International Journal of Antimicrobial Agents

BACKGROUND: The aminoglycoside apramycin has been proposed as a drug candidate for the treatment of critical Gram-negative systemic infections. However, its potential in the treatment of drug-resistant bloodstream infections (BSIs) has yet to be assessed. METHODS: The resistance gene annotations of 40 888 blood culture isolates were analyzed. In vitro profiling of apramycin comprised cell-free translation assays, broth microdilution, and frequency of resistance determination...

OBJECTIVE: Timing and dosing of antimicrobial therapy is key in the treatment of pneumonia in critically ill patients. It is uncertain whether presence of lung inflammation and injury affects tissue penetration of intravenously administered antimicrobial drugs. We determined the effects of lung inflammation and injury on tissue penetration of two commonly used antimicrobial drugs for pneumonia in an established model of unilateral lung injury. METHODS: In 13 healthy pigs, unilateral lung injury was induced in the left lung through cyclic rinsing - the right healthy lung served as control...

No abstract text is available yet for this article.

OBJECTIVES: Colistin-induced nephrotoxicity prolongs hospitalization and increases mortality. The study aimed to construct machine learning models to predict colistin-induced nephrotoxicity in patients with multidrug-resistant gram-negative infection. METHODS: Patients receiving colistin from three hospitals in the Clinical Research Database were included. Data were divided into a derivation cohort (2011∼2017) and a temporal validation cohort (2018∼2020)...

Optimizing blood culture processing is important to ensure bloodstream infections are accurately diagnosed while minimizing adverse events caused by antibiotic abuse. We evaluated the impact of optimized blood culture processes on antibiotic use, clinical outcomes and economics in intensive care unit (ICU) patients with positive blood cultures. From March 2020 to October 2021, our microbiology laboratory implemented a series of improvement measures, including the clinical utility of Fastidious Antimicrobial Neutralization (FAN® PLUS) bottles for the BacT/Alert Virtuo blood culture system, optimization of bottles reception, graded reports and an upgraded Laboratory Information System...

No abstract text is available yet for this article.

OBJECTIVES: This study aimed to discover novel antifungals targeting Candida albicans glyceraldehyde-3-phosphate dehydrogenase (CaGAPDH), have an insight into inhibitory mode, and provide evidence supporting CaGAPDH as a target for new antifungals. METHODS: Virtual screening was utilized to discover inhibitors of CaGAPDH. The inhibitory effect on cellular GAPDH was evaluated by determining the levels of ATP, NAD, NADH, etc., as well as examining GAPDH mRNA and protein expression...

No abstract text is available yet for this article.

Vancomycin is frequently used as a last line defence against infections due to multidrug resistant Staphylococcus aureus. A recent finding described the acquisition of vancomycin-resistant S. aureus (VRSA) strains by the integration of an enterococcal plasmid containing vanA operon into the chromosome of S. aureus via homologous recombination (HR) involving a specific integration site called locus L2. To characterise all mechanisms of acquisition of vanA, we analysed the 15,706 genomes of S. aureus looking for vanA and described its genetic environment...

Stenotrophomonas spp. intrinsically resistant to many β-lactam antibiotics are found throughout the environment. CESS-1 identified in Stenotrophomonas sp. KCTC 12332 is an uncharacterized class A β-lactamase. Here, CESS-1 was revealed to display hydrolytic activities toward penicillins (penicillin G and ampicillin) and cephalosporins (cephalexin, cefaclor, and cefotaxime), while its activity toward carbapenems (imipenem and meropenem) was negligible. Although cefaclor, cephalexin, and ampicillin have similar structures with identical R1 side chains, the catalytic parameters of CESS-1 toward the three β-lactam antibiotics were distinct...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

OBJECTIVE: Multiple strategies have been utilized to reduce the incidence of HIV, including PrEP and rapid antiretroviral therapy initiation. The study objectives were to evaluate the efficacy, safety, satisfaction, treatment adherence, and system retention obtained with rapid initiation of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in naïve patients. METHODS: This phase IV, multicenter, open-label, single-arm, 48-week clinical trial enrolled patients between January 2020 and June 2022...

BACKGROUND: Oritavancin and dalbavancin are long-acting lipoglycopeptide antibiotics approved for the treatment of skin and skin structure infections. Recently, they have been used for outpatient antimicrobial therapy for complicated infections. No head-to-head studies exist for this purpose. OBJECTIVE: To compare outcomes of patients treated with multiple doses of oritavancin or dalbavancin for complicated infections. PATIENTS AND METHODS: This was a single-center, retrospective cohort study evaluating adult patients who received 2 or more doses of lipoglycopeptides for complicated infections from February 2019 through December 2022...

Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses immense threats to the health of infected patients worldwide, especially in children. This study reports the infection caused by CRKP in a pediatric intensive care unit (PICU) child and its drug-resistant mutation during the treatment. Twelve Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae strains were isolated from the child. Broth microdilution method, plasmid transformation assay, and whole genome sequencing (WGS) were performed to investigate the antimicrobial susceptibility, resistance mechanisms, and genetic structural features of CRKPs...

The demand for antibiofilm molecules has increased for several years due to their potential to fight biofilm-associated infections such as those including the interkingdom Staphylococcus aureus - Candida albicans occurring in clinical settings worldwide. Recently, we have identified a pentacyclic triterpenoid compound identified as betulinic acid (BA) from invasive macrophytes with interesting antibiofilm properties. Our study aimed at providing insights into the mechanism of action of BA against the clinically relevant bi-species S...

Hypermutable Pseudomonas aeruginosa strains are highly prevalent in chronic lung infections of patients with cystic fibrosis (CF). Acute exacerbations of these infections have limited treatment options. This study aimed to investigate inhaled aztreonam and tobramycin against clinical hypermutable P. aeruginosa strains using the CDC dynamic in vitro biofilm reactor (CBR), mechanism-based mathematical modeling (MBM) and genomic studies. Two CF multidrug-resistant strains were investigated in a 168h CBR (n=2 biological replicates)...

AIMS: Fosfomycin has regained attention for treating infections caused by methicillin-resistant Staphylococcus aureus and multidrug-resistant coagulase-negative staphylococci. In this research, our objective was to investigate the mechanisms underlying fosfomycin resistance in Staphylococcus capitis. METHODS: The minimum inhibitory concentrations (MICs) of fosfomycin were assessed in 109 clinical S. capitis isolates by the agar dilution method. By cloning the fos-like genes into the shuttle vector, pTSSCm-Pcap, and observing the change in fosfomycin MICs, the gene function was verified...

BACKGROUND: Resistance of Helicobacter pylori to many antibiotics, which lowers the efficacy of eradication therapy, is increasingly prevalent. High-dose proton pump inhibitor (PPI)-amoxicillin dual therapy (HDDT) has been used for H. pylori eradication for years, and resistance to amoxicillin is relatively rare. Although many studies have compared the eradication rate of HDDT with that of guideline therapies, the reported efficacy of HDDT varies greatly and is inconsistent. AIMS: This study investigated the eradication rate and adverse effects of HDDT compared with the guidelines at the time of the study...

Cryptococcus neoformans is responsible for over 100,000 deaths annually, and the treatment of this fungal disease is expensive and not consistently effective. Unveiling new therapeutic avenues is crucial. Previous studies have suggested that the anthelmintic drug fenbendazole is an affordable and non-toxic candidate to combat cryptococcosis. However, its mechanism of anticryptococcal activity has been only superficially investigated. In this study, we examined the global cellular response of C. neoformans to fenbendazole using a proteomic approach (data are available via ProteomeXchange with identifier PXD047041)...