International Journal of Antimicrobial Agents

BACKGROUND: As one of the most common pathogens leading to fatal human infection, Pseudomonas aeruginosa has been evolving complex drug resistance, posing significant challenges to the current antibiotic-dependent healthcare system. New therapeutic approaches are urgently required to treat infections caused by P. aeruginosa. METHODS: Inspired by ferroptosis, we investigated the antibacterial effects of iron compounds on P. aeruginosa via direct exposure, and developed thermal-responsive hydrogels to carry FeCl3 as a wound dressing to treat P...

Mobile genetic elements (MGEs), such as integrative and conjugative elements (ICEs), plasmids and translocatable units (TUs), are main drivers for the spread of antibiotic resistance. Although ICEs have been reported to be capable of supporting the spread of plasmids among different bacteria, its role of mobilizing the resistance plasmids and TUs has not yet fully explored. In this study, a novel TU bearing optrA, a novel non-conjugative plasmid p5303-cfrD carrying cfr(D) and a new member of the ICESa2603 family, ICESg5301, were identified in streptococci...

We have reported enhanced levels of a dipeptide, WG-am, among elite controllers, patients who spontaneously control their HIV-1 infection. The aim of the present work was to evaluate its anti-HIV-1 activity and mechanism of action. Our data suggest that WG-am binds to the CD4 binding pocket of HIV-1 gp120 and blocks its binding to the host cell receptors. Additionally, our time course assay showed that WG-am inhibited HIV-1 also at 4-6h post-infection, suggesting a second antiviral mechanism. Drug sensitivity assays under acidic wash conditions confirmed the ability of WG-am to internalize into the host cell in an HIV independent manner...

The emergence of the carbapenem-resistant Enterobacter cloacae complex (CR-ECC) has posed significant challenges to the clinical treatment of healthcare-associated infections globally. Herein, we report the clonal outbreak of NDM-1-producing Enterobacter hormaechei with the coexistence of tmexCD2-toprJ2 and mcr-9 in China. During the outbreak (January 2018-December 2021), a total of fifteen non-repetitive multidrug-resistant E. hormaechei strains were obtained from thirteen patients in a tertiary hospital...

Pseudomonas aeruginosa are ubiquitous opportunistic pathogens that combine intrinsic and acquired multidrug resistance phenotypes. Carbapenem resistance has been expanding in this species, due to different types of acquired genes. In this study, we hypothesised that the spread of carbapenem-resistance among P. aeruginosa is influenced by phylogenomic features, being distinct for different genes. To test this hypothesis, we compared the genomes of P. aeruginosa harbouring blaVIM-2 or blaNDM-1 genes. The gene blaVIM-2 was selected because, although frequent, it is almost restricted to this species and blaNDM-1 due to its wide interspecies distribution...

BACKGROUND: Linezolid is a broad-spectrum antimicrobial but toxicity limits it use. This study aimed to evaluate linezolid toxicity in a large multicentre cohort. Secondary objectives were to identify factors contributing to toxicity, including the impact of therapeutic drug monitoring (TDM). METHODS: Patients administered linezolid between January 2017 and December 2019 were reviewed retrospectively. Data was collected on patient characteristics, linezolid therapy and outcomes...

OBJECTIVES: Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is an urgent threat to public health, with the emergence of high-level resistant strains such as the FC428 clone. This study aimed to evaluate the high-resolution melting assay of N. gonorrhoeae AMR (HRM-NG-AMR) for diagnosing of N. gonorrhoeae infection and detecting extended-spectrum cephalosporins and azithromycin resistance. METHODS: To evaluate the performance of the HRM-NG-AMR assay, we employed a multicentre collection of 1488 samples, including 770 isolates and 718 urogenital swabs...

OBJECTIVE: To define the factors associated with overprescription of antibiotics by general practitioners for patients diagnosed with COVID-19 during the first wave. METHODS: Anonymized electronic prescribing records of 1370 physicians were analyzed. Diagnosis and prescriptions were retrieved. The initiation rate by physician for 2020 was compared to 2017-2019. Prescribing habits of physicians who initiated antibiotics for more than 10% of COVID-19 patients were compared to those who did not...

Klebsiella pneumoniae is one of the most common bacteria in the hospital-acquired central nervous system (CNS) infections. CNS infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) are associated with significant mortality rates and high hospital costs due to limited antibiotic treatment options. This retrospective study aimed to evaluate the clinical efficacy of ceftazidime-avibactam (CZA) for the treatment of CNS infections caused by CRKP. In total, 21 patients with hospital-acquired CNS infections caused by CRKP who received treatment of CZA ≥ 72 hours were enrolled...

The regioisomers of the anandamide-acting drug LY2183240 exhibited specific potent and competitive inhibitory activities against class C β-lactamases. More explicitly, the 1,5- and 2,5-regioisomers inhibited AmpC from Enterobacter hormaechei (formerly Enterobacter cloacae) with Ki values of 1.8 µM and 2.45 µM, respectively. Structural molecular modelling studies revealed the interaction of the regioisomers with the relevant residues of the catalytic site of cephalosporinase from E. hormaechei P99, which included Tyr150 , Lys315 and Thr316 ...

