In vitro activity of ceftazidime, ceftaroline and aztreonam alone and in combination with avibactam against European Gram-negative and Gram-positive clinical isolates

Recent clinical isolates of key Gram-negative and Gram-positive bacteria were collected in 2012 from hospitalised patients in medical centres in four European countries (France, Germany, Italy and Spain) and were tested using standard broth microdilution methodology to assess the impact of 4 mg/L avibactam on the in vitro activities of ceftazidime, ceftaroline and aztreonam. Against Enterobacteriaceae, addition of avibactam significantly enhanced the level of activity of these antimicrobials. MIC90 values (minimum inhibitory concentration that inhibits 90% of the isolates) of ceftazidime, ceftaroline and aztreonam for Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Enterobacter aerogenes, Citrobacter freundii and Morganella morganii were reduced up to 128-fold or greater when combined with avibactam. A two-fold reduction in the MIC90 of ceftazidime to 8 mg/L was noted in Pseudomonas aeruginosa isolates when combined with avibactam, whereas little effect of avibactam was noted on the MIC values of the test compounds when tested against Acinetobacter baumannii isolates. Avibactam had little effect on the excellent activity of ceftazidime, ceftaroline and aztreonam against Haemophilus influenzae. It had no impact on the in vitro activity of ceftazidime and ceftaroline against staphylococci and streptococci. This study demonstrates that addition of avibactam enhances the activities of ceftazidime, ceftaroline and aztreonam against Enterobacteriaceae and P. aeruginosa but not against A. baumannii

BIOnic Liquids: Imidazolium-based Ionic Liquids with Antimicrobial Activity

We have synthesized twelve new ionic liquids composed of an imidazolium-based cation in combination with an anion that shows antiobiotic or analgesic activity. These BIOnic Liquids have been tested towards their antibiotic activity in a standardized microbiological assay. A surprizingly large number of compounds shows high activity towards a set of bacteria which cannot be explained as simple cumulative effects. The general concept opens up completely new possibilities for the future development of pharmaceutically active compounds

Evaluation of Quantitative Antibiotic Susceptibility Testing by Vitek 2 as a Routine Method To Predict Strain Relatedness of Coagulase-Negative Staphylococci Isolated from Blood Cultures▿

To test the hypothesis that the strain relatedness of coagulase-negative staphylococci (CoNS) recovered from blood cultures can be inferred from automated antibiotic susceptibility testing (AST) results generated by Vitek 2, concordant or discordant AST results were compared with pulsed-field gel electrophoresis (PFGE) typing results for 119 CoNS blood culture isolate pairs. Concordant AST results were highly predictive of the strain relatedness of CoNS isolates

In vitro activity of the novel fluorocycline TP-6076 against carbapenem-resistant Acinetobacter baumannii

The activity of the novel, fully synthetic fluorocycline antibiotic TP-6076 against carbapenem-resistant Acinetobacter baumannii (CRAB) isolates with defined carbapenem resistance mechanisms was compared against reference antimicrobials with known activity against Acinetobacter spp. The susceptibility of 323 non-duplicate CRAB isolates to TP-6076, amikacin, ampicillin/sulbactam (SAM), cefepime, colistin, doxycycline, eravacycline, imipenem, levofloxacin, meropenem, minocycline, rifampicin, sulbactam, tigecycline, tobramycin and trimethoprim/sulfamethoxazole (SXT) was determined by the broth microdilution method. TP-6076 showed greater activity than comparator antimicrobials of the tetracycline class, SAM, levofloxacin, amikacin, tobramycin, SXT and colistin. MIC50 and MIC90 values for TP-6076 were 0.06 mg/L and 0.25 mg/L, respectively. In comparison, doxycycline, eravacycline, minocycline and tigecycline MIC50/90 values were 32/>64, 0.5/1, 4/8 and 1/2 mg/L, respectively. Compared with other compounds, TP-6076 was the most active antimicrobial against CRAB, including isolates that were resistant to other anti-Acinetobacter reference drugs including SAM, colistin, the aminoglycosides amikacin and tobramycin, and levofloxacin. TP-6076 is a promising new agent that may be a useful addition to the limited armamentarium of drugs targeting this problematic pathogen. (C) 2019 Elsevier B.V. and International Society of Chemotherapy. All rights reserved

In-vitro activity of the novel fluorocycline eravacycline against carbapenem non-susceptible Acinetobacter baumannii

The activity of eravacycline was compared with that of anti-Acinetobacter reference antimicrobials against carbapenem non-susceptible Acinetobacter baumannii isolates associated with an acquired OXA or up-regulation of the intrinsic OXA-51-like enzyme. Antimicrobial susceptibility testing was performed by broth microdilution of 286 non-duplicate, carbapenem non-susceptible A. baumannii isolates to eravacycline, amikacin colistin, doxycycline, imipenem, levofloxacin, meropenem, minocycline, sulbactam, tigecycline and tobramycin. Eravacycline showed greater activity than the comparators of the tetracycline class, levofloxacin, amikacin, tobramycin and colistin. The eravacycline MIC50/90 valueswere 0.5/1 mg/L and those for tigecycline, minocycline and doxycycline were 1/2, 4/8 and 32/>= 64 mg/L, respectively. In conclusion, eravacycline was the most potent antibiotic of those tested against A. baumannii, including isolates that were resistant to sulbactam, imipenem/meropenem, levofloxacin and amikacin/tobramycin. Eravacycline has the potential to become a useful addition to the limited armamentarium of drugs that can be used to treat this problem pathogen. (c) 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved

Head-to-Head Comparison of Two Multi-Locus Sequence Typing (MLST) Schemes for Characterization of Acinetobacter baumannii Outbreak and Sporadic Isolates.

To compare the two Acinetobacter baumannii multi-locus sequence typing (MLST) schemes and to assess their suitability to aid in outbreak analysis we investigated the molecular epidemiology of 99 Acinetobacter baumannii isolates representing outbreak-related and sporadic isolates from 24 hospitals in four different countries (Germany, Poland, Sweden, and Turkey). Pulsed-field gel electrophoresis (PFGE) was used as the reference method to determine the epidemiologic relatedness of isolates and compared to MLST using both the Oxford and Pasteur scheme. Rep-PCR was used to define international clonal lineages (IC). We identified 26 unique outbreak strains and 21 sporadic strains. The majority of outbreaks were associated with carbapenem-resistant A. baumannii harbouring oxacillinase OXA-23-like and corresponding to IC 2. Sequence types (STs) obtained from the Oxford scheme correlate well with PFGE patterns, while the STs of the Pasteur scheme are more in accordance with rep-PCR grouping, but neither one is mirroring completely the results of the comparator. On two occasions the Oxford scheme identified two different STs within a single outbreak where PFGE patterns had only one band difference. The CCs of both MLST schemes were able to define clonal clusters that were concordant with the ICs determined by rep-PCR. IC4 corresponds to the previously described CC15 Pasteur (= CC103 Oxford). It can be concluded that both MLST schemes are valuable tools for population-based studies. In addition, the higher discriminatory power of the Oxford scheme that compares with the resolution obtained with PFGE can often aid in outbreak analysis