How do we respond to the threat of multidrug-resistant bacteria? Comparison of antibiotic appraisals from 2016 to 2020 of the French, English, and German HTA agencies.

Antimicrobial resistance (AMR) has become a worldwide growing concern over the past decades. Thus, encouraging manufacturers to develop new antibiotics is needed. We hypothesised that transparency on the regulatory appraisals of antibiotics would provide an incentive to pharmaceutical development.

The role of systemic corticosteroids when treating infections in adult primary care.

Inflammatory response to aggressive infection is responsible not only for symptoms, especially pain, but also for severity, when the inflammatory cascade is violent, and provokes a deleterious cytokine storm. Due to their anti-inflammatory properties, corticosteroids are widely used in ambulatory medical practice. While their beneficial effects on some symptoms, particularly pain, are undeniable, so are the risks associated with their other properties (immunosuppression, neurostimulation, hypermetabolism), even during short-term administration at low doses.

Defining standard and high dosages for β-lactam agents administered by intermittent, prolonged or continuous infusion: a PK/PD simulation study.

Background: The new definitions of antimicrobial susceptibility categories proposed by EUCAST in 2020 require the definition of standard and high dosages of antibiotic. For injectable β-lactams, standard and high dosages have been proposed for short-infusion regimens only.

Objectives: To evaluate dosages for β-lactams administered by prolonged infusion (PI) and continuous infusion (CI).

Swarming of : Through the lens of biophysics.

Swarming is a collective flagella-dependent movement of bacteria across a surface that is observed across many species of bacteria. Due to the prevalence and diversity of this motility modality, multiple models of swarming have been proposed, but a consensus on a general mechanism for swarming is still lacking. Here, we focus on swarming by due to the abundance of experimental data and multiple models for this species, including interpretations that are rooted in biology and biophysics.

The great divide: rhamnolipids mediate separation between and .

The interactions between bacterial species during infection can have significant impacts on pathogenesis. and are opportunistic bacterial pathogens that can co-infect hosts and cause serious illness. The factors that dictate whether one species outcompetes the other or whether the two species coexist are not fully understood.

Understanding how bacterial collectives organize on surfaces by tracking surfactant flow.

Swarming is a collective bacterial behavior in which a dense population of bacterial cells moves over a porous surface, resulting in the expansion of the population. This collective behavior can guide bacteria away from potential stressors such as antibiotics and bacterial viruses. However, the mechanisms responsible for the organization of swarms are not understood.

Antibiotic Therapy for 6 or 12 Weeks for Prosthetic Joint Infection.

Background: The management of prosthetic joint infection usually consists of a combination of surgery and antimicrobial therapy. The appropriate duration of antimicrobial therapy for this indication remains unclear.

Methods: We performed an open-label, randomized, controlled, noninferiority trial to compare 6 weeks with 12 weeks of antibiotic therapy in patients with microbiologically confirmed prosthetic joint infection that had been managed with an appropriate surgical procedure.

Roadmap on emerging concepts in the physical biology of bacterial biofilms: from surface sensing to community formation.

Bacterial biofilms are communities of bacteria that exist as aggregates that can adhere to surfaces or be free-standing. This complex, social mode of cellular organization is fundamental to the physiology of microbes and often exhibits surprising behavior. Bacterial biofilms are more than the sum of their parts: single-cell behavior has a complex relation to collective community behavior, in a manner perhaps cognate to the complex relation between atomic physics and condensed matter physics.

Time-lapse Imaging of Bacterial Swarms and the Collective Stress Response.

Swarming is a form of surface motility observed in many bacterial species including Pseudomonas aeruginosa and Escherichia coli. Here, dense populations of bacteria move over large distances in characteristic tendril-shaped communities over the course of hours. Swarming is sensitive to several factors including medium moisture, humidity, and nutrient content.

PQS Produced by the Pseudomonas aeruginosa Stress Response Repels Swarms Away from Bacteriophage and Antibiotics.

We investigate the effect of bacteriophage infection and antibiotic treatment on the coordination of swarming, a collective form of flagellum- and pilus-mediated motility in bacteria. We show that phage infection of the opportunistic bacterial pathogen abolishes swarming motility in the infected subpopulation and induces the release of the quinolone signaling molecule PQS, which repulses uninfected subpopulations from approaching the infected area. These mechanisms have the overall effect of limiting the infection to a subpopulation, which promotes the survival of the overall population.

