Avibactam is a covalent reversible non-β-lactam β-lactamase inhibitor. doi:10.1073/pnas.1501049112.Įhmann DE, Jahić H, Ross PL, Gu RF, Hu J, Kern G, Walkup GK, Fisher SL. La Bibliothque Virtuelle de Sant est une collection de sources d'information scientifiques et techniques en sant, organise et stocke dans un format lectronique dans les pays de la Rgion d'Amrique Latine et des Carabes, universellement accessible sur Internet et compatible avec les bases de donnes internationales. Genomic analysis of diversity, population structure, virulence, and antimicrobial resistance in Klebsiella pneumoniae, an urgent threat to public health. Holt KE, Wertheim H, Zadoks RN, Baker S, Whitehouse CA, Dance D, Jenney A, Connor TR, Hsu LY, Severin J, Brisse S, Cao H, Wilksch J, Gorrie C, Schultz MB, Edwards DJ, Nguyen KV, Nguyen TV, Dao TT, Mensink M, Minh VL, Nhu NT, Schultsz C, Kuntaman K, Newton PN, Moore CE, Strugnell RA, Thomson NR. Epidemiological expansion, structural studies, and clinical challenges of new β-lactamases from Gram-negative bacteria.
An update from the Infectious Diseases Society of America. 10 × '20 progress: development of new drugs active against Gram-negative bacilli. World Health Organization, Geneva, Switzerland.īoucher HW, Talbot GH, Benjamin DK, Bradley J, Guidos RJ, Jones RN, Murray BE, Bonomo RA, Gilbert D. Antimicrobial resistance: global report on surveillance. Identification of those PBP targets may allow the development of new diazabicyclooctane derivatives with improved affinity for PBPs or new combination therapies that act on multiple PBP targets. In conclusion, avibactam is able to covalently bind to some bacterial PBPs. aureus, where avibactam was used at a fixed concentration in combination with varied amounts of ceftazidime, the apparent IC50 of ceftazidime was found to be very similar to that determined for ceftazidime when used alone. Sequential Treatment of Biofilms with Aztreonam and Tobramycin Is a Novel Strategy for Combating Pseudomonas aeruginosa Chronic Respiratory Infections.
Interestingly, avibactam was able to significantly enhance labeling of S. aureus, avibactam primarily bound to PBP2, with IC50s of 0.92, 1.1, 3.0, and 51 μg/ml, respectively, whereas binding to PBP3 was observed in Streptococcus pneumoniae (IC50, 8.1 μg/ml). In Escherichia coli, Pseudomonas aeruginosa, Haemophilus influenzae, and S. Avibactam was found to selectively bind to some PBPs. Relative binding (measured here as the 50% inhibitory concentration ) to PBPs was estimated by quantification of fluorescence after gel electrophoresis. The binding of avibactam to PBPs was measured by adding increasing concentrations to membrane preparations of a variety of Gram-positive and Gram-negative bacteria prior to addition of the fluorescent reagent Bocillin FL. Staphylococcus aureus was of particular interest due to the reported β-lactamase activity of PBP4. Although avibactam presents limited antibacterial activity, its acylation ability toward bacterial penicillin-binding proteins (PBPs) was investigated. In vitro induced resistance additionally causes increased resistance against the other beta-lactam antibiotics.Avibactam is a novel non-β-lactam β-lactamase inhibitor that covalently acylates a variety of β-lactamases, causing inhibition. Bactericidal kinetics with fourfold MIC, which is equivalent to MBC, are nearly identical for aztreonam, piperacillin and cefsulodin. Thus, the activity of aztreonam against Pseudomonas aeruginosa is equivalent to that of gentamicin and cefsulodin and better than that of piperacillin and azlocillin in terms of resistance. At a concentration of 8 mg/l 83.3%, at 16 mg/l 92% of the tested strains were susceptible to aztreonam. Gentamicin, cefsulodin, piperacillin and azlocillin were used as comparative agents with known antipseudomonal activity. The possibility of resistance development in vitro was studied. Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and bactericidal kinetics were determined.
The in vitro activity of aztreonam, a synthetic monobactam, was evaluated against 245 strains of Pseudomonas aeruginosa, 130 of them being recent clinical isolates from patients and 115 from hospital environment.