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

• Main Authors: Maria Sanz Codina (Author), Milo Gatti (Author), Carla Troisi (Author), Giacomo Fornaro (Author), Zeno Pasquini (Author), Filippo Trapani (Author), Andrea Zanoni (Author), Fabio Caramelli (Author), Pierluigi Viale (Author), Federico Pea (Author)
• Format: Book
• Published: MDPI AG, 2022-07-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/pharmaceutics14081585; 1999-4923
• Keywords: critically ill patients; COVID-19; meropenem; PK/PD target attainment; microbiological failure; Gram-negative superinfections; Pharmacy and materia medica; RS1-441
• Source: Pharmaceutics, Vol 14, Iss 8, p 1585 (2022)

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 (C_ss) were calculated and the C_ss/MIC ratio was selected as a pharmacodynamic parameter of meropenem efficacy. The C_ss/MIC ratio was defined as optimal if ≥4, quasi-optimal if between 1 and 4, and suboptimal if <1. The relationship between C_ss/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. C_ss/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%; <i>p</i> = 0.53). The microbiological failure rate was significantly lower in patients with an optimal C_ss/MIC ratio compared to those with a quasi-optimal or suboptimal C_ss/MIC ratio (33.3% vs. 75.0%; <i>p</i> = 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.