eravacycline and Acinetobacter-Infections

Multidrug-resistant. To assess the efficacy of eravacycline compared with best previously available therapy in adults with difficult-to-treat resistant (DTR). This was a retrospective study of adults hospitalized for pneumonia with DTR. Ninety-three patients were included, with 27 receiving eravacycline. Eravacycline was associated with higher 30-day mortality (33%. Eravacycline-based combination therapy had similar outcomes to best previously available combination therapy for adults with DTR

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Bacteremia; COVID-19; Drug Resistance, Multiple, Bacterial; Humans; Pneumonia; Retrospective Studies; SARS-CoV-2; Tetracyclines

We evaluated the in vitro activity of eravacycline and cefoperazone/sulbactam against 42 XDR and 58 PDR Acinetobacter baumannii isolates from blood and bronchoalveolar infections. The minimum and maximum MICs for eravacycline were 0.125 and 4 mg/L, respectively. The MIC50 was 2 mg/L and the MIC90 was 3 mg/L. The minimum and maximum MICs for cefoperazone/sulbactam were 24 and >256 mg/L, respectively. The MIC50 and MIC90 were both >256 mg/L. These novel agents were not adequate for the treatment of A. baumannii infections in our hospital and we recommend that mi- crobiology laboratories perform their own evaluations before including them in clinical practice.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cefoperazone; Drug Resistance, Multiple, Bacterial; Greece; Humans; Microbial Sensitivity Tests; Sulbactam; Tertiary Care Centers; Tetracyclines

Acinetobacter baumannii is an important pathogen and presents a major burden in healthcare as strains frequently cause hospital associated opportunistic infections with high mortality rates. Due to increasing numbers of drug resistant A. baumannii strains, newly developed antibiotics are being used to treat infections caused by such strains. One novel synthetic antibiotic of the tetracycline class with activity against A. baumannii is eravacycline. To investigate possible mechanisms of eravacycline resistance, we performed an in vitro evolution experiment to select for an eravacycline resistant strain, with the clinical isolate MDR-ZJ06 as parental strain. We obtained a strain designated MDR-ZJ06-E6 that was able to grow in 64-fold MIC. Genomic mutations were identified by whole genome sequencing, where we found a deletion mutation in the gene adeS. Using complementation experiments, including growth rate determination and antibiotics susceptibility testing, we could confirm that this mutation was responsible for eravacycline resistance of strain MDR-ZJ06-E6. As a mechanism of resistance, we identified a significant overexpression of the efflux pump AdeABC which seems to be regulated by the mutation in adeS in A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; Drug Resistance, Bacterial; Gene Expression Regulation, Bacterial; Membrane Transport Proteins; Plasmids; Sequence Deletion; Tetracyclines

A novel, plasmid-mediated, high-level tigecycline resistance

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; China; Drug Resistance, Multiple, Bacterial; Gene Transfer, Horizontal; Genes, Bacterial; Humans; Microbial Sensitivity Tests; Models, Genetic; Models, Molecular; Molecular Docking Simulation; Plasmids; Tetracycline Resistance; Tetracyclines; Tigecycline

The synergistic activity of eravacycline in combination with colistin on carbapenem-resistant A. baumannii (CRAB) isolates was evaluated in this study. Minimum inhibitory concentrations (MICs) of eravacycline and colistin were determined by the broth microdilution method. MICs values ranged between 1 to 4 mg and 0.5 to 256 mg l

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Bacterial; Drug Synergism; Humans; Microbial Sensitivity Tests; Tetracyclines

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aminoglycosides; Anti-Bacterial Agents; beta-Lactamases; beta-Lactams; Colistin; Drug Resistance, Multiple, Bacterial; Fluoroquinolones; Humans; Microbial Sensitivity Tests; Tetracyclines

Eravacycline and comparators were tested against carbapenem- and tigecycline-resistant Enterobacteriaceae and Acinetobacter isolates received at the United Kingdom's national reference laboratory. Eravacycline MICs correlated closely with those of tigecycline but mostly were around 2-fold lower; both molecules retained full activity against isolates with high-level tetracycline and minocycline resistance. MIC90s of eravacycline and tigecycline were raised ca. 2-fold for carbapenem-resistant Enterobacteriaceae compared with carbapenem-susceptible controls, probably reflecting subsets of isolates with increased efflux.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Microbial Sensitivity Tests; Minocycline; Tetracyclines; Tigecycline

Eravacycline demonstrated in vitro activity against a contemporary collection of more than 4,000 Gram-negative pathogens from New York City hospitals, with MIC50/MIC90 values, respectively, for Escherichia coli of 0.12/0.5 μg/ml, Klebsiella pneumoniae of 0.25/1 μg/ml, Enterobacter aerogenes of 0.25/1 μg/ml, Enterobacter cloacae 0.5/1 μg/ml, and Acinetobacter baumannii of 0.5/1 μg/ml. Activity was retained against multidrug-resistant isolates, including those expressing KPC and OXA carbapenemases. For A. baumannii, eravacycline MICs correlated with increased expression of the adeB gene.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Hospitals; Humans; Microbial Sensitivity Tests; New York City; Tetracyclines