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

Carbonell, Nieves; Aguilar, Gerardo; Ferriols, Rafael; Huerta, Rotzel; Ferreres, José; Calabuig, Marisa; Juan, Mar; Ezquer, Carlos; Colomina, Javier; Blasco, María Luisa

doi:10.1128/aac.01782-19

Cited by 9 publications

(9 citation statements)

References 5 publications

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“…Overall, the search strategy identified 70 articles that were assessed for eligibility. Fifty-five of these articles did not fulfil the inclusion criteria, resulting in the inclusion of 15 original studies (3 population PK studies and 12 case reports) [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] assessing the PK behaviour of novel agents in critically septic patients requiring CRRT (Fig. 1).…”

Section: Pharmacokinetics (Pk) Of Novel Antibiotics In Patients Undermentioning

confidence: 99%

“…One population PK study and seven case reports assessed the PK behaviour of ceftolozane-tazobactam in 13 different critically patients requiring CRRT, including one child [24,[27][28][29][30][31][32][33]. Different dosing schedules (1.5 g or 3 g every 8 h) were administered.…”

Section: Ceftolozane-tazobactammentioning

confidence: 99%

“…Similarly, Mahmoud et al [31] found that a high-dose CI of ceftolozane-tazobactam (3 g every 8 h) reached an optimal PK/PD target in a critically obese (187 kg) patient requiring CVVHDF with a high effluent flow rate (4 L/h). Prolonged infusion and/or highdose (3 g every 8 h) ceftolozane-tazobactam achieved an aggressive PK/PD target in patients undergoing CVVH or CVVHDF with highly adsorptive membranes [27][28][29]32]. However, it is worth noting that the effluent flow rate was below 2 L/h in all patients, meaning that a higher dose could be needed in patients undergoing CRRT characterized by highly adsorptive membranes and/or greater effluent flow rates (> 2.5-3 L/h).…”

Section: Ceftolozane-tazobactammentioning

confidence: 99%

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Antimicrobial Dose Reduction in Continuous Renal Replacement Therapy: Myth or Real Need? A Practical Approach for Guiding Dose Optimization of Novel Antibiotics

Gatti

Pea

2021

Clin Pharmacokinet

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Acute kidney injury represents a common complication in critically ill patients affected by septic shock and in many cases continuous renal replacement therapy (CRRT) may be required. In this scenario, antimicrobial dose optimization is highly challenging as the extracorporeal circuit may cause several pharmacokinetic alterations, which add up to volume of distribution and clearance variations resulting from sepsis. Variations in CRRT settings (i.e. modality of solute removal, type of filter material, blood flow rate and effluent flow rate), coupled with the presence of residual and/or recovering renal function, may cause dynamic variations in the clearance of hydrophilic antimicrobials. This means that dose reduction may not always be needed. Nowadays, the lack of pharmacokinetic data for novel antimicrobials during CRRT limits evidence-based dose recommendations for critically ill patients in this setting, thus making available evidence hardly applicable in real-world scenarios. This review aims to summarize the major determinants involved in antimicrobial clearance, and the available pharmacokinetic studies performed during CRRT involving novel antibiotics used for the management of multidrug-resistant Gram-positive and Gram-negative infections (namely ceftolozane-tazobactam, ceftazidime-avibactam, cefiderocol, imipenem-relebactam, meropenem-vaborbactam, ceftaroline, ceftobiprole, dalbavancin, and fosfomycin), providing a practical approach in guiding dose optimization in this special population.

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Section: Pharmacokinetics (Pk) Of Novel Antibiotics In Patients Undermentioning

confidence: 99%

Section: Ceftolozane-tazobactammentioning

confidence: 99%

Section: Ceftolozane-tazobactammentioning

confidence: 99%

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Antimicrobial Dose Reduction in Continuous Renal Replacement Therapy: Myth or Real Need? A Practical Approach for Guiding Dose Optimization of Novel Antibiotics

