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Avibactam

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https://www.readbyqxmd.com/read/28505331/antimicrobial-susceptibility-of-clinical-isolates-of-neisseria-gonorrhoeae-to-alternative-antimicrobials-with-therapeutic-potential
#1
P R S Lagacé-Wiens, H J Adam, N M Laing, M R Baxter, I Martin, M R Mulvey, J A Karlowsky, D J Hoban, G G Zhanel
Background: The prevalence of MDR Neisseria gonorrhoeae is increasing globally and represents a public health emergency. Development and approval of new anti-gonococcal agents may take years. As a concurrent approach to developing new antimicrobials, the laboratory and clinical evaluation of currently licensed antimicrobials not widely used for the treatment of gonorrhoea may provide new options for the treatment of gonococcal infections. Objectives: To determine the in vitro activity of nine alternative, currently licensed and late-development antimicrobials with the potential to treat gonococcal infections against 112 clinical isolates of N...
May 12, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28483952/outcomes-with-ceftazidime-avibactam-in-patients-with-carbapenem-resistant-enterobacteriaceae-cre-infections-a-multi-center-study
#2
Madeline King, Emily Heil, Safia Kuriakose, Tiffany Bias, Vanthida Huang, Claudine El-Beyrouty, Dorothy McCoy, Jon Hiles, Lynette Richards, Julianne Gardner, Nicole Harrington, Kenneth Biason, Jason Gallagher
Ceftazidime-avibactam is a novel cephalosporin-beta-lactamase inhibitor combination that is active against many carbapenem-resistant Enterobacteriaceae (CRE). We describe a retrospective chart review whereby 60 patients received ceftazidime-avibactam for a CRE infection. In hospital mortality was 32%, 53% of patients had microbiological cure, and 65% had clinical success. In this severely ill population with CRE infections, ceftazidime-avibactam was an appropriate option.
May 8, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28461318/impaired-inhibition-by-avibactam-and-resistance-to-the-ceftazidime-avibactam-combination-due-to-the-d-179-y-substitution-in-the-%C3%AE-lactamase-kpc-2
#3
Fabrice Compain, Michel Arthur
The ceftazidime-avibactam combination was recently shown to be at risk of emergence of resistance under treatment. To gain insight into the underlying mechanism, we have analyzed the catalytic properties of a KPC-2 β-lactamase harboring the D(179)Y substitution. We show that impaired inhibition by avibactam combined with significant residual activity for ceftazidime hydrolysis accounts for resistance. In contrast, the D(179)Y substitution abolished hydrolysis of aztreonam and imipenem indicating these drugs might provide therapeutic alternatives...
May 1, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28439137/compatibility-of-ceftazidime-avibactam-ceftolozane-tazobactam-and-piperacillin-tazobactam-with-vancomycin-in-dextrose-5-in-water
#4
Kevin Meyer, Maressa Santarossa, Larry H Danziger, Eric Wenzler
Objectives: The compatibility of vancomycin with existing and novel β-lactam/β-lactamase inhibitors at clinically relevant concentrations in 5% dextrose in water has not been fully explored to date. Methods: Vancomycin concentrations tested ranged from 5 to 20 mg/mL. Ceftazidime-avibactam was tested at 8, 20, and 40 mg/mL, ceftolozane-tazobactam at 15 mg/mL, and piperacillin-tazobactam at 28 mg/mL. Compatibility of drug admixtures were tested via both simulated and actual y-site infusion. For the simulated y-site compatibility assessment, 1:1 mixtures of each respective drug were analyzed over 24 hours...
March 2017: Hospital Pharmacy
https://www.readbyqxmd.com/read/28416558/in-vitro-discordance-with-in-vivo-activity-humanized-exposures-of-ceftazidime-avibactam-aztreonam-and-tigecycline-alone-and-in-combination-against-new-delhi-metallo-%C3%AE-lactamase-producing-klebsiella-pneumoniae-in-a-murine-lung-infection-model
#5
M L Monogue, L M Abbo, R Rosa, J F Camargo, O Martinez, R A Bonomo, D P Nicolau
The management of infections with New Delhi Metallo-beta-lactamase-1 (NDM) producing bacteria remains clinically challenging given the multi-drug resistant (MDR) phenotype associated with these bacteria. Despite resistance in vitro, ceftazidime-avibactam previously demonstrated in vivo activity against NDM+ Enterobacteriaceae. Herein, we observed in vitro synergy with ceftazidime-avibactam and aztreonam against a MDR K. pneumoniae harboring NDM. In vivo, humanized doses of ceftazidime-avibactam monotherapy resulted in > 2 log10CFU bacterial reduction, therefore, no in vivo synergy was observed...
