Antibiotics (Oct 2021)

Assessment of a PK/PD Target of Continuous Infusion Beta-Lactams Useful for Preventing Microbiological Failure and/or Resistance Development in Critically Ill Patients Affected by Documented Gram-Negative Infections

  • Milo Gatti,
  • Pier Giorgio Cojutti,
  • Renato Pascale,
  • Tommaso Tonetti,
  • Cristiana Laici,
  • Alessio Dell’Olio,
  • Antonio Siniscalchi,
  • Maddalena Giannella,
  • Pierluigi Viale,
  • Federico Pea

DOI
https://doi.org/10.3390/antibiotics10111311
Journal volume & issue
Vol. 10, no. 11
p. 1311

Abstract

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Background: Emerging data suggest that more aggressive beta-lactam PK/PD targets could minimize the occurrence of microbiological failure and/or resistance development. This study aims to assess whether a PK/PD target threshold of continuous infusion (CI) beta-lactams may be useful in preventing microbiological failure and/or resistance development in critically ill patients affected by documented Gram-negative infections. Methods: Patients admitted to intensive care units from December 2020 to July 2021 receiving continuous infusion beta-lactams for documented Gram-negative infections and having at least one therapeutic drug monitoring in the first 72 h of treatment were included. A receiver operating characteristic (ROC) curve analysis was performed using the ratio between steady-state concentration and minimum inhibitory concentration (Css/MIC) ratio as the test variable and occurrence of microbiological failure as the state variable. Area under the curve (AUC) and 95% confidence interval (CI) were calculated. Independent risk factors for the occurrence of microbiological failure were investigated using logistic regression. Results: Overall, 116 patients were included. Microbiological failure occurred in 26 cases (22.4%). A Css/MIC ratio ≤ 5 was identified as PK/PD target cut-off with sensitivity of 80.8% (CI 60.6–93.4%) and specificity of 90.5% (CI 74.2–94.4%), and with an AUC of 0.868 (95%CI 0.793–0.924; p ss/MIC ratio ≤ 5 (odds ratio [OR] 34.54; 95%CI 7.45–160.11; p Pseudomonas aeruginosa infection (OR 4.79; 95%CI 1.11–20.79; p = 0.036). Conclusions: Early targeting of CI beta-lactams at Css/MIC ratio > 5 during the treatment of documented Gram-negative infections may be helpful in preventing microbiological failure and/or resistance development in critically ill patients.

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