Genomic investigation and clinical correlates of the β-lactam: NaHCO responsiveness phenotype among methicillin-resistant isolates from a randomized clinical trial.

NaHCO responsiveness is a novel phenotype where some methicillin-resistant (MRSA) isolates exhibit significantly lower minimal inhibitory concentrations (MIC) to oxacillin and/or cefazolin in the presence of NaHCO. NaHCO responsiveness correlated with treatment response to β-lactams in an endocarditis animal model. We investigated whether treatment of NaHCO-responsive strains with β-lactams was associated with faster clearance of bacteremia.

A statistical genomics framework to trace bacterial genomic predictors of clinical outcomes in Staphylococcus aureus bacteremia.

Outcomes of severe bacterial infections are determined by the interplay between host, pathogen, and treatments. While human genomics has provided insights into host factors impacting Staphylococcus aureus infections, comparatively little is known about S. aureus genotypes and disease severity.

Case Commentary: The hidden side of oxacillin resistance in .

Acquisition of PBP2a (encoded by the gene) is the key resistance mechanism to β-lactams in . The gene can be easily detected by PCR assays; however, these tools will miss c-independent oxacillin resistance. This phenotype is mediated by mutations in cell wall metabolism genes that can be acquired during persistent infections under prolonged antibiotic exposure.

A high-throughput cytotoxicity screening platform reveals -independent mutations in bacteraemia-associated that promote intracellular persistence.

infections are associated with high mortality rates. Often considered an extracellular pathogen, can persist and replicate within host cells, evading immune responses, and causing host cell death. Classical methods for assessing cytotoxicity are limited by testing culture supernatants and endpoint measurements that do not capture the phenotypic diversity of intracellular bacteria.

Staphylococcus aureus host interactions and adaptation.

Invasive Staphylococcus aureus infections are common, causing high mortality, compounded by the propensity of the bacterium to develop drug resistance. S. aureus is an excellent case study of the potential for a bacterium to be commensal, colonizing, latent or disease-causing; these states defined by the interplay between S.

All Staphylococcus aureus bacteraemia-inducing strains can cause infective endocarditis: Results of GWAS and experimental animal studies.

Objectives: We aimed at determining whether specific S. aureus strains cause infective endocarditis (IE) in the course of Staphylococcus aureus bacteraemia (SAB).

Methods: A genome-wide association study (GWAS) including 924 S.

Niche-specific genome degradation and convergent evolution shaping adaptation during severe infections.

During severe infections, moves from its colonising sites to blood and tissues and is exposed to new selective pressures, thus, potentially driving adaptive evolution. Previous studies have shown the key role of the locus in pathoadaptation; however, a more comprehensive characterisation of genetic signatures of bacterial adaptation may enable prediction of clinical outcomes and reveal new targets for treatment and prevention of these infections. Here, we measured adaptation using within-host evolution analysis of 2590 .

Stapled Porcine Pericardium Displays Lower Infectivity In Vitro Than Native and Sutured Porcine Pericardium.

Background: Biological xenografts using tubulized porcine pericardium are an alternative to replace infected prosthetic graft. We recently reported an innovative technique using a stapled porcine pericardial bioconduit for immediate vascular reconstruction in emergency. The objective of this study is to compare the growth and adherence to grafts of bacteria and yeast incubated with stapled porcine pericardium, sutured or naked pericardium.

Comprehensive Genomic Investigation of Adaptive Mutations Driving the Low-Level Oxacillin Resistance Phenotype in Staphylococcus aureus.

Antistaphylococcal penicillins such as oxacillin are the key antibiotics in the treatment of invasive methicillin-susceptible (MSSA) infections; however, gene-independent resistance adaptation can cause treatment failure. Despite its clinical relevance, the basis of this phenomenon remains poorly understood. Here, we investigated the genomic adaptation to oxacillin at an unprecedented scale using a large collection of 503 clinical -negative isolates and 30 -adapted isolates from independent oxacillin exposures.

Using genomics to understand meticillin- and vancomycin-resistant infections.

Resistance to meticillin and vancomycin in significantly complicates the management of severe infections like bacteraemia, endocarditis or osteomyelitis. Here, we review the molecular mechanisms and genomic epidemiology of resistance to these agents, with a focus on how genomics has provided insights into the emergence and evolution of major meticillin-resistant clones. We also provide insights on the use of bacterial whole-genome sequencing to inform management of infections and for control of transmission at the hospital and in the community.

Unstable chromosome rearrangements in cause phenotype switching associated with persistent infections.

small-colony variants (SCVs) are associated with unusually chronic and persistent infections despite active antibiotic treatment. The molecular basis for this clinically important phenomenon is poorly understood, hampered by the instability of the SCV phenotype. Here we investigated the genetic basis for an unstable SCV that arose spontaneously while studying rifampicin resistance.

