Impact of rapid antibiotic susceptibility testing for Gram-negative bacteremia varies by pathogen type and resistance: a secondary analysis of the RAPIDS GN trial.

In this secondary analysis of 386 subjects with Gram-negative bacteremia enrolled in the RAPIDS GN trial, rapid antibiotic susceptibility testing had a greater benefit on the management of bacteremia caused by antibiotic-resistant compared to antibiotic-susceptible isolates, especially for species and species.IMPORTANCERapid blood culture diagnostics are costly, and their use has not demonstrated clear clinical benefit for patients with Gram-negative sepsis, possibly because prior trials did not enroll sufficient numbers of patients with antibiotic-resistant infections. This analysis of patients with sepsis previously enrolled in a randomized controlled clinical trial demonstrates that rapid susceptibility testing of bacteria from blood cultures had the greatest impact for patients with antibiotic-resistant infections.

Interlaboratory comparison of phage susceptibility testing.

Standardized approaches to phage susceptibility testing (PST) are essential to inform selection of phages for study in patients with bacterial infections. There is no reference standard for assessing bacterial susceptibility to phage. We compared agreement between PST performed at three centers: two centers using a liquid assay standardized between the sites with the third, a plaque assay.

The Antibacterial Resistance Leadership Group: Scientific Advancements and Future Directions.

In this overview, we describe important contributions from the Antibacterial Resistance Leadership Group (ARLG) to patient care, clinical trials design, and mentorship while outlining future priorities. The ARLG research agenda is focused on 3 key areas: gram-positive infections, gram-negative infections, and diagnostics. The ARLG has developed an innovative approach to clinical trials design, the desirability of outcome ranking (DOOR), which uses an ordinal measure of global outcome to assess both benefits and harms.

Under the Hood: The Scientific Leadership, Clinical Operations, Statistical and Data Management, and Laboratory Centers of the Antibacterial Resistance Leadership Group.

Developing and implementing the scientific agenda of the Antibacterial Resistance Leadership Group (ARLG) by soliciting input and proposals, transforming concepts into clinical trials, conducting those trials, and translating trial data analyses into actionable information for infectious disease clinical practice is the collective role of the Scientific Leadership Center, Clinical Operations Center, Statistical and Data Management Center, and Laboratory Center of the ARLG. These activities include shepherding concept proposal applications through peer review; identifying, qualifying, training, and overseeing clinical trials sites; recommending, developing, performing, and evaluating laboratory assays in support of clinical trials; and designing and performing data collection and statistical analyses. This article describes key components involved in realizing the ARLG scientific agenda through the activities of the ARLG centers.

Priorities and Progress in Gram-negative Bacterial Infection Research by the Antibacterial Resistance Leadership Group.

Addressing the treatment and prevention of antibacterial-resistant gram-negative bacterial infections is a priority area of the Antibacterial Resistance Leadership Group (ARLG). The ARLG has conducted a series of observational studies to define the clinical and molecular global epidemiology of carbapenem-resistant and ceftriaxone-resistant Enterobacterales, carbapenem-resistant Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter baumannii, with the goal of optimizing the design and execution of interventional studies. One ongoing ARLG study aims to better understand the impact of fluoroquinolone-resistant gram-negative gut bacteria in neutropenic patients, which threatens to undermine the effectiveness of fluoroquinolone prophylaxis in these vulnerable patients.

The Next Generation: Mentoring and Diversity in the Antibacterial Resistance Leadership Group.

The Antibacterial Resistance Leadership Group (ARLG) Mentoring Program was established to develop and prepare the next generation of clinician-scientists for a career in antibacterial resistance research. The ARLG Diversity, Equity, and Inclusion Working Group partners with the Mentoring Committee to help ensure diversity and excellence in the clinician-scientist workforce of the future. To advance the field of antibacterial research while fostering inclusion and diversity, the Mentoring Program has developed a number of fellowships, awards, and programs, which are described in detail in this article.

Safety and microbiological activity of phage therapy in persons with cystic fibrosis colonized with Pseudomonas aeruginosa: study protocol for a phase 1b/2, multicenter, randomized, double-blind, placebo-controlled trial.

Background: Bacteriophages (phages) are a promising anti-infective option for human disease. Major gaps remain in understanding their potential utility.

