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Ceftolozane tazobactam

Andre Arizpe, Kelly R Reveles, Shrina D Patel, Samuel L Aitken
Resistance to cephalosporins is now common among Gram-negative bacterial infections, including those caused by the Enterobacteriaceae and Pseudomonas aeruginosa, posing a major threat to public health. As resistance to the traditional drugs of choice for these infections, carbapenems, has also become increasingly common, interest in cefepime and piperacillin-tazobactam as carbapenem-sparing alternatives has increased. Additionally, the availability of the novel β-lactam-β-lactamase inhibitor combinations ceftolozane-tazobactam and ceftazidime-avibactam has added to the antimicrobial armamentarium available to treat these multidrug-resistant infections...
December 2016: Current Infectious Disease Reports
Mazen S Bader, Mark Loeb, Annie A Brooks
Urinary tract infections (UTIs) caused by antibiotic-resistant Gram-negative bacteria are a growing concern due to limited therapeutic options. Gram-negative bacteria, specifically Enterobacteriaceae, are common causes of both community-acquired and hospital acquired UTIs. These organisms can acquire genes that encode for multiple antibiotic resistance mechanisms, including extended-spectrum-lactamases (ESBLs), AmpC- β -lactamase, and carbapenemases. The assessment of suspected UTI includes identification of characteristic symptoms or signs, urinalysis, dipstick or microscopic tests, and urine culture if indicated...
October 7, 2016: Postgraduate Medicine
Myra W Popejoy, David L Paterson, Daniel Cloutier, Jennifer A Huntington, Benjamin Miller, Caleb A Bliss, Judith N Steenbergen, Ellie Hershberger, Obiamiwe Umeh, Keith S Kaye
OBJECTIVES: The increase in infections caused by drug-resistant ESBL-producing Enterobacteriaceae (ESBL-ENT) is a global concern. The characteristics and outcomes of patients infected with ESBL-ENT were examined in a pooled analysis of Phase 3 clinical trials of ceftolozane/tazobactam in patients with complicated urinary tract infections (ASPECT-cUTI) and complicated intra-abdominal infections (ASPECT-cIAI). METHODS: Trials were randomized and double blind. The ASPECT-cUTI regimen was 7 days of either intravenous ceftolozane/tazobactam (1...
October 5, 2016: Journal of Antimicrobial Chemotherapy
M J Melchers, E Mavridou, A C van Mil, C Lagarde, J W Mouton
Ceftolozane is a new broad-spectrum cephalosporin and combined with tazobactam to broaden its activity against strains producing extended spectrum beta-lactamases (ESBL). We determined the pharmacodynamics (PD) of the combination in the neutropenic mouse thigh model to determine the optimal exposure of tazobactam. Treatment was started in CD-1 neutropenic mice 2h after infection with ceftolozane q2h alone or in combination with tazobactam using different dose frequencies for 24h and cfu determined in the thighs before and after treatment...
September 26, 2016: Antimicrobial Agents and Chemotherapy
Alberto Hernández-Tejedor, Carmen Débora Merino-Vega, Alfredo Martín-Vivas, Rafael Ruiz de Luna-González, Alberto Delgado-Iribarren, Ángeles Gabán-Díez, Ignacio Temprano-Gómez, Natalia de la Calle-Pedrosa, Ana Isabel González-Jiménez, Alejandro Algora-Weber
INTRODUCTION: Ceftolozane/tazobactam is a novel antibiotic approved for the treatment of complicated intra-abdominal and complicated urinary tract infections. CASE DESCRIPTION: We describe the use of off-label ceftolozane/tazobactam in the management of a multidrug-resistant Pseudomonas aeruginosa bacteremia that was already being treated with colistin and amikacin, the only active antibiotics according to the antibiogram.
September 26, 2016: Infection
P Salgado, F Gilsanz, E Maseda
The rapid spread of multidrug-resistant bacteria has become a serious threat, especially in critical care units, thereby prolonging the hospital stay. Enterobacteriaceae have a high capacity to adapt to any environment. Plasmids are the reason behind their expansion. The choice of empiric therapy for intra-abdominal or urinary infections requires knowledge of the intrinsic microbiological variability of each hospital or critical care unit, as well as the source of infection, safety or antibiotic toxicity, interaction with other drugs, the dosage regimen and the presence of risk factors...