Successful treatment with daptomycin and ceftaroline of MDR Staphylococcus aureus native valve endocarditis: a case report.

Objectives: The best therapeutic approach for treating MRSA endocarditis remains unknown, particularly in cases of high vancomycin MICs. We report here a case of daptomycin-non-susceptible, ceftaroline-resistant and fosfomycin-resistant MRSA native left valve endocarditis that was successfully treated with valve repair and a combination of high-dose daptomycin and ceftaroline.

Methods: Antimicrobial testing of the clinical strain was performed using Etest and microdilution broth methods.

Comprehensive antibiotic-linked mutation assessment by resistance mutation sequencing (RM-seq).

Mutation acquisition is a major mechanism of bacterial antibiotic resistance that remains insufficiently characterised. Here we present RM-seq, a new amplicon-based deep sequencing workflow based on a molecular barcoding technique adapted from Low Error Amplicon sequencing (LEA-seq). RM-seq allows detection and functional assessment of mutational resistance at high throughput from mixed bacterial populations.

Genomic exploration of sequential clinical isolates reveals a distinctive molecular signature of persistent Staphylococcus aureus bacteraemia.

Background: Large-scale genomic studies of within-host diversity in Staphylococcus aureus bacteraemia (SAB) are needed to understanding bacterial adaptation underlying persistence and thus refining the role of genomics in management of SAB. However, available comparative genomic studies of sequential SAB isolates have tended to focus on selected cases of unusually prolonged bacteraemia, where secondary antimicrobial resistance has developed.

Methods: To understand bacterial genetic diversity during SAB more broadly, we applied whole genome sequencing to a large collection of sequential isolates obtained from patients with persistent or relapsing bacteraemia.

Convergent Evolution Driven by Rifampin Exacerbates the Global Burden of Drug-Resistant .

Mutations in the beta-subunit of bacterial RNA polymerase (RpoB) cause resistance to rifampin (Rif), a critical antibiotic for treatment of multidrug-resistant . studies have shown that RpoB mutations confer decreased susceptibility to other antibiotics, but the clinical relevance is unknown. Here, by analyzing 7,099 genomes, we demonstrate that the most prevalent RpoB mutations promote clinically relevant phenotypic plasticity resulting in the emergence of stable lineages, associated with increased risk of therapeutic failure through generation of small-colony variants (SCVs) and coresistance to last-line antimicrobial agents.

Use of bacterial whole-genome sequencing to understand and improve the management of invasive Staphylococcus aureus infections.

Management of invasive Staphylococcus aureus infections is complex. Dramatic improvements in bacterial whole genome sequencing (WGS) offer new opportunities for personalising the treatment of S. aureus infections.

A retrospective study of deep sternal wound infections: clinical and microbiological characteristics, treatment, and risk factors for complications.

Deep sternal wound infection (DSWI) is a feared complication following cardiac surgery. This study describes clinical, microbiological, and treatment outcomes of DSWI and determines risk factors for complications. Of 55 patients with DSWI, 66% were male and mean age was 68.

Acquired Multidrug Antifungal Resistance in Candida lusitaniae during Therapy.

Candida lusitaniae is usually susceptible to echinocandins. Beta-1,3-glucan synthase encoded by FKS genes is the target of echinocandins. A few missense mutations in the C.

Sepsis: a roadmap for future research.

Sepsis is a common and lethal syndrome: although outcomes have improved, mortality remains high. No specific anti-sepsis treatments exist; as such, management of patients relies mainly on early recognition allowing correct therapeutic measures to be started rapidly, including administration of appropriate antibiotics, source control measures when necessary, and resuscitation with intravenous fluids and vasoactive drugs when needed. Although substantial developments have been made in the understanding of the basic pathogenesis of sepsis and the complex interplay of host, pathogen, and environment that affect the incidence and course of the disease, sepsis has stubbornly resisted all efforts to successfully develop and then deploy new and improved treatments.

Rapid detection of enterovirus in cerebrospinal fluid by a fully-automated PCR assay is associated with improved management of aseptic meningitis in adult patients.

Background: Enterovirus (EV) is the most frequent cause of aseptic meningitis (AM). Lack of microbiological documentation results in unnecessary antimicrobial therapy and hospitalization.

Objectives: To assess the impact of rapid EV detection in cerebrospinal fluid (CSF) by a fully-automated PCR (GeneXpert EV assay, GXEA) on the management of AM.

[Clostridial colitis: diagnosis and strategies for management].

C. difficile is transmitted in a faecal-oral mode and is widespread in hospital environment. Symptoms of Clostridial infection range from asymptomatic carriage to life-threatening toxic colitis.

[Infectious diseases].

The recommendations for the treatment of gonorrhea have been changed: ceftriaxone 500 mg IM plus azithromycin 1 g PO is recommended. Prophylaxis of recurrent cellulitis with penicillin 250 mg 2 x/d PO may be considered. E.