Influence of Concentration and Temperature on Stability of Imipenem Focused on Solutions for Extended Infusion

Sornsuvit, Chuleegone; Wientong, Purida; Uitrakul, Suriyon; Okonogi, Siriporn; Katip, Wasan

doi:10.1177/15593258211059325

Cited by 7 publications

(4 citation statements)

References 11 publications

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“…Keeping an IV line continuously could also limit patients’ mobility; however, the use of an elastomeric pump could incite the patient to ambulate and could also allow for an earlier discharge [ 59 ]. Another drawback is that it needs to take into account the stability of different molecules at different temperatures, as imipenem is only stable for 6 h at 25 °C and less at 30 °C; therefore, patients need to be instructed on how to handle the infusion notably in outpatient care [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

Optimizing Betalactam Clinical Response by Using a Continuous Infusion: A Comprehensive Review

Diamantis

Chakvetadze²,

Pontfarcy³

et al. 2023

Antibiotics

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Introduction: Antimicrobial resistance is a major healthcare issue responsible for a large number of deaths. Many reviews identified that PKPD data are in favor of the use of continuous infusion, and we wanted to review clinical data results in order to optimize our clinical practice. Methodology: We reviewed Medline for existing literature comparing continuous or extended infusion to intermittent infusion of betalactams. Results: In clinical studies, continuous infusion is as good as intermittent infusion. In the subset group of critically ill patients or those with an infection due to an organism with high MIC, a continuous infusion was associated with better clinical response. Conclusions: Clinical data appear to confirm those of PK/PD to use a continuous infusion in severely ill patients or those infected by an organism with an elevated MIC, as it is associated with higher survival rates. In other cases, it may allow for a decrease in antibiotic daily dosage, thereby contributing to a decrease in overall costs.

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Section: Discussionmentioning

confidence: 99%

Optimizing Betalactam Clinical Response by Using a Continuous Infusion: A Comprehensive Review

Diamantis

Chakvetadze²,

Pontfarcy³

et al. 2023

Antibiotics

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show abstract

“…as a way to optimize T>MIC of b-lactam in critically-ill patients. 13 However, due to imipenem chemical instability, 15 continuous infusion of imipenem requires repeated preparation of a new infusion solution of imipenem every 3 hours in order to maintain the desired PK/PD of 100 T>MIC . 14 Therefore, the continuous infusion regimen of imipenem is not yet widely practiced in clinical practice compared to prolonged regimens.…”

Section: Discussionmentioning

confidence: 99%

“…8,9 Using a continuous infusion regimen was also recommended in Optimization of the treatment with beta-lactam antibiotics in critically-ill patients-guidelines from the French Society of Pharmacology and Therapeutics and the French Society of Anaesthesia and Intensive Care Medicine as a way to optimize T>MIC of b-lactam in critically-ill patients. 13 However, due to imipenem chemical instability, 15 continuous infusion of imipenem requires repeated preparation of a new infusion solution of imipenem every 3 hours in order to maintain the desired PK/PD of 100 T>MIC. 14 Therefore, the continuous infusion regimen of imipenem is not yet widely practiced in clinical practice compared to prolonged regimens.…”

Section: Discussionmentioning

confidence: 99%

Population-Based Pharmacokinetics and Dose Optimization of Imipenem in Vietnamese Critically-Ill Patients

