Clinical experience with ceftolozane/tazobactam in patients with serious infections due to resistant  Pseudomonas aeruginosa

Xipell, Marc; Paredes, Sandra; Fresco, Leticia; Bodro, Marta; Marco, Francesc; Martínez, José Antonio; Soriano, Álex

doi:10.1016/j.jgar.2018.01.010

Cited by 30 publications

(86 citation statements)

References 16 publications

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“…The main indication in these series was respiratory tract infection, and different doses of ceftolozane-tazobactam were used, sometimes in combination therapy. Cure rates were close to 70%, with emergence of resistance of 4 to 14% in some studies and mortality rates, measured at different times, ranging from 0% (in small series of cases) to 27% (26,62,165,(281)(282)(283)(284)(285)(286)(287)(288).…”

Section: Ceftolozane-tazobactammentioning

confidence: 83%

“…Increased bacterial resistance to antibiotics in conjunction with the lack of new drugs in the pipeline has become a major clinical and public health concern worldwide, which is especially worrisome in the case of MDR, XDR and PDR P. aeruginosa (3,4). Although novel agents such as ceftolozane-tazobactam and ceftazidime-avibactam have expanded the therapeutic arsenal (67,157,(161)(162)(163)(164)(165), polymyxins continue to represent the only therapeutic option in some cases.…”

Section: Currently Available Antimicrobials For the Treatment Of Mdrmentioning

confidence: 99%

“…Most publications have analyzed patients treated with colistin (180-188, 299, 300) and, more recently, with ceftolozane-tazobactam (26,62,165,(281)(282)(283)(284)(285)(286)(287). There are some articles about patients treated with polymyxin B (207)(208)(209), ceftazidime-avibactam (163,308), and aminoglycosides (250) or with different combinations of antimicrobials (203,204,206,258).…”

Section: Critical Evaluation Of Clinical Studies Providing Informatiomentioning

confidence: 99%

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Epidemiology and Treatment of Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Infections

et al. 2019

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SUMMARYIn recent years, the worldwide spread of the so-called high-risk clones of multidrug-resistant or extensively drug-resistant (MDR/XDR)Pseudomonas aeruginosahas become a public health threat. This article reviews their mechanisms of resistance, epidemiology, and clinical impact and current and upcoming therapeutic options.In vitroandin vivotreatment studies and pharmacokinetic and pharmacodynamic (PK/PD) models are discussed. Polymyxins are reviewed as an important therapeutic option, outlining dosage, pharmacokinetics and pharmacodynamics, and their clinical efficacy against MDR/XDRP. aeruginosainfections. Their narrow therapeutic window and potential for combination therapy are also discussed. Other “old” antimicrobials, such as certain β-lactams, aminoglycosides, and fosfomycin, are reviewed here. New antipseudomonals, as well as those in the pipeline, are also reviewed. Ceftolozane-tazobactam has clinical activity against a significant percentage of MDR/XDRP. aeruginosastrains, and its microbiological and clinical data, as well as recommendations for improving its use against these bacteria, are described, as are those for ceftazidime-avibactam, which has better activity against MDR/XDRP. aeruginosa, especially strains with certain specific mechanisms of resistance. A section is devoted to reviewing upcoming active drugs such as imipenem-relebactam, cefepime-zidebactam, cefiderocol, and murepavadin. Finally, other therapeutic strategies, such as use of vaccines, antibodies, bacteriocins, anti-quorum sensing, and bacteriophages, are described as future options.

