The Pharmacodynamics of Prolonged Infusion β-Lactams for the Treatment of Pseudomonas aeruginosa Infections: A Systematic Review

Thabit, Abrar K.; Hobbs, Athena L V; Guzman, Oscar E.; Shea, Katherine M.

doi:10.1016/j.clinthera.2019.09.010

Cited by 17 publications

(15 citation statements)

References 52 publications

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“…Moreover, several clinical studies showed that an extended infusion of β-lactam antibiotics for the treatment of patients with severe infections had lower mortality (Lodise et al, 2007;Shabaan et al, 2017;Vardakas et al, 2018;Yu et al, 2018) and higher rates of clinical improvement (Abdul-Aziz et al, 2016;Shabaan et al, 2017;Yu et al, 2018) and microbiologic eradication (Shabaan et al, 2017) than short-term infusion. Our MCS analysis found that the achievement of the PTAs by the extended infusion of ertapenem were higher compared to the short infusion, findings which were similar to previous studies with other β-lactam antibiotics (Masich et al, 2018;Thabit et al, 2019). Therefore, we believe that a prolonged infusion time of drug administration for this drug should be a good strategy to augment the probability of achieving PK/PD targets and therapeutic outcomes.…”

Section: Discussionsupporting

confidence: 87%

NONMEM population pharmacokinetic and Monte Carlo dosing simulation of ertapenem in patients with sepsis

Jaruratanasirikul¹,

Nopparatana²,

Boonpeng³

et al. 2021

Afr. J. Pharm. Pharmacol.

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An alteration of pharmacokinetics (PK) due to pathophysiological changes in patients with critical illnesses have the impact on the drug levels in plasma, consequently affecting the achievement of pharmacodynamics (PD) targets of antibiotics. The objectives of this study were (i) to determine the population PK, and (ii) to assess the probability of target attainment (PTA) of ertapenem in patients with critical conditions. The study examined the population PK of ertapenem using NONMEM and performed the assessment of the PTAs of achieving 40 and 80% of the time that the free drug level exceeds over the MIC (fT >MIC ). The central and peripheral volumes of distribution were 49 (with the %CV of 67.10) and 91.90 (with the %CV of 78.90) L, respectively, and total clearance of ertapenem was 15.40 (with the %CV of 46.80) L/h. Our PD analysis for achieving a target of 40% fT >MIC in patients with normal renal function, the dosing of 1 g once daily can cover a MIC of 0.5 mg/L and for a higher minimum inhibitory concentration (MIC) of 1 mg/L, the dosing should be increased to 2 g once daily. Moreover, the achievements of PTAs in patients with lower GFRs were greater than those of PTAs in patients with higher GFRs. In conclusion, higher than maximum recommended dosing of ertapenem may be required for achieving the PD targets in septic patients with critical illnesses; however, in renal impaired patients the required dosage regimens may be lower than recommended dosing.

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Section: Discussionsupporting

confidence: 87%

NONMEM population pharmacokinetic and Monte Carlo dosing simulation of ertapenem in patients with sepsis

Jaruratanasirikul¹,

Nopparatana²,

Boonpeng³

et al. 2021

Afr. J. Pharm. Pharmacol.

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“…However, in our study, this fact was relevant only for piperacillin/tazobactam. A recent systematic review [64] concluded that, prior to the implementation of prolonged infusion of antipseudomonal beta-lactam regimens, institutions should consider its advantage according to multiple variables including local incidence of P. aeruginosa infections, MIC distributions, pharmacokinetic variables, and PTA, as well as implementation challenges.…”

Section: Discussionmentioning

confidence: 99%

Pseudomonas aeruginosa Susceptibility in Spain: Antimicrobial Activity and Resistance Suppression Evaluation by PK/PD Analysis

et al. 2021

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Pseudomonas aeruginosa remains one of the major causes of healthcare-associated infection in Europe; in 2019, 12.5% of invasive isolates of P. aeruginosa in Spain presented combined resistance to ≥3 antimicrobial groups. The Spanish nationwide survey on P. aeruginosa antimicrobial resistance mechanisms and molecular epidemiology was published in 2019. Based on the information from this survey, the objective of this work was to analyze the overall antimicrobial activity of the antipseudomonal antibiotics considering pharmacokinetic/pharmacodynamic (PK/PD) analysis. The role of PK/PD to prevent or minimize resistance emergence was also evaluated. A 10,000-subject Monte Carlo simulation was executed to calculate the probability of target attainment (PTA) and the cumulative fraction of response (CFR) considering the minimum inhibitory concentration (MIC) distribution of bacteria isolated in ICU or medical wards, and distinguishing between sample types (respiratory and non-respiratory). Ceftazidime/avibactam followed by ceftolozane/tazobactam and colistin, categorized as the Reserve by the Access, Watch, Reserve (AWaRe) classification of the World Health Organization, were the most active antimicrobials, with differences depending on the admission service, sample type, and dose regimen. Discrepancies between EUCAST-susceptibility breakpoints for P. aeruginosa and those estimated by PK/PD analysis were detected. Only standard doses of ceftazidime/avibactam and ceftolozane/tazobactam provided drug concentrations associated with resistance suppression.