Methods: This is a randomized, placebo-controlled, double-blind study of a single dose of intravenous phage in approximately 72 clinically stable adult cystic fibrosis volunteers recruited from up to 20 US sites with Pseudomonas aeruginosa airway colonization.

Clustered DNA Damage Patterns after Proton Therapy Beam Irradiation Using Plasmid DNA.

Modeling ionizing radiation interaction with biological matter is a major scientific challenge, especially for protons that are nowadays widely used in cancer treatment. That presupposes a sound understanding of the mechanisms that take place from the early events of the induction of DNA damage. Herein, we present results of irradiation-induced complex DNA damage measurements using plasmid pBR322 along a typical Proton Treatment Plan at the MedAustron proton and carbon beam therapy facility (energy 137-198 MeV and Linear Energy Transfer (LET) range 1-9 keV/μm), by means of Agarose Gel Electrophoresis and DNA fragmentation using Atomic Force Microscopy (AFM).

Black and White Patients With Staphylococcus aureus Bacteremia Have Similar Outcomes but Different Risk Factors.

Background: Staphylococcus aureus bacteremia (SAB) disproportionately affects Black patients. The reasons for this disparity are unclear.

Methods: We evaluated a prospectively ascertained cohort of patients with SAB from 1995 to 2020.

Staphylococcus aureus Bacteremia Among Patients Receiving Maintenance Hemodialysis: Trends in Clinical Characteristics and Outcomes.

Rationale & Objective: Staphylococcus aureus (Saureus) bacteremia (SAB) is associated with morbidity and mortality in patients receiving maintenance hemodialysis (HD). We evaluated changes in clinical and bacterial characteristics, and their associations with clinical outcomes with SAB in this population over a 21-year period.

Study Design: Prospective cohort study.

Requirements for Designing an Effective Metallic Nanoparticle (NP)-Boosted Radiation Therapy (RT).

Many different tumor-targeted strategies are under development worldwide to limit the side effects and improve the effectiveness of cancer therapies. One promising method is to enhance the radiosensitization of the cancer cells while reducing or maintaining the normal tissue complication probability during radiation therapy using metallic nanoparticles (NPs). Radiotherapy with MV photons is more commonly available and applied in cancer clinics than high LET particle radiotherapy, so the addition of high-Z NPs has the potential to further increase the efficacy of photon radiotherapy in terms of NP radiosensitization.

Antibacterial Resistance Leadership Group 2.0: Back to Business.

In December 2019, the Antibacterial Resistance Leadership Group (ARLG) was awarded funding for another 7-year cycle to support a clinical research network on antibacterial resistance. ARLG 2.0 has 3 overarching research priorities: infections caused by antibiotic-resistant (AR) gram-negative bacteria, infections caused by AR gram-positive bacteria, and diagnostic tests to optimize use of antibiotics.

Characterization of 16S rRNA methylase genes in Enterobacterales and Pseudomonas aeruginosa in Athens Metropolitan area, 2015-2016.

The aim of this study was to characterize the 16S rRNA methylase (RMT) genes in aminoglycoside-resistant Enterobacterales and Pseudomonas aeruginosa isolates in 2015-2016 in hospitals in Athens, Greece. Single-patient, Gram-negative clinical isolates resistant to both amikacin and gentamicin (n = 292) were consecutively collected during a two-year period (2015-2016) in five tertiary care hospitals in Athens. RMT genes were detected by PCR.

Emergence of ceftazidime-avibactam resistance through distinct genomic adaptations in KPC-2-producing Klebsiella pneumoniae of sequence type 39 during treatment.

Three ceftazidime-avibactam-resistant KPC-2-producing Klebsiella pneumoniae strains of ST39 were isolated in Greece, from rectal swabs of three patients after 10-15 days of treatment. The patients were treated with ceftazidime-avibactam as monotherapy or in combination with colistin. Two of these strains harbored a D179Y or a D179V substitution in the Ω loop of KPC-2, corresponding to KPC-33, or to the novel KPC-57, respectively.

Risk Factors for Recurrent Staphylococcus aureus Bacteremia.

Background: To understand the clinical, bacterial, and host characteristics associated with recurrent Staphylococcus aureus bacteremia (R-SAB), patients with R-SAB were compared to contemporaneous patients with a single episode of SAB (S-SAB).

Methods: All SAB isolates underwent spa genotyping. All isolates from R-SAB patients underwent pulsed-field gel electrophoresis (PFGE).

