Analysis of two Nocardia brasiliensis class A β-lactamases (BRA-1 and BRS-1) and related resistance to β-lactam antibiotics.

Objective: Molecular determinants of β-lactam resistance are poorly explored for most Nocardia species, such as Nocardia brasiliensis. In this study, we characterised resistance mediated by two β-lactamases in the reference strain N. brasiliensis HUJEG-1 and extended our analysis to nine N.

Appropriateness of empirical antibiotic prescription for bloodstream infections in an emergency department from 2006 to 2018: impact of the spread of ESBL-producing Enterobacterales.

The spread of ESBL producers in the community may impact the management of patients with bloodstream infections (BSI) involving Enterobacterales in emergency departments. Thus, from 2006 to 2018, data for all BSI episodes involving Enterobacterales from the emergency department of a French teaching hospital were retrospectively included. Antimicrobial susceptibility test results and empirical antibiotic regimens were recorded.

A Case of Phage Therapy against Pandrug-Resistant in a 12-Year-Old Lung-Transplanted Cystic Fibrosis Patient.

Bacteriophages are a promising therapeutic strategy among cystic fibrosis and lung-transplanted patients, considering the high frequency of colonization/infection caused by pandrug-resistant bacteria. However, little clinical data are available regarding the use of phages for infections with . A 12-year-old lung-transplanted cystic fibrosis patient received two rounds of phage therapy because of persistent lung infection with pandrug-resistant .

Renal abscess caused by Panton-Valentine leukocidin-producing : report of an unusual case and review of the literature.

Background: Renal abscesses are rare and mainly caused by an ascending infection due to Gram-negative microorganisms. We report the first case of a renal abscess caused by Panton-Valentine leukocidin-producing in an immunocompetent patient, and we present a comprehensive review of the literature.

Case Presentation: A 20-year-old immunocompetent woman had a 2-month history of left-sided back pain, fever and urinary symptoms.

Ceftazidime-Avibactam Resistance Mediated by the NY Substitution in Various AmpC β-Lactamases.

Chromosomal and plasmid-borne AmpC cephalosporinases are a major resistance mechanism to β-lactams in and The new β-lactamase inhibitor avibactam effectively inhibits class C enzymes and can fully restore ceftazidime susceptibility. The conserved amino acid residue Asn of AmpC cephalosporinases directly interacts with the avibactam sulfonate. Disruption of this interaction caused by the NY amino acid substitution in AmpC was previously shown to confer resistance to the ceftazidime-avibactam combination (CAZ-AVI).

Predictive factors of death associated with infective endocarditis in adult patients with congenital heart disease.

Aims: Infective endocarditis is a severe infection which can occur in adult patients with congenital heart disease. We aimed to determine outcomes and risk factors of death in adult congenital heart disease and to investigate differences with infective endocarditis in non-congenital heart disease.

Methods And Results: Between March 2000 and June 2018, 671 consecutive episodes of infective endocarditis in adult patients were retrospectively recorded.

Inhibition Activity of Avibactam against Nocardia farcinica β-Lactamase FAR.

, one of the most frequent pathogenic species responsible for nocardiosis, is characterized by frequent brain involvement and resistance to β-lactams mediated by a class A β-lactamase. Kinetic parameters for hydrolysis of various β-lactams by FAR from strain IFM 10152 were determined by spectrophotometry revealing a high catalytic activity (/ ) for amoxicillin, aztreonam, and nitrocefin. For cephems, / was lower but remained greater than 10 M s A low catalytic activity was observed for meropenem, imipenem, and ceftazidime hydrolysis.

Spread of NDM-5 and OXA-181 Carbapenemase-Producing Escherichia coli in Chad.

We detected for the first time and in isolates from hospitalized patients and healthy volunteers in Chad. These resistance genes were located on IncX3 and IncF plasmids. Despite the large diversity of clones, the identified resistant intestinal isolates belonged mainly to the same sequence type.

Accuracy of Curable Sexually Transmitted Infections and Genital Mycoplasmas Screening by Multiplex Real-Time PCR Using a Self-Collected Veil among Adult Women in Sub-Saharan Africa.

Background: Sexually transmitted infections (STIs) are highly prevalent in sub-Saharan Africa. Genital self-sampling may facilitate the screening of STIs in hard-to-reach remote populations far from large health care centers and may increase screening rates. The cross-sectional study was carried out to assess the performance of a novel genital veil (V-Veil-Up Gyn Collection Device, V-Veil-Up Pharma, Ltd.

Synergistic activity between aztreonam and amoxicillin-clavulanate against Enterobacteriaceae-producing class B and/or class D carbapenemases with or without extended-spectrum -lactamases.

Carbapenemase-producing Enterobacteriaceae have become a major public health concern over the last decade and treatment options are limited. We evaluated the synergistic activity of the combination of aztreonam (ATM) and clavulanate for 41 -lactam-resistant clinical isolates harbouring class B or/and class D carbapenemases combined or not with extended-spectrum -lactamases (ESBLs). The MICs of ATM, with and without amoxicillin-clavulanate (AMC), were determined.

Tryptophan Fluorescence Quenching in β-Lactam-Interacting Proteins Is Modulated by the Structure of Intermediates and Final Products of the Acylation Reaction.

In most bacteria, β-lactam antibiotics inhibit the last cross-linking step of peptidoglycan synthesis by acylation of the active-site Ser of d,d-transpeptidases belonging to the penicillin-binding protein (PBP) family. In mycobacteria, cross-linking is mainly ensured by l,d-transpeptidases (LDTs), which are promising targets for the development of β-lactam-based therapies for multidrug-resistant tuberculosis. For this purpose, fluorescence spectroscopy is used to investigate the efficacy of LDT inactivation by β-lactams but the basis for fluorescence quenching during enzyme acylation remains unknown.

