach gaining increased therapeutic use is combination therapy with IV fosfomycin. This article reviews the preclinical pharmacokinetic/pharmacodynamic (PK/PD) infection model and clinical data surrounding the use of combination therapy with IV fosfomycin for the treatment of serious infections caused by resistant Gram-negative bacteria...

OBJECTIVES: We performed a retrospective analysis of MRSA isolates collected at the university equine clinic including clinical isolates from 2008 to 2021 and screening environmental, equine and personnel isolates from 2016. METHODS: Screening and clinical samples were cultured on Brilliance MRSA 2 and Columbia agar (Oxoid), respectively, with enrichment for environmental samples. Antimicrobial susceptibility was assessed by disc diffusion. All the isolates were characterized by spa typing...

BACKGROUND: Although a significant number of cases of Staphylococcus aureus bacteraemia (SAB) are managed at non-referral community hospitals, the impact of a bundle-of-care intervention in this setting has not yet been explored. METHODS: We performed a quasi-experimental before-after study with the implementation of a bundle of care for the management of SAB at five non-referral community hospitals and a tertiary care university hospital. Structured recommendations for the five indicators selected to assess quality of care were provided to investigators before the implementation of the bundle and monthly thereafter...

BACKGROUND: Candida albicans can form polymicrobial biofilms with other microorganisms, such as Pseudomonas aeruginosa, at infection sites. OBJECTIVES: As biofilms are highly resistant to antibiotics there is a need for new antibiofilm agents that have unique targets and modes of action. METHODS: In this study the antibiofilm effects of two quorum-sensing molecules (QSMs), farnesol and tyrosol, were investigated alone and in combination with antibiotics (aztreonam, colistin, tobramycin) and antifungals (fluconazole, amphotericin B, caspofungin), against single- and dual-species biofilms of C...

BACKGROUND: Teicoplanin has been widely used in patients with infections caused by Staphylococcus aureus, especially for critically ill patients. The pharmacokinetics (PK) of teicoplanin vary between individuals and within the same individual. We aim to establish a prediction model via a combination of machine learning and population PK (PPK) to support personalized medication decisions for critically ill patients. METHODS: A retrospective study was performed incorporating 33 variables, including PPK parameters (clearance and volume of distribution)...

BACKGROUND: Ganaplacide, also known as KAF156, is among the new antimalarial drug candidates that have successfully reached Phase III clinical trials, and is proposed in combination with lumefantrine. This combination could replace the current front-line artemisinin-based combination therapies (ACTs) in case of Plasmodium falciparum resistance to both artemisinins and partner drugs. Indeed, the African continent, where the malaria burden is the highest, is currently experiencing worrying multiple emergences and spread of artemisinin resistance, which urges for the exploration of the antiparasitic properties of KAF156 in this context...

BACKGROUND: Fosfomycin is an antibiotic extensively used to treat uncomplicated urinary tract infections in women, and it is available in different salts and formulations. The European Medicines Agency (EMA) recommends further studies to characterize the pharmacokinetics of fosfomycin calcium for oral administration and to justify its dosage recommendation. OBJECTIVES: A population pharmacokinetic model of fosfomycin calcium was developed after oral administration to healthy women...