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28416553/pharmacokinetics-and-dialytic-clearance-of-ceftazidime-avibactam-in-a-critically-ill-patient-on-continuous-venovenous-hemofiltration
#6
Eric Wenzler, Kristen L Bunnell, Susan C Bleasdale, Scott Benken, Larry H Danziger, Keith A Rodvold
Ceftazidime-avibactam 1.25 g every 8 hours was used to treat multi-drug resistant Pseudomonas aeruginosa bacteremia in a critically ill patient on continuous venovenous hemofiltration (CVVH). Pre-filter plasma drug concentrations of ceftazidime and avibactam were measured at 0, 1, 2, 4, 6, and 8 hours along with post-filter and ultrafiltrate concentrations at hours 2 and 6. Plasma pharmacokinetic parameters of ceftazidime and avibactam, respectively, were Cmax 61.10 and 14.54 mg/L, Cmin 31.96 and 8.45 mg/L, t1/2 6...
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28396547/resistance-to-ceftazidime-avibactam-in-klebsiella-pneumoniae-due-to-porin-mutations-and-the-increased-expression-of-kpc-3
#7
Romney M Humphries, Peera Hemarajata
We reported the first clinical case of a ceftazidime-avibactam resistant KPC-3-producing Klebsiella pneumoniae (1), from a patient with no prior history of ceftazidime-avibactam therapy.….
April 10, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28392315/clinical-efficacy-of-ceftazidime-avibactam-versus-other-active-agents-for-the-treatment-of-bacteremia-due-to-carbapenemase-producing-enterobacteriaceae-in-hematologic-patients
#8
Juan J Castón, Isabel Lacort-Peralta, Pilar Martín-Dávila, Belén Loeches, Salvador Tabares, Liz Temkin, Julián Torre-Cisneros, José R Paño-Pardo
OBJECTIVES: The primary objective was to describe clinical features, treatment and outcomes in patients with carbapenemase-producing Enterobacteriaceae (CPE) bacteremia. Additionally, patients treated with ceftazidime/avibactam (study group) were compared to the rest of the patients (comparator group) to determine the influence of the treatment in both crude mortality and clinical cure. METHODS: Multicenter and retrospective study that included patients with hematologic malignancies who had CPE bacteremia...
April 6, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28389354/treating-complicated-carbapenem-resistant-enterobacteriaceae-infections-with-ceftazidime-avibactam-a-retrospective-study-with-molecular-strain-characterisation
#9
Fiorella Krapp, Jennifer L Grant, Sarah H Sutton, Egon A Ozer, Viktorija O Barr
Ceftazidime/avibactam (CAZ/AVI) is the first antimicrobial agent with activity against carbapenem-resistant Enterobacteriaceae (CRE) approved by the US Food and Drug Administration (FDA). Notably, human clinical outcome data for this indication are limited. Therefore, a retrospective study was performed to evaluate the clinical outcomes and bacterial genomic characteristics of patients hospitalised at a tertiary medical centre with CRE infections treated for the first time with CAZ/AVI. From a total of 44 patients with CRE infections, 6 patients were treated with CAZ/AVI...
June 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28374117/virtual-screening-for-potential-inhibitors-of-ctx-m-15-protein-of-klebsiella-pneumoniae
#10
Tayebeh Farhadi, Atefeh Fakharian, Roman S Ovchinnikov
The Gram-negative bacterium Klebsiella pneumoniae, responsible for a wide variety of nosocomial infections in immuno-deficient patients, involves the respiratory, urinary and gastrointestinal tract infections and septicemia. Extended spectrum β-lactamases (ESBL) belong to β-lactamases capable of conferring antibiotic resistance in Gram-negative bacteria. CTX-M-15, a prevalent ESBL reported from Enterobacteriaceae including K. pneumoniae, was selected as a potent anti-bacterial target. To identify the novel drug-like compounds, structure-based screening procedure was employed against downloaded drug-like compounds from ZINC database...