Multicentre randomised controlled trial to investigate usefulness of the rapid diagnostic βLACTA test performed directly on bacterial cell pellets from respiratory, urinary or blood samples for the early de-escalation of carbapenems in septic intensive care unit patients: the BLUE-CarbA protocol.

Introduction: The dramatic increase of the incidence of infections caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) has led to an increase of 50% of carbapenem consumption all around Europe in only 5 years. This favours the spread of carbapenem-resistant Gram-negative bacilli (GNB), causing life-threatening infections. In order to limit use of carbapenems for infections actually due to ESBL-PE, health authorities promote the use of rapid diagnostic tests of bacterial resistance.

Performance evaluation of the βLACTA™ Test for rapid detection of ceftazidime resistance in Pseudomonas aeruginosa isolates from cystic fibrosis patients.

The chromogenic βLACTA™ test was evaluated to detect ceftazidime resistance in P. aeruginosa isolates from patients with cystic fibrosis. Best results were obtained after one hour of incubation with low sensitivity (64.

In vitro activity of β-lactams in combination with avibactam against multidrug-resistant Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Achromobacter xylosoxidans isolates from patients with cystic fibrosis.

The in vitro activity of anti-pseudomonal β-lactams in combination with avibactam was evaluated against 54 multidrug-resistant non-fermenting Gram-negative bacilli isolated from cystic fibrosis patients. Avibactam increased and/or restored the antibacterial activities of ceftazidime and aztreonam against Pseudomonas aeruginosa and Stenotrophomonas maltophilia, respectively. No β-lactam-avibactam combination was active against Achromobacter xylosoxidans.

Combination of Amino Acid Substitutions Leading to CTX-M-15-Mediated Resistance to the Ceftazidime-Avibactam Combination.

Single amino acid substitutions in the Ω loop of KPC β-lactamases are known to lead to resistance to the ceftazidime-avibactam combination. Here, we investigate this mechanism of resistance in CTX-M enzymes, which are the most widely spread extended-spectrum β-lactamases worldwide. Nine single amino acid polymorphisms were identified in the Ω loop of the 172 CTX-M sequences present in the Lahey database of β-lactamases.

Synthesis of Avibactam Derivatives and Activity on β-Lactamases and Peptidoglycan Biosynthesis Enzymes of Mycobacteria.

There is a renewed interest for β-lactams for treating infections due to Mycobacterium tuberculosis and M. abscessus because their β-lactamases are inhibited by classical (clavulanate) or new generation (avibactam) inhibitors, respectively. Here, access to an azido derivative of the diazabicyclooctane (DBO) scaffold of avibactam for functionalization by the Huisgen-Sharpless cycloaddition reaction is reported.

In vitro activity of tedizolid against the Mycobacterium abscessus complex.

Infections due to Mycobacterium abscessus carry a poor prognosis since this rapidly growing mycobacterium is intrinsically resistant to most antibiotics. Here, we evaluate the in vitro activity of the new oxazolidinone tedizolid against a collection of 44M. abscessus clinical isolates.

In vitro activity of tedizolid and comparator agents against Gram-positive pathogens responsible for bone and joint infections.

Tedizolid, a second-generation oxazolidinone that displays a potent activity against Gram-positive pathogens, could be an interesting option for the treatment of bone and joint infections (BJIs). The aim of the study was to determine minimal inhibitory concentration (MIC) of tedizolid against a collection of 359 clinical isolates involved in clinically-documented BJIs and to compare them to those of comparator agents used in Gram-positive infections. Of the 104 Staphylococcusaureus and 102 coagulase-negative staphylococci (CoNS) isolates, 99 and 92 % were categorized as susceptible to tedizolid, respectively (MIC25=0.

Successful treatment of Pseudomonas aeruginosa osteomyelitis with antibiotic monotherapy of limited duration.

Objectives: The aim of this study was to present a 15-year experience and provide a comprehensive analysis of a large cohort of patients with Pseudomonas aeruginosa osteomyelitis.

Methods: We reviewed the medical records of patients admitted to a large French university hospital for P. aeruginosa osteomyelitis over a 15-year period.

Fatal Pulmonary Mucormycosis due to Rhizopus homothallicus.

We report here a case of cavitary pneumonia due to Rhizopus homothallicus in a diabetic patient. This is the first proven case of R. homothallicus infection in Western countries and the third case described worldwide.

Impaired Inhibition by Avibactam and Resistance to the Ceftazidime-Avibactam Combination Due to the DY Substitution in the KPC-2 β-Lactamase.

The ceftazidime-avibactam antibiotic combination was recently shown to be at risk for the emergence of resistance under treatment. To gain insight into the underlying mechanism, we have analyzed the catalytic properties of a carbapenemase type 2 (KPC-2) β-lactamase harboring the DY substitution. We show that impaired inhibition by avibactam combined with significant residual activity for ceftazidime hydrolysis accounts for the resistance.

Central venous catheters and biofilms: where do we stand in 2017?

The use of central venous catheters (CVC) is associated with a risk of microbial colonization and subsequent potentially severe infection. Microbial contamination of the catheter leads to the development of a microbial consortia associated with the CVC surface and embedded in an extracellular matrix, named biofilm. This biofilm provides bacterial cells the ability to survive antimicrobial agents and the host immune system and to disseminate to other sites of the body.