Gatti

Pea

2021

Clin Pharmacokinet

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“…Of the 83 studies included in the SLR, 61 were published as peer-reviewed publications [ 18 – 78 ], and 22 were conference proceedings (availability as abstracts or posters) [ 79 – 100 ]. Including studies that recruited patients from multiple countries, the most common study locations were the US (N = 50), [ 21 , 22 , 24 , 27 – 29 , 33 , 34 , 39 – 41 , 43 – 45 , 50 , 51 , 54 , 56 , 57 , 59 , 61 , 62 , 68 – 71 , 73 – 77 , 79 – 85 , 87 – 92 , 94 , 95 , 97 – 100 ] Spain (N = 15) [ 26 , 28 , 30 – 32 , 35 – 37 , 42 , 47 , 49 , 58 , 66 , 79 , 96 ], and Italy (N = 13) [ 18 , 20 , 23 , 25 , 48 , 52 , 53 , 55 , 64 , 67 , 72 , 79 , 86 ]. A variety of study designs were captured: 27 were non-comparative retrospective studies [ 18 , 19 , 22 ,…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, this review identified 30 publications reporting a total of 364 immunocompromised patients [ 22 , 26 , 27 , 30 , 34 , 37 – 39 , 41 , 43 , 48 , 49 , 51 , 53 , 59 – 61 , 63 , 68 , 73 , 79 , 83 – 86 , 90 , 91 , 96 – 98 ]. Immunocompromised patients include those with a history of organ transplant, disease suppressing immunity (e.g.…”

Section: Resultsmentioning

confidence: 99%

Real-world use of ceftolozane/tazobactam: a systematic literature review

Puzniak

Dillon

Palmer

et al. 2021

Antimicrob Resist Infect Control

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Background Antibacterial-resistant gram-negative infections are a serious risk to global public health. Resistant Enterobacterales and Pseudomonas aeruginosa are highly prevalent, particularly in healthcare settings, and there are limited effective treatment options. Patients with infections caused by resistant pathogens have considerably worse outcomes, and incur significantly higher costs, relative to patients with susceptible infections. Ceftolozane/tazobactam (C/T) has established efficacy in clinical trials. This review aimed to collate data on C/T use in clinical practice. Methods This systematic literature review searched online biomedical databases for real-world studies of C/T for gram-negative infections up to June 2020. Relevant study, patient, and treatment characteristics, microbiology, and efficacy outcomes were captured. Results There were 83 studies comprising 3,701 patients were identified. The most common infections were respiratory infections (52.9% of reported infections), urinary tract infections (UTIs; 14.9%), and intra-abdominal infections (IAIs; 10.1%). Most patients included were seriously ill and had multiple comorbidities. The majority of patients had infections caused by P.aeruginosa (90.7%), of which 86.0% were antimicrobial-resistant. C/T was used as both a 1.5 g q8h and 3 g q8h dose, for a median duration of 7–56 days (varying between studies). Outcome rates were comparable between studies: clinical success rates ranged from 45.7 to 100.0%, with 27 studies (69%) reporting clinical success rates of > 70%; microbiological success rates ranged from 31 to 100%, with 14 studies (74%) reporting microbiological success rates of > 70%. Mortality rates ranged from 0 to 50%, with 31 studies (69%) reporting mortality rates of ≤ 20%. In comparative studies, C/T was as effective as aminoglycoside- or polymyxin-based regimens, and in some instances, significantly more effective. Conclusions The studies identified in this review demonstrate that C/T is effective in clinical practice, despite the diverse group of seriously ill patients, different levels of resistance of the pathogens treated, and varying dosing regimens used. Furthermore, comparative studies suggest that C/T offers a successful alternative to standard of care (SoC).

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Pharmacokinetic/pharmacodynamic target attainment in critically ill renal patients on antimicrobial usage: focus on novel beta-lactams and beta lactams/beta-lactamase inhibitors

Gatti

Pea

2021

Expert Review of Clinical Pharmacology

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

Abstract: Ceftolozane pharmacokinetics in a septic critically ill patient under different extracorporeal replacement therapies. Antimicrob Agents Chemother 64:e01782-19.

Cited by 9 publications

References 5 publications

Antimicrobial Dose Reduction in Continuous Renal Replacement Therapy: Myth or Real Need? A Practical Approach for Guiding Dose Optimization of Novel Antibiotics

Antimicrobial Dose Reduction in Continuous Renal Replacement Therapy: Myth or Real Need? A Practical Approach for Guiding Dose Optimization of Novel Antibiotics

Real-world use of ceftolozane/tazobactam: a systematic literature review

Pharmacokinetic/pharmacodynamic target attainment in critically ill renal patients on antimicrobial usage: focus on novel beta-lactams and beta lactams/beta-lactamase inhibitors

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