April 3, 2017: Interdisciplinary Sciences, Computational Life Sciences
https://www.readbyqxmd.com/read/28369471/activity-of-cefiderocol-s-649266-against-carbapenem-resistant-gram-negative-bacteria-collected-from-inpatients-in-greek-hospitals
#11
Matthew E Falagas, Tilemachos Skalidis, Konstantinos Z Vardakas, Nicholas J Legakis
Background: Cefiderocol (S-649266), a siderophore cephalosporin, utilizes a novel mechanism of entry into the periplasmic space of Gram-negative bacteria and is broadly stable to ESBLs and carbapenemases. Methods: A collection of carbapenem-resistant Gram-negative bacteria isolated from clinical specimens in 18 Greek hospitals was tested for susceptibility to cefiderocol, meropenem, ceftazidime, cefepime, ceftazidime/avibactam, ceftolozane/tazobactam, aztreonam, amikacin, ciprofloxacin, colistin and tigecycline...
June 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28363526/a-randomised-double-blind-phase-3-study-comparing-the-efficacy-and-safety-of-ceftazidime-avibactam-plus-metronidazole-versus-meropenem-for-complicated-intra-abdominal-infections-in-hospitalised-adults-in-asia
#12
Xinyu Qin, Binh Giang Tran, Min Ja Kim, Lie Wang, Dung Anh Nguyen, Qian Chen, Jie Song, Peter J Laud, Gregory G Stone, Joseph W Chow
Ceftazidime/avibactam comprises the broad-spectrum cephalosporin ceftazidime and the non-β-lactam β-lactamase inhibitor avibactam. This phase 3, randomised, double-blind study (NCT01726023) assessed the efficacy and safety of ceftazidime/avibactam plus metronidazole compared with meropenem in patients with complicated intra-abdominal infection (cIAI) in Asian countries. Subjects aged 18-90 years and hospitalised with cIAI requiring surgical intervention were randomised 1:1 to receive every 8 h either: ceftazidime/avibactam (2000/500 mg, 2-h infusion) followed by metronidazole (500 mg, 60-min infusion); or meropenem (1000 mg, 30-min infusion)...
March 29, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28362938/the-use-of-noncarbapenem-%C3%AE-lactams-for-the-treatment-of-extended-spectrum-%C3%AE-lactamase-infections
#13
Pranita D Tamma, Jesus Rodriguez-Bano
The continued rise in infections caused by extended-spectrum β-lactamase (ESBL)-producing pathogens is recognized globally as one of the most pressing concerns facing the healthcare community. Carbapenems are widely regarded as the antibiotics of choice for the treatment of ESBL-producing infections, even when in vitro activity to other β-lactams has been demonstrated. However, indiscriminant carbapenem use is not without consequence, and carbapenem overuse has contributed to the emergence of carbapenem-resistant Enterobacteriaceae...
April 1, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28348157/exploring-the-landscape-of-diazabicyclooctane-dbo-inhibition-avibactam-avi-inactivation-of-per-2-%C3%AE-lactamase
#14
Melina Ruggiero, Krisztina M Papp-Wallace, Magdalena A Taracila, Maria F Mojica, Christopher R Bethel, Susan D Rudin, Elise T Zeiser, Gabriel Gutkind, Robert A Bonomo, Pablo Power
PER β-lactamases are an emerging family of extended-spectrum β-lactamases (ESBL) found in Gram negative bacteria. PER β-lactamases are unique among class A enzymes as they possess an inverted Ω loop and extended B3 β-strand. These singular structural differences are hypothesized to contribute to their hydrolytic profile against oxyimino-cephalosporins (e.g., cefotaxime and ceftazidime). Here, we tested the ability of avibactam (AVI), a novel non-β-lactam β-lactamase inhibitor to inactivate PER-2. Interestingly, the PER-2 inhibition constants (i...
March 27, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28348155/molecular-%C3%AE-lactamase-characterization-of-aerobic-gram-negative-pathogens-recovered-from-patients-enrolled-in-the-ceftazidime-avibactam-phase-3-trials-for-complicated-intra-abdominal-infections-efficacies-analyzed-against-susceptible-and-resistant-subsets
#15
Rodrigo E Mendes, Mariana Castanheira, Leah N Woosley, Gregory G Stone, Patricia A Bradford, Robert K Flamm
The correlation of clinical efficacy of ceftazidime-avibactam (plus metronidazole) and meropenem was evaluated in subjects infected with Gram-negative isolates having characterized β-lactam resistance mechanisms from the complicated intra-abdominal infection (cIAI) phase 3 clinical trials. Enterobacteriaceae displaying ceftriaxone and/or ceftazidime MIC values of ≥2 μg/ml and Pseudomonas aeruginosa with ceftazidime MIC values of ≥16 μg/ml were characterized for extended-spectrum β-lactamase (ESBL) content...
