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ceftazidime-avibactam

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https://www.readbyqxmd.com/read/29232103/game-changers-new-%C3%AE-lactamase-inhibitor-combinations-targeting-antibiotic-resistance-in-gram-negative-bacteria
#1
Karen Bush
Recent regulatory approvals for the β-lactam inhibitor combinations of ceftazidime-avibactam and meropenem-vaborbactam have provided two novel therapeutic options for the treatment of multidrug-resistant infections caused by Gram-negative bacteria. Most importantly, these combination agents have satisfied an important medical need related to antibiotic-resistant Klebsiella pneumoniae that produce serine carbapenemases, especially the Klebsiella pneumoniae carbapenemase (KPC) enzymes. Both combinations contain non-β-lactam β-lactamase inhibitors of novel chemical classes not previously developed as antibacterial agents, the diazabicyclooctanes and cyclic boronic acid derivatives...
December 12, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29228202/activity-of-ceftazidime-avibactam-against-problem-enterobacteriaceae-and-pseudomonas-aeruginosa-in-the-uk-2015-16
#2
David M Livermore, Danièle Meunier, Katie L Hopkins, Michel Doumith, Robert Hill, Rachel Pike, Peter Staves, Neil Woodford
Background: Ceftazidime/avibactam combines an established oxyimino-cephalosporin with the first diazabicyclooctane β-lactamase inhibitor to enter clinical use. We reviewed its activity against Gram-negative isolates, predominantly from the UK, referred for resistance investigation in the first year of routine testing, beginning in July 2015. Methods: Isolates were as received from referring laboratories; there is a bias to submit those with suspected carbapenem resistance...
December 8, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29206750/ceftazidime-avibactam-antimicrobial-activity-and-spectrum-when-tested-against-gram-negative-organisms-from-pediatric-patients-results-from-the-inform-surveillance-program-united-states-2011-2015
#3
Helio S Sader, Michael D Huband, Leonard R Duncan, Robert K Flamm
BACKGROUND: Ceftazidime-avibactam was approved by the US Food and Drug Administration in 2015 to treat complicated intra-abdominal and urinary tract infections in adults, and is under clinical development for treating pediatric patients. METHODS: Among 53,381 gram-negative organisms (1 per patient) collected in 2011-2015, 8,461 (15.9%) were from pediatric (≤17 years-old [yo]) patients. The isolates were collected from 82 US medical centers and susceptibility tested against ceftazidime-avibactam (avibactam at fixed 4 µg/mL) and comparators by reference broth microdilution methods...
December 4, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/29191131/efficacy-of-ceftazidime-avibactam-in-a-rat-intra-abdominal-abscess-model-against-a-ceftazidime-and-meropenem-resistant-isolate-of-klebsiella-pneumoniae-carrying-blakpc-2
#4
Taryn Sleger, Eric Gangl, Petar Pop-Damkov, Kevin M Krause, Peter J Laud, Andrew M Slee, Wright W Nichols
Efficacies of ceftazidime-avibactam (4:1 w/w) and ceftazidime were tested against ceftazidime-susceptible (blaKPC-2-negative), and meropenem- and ceftazidime-resistant (blaKPC-2-positive), Klebsiella pneumoniae in a 52-h, multiple dose, abdominal abscess model in the rat. Efficacies corresponded to minimum inhibitory concentrations (MICs) measured in vitro and were consistent with drug exposures modelled from pharmacokinetics in infected animals. The ceftazidime, ceftazidime-avibactam and meropenem control treatments were effective in the rat abscess model against the susceptible strain, whereas only ceftazidime-avibactam was effective against K...
November 30, 2017: Journal of Chemotherapy
https://www.readbyqxmd.com/read/29186402/in-vitro-and-in-vivo-activity-of-single-and-dual-antimicrobial-agents-against-kpc-producing-klebsiella-pneumoniae
#5
Sarath Nath, Farzad Moussavi, Daniel Abraham, David Landman, John Quale
Objectives: Options for treatment of infections due to KPC-producing Klebsiella pneumoniae are limited and combination therapy is often recommended. In this report, the in vitro and in vivo activity of potential therapeutic agents and combinations was assessed against four KPC-producing K. pneumoniae isolates. Methods: Using clinically relevant concentrations, time-kill experiments and the Galleria mellonella model of infection were used to examine the activity of polymyxin B, ceftazidime/avibactam, meropenem, rifampicin and amikacin alone and in combination...