September 2016: Revista Española de Quimioterapia: Publicación Oficial de la Sociedad Española de Quimioterapia
Ivan Gentile, Alberto Enrico Maraolo, Guglielmo Borgia
No abstract text is available yet for this article.
October 2016: Expert Review of Anti-infective Therapy
Marguerite L Monogue, Rebecca S Pettit, Marianne Muhlebach, Jeffrey J Cies, David P Nicolau, Joseph L Kuti
Ceftolozane/tazobactam has potent activity against Pseudomonas aeruginosa, a pathogen associated with cystic fibrosis (CF) acute pulmonary exacerbations (APE). Due to the rapid elimination of many antibiotics, CF patients frequently have altered pharmacokinetics. In this multicenter, open-label study, we describe the population pharmacokinetics and safety of ceftolozane/tazobactam 3g every 8 hours (q8h) in 20 adult CF patients admitted with APE. Population pharmacokinetics were performed by Non-Parametric Adaptive Grid in Pmetrics for R...
August 22, 2016: Antimicrobial Agents and Chemotherapy
Stephen B Vickery, David McClain, Kurt A Wargo
Ceftolozane-tazobactam, a novel β-lactam/β-lactamase inhibitor, was recently approved for the treatment of complicated urinary tract and intraabdominal infections, as monotherapy and in combination with metronidazole, respectively. Ceftolozane-tazobactam exhibits a wide spectrum of activity against both gram-positive bacteria, gram-negative bacteria including multidrug-resistant (MDR) Pseudomonas aeruginosa, and some anaerobic bacteria. Although not currently approved for any pulmonary indication, studies have demonstrated excellent distribution to epithelial lining fluid, indicating that it may be an alternative agent to use in the treatment of respiratory tract infections caused by MDRP...
October 2016: Pharmacotherapy
Anthony Aiudi, Benjamin Miller, Gopal Krishna, Adedayo Adedoyin, Alan Xiao
Ceftolozane/tazobactam, a novel antibacterial with potent activity against Gram-negative pathogens, was developed for treatment of complicated urinary tract infections, including pyelonephritis, and intra-abdominal infections. A phase 1 pharmacokinetic (PK) study of ceftolozane/tazobactam in healthy Japanese, Chinese, and white volunteers was conducted to assess the potential effect of ethnicity on PK. The PK of ceftolozane, tazobactam and tazobactam metabolite M1 were compared after single 1.5-g and 3-g intravenous doses of ceftolozane/tazobactam...
July 30, 2016: Fundamental & Clinical Pharmacology
Jeffrey C Jolliff, Jackie Ho, Jeremiah Joson, Arash Heidari, Royce Johnson
Stenotrophomonas maltophilia is an inherently multidrug resistant (MDR) opportunistic pathogen with many mechanisms of resistance. SENTRY studies reveal decreasing sensitivities of S. maltophilia to trimethoprim-sulfamethoxazole and fluoroquinolones. Ceftolozane-tazobactam (Zerbaxa, Merck & Co., Inc.) a novel intravenous combination agent of a third-generation cephalosporin and β-lactamase inhibitor was demonstrated to have in vitro activity against many Gram-positive, Gram-negative, and MDR organisms. Data for ceftolozane-tazobactam's use outside of Food and Drug Administration (FDA) approved indications has been limited thus far to two case reports which demonstrated its efficacy in pan-resistant Pseudomonas aeruginosa pneumonia...
2016: Case Reports in Infectious Diseases
Mohamed Teleb, Enrique Soto-Ruiz, Delfina C Domínguez, Suresh Antony
Multi drug resistant (MDR) Pseudomonas aeruginosa and Extended-Spectrum-lactamase (ESBL) Enterobacteriaceae are becoming an increasing difficult clinical problem. Immediate resistance to some of the new antimicrobials such as ceftolozane/tazobactam is unusual and is due to a variety of mechanisms such as hy-per-production of inactivating enzymes and gene mutation. In addition, previous antimicrobial administration is a well-recognized risk factor to develop resistance. We present a patient with a liver abscess where the organism was resistant to ceftolozane/tazobactam resulting in a poor clinical outcome...
July 13, 2016: Infectious Disorders Drug Targets
Adamantia Liapikou, Antoni Torres
INTRODUCTION: Hospital-acquired pneumonia (HAP) is one of the leading nosocomial infections worldwide and is associated with an elevated morbidity and mortality and increased hospital costs. Nevertheless, prompt and adequate antimicrobial treatment is mandatory following VAP development, especially in the face of multidrug resistant pathogens. AREAS COVERED: We searched Pubmed and site reports in English language of phase III clinical trials, between 2000-2016 referring to the antibiotic treatment of nosocomial pneumonia...
