Clinical efficacy and safety in patients treated with teicoplanin with a target trough concentration of 20 μg/mL using a regimen ... View Full Text


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Article Info

DATE

2020-07-08

AUTHORS

Takashi Ueda, Yoshio Takesue, Kazuhiko Nakajima, Kaoru Ichiki, Kaori Ishikawa, Yoshiko Takai, Kumiko Yamada, Toshie Tsuchida, Naruhito Otani, Yoshiko Takahashi, Mika Ishihara, Shingo Takubo, Hiroki Ikeuchi, Motoi Uchino, Takeshi Kimura

ABSTRACT

BackgroundA 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.MethodsPharmacokinetics 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.ResultsOverall, 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.ConclusionA 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. More... »

PAGES

50

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s40360-020-00424-3

DOI

http://dx.doi.org/10.1186/s40360-020-00424-3

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https://app.dimensions.ai/details/publication/pub.1129058360

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/32641110


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26 schema:description BackgroundA 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.MethodsPharmacokinetics 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.ResultsOverall, 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.ConclusionA 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.
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32 schema:keywords Cmin
33 MRSA infection
34 MethodsPharmacokinetics
35 ResultsOverall
36 Staphylococcus aureus infection
37 adverse events
38 analysis
39 aureus infection
40 better clinical outcomes
41 clinical efficacy
42 clinical evidence
43 clinical outcomes
44 clinical response
45 concentration
46 conventional regimen
47 days
48 differences
49 dose
50 dose regimen
51 doses
52 early clinical response
53 efficacy
54 eligible patients
55 endpoint
56 events
57 evidence
58 factors
59 first dose
60 higher Cmin
61 independent factors
62 infection
63 loading dose regimen
64 mL
65 methicillin-resistant Staphylococcus aureus (MRSA) infections
66 multivariate analysis
67 occurrence
68 outcomes
69 patients
70 primary endpoint
71 proportion
72 proportion of patients
73 range
74 regimen
75 response
76 safety
77 serious methicillin-resistant Staphylococcus aureus (MRSA) infections
78 significant differences
79 start
80 start of therapy
81 sufficient clinical evidence
82 target Cmin
83 target concentration
84 target trough concentration
85 teicoplanin
86 therapy
87 treatment
88 treatment efficacy
89 trough concentrations
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