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Section: Ceftolozane-tazobactammentioning

confidence: 83%

Section: Currently Available Antimicrobials For the Treatment Of Mdrmentioning

confidence: 99%

Section: Critical Evaluation Of Clinical Studies Providing Informatiomentioning

confidence: 99%

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Epidemiology and Treatment of Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Infections

et al. 2019

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“…Currently available data on the clinical effectiveness of C/T for respiratory infections and VAP derive from case series and case-reports with variable dosage regimens and in combination with other antibiotics. An overall clinical success of 61.4% among patients with P. aeruginosa pneumonia treated with C/T is estimated (151–156), whereas a clinical efficacy of 71% was reported a single study of infections by MDR P. aeruginosa (152). Clinical failures have been associated with an MIC higher than 4 mg/L and the use of the lower dosage regimen (157).…”

Section: New Antibioticsmentioning

confidence: 99%

The “Old” and the “New” Antibiotics for MDR Gram-Negative Pathogens: For Whom, When, and How

Karaiskos

Lagou

Pontikis

et al. 2019

Front. Public Health

231

166

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The recent expansion of multidrug resistant and pan-drug-resistant pathogens poses significant challenges in the treatment of healthcare associated infections. An important advancement, is a handful of recently launched new antibiotics targeting some of the current most problematic Gram-negative pathogens, namely carbapenem-producing Enterobacteriaceae (CRE) and carbapenem-resistant P. aeruginosa (CRPA). Less options are available against carbapenem-resistant Acinetobacter baumannii (CRAB) and strains producing metallo-beta lactamases (MBL). Ceftazidime-avibactam signaled a turning point in the treatment of KPC and partly OXA- type carbapenemases, whereas meropenem-vaborbactam was added as a potent combination against KPC-producers. Ceftolozane-tazobactam could be seen as an ideal beta-lactam backbone for the treatment of CRPA. Plazomicin, an aminoglycoside with better pharmacokinetics and less toxicity compared to other class members, will cover important proportions of multi-drug resistant pathogens. Eravacycline holds promise in the treatment of infections by CRAB, with a broad spectrum of activity similar to tigecycline, and improved pharmacokinetics. Novel drugs and combinations are not to be considered “panacea” for the ongoing crisis in the therapy of XDR Gram-negative bacteria and colistin will continue to be considered as a fundamental companion drug for the treatment of carbapenem-resistant Enterobacteriaceae (particularly in areas where MBL predominate), for the treatment of CRPA (in many cases being the only in vitro active drug) as well as CRAB. Aminoglycosides are still important companion antibiotics. Finally, fosfomycin as part of combination treatment for CRE infections and P. aeruginosa , deserves a greater attention. Optimal conditions for monotherapy and the “when and how” of combination treatments integrating the novel agents will be discussed.

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“…C eftolozane-tazobactam (C/T), a novel fifth-generation cephalosporin/␤-lactamase inhibitor combination active against multidrug-resistant (MDR) Pseudomonas aeruginosa, is currently approved by the U.S. Food and Drug Administration (FDA) to treat complicated intra-abdominal and urinary tract infections at the label dosage (1 g/0.5 g/8 h intravenously), as well as nosocomial and ventilator-associated pneumonia at a high dose (2 g/1 g/8 h). In the era of MDR and with critical patients underrepresented in pivotal studies, off-label use of antimicrobials offers good clinical responses (1). Ceftolozane pharmacokinetics (C-PK) have been assessed under renal support with continuous venovenous hemodiafiltration (CVVHDF) (2-4), but the effect of molecularadsorbent-recirculating-system (MARS; Baxter, Deerfield, IL) since liver support on C-PK has yet to be documented.…”

mentioning

confidence: 99%

Ceftolozane Pharmacokinetics in a Septic Critically Ill Patient under Different Extracorporeal Replacement Therapies

Carbonell

Aguilar

Ferriols

et al. 2019

Antimicrob Agents Chemother

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Clinical experience with ceftolozane/tazobactam in patients with serious infections due to resistant Pseudomonas aeruginosa

Cited by 30 publications

References 16 publications

Epidemiology and Treatment of Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Infections

Epidemiology and Treatment of Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Infections

The “Old” and the “New” Antibiotics for MDR Gram-Negative Pathogens: For Whom, When, and How

Ceftolozane Pharmacokinetics in a Septic Critically Ill Patient under Different Extracorporeal Replacement Therapies

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