Relationship between Pharmacokinetic/Pharmacodynamic Target Attainment and Microbiological Outcome in Critically Ill COVID-19 Patients with Documented Gram-Negative Superinfections Treated with TDM-Guided Continuous-Infusion Meropenem

Abstract

Objectives: The objective of this study was to explore the relationship between pharmacokinetic/pharmacodynamic (PK/PD) target attainment of continuous-infusion (CI) meropenem and microbiological outcome in critical COVID-19 patients with documented Gram-negative superinfections. Methods: Patients receiving CI meropenem for documented Gram-negative infections at the COVID ICU of the IRCCS Azienda Ospedaliero-Universitaria di Bologna and undergoing therapeutic drug monitoring from January 2021 to February 2022 were retrospectively assessed. Average steady-state meropenem concentrations (Css) were calculated and the Css/MIC ratio was selected as a pharmacodynamic parameter of meropenem efficacy. The Css/MIC ratio was defined as optimal if ≥4, quasi-optimal if between 1 and 4, and suboptimal if <1. The relationship between Css/MIC and microbiological outcome was assessed. Results: Overall, 43 critical COVID-19 patients with documented Gram-negative infections were retrieved. Combination therapy was implemented in 26 cases. Css/MIC ratios were optimal in 27 (62.8%), quasi-optimal in 7 (16.3%), and suboptimal in 9 cases (20.9%). Microbiological failure occurred in 21 patients (48.8%), with no difference between monotherapy and combination therapy (43.8% vs. 53.8%; p = 0.53). The microbiological failure rate was significantly lower in patients with an optimal Css/MIC ratio compared to those with a quasi-optimal or suboptimal Css/MIC ratio (33.3% vs. 75.0%; p = 0.01). Conclusion: Suboptimal attainment of meropenem PK/PD targets may be a major determinant impacting on microbiological failure in critical COVID-19 patients with Gram-negative superinfections.

Relationship Between Real-time TDM-guided Pharmacodynamic Target Attainment of Continuous Infusion Beta-lactam Monotherapy and Microbiologic Outcome in the Treatment of Critically Ill Children With Severe Documented Gram-negative Infections

“…This is consistent with what was previously observed with both traditional and novel beta-lactams in critically ill adult patients. 14,15,[30][31][32][33][34] The need for a TDM-based approach is also supported by the fact that PICU patients may frequently have major pathophysiologic alterations that may affect the PK behavior of beta-lactams. 7 Occurrence of ARC or transient acute kidney injury, vasopressors requirement, use of loop diuretics and negative fluid balance may be key determinants in affecting beta-lactam exposure.…”

“…This is consistent with what was previously observed with both traditional and novel beta-lactams in critically ill adult patients. 14,15,30–34…”

Pharmacokinetic/Pharmacodynamic Target Attainment of Continuous Infusion Piperacillin–Tazobactam or Meropenem and Microbiological Outcome among Urologic Patients with Documented Gram-Negative Infections

“…Total meropenem concentrations were measured and, according to a plasma protein binding of 2% reported in the literature [ 35 ], the f was calculated multiplying total meropenem C ss by 0.98. PK/PD target attainment, which was defined as optimal when f C ss /MIC ratio was >4 and quasi-optimal or suboptimal when f C ss /MIC ratio was 1–4 or <1, respectively, as previously reported [ 36 ]. In patients performing more than one TDM-guided ECPA for meropenem dosing personalization, the average f C ss was calculated as the mean of all the meropenem C ss values assessed (the first one before any dosage adjustment and the subsequent ones after eventual dosage adjustments).…”

Electrochemical Sensor for Meropenem Therapeutic Monitoring in Human Plasma Based on Carbon Nanotubes Modified Basal Pyrolytic Graphite Electrode

“…2 Moreover, MER was recommended in the treatment guidelines of COVID-19 for secondary bacterial infections. [3][4][5] The term Therapeutic drug monitoring (TDM) has acquired significant importance over the past years especially in anti-infective therapy. 6 The main expected benefits of TDM is the enhancement of the body response to the drug, minimizing the antibiotic resistance, and avoiding toxic side effects resulting from higher serum concentration of the antibiotics.…”

“…Therefore, meropenem TDM is crucial to maintain the drug within the therapeutic plasma levels. 5,11,12 HPLC-MS/MS is a very powerful tool for TDM routines and has many advantages. In recent years, several HPLC-MS/MS papers have been published for the determination of various β-lactam antibiotics in human fluids but HPLC-MS/MS is an expensive technique in terms of capital and analysis costs, has a high maintenance cost as compared to other analytical tools and requires a skilled and trained person.…”