A milestone in the development of novel anti-tuberculosis drugs is demonstrating early bactericidal activity (EBA) in a phase IIa clinical trial. The significant variability in measurements of bacterial load complicates the data analysis in these trials. We performed a systematic review and evaluation of methods for determination of EBA in pulmonary tuberculosis studies. Bacterial load quantification biomarkers, reporting intervals, calculation methods, statistical testing, and handling of negative culture result were extracted...

Aztreonam/avibactam is being developed on the rationale that aztreonam evades metallo-β-lactamases (MBLs) whilst avibactam protects against co-produced serine β-lactamases. We measured the activity of aztreonam/avibactam against MBL-producing Enterobacterales referred to the UKHSA in 2015, 2017, 2019. MICs were determined by broth microdilution, genome sequences with Illumina technology. For Klebsiella and Enterobacter spp. with NDM, IMP or VIM enzymes, the MICs of aztreonam/avibactam were unimodally distributed, with >90% of isolates inhibited at 1+4 mg/L, and all inhibited at 8+4 mg/L...

Multidrug-resistant (MDR) Pseudomonas aeruginosa infections compromise both empirical and definitive antimicrobial therapies. The Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance program identified 943 MDR P. aeruginosa (23.1% from a total of 4086 P. aeruginosa isolates) collected at 32 clinical laboratories in six countries in Western Europe from 2017 to 2020. MICs for ceftolozane/tazobactam and 10 comparator agents were determined by broth microdilution and interpreted using 2021 EUCAST breakpoints...

OBJECTIVE: To describe the relationship between maintenance over time of pharmacokinetic/pharmacodynamic (PK/PD) dalbavancin efficacy thresholds and clinical outcome in a case series of patients who underwent therapeutic drug monitoring (TDM) during long-term treatment of staphylococcal osteoarticular infections (OIs). METHODS: Patients who received two 1500 mg dalbavancin doses one week apart for documented staphylococcal OIs, underwent TDM assessment, and had clinical outcome assessable at follow-up were retrospectively included...

INTRODUCTION: The aim of this study was to determine the correlation between antimicrobial consumption (AMC) and antimicrobial resistance (AMR) in Escherichia coli at a hospital level, and assess the capacity of dynamic regression (DR) models to predict AMR to use them for the deployment of antimicrobial stewardship programs (ASPs). METHODS: We conducted a retrospective epidemiological study in a French tertiary hospital between 2014 and 2019. DR models were used to assess the correlation between AMC and AMR between 2014 and 2018...

Herpes simplex virus 2 (HSV-2) rarely causes severe disease, even in solid organ transplant recipients. We describe here a fatal case of HSV-2 infection probably transmitted from a donor to a kidney transplant recipient. The donor was seropositive for HSV-2 but not for HSV-1, whereas the recipient was seronegative for both viruses before transplantation, suggesting that the graft was the source of infection. The recipient received valganciclovir prophylaxis due to cytomegalovirus seropositivity. Three months after transplantation, the recipient presented with rapidly disseminated cutaneous HSV-2 infection with meningoencephalitis...

OBJECTIVES: To investigate HIV-DNA and residual viremia (RV) levels over 96 weeks (W96) in virologically suppressed HIV-1 infected individuals enrolled in the Be-OnE Study. Individuals were randomized to continue a two-drug regimen with dolutegravir (DTG) plus one RTI or to switch to elvitegravir/cobicistat/emtricitabine/tenofovir-alafenamide (E/C/F/TAF). STUDY DESIGN: Total HIV-DNA and RV were evaluated at baseline, W48 and W96 with ddPCR technique. Potential relationships between viro-immunological parameters and between/within arms were also assessed...

BACKGROUND: There is a growing interest in the utilization of daptomycin for the treatment of multi-drug resistant, Gram-positive infections. Pharmacokinetic studies suggest that daptomycin could penetrate into the cerebrospinal fluid, albeit to a small extent. The objective of this review was to evaluate the available clinical evidence for daptomycin use in acute bacterial meningitis of both pediatric and adult patients. METHODS: Electronic databases were searched up to June 2022 for studies published on the topic...

BACKGROUND: Klebsiella pneumoniae strains pose a significant threat to public health. Currently, it is inconclusive as to whether hypermucoviscous K. pneumoniae (hmKp; this phenotype has been semi-quantitatively defined by a positive "string test") bacteremia is clinically more severe than non-hmKp bacteremia. Hence, we aimed to conduct this systematic review and meta-analysis to draw some conclusions on hypermucoviscosity and bacteremia. METHODS: We searched PubMed and Web of Science databases for all relevant publications from January 2000 to March 2022...

Due to its bacteriological spectrum and efficacy in skin and soft tissue infections, ceftobiprole may be of interest for extracorporeal membrane oxygenation (ECMO) cannula-related infection. Whether or not ceftobiprole pharmacokinetic is changed by ECMO is not known. We performed a retrospective monocentric cohort study of 35 patients with suspected ECMO-related cannula infections (28 on ECMO, 7 after ECMO removal), who received ceftobiprole as empiric treatment, and had ceftobiprole blood levels measured at trough, peak and CT50 (50% of the dosing interval)...