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Research article
Clinical efficacy and safety in patients treated with teicoplanin with a target trough concentration of 20 μg/mL using a regimen of 12 mg/kg for five doses within the initial 3 days
Takashi Ueda
Hyogo College of Medicine
Corresponding Author
ORCiD: https://orcid.org/0000-0002-5176-9050
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at BMC Pharmacology and Toxicology.
Background: A trough concentration (Cmin) ≥20 μg/mL of teicoplanin is recommended for the treatment of serious methicillin-resistant Staphylococcus aureus (MRSA) infections. However, sufficient clinical evidence to support the efficacy of this target Cmin has not been obtained. Even though the recommended high Cmin of teicoplanin was associated with better clinical outcome, reaching the target concentration is challenging.
Methods: Pharmacokinetics and adverse events were evaluated in all eligible patients. For clinical efficacy, patients who had bacteremia/complicated MRSA infections were analyzed. The primary endpoint for clinical efficacy was an early clinical response at 72–96 h after the start of therapy. Five dosed of 12 mg/kg or 10 mg/kg was administered as an enhanced or conventional high loading dose regimen, respectively. The Cmin was obtained at 72 h after the first dose.
Results: Overall, 512 patients were eligible, and 76 patients were analyzed for treatment efficacy. The proportion of patients achieving the target Cmin range (20–40 μg/mL) by the enhanced regimen was significantly higher than for the conventional regimen (75.2% versus 41.0%, p < 0.001). In multivariate analysis, Cmin ≥20 μg/mL was an independent factor for an early clinical response (odds ratio 3.95, 95% confidence interval 1.25–12.53). There was no significant difference in the occurrence of adverse events between patients who did or did not achieve a Cmin ≥20 μg/mL.
Conclusion: A target Cmin ≥20 μg/mL might improve early clinical responses during the treatment of difficult MRSA infections using 12 mg/kg teicoplanin for five doses within the initial 3 days.
Keywords
Teicoplanin; Loading dose; Trough concentration; Hypoalbuminemia; Therapeutic drug monitoring
Due to technical limitations the Tables are available as a download in the Supplementary Files.
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CURRENT STATUS: Published
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Posted 10 Jun, 2020
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On 08 Jul, 2020
No community comments so far
Editor assigned
On 04 Jun, 2020
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On 03 Jun, 2020
Editor invited
On 03 Jun, 2020
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Editorial decision: Minor revision
On 26 May, 2020
Review #4 received
Received 11 May, 2020
Review #3 received
Received 11 May, 2020
Review #2 received
Received 10 May, 2020
Review #1 received
Received 10 May, 2020
Reviewer #4 agreed
On 27 Apr, 2020
Reviewer #5 agreed
On 27 Apr, 2020
Reviewer #6 agreed
On 27 Apr, 2020
Reviewer #3 agreed
On 25 Apr, 2020
Reviewer #1 agreed
On 23 Apr, 2020
Reviewer #2 agreed
On 23 Apr, 2020
Editor assigned
On 22 Apr, 2020
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On 21 Apr, 2020
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This preprint is under consideration at BMC Pharmacology and Toxicology. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Clinical efficacy and safety in patients treated with teicoplanin with a target trough concentration of 20 μg/mL using a regimen of 12 mg/kg for five doses within the initial 3 days
Takashi Ueda
Hyogo College of Medicine
Corresponding Author
ORCiD: https://orcid.org/0000-0002-5176-9050
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Version 2
Posted 10 Jun, 2020
Published
On 08 Jul, 2020
No community comments so far
Editor assigned
On 04 Jun, 2020
Submission checks complete
On 03 Jun, 2020
Editor invited
On 03 Jun, 2020
No comments provided
Editorial decision: Minor revision
On 26 May, 2020
Review #4 received
Received 11 May, 2020
Review #3 received
Received 11 May, 2020
Review #2 received
Received 10 May, 2020
Review #1 received
Received 10 May, 2020
Reviewer #4 agreed
On 27 Apr, 2020
Reviewer #5 agreed
On 27 Apr, 2020
Reviewer #6 agreed
On 27 Apr, 2020
Reviewer #3 agreed
On 25 Apr, 2020
Reviewer #1 agreed
On 23 Apr, 2020
Reviewer #2 agreed
On 23 Apr, 2020
Editor assigned
On 22 Apr, 2020
Reviewers invited
Invitations sent on 22 Apr, 2020
Submission checks complete
On 21 Apr, 2020
Editor invited
On 21 Apr, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at BMC Pharmacology and Toxicology.
Background: A trough concentration (Cmin) ≥20 μg/mL of teicoplanin is recommended for the treatment of serious methicillin-resistant Staphylococcus aureus (MRSA) infections. However, sufficient clinical evidence to support the efficacy of this target Cmin has not been obtained. Even though the recommended high Cmin of teicoplanin was associated with better clinical outcome, reaching the target concentration is challenging.
Methods: Pharmacokinetics and adverse events were evaluated in all eligible patients. For clinical efficacy, patients who had bacteremia/complicated MRSA infections were analyzed. The primary endpoint for clinical efficacy was an early clinical response at 72–96 h after the start of therapy. Five dosed of 12 mg/kg or 10 mg/kg was administered as an enhanced or conventional high loading dose regimen, respectively. The Cmin was obtained at 72 h after the first dose.
Results: Overall, 512 patients were eligible, and 76 patients were analyzed for treatment efficacy. The proportion of patients achieving the target Cmin range (20–40 μg/mL) by the enhanced regimen was significantly higher than for the conventional regimen (75.2% versus 41.0%, p < 0.001). In multivariate analysis, Cmin ≥20 μg/mL was an independent factor for an early clinical response (odds ratio 3.95, 95% confidence interval 1.25–12.53). There was no significant difference in the occurrence of adverse events between patients who did or did not achieve a Cmin ≥20 μg/mL.
Conclusion: A target Cmin ≥20 μg/mL might improve early clinical responses during the treatment of difficult MRSA infections using 12 mg/kg teicoplanin for five doses within the initial 3 days.
Due to technical limitations the Tables are available as a download in the Supplementary Files.