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ceftazidime-avibactam

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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
#1
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-carbapenemase-non-producing-pseudomonas-aeruginosa-and-associated-resistance-mechanisms
#2
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 carbapenemase non-producing CRPA isolates. Forty-two carbapenemase non-producing CRPA isolates from a previous study (Int J Antimicrob Agents 2012;40:168-72) were included...
November 13, 2017: 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
#3
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
#4
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
#5
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
#6
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
#7
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-anti-pseudomonal-%C3%AE-lactams-on-time-to-detection-and-organism-growth-in-blood-culture-bottles
#8
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, 1 resistant), followed by fresh whole blood containing the peak, midpoint, or trough plasma concentrations for meropenem, ceftolozane/tazobactam, and ceftazidime/avibactam...
October 11, 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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/28942664/-clinical-aspects-of-severe-infections-caused-by-antibiotic-resistant-gram-negative-bacteria-the-empire-strikes-back
#14
János Sinkó
In our days, growing incidence of antibiotic resistant bacteria has become an eminent public health problem. For survival Gram-negative species possess several different tools to withstand antibiotics: they produce degrading and modifying enzymes, decrease their permeability or expel drug molecules. An increasing proportion of severe nosocomial infections are caused by strains resistant to several antimicrobials (multiresistant, extensively resistant or panresistant species). Development of new antibiotic compounds may serve as a possible solution to this problem...
October 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/28922809/a-novel-ceftazidime-avibactam-rifabutin-tedizolid-and-moxifloxacin-cartm-regimen-for-pulmonary-mycobacterium-avium-disease
#15
Devyani Deshpande, Shashikant Srivastava, Jotam G Pasipanodya, Pooi S Lee, Tawanda Gumbo
Objectives: To compare the efficacy of ceftazidime/avibactam plus tedizolid-based combination regimens with the standard therapy of azithromycin, ethambutol and rifabutin for the treatment of pulmonary Mycobacterium avium complex (MAC) disease. Methods: We mimicked the human pulmonary concentration-time profiles of ceftazidime/avibactam and tedizolid in combination, ceftazidime/avibactam, rifabutin, tedizolid and moxifloxacin (CARTM), and the standard regimen and examined microbial kill in triplicate hollow-fibre system model of intracellular pulmonary MAC (HFS-MAC) units...
September 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28922808/the-discovery-of-ceftazidime-avibactam-as-an-anti-mycobacterium-avium-agent
#16
Devyani Deshpande, Shashikant Srivastava, Moti L Chapagain, Pooi S Lee, Kayle N Cirrincione, Jotam G Pasipanodya, Tawanda Gumbo
Objectives: To determine if ceftaroline and ceftazidime combined with avibactam are efficacious against pulmonary Mycobacterium avium complex (MAC) disease. Methods: First, we performed a concentration-effect study of ceftaroline and ceftaroline/avibactam against extracellular MAC in test tubes. Given the difficulty of obtaining avibactam at the time of experimentation, we used a single concentration of commercial ceftazidime/avibactam, and two sets of non-treated controls, one with ceftazidime/avibactam and the other without...
September 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28893690/new-agents-for-the-treatment-of-infections-with-gram-negative-bacteria-restoring-the-miracle-or-false-dawn
#17
REVIEW
H Wright, R A Bonomo, D L Paterson
BACKGROUND: Antibiotic resistance in Gram-negative resistance has developed without a commensurate response in the successful development of antibiotic agents, though recent progress has been made. AIMS: This review aims to provide a summary of the existing evidence on efficacy, spectrum of activity and the development of resistance of new agents that have been licensed or have completed advanced clinical trials and that possess activity against resistant Gram-negative organisms...
October 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28882013/antimicrobial-management-in-nosocomial-peritonitis-microbiota-drug-and-time
#18
REVIEW
A Montero, P Salgado Aranda, F Gilsanz, E Maseda
Complicated intra-abdominal infection requires surgical treatment and broad-spectrum empiric antibiotic treatment used early. The rapid spread of multidrug-resistant bacteria has become a serious threat, especially in critical care units. The excessive use of carbapenems has led to carbapenemase-producing Enterobacteriaceae, leaving tigecycline and colistin as therapeutical options. The new antimicrobials, ceftazidime-avibactam and ceftolozane-tazobactam open new horizons in the treatment of multi-drug resistant Enterobacteriaceae...
September 2017: Revista Española de Quimioterapia: Publicación Oficial de la Sociedad Española de Quimioterapia
https://www.readbyqxmd.com/read/28876489/structural-mechanistic-insights-into-the-efficacy-of-nonclassical-%C3%AE-lactamase-inhibitors-against-extensively-drug-resistant-stenotrophomonas-maltophilia-clinical-isolates
#19
Karina Calvopiña, Philip Hinchliffe, Jürgen Brem, Kate J Heesom, Samar Johnson, Ricky Cain, Christopher T Lohans, Colin W G Fishwick, Christopher J Schofield, James Spencer, Matthew B Avison
Clavulanic acid and avibactam are clinically deployed serine β-lactamase inhibitors, important as a defence against antibacterial resistance. Bicyclic boronates are recently discovered inhibitors of serine and some metallo β-lactamases. Here, we show that avibactam and a bicyclic boronate inhibit L2 (serine β-lactamase) but not L1 (metallo β-lactamase) from the extensively drug resistant human pathogen Stenotrophomonas maltophilia. X-ray crystallography revealed that both inhibitors bind L2 by covalent attachment to the nucleophilic serine...
November 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28875168/ceftazidime-avibactam-has-potent-sterilizing-activity-against-highly-drug-resistant-tuberculosis
#20
Devyani Deshpande, Shashikant Srivastava, Moti Chapagain, Gesham Magombedze, Katherine R Martin, Kayle N Cirrincione, Pooi S Lee, Thearith Koeuth, Keertan Dheda, Tawanda Gumbo
There are currently many patients with multidrug-resistant and extensively drug-resistant tuberculosis. Ongoing transmission of the highly drug-resistant strains and high mortality despite treatment remain problematic. The current strategy of drug discovery and development takes up to a decade to bring a new drug to clinical use. We embarked on a strategy to screen all antibiotics in current use and examined them for use in tuberculosis. We found that ceftazidime-avibactam, which is already used in the clinic for multidrug-resistant Gram-negative bacillary infections, markedly killed rapidly growing, intracellular, and semidormant Mycobacterium tuberculosis in the hollow fiber system model...
August 2017: Science Advances
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