Reduce LZD Empirical Dose for Renal Insufficiency Patient by TDM
发布日期：
2024-04-17
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Current clinical application status of linezolid


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Linezolid is the first synthetic oxazolidinone drug used to treat multidrug-resistant pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant coagulase-negative staphylococci (MR-CoNS), vancomycin-resistant enterococci and Mycobacterium tuberculosis, etc. Similar to other antibacterial drugs, linezolid often causes various adverse reactions, among which thrombocytopenia is the most common exposure-dependent adverse reaction of linezolid treatment, which often leads to treatment interruption.

Since 30%-40% of linezolid is excreted through urine, normal renal function significantly affects the plasma concentration of linezolid. Studies have shown that thrombocytopenia occurs more commonly in patients with renal impairment receiving standard linezolid doses. Renal impairment has been identified as an important risk factor for linezolid safety.

However, in current clinical practice, linezolid is often used in a fixed dose (600mg/12h) without considering the patient's renal function. Therefore, some scholars suggest using TDM to assist dose adjustment to improve the safe and effective use of linezolid.


TDM intervention reduces risk of treatment failure in renal insufficiency (RI) patients



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This study included 108 patients and divided them into multiple categories to analyze the efficacy and side effects according to whether their renal function was impaired and whether there was TDM intervention to adjust the dosage.

A comparative analysis based only on the "presence or absence" of renal function impairment (RI group vs non-RI group) shows that if both are taken at a fixed dose (600mg/12h), the median Cmin value of the RI patient group (25.6 ± 10.4 mg/L) was twice that of the non-RI group (14.1 ± 8.8 mg/L), and its treatment maintenance time was shorter than that of the non-RI group (16 days vs 21 days). Most importantly, 62.9% of patients in the RI group developed thrombocytopenia, compared with only 31.3% in the non-RI group.

A comparative analysis based on interventional dose adjustment with or without TDM (TDM group vs. non-TDM group) found that the treatment duration of the TDM group was significantly longer than that of the non-TDM group, but the difference in the probability of failure due to persistent infection between the TDM group and the non-TDM group was not statistically significant. Combined with the influencing factors of RI, it can be seen that in the non-RI group, there is no significant difference in the failure rate between the two groups. While in the RI group, overall failure and hematological toxicity were relatively significantly lower in the TDM group, although there were no significant differences in patient general characteristics, baseline hematological parameters, and concomitant drug therapy.

In the TDM group, 90.5% of episodes in the RI group required dosage adjustments to avoid potential linezolid overexposure, compared with only 62.9% in the non-RI group (P = 0.031). In the TDM interventional therapy group, if the dose was adjusted from 600 mg/12h to 300 mg/12h, the corresponding Cmin was still ≥ 2.0 mg/L, and insufficient linezolid exposure did not occur. Supplementary analysis of 53 episodes showed that using standard dosage for 2 days was enough to quickly reach the effective therapeutic concentration in the RI group, and then using the 300mg/12h strategy, Cmin could still be maintained above the effective exposure


Reducing empirical medication under the intervention of TDM can help patients take medication safely



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Taken together, the results of this study suggest that TDM-guided dose adjustment to maintain linezolid Cmin in the range of 2-8 mg/L will help prevent treatment failure and recovery from thrombocytopenia. An initial fixed-dose administration for 2 days may be sufficient to rapidly achieve effective therapeutic concentrations, and empirical dose reduction to 300 mg every 12 hours under TDM-assisted control can still ensure a balance between therapeutic safety and efficacy.



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