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ceftazidime avibactam

Norelle Sherry, Benjamin Howden
Multidrug-resistant (MDR) and extensively-drug-resistant (XDR) Gram-negative bacteria have emerged as a major threat to human health globally. This has resulted in the "re-discovery" of some older antimicrobials and development of new agents, however resistance has also rapidly emerged to these agents. Areas Covered: Here we describe recent developments in resistance to three of the most important last-line antimicrobials for treatment of MDR and XDR Gram negatives: fosfomycin, colistin and ceftazidime-avibactam...
March 15, 2018: Expert Review of Anti-infective Therapy
David P Nicolau, Brittany A Rodrigueza, Jennifer E Girottoa
The rise in multidrug-resistant (MDR) infections has become a significant problem in both the developing countries and in the United States (U.S.). Specifically, MDR gram-negative infections are emerging, affecting not only adults but children as well. The specific gram-negative organisms that have been most concerning within the pediatric population include MDR P. aeruginosa, Enterobacteriaceae, and Acinetobacter spp. The increase in antimicrobial resistance rates are associated with various mechanisms, with, one of the most common being the production of beta-lactamases...
March 8, 2018: Current Pediatric Reviews
Ryan K Shields, M Hong Nguyen, Liang Chen, Ellen G Press, Barry N Kreiswirth, Cornelius J Clancy
Ceftazidime-avibactam was used to treat 77 patients with carbapenem-resistant Enterobacteriaceae (CRE) infections at our center. Thirty- and 90-day survival rates were 81% and 69%, respectively; rates were higher than predicted by SAPS II and SOFA scores at the onset of infection. Clinical success was achieved in 55% of patients, but varied by site of infection. Success rates were lowest for pneumonia (36%) and higher for bacteremia (75%) and urinary tract infections (88%). By multivariate analysis, pneumonia ( P =0...
March 5, 2018: Antimicrobial Agents and Chemotherapy
Norelle L Sherry, Sarah L Baines, Benjamin P Howden
Avibactam is a novel β-lactamase inhibitor active against classes A, C and some class D β-lactamases. In combination with ceftazidime, it may be useful for the treatment of infections due to carbapenemase-producing Gram negative (CPGN) bacteria from these classes; however, susceptibility data for some of the less-common carbapenemases are limited. To assess the in vitro activity of ceftazidime-avibactam (CZA), we tested a panel of fifty diverse CPGN collected from clinical isolates in Victoria, Australia, containing KPC, GES, SME, OXA-23 and OXA-48-like carbapenemases for CZA susceptibility using broth microdilution (BMD), E-tests and disc diffusion...
February 27, 2018: International Journal of Antimicrobial Agents
Jesús Rodríguez-Baño, Belén Gutiérrez-Gutiérrez, Isabel Machuca, Alvaro Pascual
Therapy of invasive infections due to multidrug-resistant Enterobacteriaceae (MDR-E) is challenging, and some of the few active drugs are not available in many countries. For extended-spectrum β-lactamase and AmpC producers, carbapenems are the drugs of choice, but alternatives are needed because the rate of carbapenem resistance is rising. Potential active drugs include classic and newer β-lactam-β-lactamase inhibitor combinations, cephamycins, temocillin, aminoglycosides, tigecycline, fosfomycin, and, rarely, fluoroquinolones or trimethoprim-sulfamethoxazole...
April 2018: Clinical Microbiology Reviews
Sherwin K B Sy, Luning Zhuang, Huiming Xia, Marie-Eve Beaudoin, Virna J Schuck, Wright W Nichols, Hartmut Derendorf
Objectives: To characterize quantitatively the effect of avibactam in potentiating ceftazidime against MDR Pseudomonas aeruginosa by developing a mathematical model to describe the bacterial response to constant concentration time-kill information and validating it using both constant and time-varying concentration-effect data from in vitro and in vivo infection systems. Methods: The time course of the bacterial population dynamics in the presence of static concentrations of ceftazidime and avibactam was modelled using a two-state pharmacokinetic/pharmacodynamic (PK/PD) model, consisting of active and resting states, to account for bactericidal activities, bacteria-mediated ceftazidime degradation and inhibition of degradation by avibactam...
February 3, 2018: Journal of Antimicrobial Chemotherapy
Barbara A Santevecchi, Tiffeny T Smith, Shawn H MacVane
BACKGROUND: Ceftazidime/avibactam is a newly approved β-lactam/β-lactamase inhibitor combination with activity against antibiotic-resistant gram-negative organisms, including many carbapenem-resistant strains. While this agent may offer a promising treatment option for serious infections with limited alternatives available, clinical experience with ceftazidime/avibactam in treatment of infections caused by multidrug-resistant gram-negative organisms outside of Klebsiella pneumoniae is limited...
