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
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 mic...
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MDPI AG
2021
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oai:doaj.org-article:03de6b031cb54ca19992da7872528a0a2021-11-25T16:22:35ZAssessment 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 Infections10.3390/antibiotics101113112079-6382https://doaj.org/article/03de6b031cb54ca19992da7872528a0a2021-10-01T00:00:00Zhttps://www.mdpi.com/2079-6382/10/11/1311https://doaj.org/toc/2079-6382Background: 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 (C<sub>ss</sub>/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 C<sub>ss</sub>/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; <i>p</i> < 0.001). At multivariate regression, independent predictors of microbiological failure were C<sub>ss</sub>/MIC ratio ≤ 5 (odds ratio [OR] 34.54; 95%CI 7.45–160.11; <i>p</i> < 0.001) and <i>Pseudomonas aeruginosa</i> infection (OR 4.79; 95%CI 1.11–20.79; <i>p</i> = 0.036). Conclusions: Early targeting of CI beta-lactams at C<sub>ss</sub>/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.Milo GattiPier Giorgio CojuttiRenato PascaleTommaso TonettiCristiana LaiciAlessio Dell’OlioAntonio SiniscalchiMaddalena GiannellaPierluigi VialeFederico PeaMDPI AGarticlePK/PD target attainmentbeta-lactamscontinuous infusioncritically ill patientsmicrobiological failureresistance developmentTherapeutics. PharmacologyRM1-950ENAntibiotics, Vol 10, Iss 1311, p 1311 (2021) |
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| collection |
DOAJ |
| language |
EN |
| topic |
PK/PD target attainment beta-lactams continuous infusion critically ill patients microbiological failure resistance development Therapeutics. Pharmacology RM1-950 |
| spellingShingle |
PK/PD target attainment beta-lactams continuous infusion critically ill patients microbiological failure resistance development Therapeutics. Pharmacology RM1-950 Milo Gatti Pier Giorgio Cojutti Renato Pascale Tommaso Tonetti Cristiana Laici Alessio Dell’Olio Antonio Siniscalchi Maddalena Giannella Pierluigi Viale Federico Pea 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 |
| description |
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 (C<sub>ss</sub>/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 C<sub>ss</sub>/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; <i>p</i> < 0.001). At multivariate regression, independent predictors of microbiological failure were C<sub>ss</sub>/MIC ratio ≤ 5 (odds ratio [OR] 34.54; 95%CI 7.45–160.11; <i>p</i> < 0.001) and <i>Pseudomonas aeruginosa</i> infection (OR 4.79; 95%CI 1.11–20.79; <i>p</i> = 0.036). Conclusions: Early targeting of CI beta-lactams at C<sub>ss</sub>/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. |
| format |
article |
| author |
Milo Gatti Pier Giorgio Cojutti Renato Pascale Tommaso Tonetti Cristiana Laici Alessio Dell’Olio Antonio Siniscalchi Maddalena Giannella Pierluigi Viale Federico Pea |
| author_facet |
Milo Gatti Pier Giorgio Cojutti Renato Pascale Tommaso Tonetti Cristiana Laici Alessio Dell’Olio Antonio Siniscalchi Maddalena Giannella Pierluigi Viale Federico Pea |
| author_sort |
Milo Gatti |
| title |
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 |
| title_short |
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 |
| title_full |
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 |
| title_fullStr |
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 |
| title_full_unstemmed |
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 |
| title_sort |
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 |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/03de6b031cb54ca19992da7872528a0a |
| work_keys_str_mv |
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