Dinh¹,

Nguyen²,

Le³

et al. 2022

IDR

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Purpose The purpose of this study was to characterize the population-based pharmacokinetic (POP-PK) profile of imipenem in Vietnamese adult patients and to assess the probability of target attainment (PTA) of the pharmacokinetic/pharmacodynamic (PK/PD) parameter to determine the optimal dose. Patients and Methods A POP-PK model of imipenem was developed in patients with severe infection from a 1500-bed general hospital in Vietnam, using MONOLIX 2019. After the initial dose infusion, 6 blood samples per patient were collected to measure plasma imipenem levels. Eight covariates (eg, age, weight) were investigated to ascertain their influence on imipenem’s PK. Monte Carlo simulations were performed to determine the PTA for the time in which the total steady-state imipenem concentrations remained above the MIC (T>MIC) for 40% and 100% of the dosing interval. Results The best fit to the PK data was a two-compartment model with inter-individual variability (IIV) in clearance (CL), central volume of distribution (Vc), intercompartmental clearance (Q), and peripheral volume of distribution (Vp). Only creatinine clearance was retained as a covariate on CL in the final model. The typical value of CL and Vc were estimated to be 4.79 L/h and 11.1 L, respectively. The between-subject variability in this population was noted to be high (>38%, especially for IIV on Q at 110%). Prolonged or continuous infusion demonstrated efficacy (40% T>MIC ) against bacteria with a MIC of 4mg/L. To achieve 100% T>MIC or bacteria with MIC>4 mg/L, however, the number of doses must be increased while maintaining the same daily dose for the 3-hour prolonged infusion regimen. Conclusion A population pharmacokinetic model of imipenem was developed for Vietnamese adult patients with severe illness. By using Monte Carlo simulation, the appropriate dose has been suggested based on the bacterial MIC value and the targeted PK/PD goal.

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“…41 In addition, the stability of carbapenem injection solution may contribute to the antibacterial effect. 42 Because the stability of meropenem is associated with concentrations, time and temperature, [42][43][44] which may partly explain why the therapeutic effect of higher dose of meropenem is not better than that of standard dose. Therefore, results of further studies have yielded conflicting conclusions regarding the optimal regimens for critically ill patients, making it difficult to determine the best approach.…”

mentioning

confidence: 99%

Meropenem Pharmacokinetics and Target Attainment in Critically Ill Patients

Gan¹,

Meng²,

Lei³

et al. 2023

IDR

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Purpose This study aimed to investigate the pharmacokinetics and target attainment of meropenem and compare the effect of meropenem dosing regimens in critically ill patients. Patients and Methods Thirty-seven critically ill patients who were administered meropenem in intensive care units were analyzed. Patients were classified according to their renal function. Pharmacokinetic parameters were assessed based on Bayesian estimation. The target attainment of 40%fT > MIC (fraction time that the free concentration exceeds the minimum inhibitory concentration) and 100%fT > MIC with the pathogen MIC of 2 mg/L and 8 mg/L were specially focused. Furthermore, the effects of standard dosing (1g meropenem, 30 min intravenous infusion every 8h) and non-standard dosing (dosage regimens except standard dosing) were compared. Results The results showed that the values of meropenem clearance (CL), central volume of distribution (V1), intercompartmental clearance (Q), and peripheral volume of distribution (V2) were 3.3 L/h, 9.2 L, 20.1 L/h and 12.8 L, respectively. The CL of the patients among renal function groups was significantly different ( p < 0.001). The tow targets attainment for the pathogen MIC of 2 mg/L and 8 mg/L were 89%, 73%, 49% and 27%, respectively. The severe renal impairment group has higher fraction of target attainment than the other group. The standard dosing achieved the target of 40%fT > 2/8 mg/L (85.7% and 81%, respectively) and patients with severe renal impairment achieved the target fraction of 100% for 40%fT > MIC. Additionally, there was no significant difference between standard and non-standard dosing group in target attainment. Conclusion Our findings indicate that renal function is an important covariate for both meropenem pharmacokinetics parameters and target attainment. The target attainment between standard and non-standard dosing group was not comparable. Therefore, therapeutic drug monitoring is indispensable in the dosing adjustment for critically ill patients if it is available.

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Influence of Concentration and Temperature on Stability of Imipenem Focused on Solutions for Extended Infusion

Cited by 7 publications

References 11 publications

Optimizing Betalactam Clinical Response by Using a Continuous Infusion: A Comprehensive Review

Optimizing Betalactam Clinical Response by Using a Continuous Infusion: A Comprehensive Review

Population-Based Pharmacokinetics and Dose Optimization of Imipenem in Vietnamese Critically-Ill Patients

Meropenem Pharmacokinetics and Target Attainment in Critically Ill Patients

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