Loading dose plus continuous/extended infusion versus intermittent bolus of β-lactams for the treatment of Gram-negative bacteria bloodstream infections : a propensity score-adjusted retrospective cohort study
© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com..
BACKGROUND: Optimal β-lactam dosing for the treatment of Gram-negative bacteria bloodstream infections (GNB-BSIs) remains a debated issue. Herein, the efficacy and safety of a loading dose (LD) followed by extended/continuous infusion (EI/CI) versus intermittent bolus (IB) of these drugs for the treatment of GNB-BSIs was evaluated.
METHODS: This is a retrospective observational study enrolling patients with GNB-BSIs treated with β-lactams from 1 October 2020 to 31 March 2022. The 30 day infection-related mortality rate was assessed with Cox regression, while mortality risk reduction was evaluated by an inverse probability of treatment weighting regression adjustment (IPTW-RA) model.
RESULTS: Overall, 224 patients were enrolled: 140 and 84 in the IB and EI/CI groups, respectively. β-Lactam regimens were chosen according to pathogen antibiogram, clinical judgement and current guidelines. Interestingly, the LD + EI/CI regimen was associated with a significant lower mortality rate (17% versus 32%, P = 0.011). Similarly, β-lactam LD + EI/CI was significantly associated with a reduced risk of mortality at multivariable Cox regression [adjusted HR (aHR) = 0.46; 95%CI = 0.22-0.98; P = 0.046]. Finally, the IPTW-RA (adjusted for multiple covariates) was performed, showing a significant risk reduction in the overall population [-14% (95% CI = -23% to -5%)]; at the subgroup restricted analysis, a significant risk reduction (>15%) was observed in the case of GNB-BSI in severely immunocompromised patients (P = 0.003), for SOFA score > 6 (P = 0.014) and in septic shock (P = 0.011).
CONCLUSIONS: The use of LD + EI/CI of β-lactams in patients with a GNB-BSI may be associated with reduced mortality; also in patients with severe presentation of infection or with additional risk factors, such as immunodepression.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:78 |
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| Enthalten in: |
The Journal of antimicrobial chemotherapy - 78(2023), 9 vom: 05. Sept., Seite 2175-2184 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bavaro, Davide Fiore [VerfasserIn] |
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| Links: |
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| Themen: |
Anti-Bacterial Agents |
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| Anmerkungen: |
Date Completed 06.09.2023 Date Revised 07.09.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/jac/dkad215 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM359290566 |
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| 245 | 1 | 0 | |a Loading dose plus continuous/extended infusion versus intermittent bolus of β-lactams for the treatment of Gram-negative bacteria bloodstream infections |b a propensity score-adjusted retrospective cohort study |
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| 520 | |a © The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com. | ||
| 520 | |a BACKGROUND: Optimal β-lactam dosing for the treatment of Gram-negative bacteria bloodstream infections (GNB-BSIs) remains a debated issue. Herein, the efficacy and safety of a loading dose (LD) followed by extended/continuous infusion (EI/CI) versus intermittent bolus (IB) of these drugs for the treatment of GNB-BSIs was evaluated | ||
| 520 | |a METHODS: This is a retrospective observational study enrolling patients with GNB-BSIs treated with β-lactams from 1 October 2020 to 31 March 2022. The 30 day infection-related mortality rate was assessed with Cox regression, while mortality risk reduction was evaluated by an inverse probability of treatment weighting regression adjustment (IPTW-RA) model | ||
| 520 | |a RESULTS: Overall, 224 patients were enrolled: 140 and 84 in the IB and EI/CI groups, respectively. β-Lactam regimens were chosen according to pathogen antibiogram, clinical judgement and current guidelines. Interestingly, the LD + EI/CI regimen was associated with a significant lower mortality rate (17% versus 32%, P = 0.011). Similarly, β-lactam LD + EI/CI was significantly associated with a reduced risk of mortality at multivariable Cox regression [adjusted HR (aHR) = 0.46; 95%CI = 0.22-0.98; P = 0.046]. Finally, the IPTW-RA (adjusted for multiple covariates) was performed, showing a significant risk reduction in the overall population [-14% (95% CI = -23% to -5%)]; at the subgroup restricted analysis, a significant risk reduction (>15%) was observed in the case of GNB-BSI in severely immunocompromised patients (P = 0.003), for SOFA score > 6 (P = 0.014) and in septic shock (P = 0.011) | ||
| 520 | |a CONCLUSIONS: The use of LD + EI/CI of β-lactams in patients with a GNB-BSI may be associated with reduced mortality; also in patients with severe presentation of infection or with additional risk factors, such as immunodepression | ||
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