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A Gramegna, B C Millar, F Blasi, J S Elborn, D G Downey, J E Moore
INTRODUCTION: Pulmonary exacerbations in people with Cystic Fibrosis (CF), with chronic Gram-negative pathogens, are associated with reduced survival. These pathogens are usually treated with repeated courses of systemic antibiotics. However there is a linked emergence of multidrug resistant (MDR) pathogens. Ceftolozane/tazobactam is a new cephalosporin/beta-lactamase inhibitor combination that has been demonstrated to have good activity against MDR Pseudomonas aeruginosa. MATERIAL & METHODS: In this study ceftolozane/tazobactam was compared to other commonly used intravenous antibiotics against 193 non-fermenting Gram-negative bacteria isolated from CF sputum specimens, including P...
March 17, 2018: Journal of Global Antimicrobial Resistance
M Montero, Brian D VanScoy, Carla López-Causapé, Haley Conde, Jonathan Adams, Concepción Segura, Laura Zamorano, Antonio Oliver, Juan P Horcajada, Paul G Ambrose
The aim of this study was to investigate the efficacy of ceftolozane-tazobactam in combination with meropenem against an extensively drug-resistant (XDR) Pseudomonas aeruginosa high-risk clone, ST175, isolated in a Spanish university hospital. A 14-day hollow-fiber infection model was used to simulate clinical exposure of the 2 drug regimens alone and in combination, and serial samples were collected to determine drug concentrations and colony-forming unit (CFU) counts. The untreated control failed, as did each study regimen when administered alone...
March 12, 2018: Antimicrobial Agents and Chemotherapy
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
Brian Yu, Adedayo Adedoyin, Ellie Hershberger, Luzelena Caro, Alan Xiao, Elizabeth G Rhee, Jennifer A Huntington
Ceftolozane/tazobactam is an antibacterial approved at 1.5 g (1g/0.5 g) every 8 hours (q8h); higher doses may provide additional benefits in difficult-to-treat infections. We conducted a phase I trial in healthy adults evaluating safety, tolerability, and pharmacokinetics of 3 g (2 g/1 g) ceftolozane/tazobactam administered q8h for 10 days. Sixteen participants were randomized (2:1:1) to 3 g ceftolozane/tazobactam, 1.5 g ceftolozane/tazobactam, or placebo. Participants underwent regular safety and plasma drug level assessments, with a follow-up safety visit 7 days after completion...
March 8, 2018: Clinical Pharmacology in Drug Development
Daniele Roberto Giacobbe, Matteo Bassetti, Francesco Giuseppe De Rosa, Valerio Del Bono, Paolo Antonio Grossi, Francesco Menichetti, Federico Pea, Gian Maria Rossolini, Mario Tumbarello, Pierluigi Viale, Claudio Viscoli
Ceftolozane/tazobactam (C/T) is a new antibiotic resulting from the combination of a novel cephalosporin, structurally similar to ceftazidime, with tazobactam, a well-known beta-lactamase inhibitor. C/T remains active against extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and multi-drug resistant (MDR) P. aeruginosa, and has been recently approved for the treatment of complicated intra-abdominal infections (cIAI) and complicated urinary tract infections (cUTI). A trial on hospital-acquired pneumonia is ongoing...
March 9, 2018: Expert Review of Anti-infective Therapy
V Rico-Caballero, Safa Almarzoky Abuhussain, Joseph L Kuti, David P Nicolau
Combination therapy is an attractive option for the treatment of multidrug resistant (MDR) Pseudomonas aeruginosa infections; however, limited data are available on combinations with ceftolozane/tazobactam (C/T). The in vitro pharmacodynamic chemostat model was employed to compare human simulated exposures of C/T 3g q8h alone or in combination with amikacin 25 mg/kg daily or colistin 360 mg daily against four MDR P. aeruginosa isolates. C/T alone resulted in 24 hour CFU changes of -0.02±0.21, -1.81±0.55, -1...
February 26, 2018: Antimicrobial Agents and Chemotherapy
Elaine Chan, Paolo Martelli, Suk-Wai Hui, Jade L L Teng, Susanna K P Lau, Patrick C Y Woo
Burkholderia pseudomallei is the cause of melioidosis, a potentially serious and fatal disease characterized by community-acquired pneumonia and/or sepsis mainly in Southeast Asia and Northern Australia, and high case-fatality rates of up to 19% are observed in endemic areas (1).
February 26, 2018: Antimicrobial Agents and Chemotherapy
Morgan Hakki, James S Lewis
Multidrug-resistant (MDR) Pseudomonas aeruginosa infection causes significant mortality among patients with hematologic malignancies and hematopoietic-cell transplant recipients. Ceftolozane-tazobactam (C-T) is a novel therapeutic option for MDR-P. aeruginosa infections but clinical experience in these patients is limited. We report favorable clinical outcomes and lack of limiting toxicities using C-T monotherapy to treat invasive MDR-P. aeruginosa infections in these patient populations.
