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junio 1, 2021

Concise Chemoenzymatic Synthesis of Fasamycin A

We report the development of a chemoenzymatic approach toward fasamycin A, a halogenated naphthacenoid that exhibits activities against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis. The synthesis was accomplished in a convergent manner: two fragments were combined together in a Sammes annulation to afford a dimethylnaphthacenone system. Finally, an enzymatic halogenation was employed to introduce the requisite chlorine substituent of the natural…

Methicillin-resistant Staphylococcus aureus (MRSA) submandibular abscess in a neonate

Neonatal suppurative submandibular sialadenitis and abscess formation is an exceedingly rare entity. This report describes a complex case of a male neonate with a methicillin-resistant Staphylococcus aureus (MRSA) submandibular abscess, requiring emergency intubation due to acute airway compromise. The patient was admitted to the paediatric intensive care unit, received appropriate antibiotic treatment and underwent urgent surgical drainage of the abscess. He made a full recovery and remains…

Hyperexpression of CDRs and HWP1 genes negatively impacts on Candida albicans virulence

C. albicans is a commensal organism present in the human microbiome of more than 60% of the healthy population. Transition from commensalism to invasive candidiasis may occur after a local or a general failure of host’s immune system. This transition to a more virulent phenotype may reside either on the capacity to form hyphae or on an acquired resistance to antifungal drugs. Indeed, overexpression of genes coding drug efflux pumps or adhesins, cell wall proteins facilitating the contact between…

ABO blood group and COVID-19: an updated systematic literature review and meta-analysis

BACKGROUND: Following the first reports in the literature, the association between the ABO blood group and SARS-CoV-2 infection has been investigated by a number of studies, although with varying results. The main object of this systematic review was to assess the relationship between the ABO blood group and the occurrence and severity of COVID-19.

Aztreonam-Avibactam Susceptibility Testing Program for Metallo-beta-lactamase-producing Enterobacterales in the Antibiotic Resistance Laboratory Network, March 2019-December 2020

Aztreonam-avibactam is a drug combination pending phase 3 clinical trials and is suggested for treatment of severe infections caused by metallo-beta-lactamase (MBL)-producing Enterobacterales by combining ceftazidime-avibactam and aztreonam. Beginning in 2019, four Antibiotic Resistance Laboratory Network regional laboratories offered aztreonam-avibactam susceptibility testing by broth microdilution. For 64 clinical isolates tested, the MIC(50) and MIC(90) of aztreonam-avibactam were 0.5/4 μg/mL…

Emergence of resistance to novel cephalosporin-β-lactamase inhibitor combinations through the modification of the <em>Pseudomonas aeruginosa</em> MexCD-OprJ efflux pump

A ceftolozane/tazobactam and ceftazime/avibactam resistant Pseudomonas aeruginosa isolate was recovered after treatment (including azithromycin, meropenem and ceftolozane/tazobactam) from a patient that had developed ventilator associated pneumonia after Covid-19 infection. Whole genome sequencing revealed that the strain, belonging to ST274, had acquired a nonsense mutation leading to a truncated carbapenem porin OprD (W277X), a 7-bp deletion (nt213Δ7) in NfxB (negative regulator of the efflux…

Pulmonary Mycobacterium abscessus Infection in an 11-Year-Old Child, Successfully Treated with Inhaled/Parenteral Amikacin: A Case Report and Review of Literature

Mycobacterium abscessus appears to be increasing cause of pulmonary infection in children with underlying risk factors including cystic fibrosis, chronic lung disease and immunodeficiency syndromes. We present a case of pulmonary M. abscessus infection in a pediatric patient with primary ciliary dyskinesia and he was successfully treated with parenteral amikacin, linezolid and oral clarithromycin combined with inhaled amikacin. Clinical improvement was observed after adding inhaled amikacin to…

Effect of vancomycin on cytoplasmic peptidoglycan intermediates and <em>van</em> operon mRNA levels in VanA-type vancomycin resistant <em>Enterococcus faecium</em>

Resistance in VanA-type vancomycin resistant Enterococcus faecium (VREfm) is due to an inducible gene cassette encoding seven proteins (vanRSHAXYZ). This provides for an alternative peptidoglycan (PG) biosynthesis pathway whereby d-Alanyl-d-Alanine (d-Ala-d-Ala) is replaced with d-Alanyl-d-Lactate (d-Ala-d-Lac), to which vancomycin cannot bind effectively. This study aimed to quantify cytoplasmic levels of normal and alternative pathway PG intermediates in VanA-type VREfm by liquid chromatograph…