In vitro activity of ceftolozane/tazobactam alone and in combination with amikacin against MDR/XDR Pseudomonas aeruginosa isolates from Greece.

Objectives: We evaluated the in vitro activity of ceftolozane/tazobactam and comparator agents against MDR non-MBL Pseudomonas aeruginosa isolates collected from nine Greek hospitals and we assessed the potential synergistic interaction between ceftolozane/tazobactam and amikacin.

Methods: A total of 160 non-MBL P. aeruginosa isolates collected in 2016 were tested for susceptibility to ceftolozane/tazobactam and seven comparator agents including ceftazidime/avibactam.

Outbreak of KPC-2-producing endowed with ceftazidime-avibactam resistance mediated through a VEB-1-mutant (VEB-25), Greece, September to October 2019.

From September to October 2019, seven patients colonised or infected with a ceftazidime-avibactam (CZA)-resistant carbapenemase (KPC)-2-producing were detected in two intensive care units of a Greek general hospital. The outbreak strain was sequence type (ST)147 and co-produced KPC-2 and the novel plasmid-borne Vietnamese extended-spectrum β-lactamase (VEB)-25 harbouring a K234R substitution associated with CZA resistance. Epidemiological investigations revealed that the resistance was probably acquired by horizontal transmission independently from previous CZA exposure.

Dissemination of International Clone II Strains Coproducing OXA-23 Carbapenemase and 16S rRNA Methylase ArmA in Athens, Greece.

The aim of this study was to study the molecular epidemiology of 16S rRNA-methylase (RMT)-producing clinical isolates from hospitals in Athens, Greece. Single-patient clinical isolates, coresistant to amikacin and gentamicin ( = 347), from five tertiary care hospitals, were submitted to minimum inhibitory concentration determination and molecular testing for carbapenemase and RMT genes. resistant to amikacin and gentamicin, was isolated at participating institutions at a mean rate of 67.

Correction to: In vitro activity of imipenem-relebactam against non-MBL carbapenemase-producing Klebsiella pneumoniae isolated in Greek hospitals in 2015-2016.

The publisher regrets that the article has been published online on 01 March 2019 with errors in Table 1. In the originally published Table 1, the percentage of Imipenem-relebactam susceptibility was incorrectly written as 8 0, while correct data is 98.0.

Changing Characteristics of Staphylococcus aureus Bacteremia: Results From a 21-Year, Prospective, Longitudinal Study.

Background: We conducted a longitudinal study to evaluate changes in the clinical presentation and epidemiology of Staphylococcus aureus bacteremia (SAB) in an academic, US medical center.

Methods: Consecutive patients with monomicrobial SAB were enrolled from January 1995 to December 2015. Each person's initial bloodstream S.

Correction to: Nationwide epidemiology of carbapenem resistant Klebsiella pneumoniae isolates from Greek hospitals, with regards to plazomicin and aminoglycoside resistance.

Following publication of the original article [1].

In vitro activity of imipenem-relebactam against non-MBL carbapenemase-producing Klebsiella pneumoniae isolated in Greek hospitals in 2015-2016.

Relebactam is a β-lactamase inhibitor of class A and class C β-lactamases, including carbapenemases. We evaluated the ability of relebactam to restore imipenem susceptibility against a collection of Klebsiella pneumoniae isolates from Greek hospitals. We tested 314 non-MBL carbapenemase-producing K.

Nationwide epidemiology of carbapenem resistant Klebsiella pneumoniae isolates from Greek hospitals, with regards to plazomicin and aminoglycoside resistance.

Background: To evaluate the in vitro activities of plazomicin and comparator aminoglycosides and elucidate the underlying aminoglycoside resistance mechanisms among carbapenemase-producing K. pneumoniae isolates collected during a nationwide surveillance study in Greek hospitals.

Methods: Three hundred single-patient carbapenemase-producing K.

Novel β-lactam-β-lactamase inhibitor combinations: expectations for the treatment of carbapenem-resistant Gram-negative pathogens.

The burden of antimicrobial resistance among Gram-negative bacteria is increasing and growing into a major threat of public health. Treatment options for carbapenem-resistant Enterobacteriaceae are limited and resistance rates to existing compounds are mounting. The pipeline includes only a small number of novel anti-infective agents in development or in the market with promising results against multidrug-resistant (MDR) Gram-negative.