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“…Notably, CI of high-dose piperacillin-tazobactam (18g) should be strongly recommended to achieve optimal PK/PD target in critically ill patients affected by ESBL-producing Enterobacterales infections, especially when dealing with isolates exhibiting high MIC values. 50 , 51 Evidence supporting ceftolozane-tazobactam and/or ceftazidime-avibactam as carbapenem-sparing options for the treatment of for BSIs, cUTIs, and cIAIs caused by ESBL-producing Enterobacterales came from the non-inferiority showed vs carbapenems in pivotal Phase III trials. 52–57 Indeed, it should be recognized that the overall proportion of ESBL-producing isolates was 100% only in one study that enrolled exclusively patients with documented ceftazidime-resistant infections, 57 whereas it was <20% in all of the others.…”

Section: Methodsmentioning

confidence: 99%

“…Overall, altered dosing strategies of beta-lactams based on CI administration are strongly recommended for attaining very aggressive PK/PD target of 100% fT >4-8xMIC . 51 , 105 This approach may both maximize clinical efficacy and prevent the development of resistance. 105 CI is feasible with a unique daily solution infused over 24 hours for those drugs that are stable in aqueous solution at room temperature for ≥ 1 day (eg, piperacillin-tazobactam, ceftolozane-tazobactam).…”

Section: Overview Of Recommendationsmentioning

confidence: 99%

An Evidence-Based Multidisciplinary Approach Focused at Creating Algorithms for Targeted Therapy of BSIs, cUTIs, and cIAIs Caused by Enterobacterales in Critically Ill Adult Patients

Gatti¹,

Viaggi²,

Rossolini³

et al. 2021

IDR

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Prompt implementation of appropriate targeted antibiotic therapy represents a valuable approach in improving clinical and ecological outcome in critically septic patients. This multidisciplinary opinion article focused at developing evidence-based algorithms for targeted antibiotic therapy of bloodstream (BSIs), complicated urinary tract (cUTIs), and complicated intrabdominal infections (cIAIs) caused by Enterobacterales . The aim was to provide a guidance for intensive care physicians either in appropriately placing novel antibiotics or in considering strategies for sparing the broadest-spectrum antibiotics. A multidisciplinary team of experts (one intensive care physician, one infectious disease consultant, one clinical microbiologist and one MD clinical pharmacologist), performed several rounds of assessment to reach agreement in developing six different algorithms according to the susceptibility pattern (one each for multi-susceptible, extended-spectrum beta-lactamase-producing, AmpC beta-lactamase-producing, Klebsiella pneumoniae carbapenemase (KPC)-producing, OXA-48-producing, and Metallo-beta-lactamase (MBL)-producing Enterobacterales ). Whenever multiple therapeutic options were feasible, a hierarchical scale was established. Recommendations on antibiotic dosing optimization were also provided. In order to retrieve evidence-based support for the therapeutic choices proposed in the algorithms, a comprehensive literature search was performed by a researcher on PubMed-MEDLINE from inception until March 2021. Quality and strength of evidence was established according to a hierarchical scale of the study design. Only articles published in English were included. It is expected that these algorithms, by allowing prompt revision of antibiotic regimens whenever feasible, appropriate place in therapy of novel beta-lactams, implementation of strategies for sparing the broadest-spectrum antibiotics, and pharmacokinetic/pharmacodynamic optimization of antibiotic dosing regimens, may be helpful either in improving clinical outcome or in containing the spread of antimicrobial resistance.

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The Pharmacodynamics of Prolonged Infusion β-Lactams for the Treatment of Pseudomonas aeruginosa Infections: A Systematic Review

Cited by 17 publications

References 52 publications

NONMEM population pharmacokinetic and Monte Carlo dosing simulation of ertapenem in patients with sepsis

NONMEM population pharmacokinetic and Monte Carlo dosing simulation of ertapenem in patients with sepsis

Pseudomonas aeruginosa Susceptibility in Spain: Antimicrobial Activity and Resistance Suppression Evaluation by PK/PD Analysis

An Evidence-Based Multidisciplinary Approach Focused at Creating Algorithms for Targeted Therapy of BSIs, cUTIs, and cIAIs Caused by Enterobacterales in Critically Ill Adult Patients

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