New findings on SNP variants of human protein L-isoaspartyl methyltransferase that affect catalytic activity, thermal stability, and aggregation.

Protein L-isoaspartyl methyltransferase (PIMT/PCMT1), a product of the pcmt1 gene, catalyzes repair of abnormal L-isoaspartyl linkages in age-damaged proteins. Pcmt1 knockout mice exhibit a profound neuropathology and die 30-60 days postnatal from an epileptic seizure. Here we characterize four new SNP variants of human PIMT with respect to enzymatic activity, thermal stability, and propensity to aggregation.

Polymorphic Variants of Human Protein l-Isoaspartyl Methyltransferase Affect Catalytic Activity, Aggregation, and Thermal Stability: IMPLICATIONS FOR THE ETIOLOGY OF NEUROLOGICAL DISORDERS AND COGNITIVE AGING.

Protein l-isoaspartyl methyltransferase (PIMT/PCMT1), a product of the human gene, catalyzes repair of abnormal l-isoaspartyl linkages in age-damaged proteins. Pcmt1 knock-out mice exhibit a profound neuropathology and die 30-60 days postnatal from an epileptic seizure. Here we express 15 reported variants of human PIMT and characterize them with regard to their enzymatic activity, thermal stability, and propensity to aggregation.

Application of guidelines for aminoglycosides use in French hospitals in 2013-2014.

In 2011, the French Agency for Safety of Health Products issued guidelines underlining the principles of proper aminoglycosides' use. The aim of the survey was to evaluate adherence to these guidelines two years after their issue. Characteristics of patients receiving aminoglycosides were recorded by voluntary facilities during a 3-month survey in 2013-2014.

Antibiotic use and good practice in 314 French hospitals: The 2010 SPA2 prevalence study.

Objectives: We aimed to assess antibiotic prescriptions to identify potential targets for improvement.

Methods: We conducted a point prevalence survey (November 2010) of antibiotic use in 314 voluntary hospitals recruited by the French Infectious Diseases Society (SPILF) and the National Observatory for Epidemiology of Bacterial Resistance to Antimicrobials (ONERBA). Data were entered online, immediately analyzed and exported.

Carbapenem use in French hospitals: A nationwide survey at the patient level.

The objective of this study was to evaluate the characteristics of carbapenem use in French healthcare settings in order to guide future actions. Healthcare facilities voluntarily participated in a nationwide cross-sectional survey in 2011. Medical data and reasons for carbapenem treatment (CPR) and discontinuation were recorded for all patients treated with carbapenems.

Guidelines for management of intra-abdominal infections.

Intra-abdominal infections are one of the most common gastrointestinal emergencies and a leading cause of septic shock. A consensus conference on the management of community-acquired peritonitis was published in 2000. A new consensus as well as new guidelines for less common situations such as peritonitis in paediatrics and healthcare-associated infections had become necessary.

Antibiotic treatment for 6 weeks versus 12 weeks in patients with pyogenic vertebral osteomyelitis: an open-label, non-inferiority, randomised, controlled trial.

Background: Duration of treatment for patients with vertebral osteomyelitis is mainly based on expert recommendation rather than evidence. We aimed to establish whether 6 weeks of antibiotic treatment is non-inferior to 12 weeks in patients with pyogenic vertebral osteomyelitis.

Methods: In this open-label, non-inferiority, randomised controlled trial, we enrolled patients aged 18 years or older with microbiologically confirmed pyogenic vertebral osteomyelitis and typical radiological features from 71 medical care centres across France.

Ceftaroline for the treatment of prosthetic valve endocarditis due to methicillin-resistant Staphylococcus aureus.

The case is described of a frail patient who developed prosthetic valve endocarditis due to methicillin-resistant Staphylococcus aureus (MRSA). Conventional antimicrobial treatments either failed or were contraindicated, and the patient was judged unsuitable for a further valve replacement. A salvage therapy with high doses of a new cephalosporin, ceftaroline, given three times daily was undertaken; subsequently, the patient had not relapsed at two months after completing a six-week course of ceftaroline.