November 23, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29167294/verification-of-ceftazidime-avibactam-and-ceftolozane-tazobactam-susceptibility-testing-methods-against-carbapenem-resistant-enterobacteriaceae-and-pseudomonas-aeruginosa
#6
Ryan K Shields, Cornelius J Clancy, A William Pasculle, Ellen G Press, Ghady Haidar, Binghua Hao, Liang Chen, Barry N Kreiswirth, M Hong Nguyen
Ceftazidime-avibactam and ceftolozane-tazobactam are newly approved agents for the treatment of infections caused by multidrug-resistant Gram negative bacteria. Resistance to both agents has been described clinically. Susceptibility testing for either agent is unavailable on automated systems. Our objective was to compare disk diffusion and Etest against standard broth microdilution (BMD) methods for testing ceftazidime-avibactam and ceftolozane-tazobactam against a diverse collection of carbapenem-resistant Enterobacteriaceae (CRE) and Pseudomonas aeruginosa (CRP), respectively...
November 22, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/29165563/ceftazidime-avibactam-alone-or-in-combination-with-aztreonam-against-colistin-resistant-and-carbapenemase-producing-klebsiella-pneumoniae
#7
Aurélie Jayol, Patrice Nordmann, Laurent Poirel, Véronique Dubois
No abstract text is available yet for this article.
November 18, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29149337/mechanisms-leading-to-in-vivo-ceftolozane-tazobactam-resistance-development-during-the-treatment-of-infections-caused-by-mdr-pseudomonas-aeruginosa
#8
Pablo A Fraile-Ribot, Gabriel Cabot, Xavier Mulet, Leonor Periañez, M Luisa Martín-Pena, Carlos Juan, José L Pérez, Antonio Oliver
Objectives: Characterization of the mechanisms driving ceftolozane/tazobactam resistance development in 5 of 47 (10.6%) patients treated for MDR Pseudomonas aeruginosa infections in a Spanish hospital. Methods: Five pairs of ceftolozane/tazobactam-susceptible/resistant P. aeruginosa isolates were studied. MICs were determined by broth microdilution, clonal relatedness was assessed by MLST and resistance mechanisms were investigated by phenotypic and genotypic methods, including WGS...
November 14, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29133568/activity-of-ceftolozane-tazobactam-against-carbapenem-resistant-non-carbapenemase-producing-pseudomonas-aeruginosa-and-associated-resistance-mechanisms
#9
Yu Mi Wi, Kerryl E Greenwood-Quaintance, Audrey N Schuetz, Kwan Soo Ko, Kyong Ran Peck, Jae-Hoon Song, Robin Patel
Although carbapenems are effective for treating serious multidrug-resistant Pseudomonas aeruginosa infections, carbapenem-resistant P. aeruginosa (CRPA) is now being reported worldwide. Ceftolozane-tazobactam (C/T) demonstrates activity against many multidrug-resistant isolates. We evaluated the activity of C/T and compared its activity to that of ceftazidime-avibactam (C/A) using a well-characterized collection of non-carbapenemase-producing CRPA isolates. Forty-two non-carbapenemase-producing CRPA isolates from a previous study (J...
January 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29125052/prevalence-of-extended-spectrum-beta-lactamase-and-carbapenemase-producing-bloodstream-isolates-of-klebsiella-pneumoniae-in-a-tertiary-care-hospital
#10
Henrietta Abodakpi, Kai-Tai Chang, Ana María Sánchez Díaz, Rafael Cantón, Todd M Lasco, Katrina Chan, Amelia K Sofjan, Vincent H Tam
To improve prescribing of empiric therapy, the local molecular epidemiology of extended-spectrum beta-lactamases (ESBLs) and Klebsiella pneumoniae carbapenemases (KPCs) in bloodstream isolates of K. pneumoniae were evaluated. Isolates resistant to third generation cephalosporins were screened phenotypically for ESBLs and carbapenemases, and subsequently confirmed by PCR for the presence of ESBL (blaTEM, blaSHV and blaCTX-M) and carbapenemase (blaKPC, blaVIM, blaNDM and blaOXA-48) genes. Hydrolytic activity (functional gene expression) was quantified using a nitrocefin degradation assay and correlated to ceftazidime or meropenem MIC...