February 2, 2018: International Journal of Antimicrobial Agents
Chau-Chyun Sheu, Shang-Yi Lin, Ya-Ting Chang, Chun-Yuan Lee, Yen-Hsu Chen, Po-Ren Hsueh
The spread of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae has become a major public health threat worldwide. Area covered: A thorough systematic literature review describing the current evidence and future prospects of therapeutic options for infections caused by ESBL-producing Enterobacteriaceae. Expert commentary: The methods of detecting ESBLs have been evolving. The Clinical and Laboratory Standards Institute and the European Committee on Antimicrobial Susceptibility Testing lowered the MIC breakpoints of cephalosporins against ESBL-producing Enterobacteriaceae in 2010...
March 2018: Expert Review of Anti-infective Therapy
Marco Falcone, Pierluigi Viale, Giusy Tiseo, Manjunath Pai
Ceftazidime-avibactam (CAZ-AVI) is a combination of a third-generation cephalosporin and a non-β-lactam, β-lactamase inhibitor, recently approved for urinary tract infections and complicated abdominal infections. Moreover, it represents a treatment option for patients with hospital acquired pneumonia (HAP), especially when caused by multidrug-resistant (MDR) bacteria. Areas covered: The review focuses on the pharmacokinetics (PK) of CAZ-AVI in HAP and on preclinical and clinical studies evaluating PK/pharmacodynamics (PD) in this field...
January 31, 2018: Expert Opinion on Drug Metabolism & Toxicology
María García-Castillo, Sergio García-Fernández, Rosa Gómez-Gil, Cristina Pitart, Marina Oviaño, Irene Gracia-Ahufinger, Jazmín Díaz-Regañón, Marta Tato, Rafael Cantón
The increasing rates of carbapenemase-producing Enterobacteriaceae (CPE) represent an important threat to health care systems and make treatment of CPE infections a challenge. The aim of the infection-carbapenem resistance evaluation surveillance trial (iCREST) was to determinate the prevalence of CPE in urine specimens in Spain and to evaluate the in vitro activity of ceftazidime-avibactam. Urine specimens (n=11,826) were included and activity of ceftazidime-avibactam and comparators were investigated by broth microdilution in CPE...
January 22, 2018: International Journal of Antimicrobial Agents
Eris Cani, Farzad Moussavi, Eric Ocheretyaner, Roopali Sharma, Clinton Brown, Brandon Eilertson
Ceftazidime-avibactam (CAZ-AVI) is a novel cephalosporin beta lactamase inhibitor combination that has shown activity against carbapenem-resistant Enterobactericeae. Data are limited on its utilization in the treatment of carbapenem-resistant Klebsiella pneumoniae osteomyelitis in solid organ transplant patients. We describe a case report on the use of CAZ-AVI in the treatment of vertebral osteomyelitis in a renal transplant recipient. This article is protected by copyright. All rights reserved.
January 23, 2018: Transplant Infectious Disease: An Official Journal of the Transplantation Society
Matteo Bassetti, Antionio Vena, Nadia Castaldo, Elda Righi, Maddalena Peghin
PURPOSE OF REVIEW: Ventilator-associated pneumonia (VAP) caused by multidrug-resistant (MDR) bacteria represents a global emerging problem. Delayed prescription of an adequate treatment for VAP has been associated with higher morbidity and mortality. New molecules have been developed to face the need of compounds that are active against resistant Gram-positive and Gram-negative pathogens. The aim of this review is to summarize the current scenario of new therapeutic options for the treatment of VAP...
April 2018: Current Opinion in Infectious Diseases
Novella Carannante, Carlo Pallotto, Mariano Bernardo, Giovanni Di Caprio, Carlo Tascini
KPC-producing Klebsiella pneumoniae (KPC-Kp) is nowadays a global concern. Ceftazidime/avibactam is the most promising novel antibiotic combination available at the moment. We describe the case of a migrant with no risk factors for an infection due to multidrug resistant bacteria. He suffered from a KPC-Kp cellulitis and was treated with a ceftazidime/avibactam-meropenem-fosfomycin combination that not only eradicated the infection but also decontaminated his gut. Ceftazidime/avibactam-based treatment can be useful also in decontamination procedures...
January 16, 2018: Journal of Chemotherapy
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
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
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
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
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...
February 1, 2018: Journal of Antimicrobial Chemotherapy
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 on automated systems is unavailable for either agent. Our objective was to compare the disk diffusion and Etest methods to standard broth microdilution (BMD) methods for testing ceftazidime-avibactam and ceftolozane-tazobactam against a diverse collection of carbapenem-resistant Enterobacteriaceae (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRP) isolates, respectively...
February 2018: Journal of Clinical Microbiology
Aurélie Jayol, Patrice Nordmann, Laurent Poirel, Véronique Dubois
No abstract text is available yet for this article.
November 18, 2017: Journal of Antimicrobial Chemotherapy
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