Ceftolozane/tazobactam: place in therapy

Giacobbe, Daniele Roberto; Bassetti, Matteo; Rosa, Francesco Giuseppe De; Bono, Valerio Del; Grossi, Paolo; Menichetti, Francesco; Pea, Federico; Rossolini, Gian María; Tumbarello, Mario; Viale, Pierluigi; Viscoli, Claudio; Isgri-Sita,

doi:10.1080/14787210.2018.1447381

Cited by 113 publications

(77 citation statements)

References 106 publications

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“…Ceftolozane-tazobactam is a novel combination of a cephalosporin with a β-lactamase inhibitor that exhibits excellent in vitro activity against a broad spectrum of Enterobacterales and Pseudomonas aeruginosa, including ESBL strains, and has been recently approved for the treatment of complicated intra-abdominal infections (cIAI) and cUTI [36]. The in vitro activity of ceftolozane-tazobactam against ESBL-PE from U.S. hospitals revealed an overall susceptibility of 83.9% (CLSI/EUCAST breakpoints) to ceftolozane-tazobactam.…”

Section: Ceftolozane-tazobactammentioning

confidence: 99%

Carbapenem-Sparing Strategies for ESBL Producers: When and How

2020

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Extended spectrum β-lactamase (ESBL)-producing bacteria are prevalent worldwide and correlated with hospital infections, but they have been evolving as an increasing cause of community acquired infections. The spread of ESBL constitutes a major threat for public health, and infections with ESBL-producing organisms have been associated with poor outcomes. Established therapeutic options for severe infections caused by ESBL-producing organisms are considered the carbapenems. However, under the pressure of carbapenem overuse and the emergence of resistance, carbapenem-sparing strategies have been implemented. The administration of carbapenem-sparing antibiotics for the treatment of ESBL infections has yielded conflicting results. Herein, the current available knowledge regarding carbapenem-sparing strategies for ESBL producers is reviewed, and the optimal conditions for the “when and how” of carbapenem-sparing agents is discussed. An important point of the review focuses on piperacillin–tazobactam as the agent arousing the most debate. The most available data regarding non-carbapenem β-lactams (i.e., ceftolozane–tazobactam, ceftazidime–avibactam, temocillin, cephamycins and cefepime) are also thoroughly presented as well as non β-lactams (i.e., aminoglycosides, quinolones, tigecycline, eravacycline and fosfomycin).

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Section: Ceftolozane-tazobactammentioning

confidence: 99%

Carbapenem-Sparing Strategies for ESBL Producers: When and How

2020

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“…At the registered dose of 1.5 g (1 g/0.5 g) every 8 hours, ceftolozane-tazobactam is currently approved for the therapy of complicated urinary tract and intra-abdominal infections (in the latter case in association with metronidazole). (1, 2) Ceftolozane-tazobactam has been successfully used for treatment of lower respiratory tract infections (LRTI) caused by MDR P. aeruginosa , also in cystic fibrosis patients. (3–5) Results of a phase 3 safety and efficacy study of ceftolozane/tazobactam to treat ventilated nosocomial pneumonia (MK-7625A-008) will be available in the next future.…”

Section: Tablementioning

confidence: 99%

Ceftolozane-tazobactam pharmacokinetics during extracorporeal membrane oxygenation in a lung transplant recipient