November 10, 2017: Journal of Chemotherapy
https://www.readbyqxmd.com/read/29110143/pharmacological-aspects-and-spectrum-of-action-of-ceftazidime-avibactam-a-systematic-review
#11
REVIEW
Felipe Francisco Tuon, Jaime L Rocha, Marcelo R Formigoni-Pinto
PURPOSE: Ceftazidime-avibactam is an antimicrobial association active against several Enterobacteriaceae species, including those resistant to carbapenem. Considering the importance of this drug in the current panorama of multidrug-resistant bacteria, we performed a systematic review about ceftazidime-avibactam with emphasis on clinical and pharmacological published data. METHODS: A systematic search of the medical literature was performed. The databases searched included MEDLINE, EMBASE and Web of Science (until September 2017)...
November 7, 2017: Infection
https://www.readbyqxmd.com/read/29089425/klebsiella-pneumoniae-carbapenemase-2-kpc-2-substitutions-at-ambler-position-asp179-and-resistance-to-ceftazidime-avibactam-unique-antibiotic-resistant-phenotypes-emerge-from-%C3%AE-lactamase-protein-engineering
#12
Melissa D Barnes, Marisa L Winkler, Magdalena A Taracila, Malcolm G Page, Eric Desarbre, Barry N Kreiswirth, Ryan K Shields, Minh-Hong Nguyen, Cornelius Clancy, Brad Spellberg, Krisztina M Papp-Wallace, Robert A Bonomo
The emergence of Klebsiella pneumoniae carbapenemases (KPCs), β-lactamases that inactivate "last-line" antibiotics such as imipenem, represents a major challenge to contemporary antibiotic therapies. The combination of ceftazidime (CAZ) and avibactam (AVI), a potent β-lactamase inhibitor, represents an attempt to overcome this formidable threat and to restore the efficacy of the antibiotic against Gram-negative bacteria bearing KPCs. CAZ-AVI-resistant clinical strains expressing KPC variants with substitutions in the Ω-loop are emerging...
October 31, 2017: MBio
https://www.readbyqxmd.com/read/29075539/successful-treatment-of-klebsiella-pneumoniae-harboring-a-klebsiella-pneumoniae-carbapenemase-isolated-from-lumbar-wound-infection-and-blood-in-a-patient-with-hardware-retention
#13
Alan Bulbin, Carol Bono, Tena Philp, Noriel Mariano, Carl Urban
Infections caused by carbapenem-resistant Enterobacteriaceae, especially carbapenemase producing Klebsiella pneumoniae, represent an urgent threat as outlined by the Centers for Disease Control and Prevention (CDC). We present a 66-year-old male with spinal stenosis who underwent elective L2-pelvis posterior spinal fusion at an outside institution and rapidly developed a complicated infection with Klebsiella pneumoniae harboring Klebsiella pneumoniae carbapenemase. This is the first described case of a patient with Klebsiella pneumoniae harboring Klebsiella pneumoniae carbapenemase causing postoperative lumbar wound infection and bacteremia, successfully treated with ceftazidime-avibactam in combination with additional synergistic antibacterials and without hardware removal...
2017: Case Reports in Infectious Diseases
https://www.readbyqxmd.com/read/29040635/ceftazidime-avibactam-use-for-carbapenem-resistant-klebsiella-pneumoniae-meningitis-a-case-report
#14
Amanda Holyk, Valerie Belden, Jonathan J Lee, William Musick, Ryan Keul, Gavin W Britz, Jiejian Lin
No abstract text is available yet for this article.
October 10, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29021155/effects-of-clinically-meaningful-concentrations-of-antipseudomonal-%C3%AE-lactams-on-time-to-detection-and-organism-growth-in-blood-culture-bottles
#15
Mordechai Grupper, David P Nicolau, Jaber Aslanzadeh, Linda K Tanner, Joseph L Kuti
The effectiveness of antimicrobial binding resins present in blood culture (BC) bottles in removing meropenem, ceftolozane-tazobactam, and ceftazidime-avibactam is unknown. We assessed the time to detection (TTD) and growth of 2 Pseudomonas aeruginosa isolates in the presence of clinically meaningful concentrations of these antibiotics. Bactec Plus Aerobic/F and BacT/Alert FA Plus BC bottles were inoculated with one of two isolates (1 meropenem susceptible and 1 resistant), followed by fresh whole blood containing the peak, midpoint, or trough plasma concentrations for meropenem, ceftolozane-tazobactam, and ceftazidime-avibactam...
