Therapeutic Drug Monitoring of Meropenem and Piperacillin in Critical Illness—Experience and Recommendations from One Year in Routine Clinical Practice

Abstract

Various studies have reported insufficient beta-lactam concentrations in critically ill patients. The extent to which therapeutic drug monitoring (TDM) in clinical practice can reduce insufficient antibiotic concentrations is an ongoing matter of investigation. We retrospectively evaluated routine meropenem and piperacillin measurements in critically ill patients who received antibiotics as short infusions in the first year after initiating a beta-lactam TDM program. Total trough concentrations above 8.0 mg/L for meropenem and above 22.5 mg/L for piperacillin were defined as the breakpoints for target attainment. We included 1832 meropenem samples and 636 piperacillin samples. We found that 39.3% of meropenem and 33.6% of piperacillin samples did not reach the target concentrations. We observed a clear correlation between renal function and antibiotic concentration (meropenem, r = 0.53; piperacillin, r = 0.63). Patients with renal replacement therapy or creatinine clearance (CrCl) of <70 mL/min had high rates of target attainment with the standard dosing regimens. There was a low number of patients with a CrCl >100 mL/min that achieved the target concentrations with the maximum recommended dosage. Patients with impaired renal function only required TDM if toxic side effects were noted. In contrast, patients with normal renal function required different dosage regimens and TDM-guided therapy to reach the breakpoints of target attainment.

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“…How to predict those changes and adapt dosing to achieve optimal antibiotic efficacy has been at the center of ongoing discussions [ 10 , 11 ]. Numerous reports of subtherapeutic concentrations of beta-lactams, especially in patients with hyperdynamic kidney function, highlight the importance of detecting patients at risk of subtherapeutic concentrations and call for a targeted optimization of dosing [ 12 , 13 , 14 , 15 , 16 ].…”

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“…Meropenem is an important anti-Gram-negative bacteria drug that is often used in the treatment of infections of the abdomen, and the skin. Thus, the TDM of meropenem is highly recommended for patients to avoid a higher risk of kidney failure [ 11 , 14 ] and prevention of the creation of the resistant bacteria which has been spreading recently [ 50 , 51 , 52 , 53 ]. Theophylline is also a crucial drug widely used for the treatment of chronic lung diseases such as asthma and chronic obstructive pulmonary disease.…”

“…Most of these drugs are used for treating chronic conditions such as epilepsy, chronic asthma, intra-abdominal infections, and some severe bacterial infections [ 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. Still, certain toxic antibiotics, such as vancomycin and meropenem, require TDM if used for more than two days [ 11 , 12 , 13 , 14 ].…”

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“…Notes: Data from these studies. [19][20][21][22][23][24][25][26][27][28] Abbreviations: c.i., continuous infusion; E, efficacy; PAS, para-aminosalicylic acid; T, prevent toxicity; TDM, therapeutic drug monitoring. TB patients.…”