February 19, 2018: Infection
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
Helena Žemličková, Vladislav Jakubů, Marta Fridrichová
OBJECTIVE: Ceftolozane/tazobactam is an antibiotic effective against Gram-negative bacteria(including Pseudomonas aeruginosa).The study aimed at determining the effectiveness of the novel antibiotic in the Czech Republic. MATERIAL AND METHODS: The effectiveness of the antibiotic was studied in 16 Czech laboratories in 822 Enterobacteriaceae isolates (including AmpC and ESBL producers) and P. aeruginosa causing complicated intraabdominal or urinary tract infections...
December 2017: Klinická Mikrobiologie a Infekc̆ní Lékar̆ství
Marc Xipell, Sandra Paredes, Leticia Fresco, Marta Bodro, Francesc Marco, J A Martínez, Alex Soriano
The incidence of infections caused by multidrug resistant Pseudomonas aeruginosa (MDR-PA) has become a concern of increasing relevance nowadays. Ceftolozane/tazobactam is a novel 5th generation cephalosporin/β-lactamase inhibitor combination with activity against MDR-PA.
January 20, 2018: Journal of Global Antimicrobial Resistance
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
Sidra Hassan, Mani D Kahn, Nidhi Saraiya, Priya Nori
According to the Centers for Disease Control and Prevention (CDC), approximately 51 000 healthcare-associated infections caused by Pseudomonas aeruginosa occur annually in the USA, more than 6000 of which (13%) are caused by multidrug resistant (MDR) strains. Ceftolozane/tazobactam (TOL/TAZ) (Zerbaxa) was approved by the US Food and Drug Administration (FDA) in December 2014 for the treatment of complicated intra-abdominal and urinary tract infections. At this time, clinical data on the role of TOL/TAZ treatment outside of FDA-approved indications is limited...
January 5, 2018: BMJ Case Reports
Andrew Walkty, Heather Adam, Melanie Baxter, Philippe Lagacé-Wiens, James A Karlowsky, Daryl J Hoban, George G Zhanel
Objectives: Ceftolozane/tazobactam is a novel β-lactam β-lactamase inhibitor combination with a broad spectrum of activity that includes Pseudomonas aeruginosa. The purpose of this study was to evaluate the in vitro activity of ceftolozane/tazobactam and relevant comparators versus a large collection of antimicrobial non-susceptible P. aeruginosa clinical isolates recovered from patients across Canada (CANWARD, 2008-16). Methods: Susceptibility testing was performed on P...
December 12, 2017: Journal of Antimicrobial Chemotherapy
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
Tommaso Giani, Fabio Arena, Simona Pollini, Vincenzo Di Pilato, Marco Maria D'Andrea, Lucia Henrici De Angelis, Matteo Bassetti, Gian Maria Rossolini
Objectives: Pseudomonas aeruginosa is a major cause of severe healthcare-associated infections and often shows MDR phenotypes. Ceftolozane/tazobactam is a new cephalosporin/β-lactamase inhibitor combination with potent activity against P. aeruginosa. This survey was carried out to evaluate the susceptibility of P. aeruginosa, circulating in Italy, to ceftolozane/tazobactam and comparators and to investigate the molecular epidemiology of carbapenemase-producing strains. Methods: Consecutive non-replicate P...
December 5, 2017: Journal of Antimicrobial Chemotherapy
Romney M Humphries, Janet A Hindler, Paul Magnano, Annie Wong-Beringer, Robert Tibbetts, Shelley A Miller
The performance characteristics of the ceftolozane-tazobactam (C-T) Etest (bioMérieux, Marcy l'Etoile, France), MIC test strips (MTS; Liofilchem, Italy), and disk diffusion (Hardy, Santa Ana, CA) were evaluated for a collection of 308 beta-lactam-resistant isolates of Pseudomonas aeruginosa recovered from three institutions in Los Angeles, CA. Reference testing was performed by the reference broth microdilution (rBMD) method. MIC and disk results were interpreted using Clinical and Laboratory Standards Institute breakpoints...
March 2018: Journal of Clinical Microbiology
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
Katie Stokem, Jonathan B Zuckerman, David P Nicolau, Minkey Wungwattana, Edmund H Sears
We report the successful use of ceftolozane/tazobactam (C/T) to treat a pulmonary exacerbation in a 35 year old female, post lung transplant, with cystic fibrosis (CF), malnutrition, chronic kidney disease, and multi-drug resistant Pseudomonas aeruginosa infection (MDR PSA). Given the complexity of the clinical profile, we measured drug levels of C/T during treatment of her current exacerbation to determine pharmacokinetics. The patient achieved an estimated ceftolozane peak of 174.1 μg/mL and trough of 9...
2018: Respiratory Medicine Case Reports
B Dietl, I Sánchez, P Arcenillas, E Cuchi, L Gómez, F J González de Molina, L Boix-Palop, J Nicolás, E Calbo
Infections due to multidrug-resistant bacteria (MDR) are currently a clinical challenge, mainly in elderly patients. The antimicrobial spectrum, safety and efficacy of ceftolozane/tazobactam (C/T) make it an attractive option for the treatment of MDR bacterial infections beyond the indications approved to date. Here we report our experience with C/T in four cases of osteomyelitis and three cases of skin and soft-tissue infections due to extensively-drug-resistant Pseudomonas aeruginosa.
March 2018: International Journal of Antimicrobial Agents
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