December 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/29021086/genomic-characterization-of-an-extensively-drug-resistant-kpc-2-producing-klebsiella-pneumoniae-st855-cc258-only-susceptible-to-ceftazidime-avibactam-isolated-in-brazil
#16
Caio Augusto Martins Aires, Michael J Rybak, Juwon Yim, Polyana Silva Pereira, Cláudio M Rocha-de-Souza, Rodolpho Mattos Albano, Valdelucia Oliveira Cavalcanti, Ana Paula D'Alincourt Carvalho-Assef, Marisa Zenaide Ribeiro Gomes, Marise Dutra Asensi
In this study, we describe the genetic features of an XDR KPC-2-producing Klebsiella pneumoniae isolate by using whole-genome sequencing, its clinical-epidemiological context and susceptibility against antimicrobial combinations. The isolate belongs to clonal complex 258 and harbors several acquired genes and mutations associated with antimicrobial resistance.
August 25, 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/29020404/colistin-vs-ceftazidime-avibactam-in-the-treatment-of-infections-due-to-carbapenem-resistant-enterobacteriaceae
#17
David van Duin, Judith J Lok, Michelle Earley, Eric Cober, Sandra S Richter, Federico Perez, Robert A Salata, Robert C Kalayjian, Richard R Watkins, Yohei Doi, Keith S Kaye, Vance G Fowler, David L Paterson, Robert A Bonomo, Scott Evans
Background: The efficacy of ceftazidime-avibactam - a cephalosporin-β-lactamase inhibitor combination with in vitro activity against Klebsiella pneumoniae carbapenemase (KPC)-producing carbapenem-resistant Enterobacteriaceae (CRE) - as compared to colistin remains unknown. Methods: Patients initially treated with either ceftazidime-avibactam or colistin for CRE infections were selected from the Consortium on resistance against carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE), a prospective, multicenter, observational study...
September 4, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28993338/activity-of-ceftolozane-tazobactam-and-ceftazidime-avibactam-against-beta-lactam-resistant-pseudomonas-aeruginosa-isolates
#18
Romney M Humphries, Janet A Hindler, Annie Wong-Beringer, Shelley A Miller
Ceftolozane-tazobactam (C/T) and ceftazidime-avibactam (CZA) minimum inhibitory concentrations were evaluated for a collection of 309 beta-lactam resistant isolates of Pseudomonas aeruginosa recovered from three institutions in Los Angeles, CA. Overall, 12.0% of isolates were susceptible to imipenem, 15.9% to meropenem, 20.7% to piperacillin-tazobactam, 24.6% to ceftazidime and 25.9% to cefepime, 72.5% to C/T and 61.8% to CZA. Among C/T-resistant isolates, 9.1% were CZA-susceptible, whereas 36.4% of CZA-resistant isolates were susceptible to C/T...
October 9, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28978681/high-stringency-evaluation-of-the-automated-bd-phoenix%C3%A2-cpo-detect-and-rapidec%C3%A2-carba-np-tests-for-detection-and-classification-of-carbapenemases
#19
Gina Thomson, David Turner, William Brasso, Susan Kircher, Thierry Guillet, Kenneth Thomson
There is an urgent need for rapid, accurate detection and classification of carbapenemases. The current study evaluated the automated BD Phoenix™ CPO Detect and the manual bioMérieux RAPIDEC® CARBA NP for meeting these needs. Both tests were challenged with 294 Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii chosen to provide extreme diagnostic difficulty. Carbapenemases such as KPC, NMC-A, IMI, SME, NDM, SPM, IMP, VIM, OXA-23, 40, 48, 58, 72, 181, and 232 were produced by 243 isolates and 51 carbapenemase-negative isolates included porin mutants and producers of ESBLs, AmpCs, K1, and broad spectrum β-lactamases...
October 4, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28951106/in-vitro-interaction-of-ceftazidime-avibactam-in-combination-with-different-antimicrobials-against-kpc-producing-klebsiella-pneumoniae-clinical-isolates
#20
Paolo Gaibani, Russell E Lewis, Silvia L Volpe, Maddalena Giannella, Caterina Campoli, Maria Paola Landini, PierLuigi Viale, Maria Carla Re, Simone Ambretti
OBJECTIVES: Combination therapy has been recommended when using ceftazidime-avibactam (CAZ-AVI) for the treatment of KPC-producing Klebsiella pneumoniae (KPC-Kp), but the optimal combination is unknown. Six common antimicrobial agents (ertapenem, imipenem, meropenem, gentamicin, tigecycline, and ciprofloxacin) were evaluated for synergy with the recently approved cephalosporin-β-lactamase inhibitor combination CAZ-AVI in this study. METHODS: Different antimicrobial combinations were tested against 13 KPC-Kp, including CAZ-AVI-susceptible (n=11) and resistant (n=2) clinical isolates...
September 22, 2017: International Journal of Infectious Diseases: IJID
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