March 27, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28338347/ceftazidime-avibactam-novel-antimicrobial-combination-for-the-treatment-of-complicated-urinary-tract-infections
#16
Jakhongir F Alidjanov, Moritz Fritzenwanker, Ivan Hoffman, Florian M Wagenlehner
Ceftazidime-avibactam is a combination of a third-generation cephalosporin and a novel non-beta-lactam beta-lactamase inhibitor. This combination was recently recommended for the treatment of complicated urinary tract infections, including acute pyelonephritis, in adults with limited or no alternative treatment options. The current review is aimed to determine activity, efficacy and safety of ceftazidime-avibactam in the treatment of patients with complicated urinary tract infections.
March 24, 2017: Future Microbiology
https://www.readbyqxmd.com/read/28333323/high-ceftazidime-hydrolysis-activity-and-porin-ompk35-deficiency-contribute-to-the-decreased-susceptibility-to-ceftazidime-avibactam-in-kpc-producing-klebsiella-pneumoniae
#17
Zhen Shen, Baixing Ding, Meiping Ye, Peng Wang, Yingmin Bi, Shi Wu, Xiaogang Xu, Qinglan Guo, Minggui Wang
Objectives: To investigate mechanisms for the decreased susceptibility to ceftazidime/avibactam in KPC-producing Klebsiella pneumoniae (KPC-KP). Methods: A total of 24 isolates, 8 each with ceftazidime/avibactam MICs of 4-8, 1-2 and ≤0.5 mg/L, were randomly selected from 214 clinical isolates of KPC-KP, and the β-lactamase hydrolysis activity and porin expression profiles were determined. Plasmid profile and relative expression and copy number of the bla KPC gene were also analysed...
March 15, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28326811/combinations-of-avibactam-and-carbapenems-exhibit-enhanced-potencies-against-drug-resistant-mycobacterium-abscessus
#18
Amit Kaushik, Chhavi Gupta, Stefanie Fisher, Elizabeth Story-Roller, Christos Galanis, Nicole Parrish, Gyanu Lamichhane
AIM: The objective of this study was to assess if avibactam, a new β-lactamase inhibitor, can restore the potency of carbapenems, a sub-class of β-lactams, against Mycobacterium abscessus clinical isolates. MATERIALS & METHODS: Twenty-eight M. abscessus clinical isolates that are resistant to multiple drugs currently used to treat its infection were included. MIC of carbapenems alone and in combination with avibactam against these strains were determined. RESULTS: Tebipenem, an oral carbapenem, and ertapenem and panipenem exhibited the greatest shift in MIC when supplemented with avibactam...
February 16, 2017: Future Microbiology
https://www.readbyqxmd.com/read/28314920/-new-antibiotics-standstill-or-progress
#19
J Rademacher, T Welte
The development of resistance to antibiotics has been ignored for a long time. But nowadays, increasing resistance is an important topic. For a decade no new antibiotics had been developed and it is not possible to quickly close this gap of new resistance and no new drugs. This work presents six new antibiotics (ceftaroline, ceftobiprole, solithromycin, tedizolid, ceftolozane/tazobactam, ceftazidime/avibactam). In part, only expert opinions are given due to lack of study results.The two 5th generation cephalosporins ceftaroline and ceftobiprole have beside their equivalent efficacy to ceftriaxone (ceftaroline) and cefipim (ceftobiprole) high activity against MRSA...
March 17, 2017: Medizinische Klinik, Intensivmedizin und Notfallmedizin
https://www.readbyqxmd.com/read/28303449/novel-beta-lactamase-inhibitors-unlocking-their-potential-in-therapy
#20
REVIEW
Darren Wong, David van Duin
Carbapenem-resistant Enterobacteriaceae are amongst the most feared pathogens due to severely limited treatment options. In response to this threat, three novel β-lactamase inhibitors have been developed in an attempt to reinvigorate and sustain our current antimicrobial therapies. Avibactam, vaborbactam, and relebactam are inhibitor agents with high affinity to Ambler class A and C β-lactamases and favorable outcomes in current clinical trials. However, although they do possess key similarities, these agents have unique differences which may have important clinical implications...
April 2017: Drugs
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