September 2016: Expert Opinion on Emerging Drugs
(no author information available yet)
No abstract text is available yet for this article.
June 2016: Australian Prescriber
Florian M Wagenlehner, Jakhongir F Alidjanov
INTRODUCTION: Urinary tract infections (UTIs) are the second most common nosocomially acquired infections, responsible for approximately 21% of healthcare-associated pyelonephritis and 10.5% of urosepsis. Worldwide trends of increasing resistance resulted in the urgent need for novel antimicrobials that would be active against bacterial resistance mechanisms as an alternative to carbapenems, which are considered last resort antibiotics. AREAS COVERED: The current review is based on a Medline search of published English language literature and contains summary information regarding the evaluation of pharmacologic properties, efficacy, safety and activity of ceftolozane+tazobactam against common bacterial resistance mechanisms...
August 2016: Expert Opinion on Drug Metabolism & Toxicology
Christina A Sutherland, Jamie E Verastegui, David P Nicolau
BACKGROUND: The purpose of this study was to define the potency of amikacin and comparator agents against a collection of blood and respiratory nosocomial isolates implicated in ICU based pulmonary infections gathered from US hospitals. METHODS: Minimum inhibitory concentrations of amikacin, aztreonam, cefepime, ceftazidime, ceftolozane/tazobactam, ceftriaxone, ciprofloxacin, imipenem, meropenem, piperacillin/tazobactam and tobramycin were tested against 2460 Gram-negative isolates...
2016: Annals of Clinical Microbiology and Antimicrobials
Stephanie E Giancola, Monica V Mahoney, Tiffany E Bias, Elizabeth B Hirsch
The rise in resistant Gram-negative pathogens continues to challenge clinicians treating infections. These resistant infections have inspired the development of new antimicrobial agents, including ceftolozane-tazobactam, a novel β-lactam/β-lactamase inhibitor combination approved by the US Food and Drug Administration for the treatment of complicated urinary tract infections (cUTIs) and complicated intra-abdominal infections (cIAIs) in combination with metronidazole. Ceftolozane exhibits bactericidal activity by inhibiting penicillin-binding proteins (PBPs), with high affinity for PBP1b, PBP1c, and PBP3...
2016: Therapeutics and Clinical Risk Management
Samuel L Aitken, Dimitrios P Kontoyiannis, April M DePombo, Micah M Bhatti, Frank P Tverdek, Suzanne C Gettys, David P Nicolau, Cesar A Nunez
Multidrug-resistant Pseudomonas aeruginosa is of increasing concern in pediatric patients. Ceftolozane/tazobactam is a novel cephalosporin/β-lactamase inhibitor combination with activity against multidrug-resistant Pseudomonas; however, no data exist on its use in children. This report summarizes the treatment of a multidrug-resistant P. aeruginosa bloodstream infection in a pediatric leukemia patient with ceftolozane/tazobactam and provides the first description of its pharmacokinetics in pediatrics.
September 2016: Pediatric Infectious Disease Journal
Dalia Deak, Kevin Outterson, John H Powers, Aaron S Kesselheim
A weak antibiotic pipeline and the increase in drug-resistant pathogens have led to calls for more new antibiotics. Eight new antibiotics were approved by the U.S. Food and Drug Administration (FDA) between January 2010 and December 2015: ceftaroline, fidaxomicin, bedaquiline, dalbavancin, tedizolid, oritavancin, ceftolozane-tazobactam, and ceftazidime-avibactam. This study evaluates the development course and pivotal trials of these antibiotics for their innovativeness, development process, documented patient outcomes, and cost...
September 6, 2016: Annals of Internal Medicine
Andrew W Hahn, Rupali Jain, David H Spach
Antimicrobial drug-resistance continues to force adaptation in our clinical practice. We explore new evidence regarding adjunctive antibiotic therapy for skin and soft tissue abscesses as well as duration of therapy for intra-abdominal abscesses. As new evidence refines optimal practice, it is essential to support clinicians in adopting practice patterns concordant with evidence-based guidelines. We review a simple approach that can 'nudge' clinicians towards concordant practices. Finally, the use of novel antimicrobials will play an increasingly important role in contemporary therapy...
July 2016: Medical Clinics of North America
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