Ceftolozane/tazobactam for the treatment of serious Pseudomonas aeruginosa infections: a multicentre nationwide clinical experience

Bassetti, Matteo; Castaldo, Nadia; Cattelan, Anna María; Mussini, Cristina; Righi, Elda; Tascini, Carlo; Menichetti, Francesco; Mastroianni, Claudio Maria; Tumbarello, Mario; Grossi, Paolo; Artioli, Stefania; Carannante, Novella; Cipriani, Ludovica; Coletto, Davide; Russo, Gianluca; Digaetano, Margherita; Losito, Angela Raffaella; Peghin, Maddalena; Capone, Alessandro; Nicolè, Stefano; Vena, Antonio

doi:10.1016/j.ijantimicag.2018.11.001

Cited by 127 publications

(109 citation statements)

References 44 publications

(77 reference statements)

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“…In a recent study (10), the use of CRRT was identified as an independent risk factor for treatment failure of ceftolozane-tazobactam in the treatment of Pseudomonas aeruginosa infections. Although the authors did not investigate why treatment failure was high during CRRT, they alluded to the fact that there is no clearly defined dosing recommendation for ceftolozane-tazobactam in the different forms of CRRT.…”

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confidence: 99%

A Population Pharmacokinetic Model-Guided Evaluation of Ceftolozane-Tazobactam Dosing in Critically Ill Patients Undergoing Continuous Venovenous Hemodiafiltration

Sime

Lassig-Smith

Starr

et al. 2019

Antimicrob Agents Chemother

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The aim of this work was to describe optimized dosing regimens of ceftolozane-tazobactam for critically ill patients receiving continuous venovenous hemodiafiltration (CVVHDF). We conducted a prospective observational pharmacokinetic study in adult critically ill patients with clinical indications for ceftolozane-tazobactam and CVVHDF. Unbound drug concentrations were measured from serial prefilter blood, postfilter blood, and ultrafiltrate samples by a chromatographic assay. Population pharmacokinetic modeling and dosing simulations were performed using Pmetrics. A four-compartment pharmacokinetic model adequately described the data from six patients. The mean (± standard deviation [SD]) extraction ratios for ceftolozane and tazobactam were 0.76 ± 0.08 and 0.73 ± 0.1, respectively. The mean ± SD sieving coefficients were 0.94 ± 0.24 and 1.08 ± 0.30, respectively. Model-estimated CVVHDF clearance rates were 2.7 ± 0.8 and 3.0 ± 0.6 liters/h, respectively. Residual non-CVVHDF clearance rates were 0.6 ± 0.5 and 3.3 ± 0.9 liters/h, respectively. In the initial 24 h, doses as low as 0.75 g every 8 h enabled cumulative fractional response of ≥85% for empirical coverage against Pseudomonas aeruginosa, considering a 40% fT>MIC (percentage of time the free drug concentration was above the MIC) target. For 100% fT>MIC, doses of at least 1.5 g every 8 h were required. The median (interquartile range) steady-state trough ceftolozane concentrations for simulated regimens of 1.5 g and 3.0 g every 8 h were 28 (21 to 42) and 56 (42 to 84) mg/liter, respectively. The corresponding tazobactam concentrations were 6.1 (5.5 to 6.7) and 12.1 (11.0 to 13.4) mg/liter, respectively. We suggest a front-loaded regimen with a single 3.0-g loading dose followed by 0.75 g every 8 h for critically ill patients undergoing CVVHDF with study blood and dialysate flow rates.

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confidence: 99%

A Population Pharmacokinetic Model-Guided Evaluation of Ceftolozane-Tazobactam Dosing in Critically Ill Patients Undergoing Continuous Venovenous Hemodiafiltration

Sime

Lassig-Smith

Starr

et al. 2019

Antimicrob Agents Chemother

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“…These vaccines, which consist of inactivated microorganisms, can be used in the treatment of chronic or recurrent infections [7,8]. Their utilization in humans is seldom, and they are proven to boost cytokine levels, but not a specific immune response towards a particular microorganism [7]. There were no clinical benefits of this treatment in our patient, since the infection persisted with the same intensity and the swab of the ulcer remained positive.…”

Section: Discussionmentioning

confidence: 72%

“…In our first case, we tried additional therapy with autovaccination. These vaccines, which consist of inactivated microorganisms, can be used in the treatment of chronic or recurrent infections [7,8]. Their utilization in humans is seldom, and they are proven to boost cytokine levels, but not a specific immune response towards a particular microorganism [7].…”

Section: Discussionmentioning

confidence: 99%

Ecthyma gangrenosum in hematological patients - a report of two cases

et al. 2019

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Introduction. Ecthyma gangrenosum is a rare skin disorder which commonly affects immunocompromised patients. Case Report. We report two hematological patients suffering from ecthyma gangrenosum. Pseudomonas aeruginosa was isolated from skin lesions of both patients, but bacteremia was present only in the first case. These two cases had different pathogenic mechanisms and outcomes. Conclusion. Early diagnosis and prompt combination antibiotic therapy are of utmost importance in the treatment of this condition. On the other hand, the underlying disease has a great impact on the outcome as well.

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“…Two newer cephalosporin-b-lactamase inhibitor combinations, CZA and C-T, are increasingly used in the treatment of patients with MDR-PSA infections. [62][63][64][65][66][67][68][69][70][71] Ceftazidime is a third-generation antipseudomonal cephalosporin with a wellestablished efficacy and safety profile, and avibactam is a diazabicyclooctane b-lactamase inhibitor. Avibactam has no intrinsic activity alone, but expands the spectrum of activity of ceftazidime certain PSA strains by inhibiting a broad range of serine b-lactamases, including Ambler class A (extended spectrum b-lactamase and Klebsiella pneumoniae carbapenemase), class C (AmpC), and some class D (such as OXA-48) enzymes.…”

Section: Ceftazidime-avibactam and Ceftolozane-tazobactammentioning

confidence: 99%

Approach to the Treatment of Patients with Serious Multidrug‐Resistant Pseudomonas aeruginosa Infections

2020

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Multidrug resistance(MDR) among Pseudomonas aeruginosa (PSA) isolates presents a significant clinical challenge and can substantially complicate the approach to selection of optimal antibiotic therapy. This review addresses major considerations in antibiotic selection for patients with suspected or documented serious MDR‐PSA infections. Common mechanisms contributing to MDR among clinical PSA isolates are summarized. Empiric and definitive therapy considerations are addressed including the potential role of combination therapy. Newer agents with in vitro activity against MDR‐PSA (e.g., ceftolozane‐tazobactam, ceftazidime‐avibactam, imipenem‐relebactam, and cefiderocol) and their potential roles in clinical settings are discussed. Although these newer agents are promising options for the treatment of MDR‐PSA, clinical data remain generally limited. Future studies are needed to determine optimal agents for the empiric and definitive treatment of MDR‐PSA.

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Ceftolozane/tazobactam for the treatment of serious Pseudomonas aeruginosa infections: a multicentre nationwide clinical experience

Cited by 127 publications

References 44 publications

A Population Pharmacokinetic Model-Guided Evaluation of Ceftolozane-Tazobactam Dosing in Critically Ill Patients Undergoing Continuous Venovenous Hemodiafiltration

A Population Pharmacokinetic Model-Guided Evaluation of Ceftolozane-Tazobactam Dosing in Critically Ill Patients Undergoing Continuous Venovenous Hemodiafiltration

Ecthyma gangrenosum in hematological patients - a report of two cases

Approach to the Treatment of Patients with Serious Multidrug‐Resistant Pseudomonas aeruginosa Infections

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