Arena¹,

Marchetti

Angelis³

et al. 2018

Preprint

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22Ceftolozane-tazobactam pharmacokinetics during extracorporeal membrane oxygenation (ECMO) 23 has not been previously studied. In this work we report on the ceftolozane and tazobactam 24 plasmatic levels in a lung transplant recipient during ECMO, treated with ceftolozane-tazobactam 25 (2g/1g, intravenously every 8 h, 1 h infusion) for a Pseudomonas aeruginosa pulmonary infection. 26Ceftolozane Cmax and Cmin, monitored during 96 hrs, remained above 60 and 20 µg/mL, 27 respectively, with optimal drug exposure (100% %T MIC ). Tazobactam levels were above 1.9 µg/mL. 28 29 30patient had a normal renal function with creatinine clearance, estimated using the Cockcroft-Gault 83 formula, above 90 mg/min (range 90-150 mg/min) ( Figure 1). 84Ceftolozane and tazobactam plasma concentrations were monitored for 96 h following the first 85 administration. Plasma samples were obtained ½ h after the end of each ceftolozane-tazobactam 86 infusion and immediately before the beginning of the following dose (Cmax and Cmin 87 respectively). The samples were centrifuged at 1,600 g for 10 min to yield at least 1 ml of plasma. 88 Plasma samples were stored at −80°C until the assay. Ceftolozane and tazobactam concentrations 89 were quantified using a validated HPLC method at the Chemotherapy Laboratory of the Department 90 of Health Sciences (University of Florence, Italy). (11) 91In the following days the patient clinical conditions improved and, on day 3 after the lung 92 transplant, the vaECMO was switched again to vvECMO. 93In the 96 h of drug monitoring, the ceftolozane levels remained constantly above the isolate MIC. In 94 the first 48 h, ceftolozane Cmax were persistently above 100 µg/mL. Later, from 48 to 96 h, there 95 was a decline in Cmax and Cmin, which, however, remained above 60 and 20 µg/mL, respectively 96 ( Figure 1). Tazobactam concentration were above 1.9 µg/mL for all the monitored period. 97ECMO was halted on day 8 after lung transplantation. The patient's conditions eventually improved 98 and, on day 15 after lung transplantation, the antimicrobial therapy was discontinued. No adverse 99 events were attributed to the ceftolozane-tazobactam administration. Four consecutive tracheal 100 aspirate cultural exams, performed in the last day of treatment and 3, 4, and 7 days after the 101 antibiotics discontinuation, did not grow P. aeruginosa or any other pathogen. 102Concluding, we documenting the success of ceftolozane-tazobactam treatment for a case of 103 carbapenem-resistant P. aeruginosa LRTI in a lung transplant recipient subjected to ECMO 104 support. TDM revealed that optimal drug exposure was achieved, with a ceftolozane concentration 105 at 100% %T MIC . Of note, in this case, optimal Cmax and Cmin were obtained using a 3 g 106 cefotolozane-tazobactam dose every 8 h, using a standard 1 h infusion time. During the TDM 107 period we assisted to a decrease of ceftolozane/tazobactam Cmin and Cmax that could be attributed 108 6 to the increase in the patient's creatinine clearance values. In fact, it was previo...

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“…This combination displays a potent activity against P. aeruginosa, including MDR isolates, because it is not removed by efflux pumps and displays a higher affinity with penicillin-binding proteins of cell membrane, in addition to stability against extended-spectrum β-lactamases (ESBLs) and overexpression of AmpC. However, ceftolozane/tazobactam has no activity against carbapenemases [15][16][17][18][19][20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Ceftazidime/Avibactam and Ceftolozane/Tazobactam for Multidrug-Resistant Gram Negatives in Patients with Hematological Malignancies: Current Experiences

Criscuolo

Trecarichi

2020

Antibiotics

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Patients suffering from hematological malignancies are at high risk for severe infections, including in particular bloodstream infections, which represent one of the most frequent life-threatening complications for these patients, with reported mortality rates reaching 40%. Furthermore, a worrisome increase in antimicrobial resistance of Gram-negative bacteria (e.g., cephalosporin- and/or carbapenem-resistant Enterobacteriaceae and multidrug-resistant (MDR) Pseudomonas aeruginosa) involved in severe infectious complications among patients with hematological malignancies has been reported during the last years. The two novel combination of cephalosporins and β-lactamase inhibitors, ceftolozane/tazobactam and ceftazidime/avibactam, were recently approved for treatment of complicated intra-abdominal and urinary tract infections and nosocomial pneumonia and display activity against several MDR Gram-negative strains. Although not specifically approved for neutropenic and/or cancer patients, these drugs are used in this setting due to increasing rates of infections caused by MDR Gram-negative bacteria. The aim of this review is to describe the actual evidence from scientific literature about the “real-life” use of these two novel drugs in patients with hematological malignancies and infections caused by MDR Gram-negative bacteria.

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Ceftolozane/tazobactam: place in therapy

Cited by 113 publications

References 106 publications

Carbapenem-Sparing Strategies for ESBL Producers: When and How

Carbapenem-Sparing Strategies for ESBL Producers: When and How

Ceftolozane-tazobactam pharmacokinetics during extracorporeal membrane oxygenation in a lung transplant recipient

Ceftazidime/Avibactam and Ceftolozane/Tazobactam for Multidrug-Resistant Gram Negatives in Patients with Hematological Malignancies: Current Experiences

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