Loading Regimen，Serum Trough Concentrations，Efficacy and Safety in Pneumonia Patients With Gram-positive Infections

A Retrospective Study of Relationships Between Loading Regimen，Serum Trough Concentrations，Efficacy and Safety in Pneumonia Patients With Gram-positive Infections Treated With Teicoplanin

This was a retrospective study that all teicoplanin-treated adult patients with Gram-positive infections admitted to Zhengzhou Central Hospital affiliated to Zhengzhou University from February 2015 to August 2016.

Study Overview

• Status: Completed
• Conditions: Pneumonia Gram-Positive Bacterial
• Intervention / Treatment: Device: other antibacterial agents，breathing machine

Detailed Description

1. Patients and protocol This was a retrospective study that all teicoplanin-treated adult patients with Gram-positive infections admitted to Zhengzhou Central Hospital affiliated to Zhengzhou University from February 2015 to August 2016. Patients were included who met the following criteria: (1) age≥18 years, (2) duration of teicoplanin therapy≥5 days, (3) written informed consent was obtained from each patients. Patients were excluded who fulfilled any of the following criteria: (1) Patients who were allergy to teicoplanin, (2) pregnant women, (3) patients with hematopoietic function, (4) patients unable to evaluate efficacy and safety. This study was approved by the research ethics committee of the Zhengzhou Central Hospital affiliated to Zhengzhou University.
2. Treatment regimen and groups According to CLcr and teicoplanin loading dose regimen, all patients were divided into four groups. Group A (CLcr≥60mL/min) : Teicoplanin was intravenously administered 3 times for moderate infections (skin, soft tissue and respiratory infections) or 6 times for severe infections(endocarditis caused by MRSA or severe pneumonia) at the loading dose of 400 mg at 12h intervals, followed by maintenance dosing 400 mg/d. Group B (40 mL/min≤CLcr<60mL/min) : Teicoplanin was intravenously administered 3 times at the loading dose of 400 mg at 12h intervals, followed by maintenance dosing 400 mg/d. Group C (CLcr<40mL/min) : Teicoplanin was intravenously administered 2 times at the loading dose of 400 mg at 12h intervals, followed by maintenance dosing 200 mg/d. Group D (standard regimen) : Teicoplanin was intravenously administered 1-3 times at the loading dose of 400 mg at 12h intervals, followed by maintenance dosing 200 mg/d. The maintenance dosing was adjusted by Cmin and CLcr in all groups. The target Cmin was set to 15~30 mg/L. If Cmin<15 mg/L or >30 mg/L, the maintenance dosage was increased or decreased appropriately up to target Cmin range. CLcr values for male and female were calculated based on the following equations, respectively.

• Study Type: Observational
• Enrollment (Actual): 113

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The clinical data of 113 patients who were suffered with severe Gram-positive infection and treated with teicoplanin from February 2015 to August 2016 were retrospectively analyzed.

Description

Inclusion Criteria:

• age≥18 years
• duration of teicoplanin therapy≥5 days
• written informed consent was obtained from each patients

Exclusion Criteria:

• Patients who were allergy to teicoplanin
• pregnant women
• patients with hematopoietic function
• patients unable to evaluate efficacy and safety

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group A; Group A (CLcr≥60mL/min) : Teicoplanin was intravenously administered 3 times for moderate infections (skin, soft tissue and respiratory infections) or 6 times for severe infections(endocarditis caused by MRSA or severe pneumonia) at the loading dose of 400 mg at 12h intervals, followed by maintenance dosing 400 mg/d.	Device: other antibacterial agents，breathing machine; If treatment failure for patients in group A，group B，group C and group D，change dose of teicoplanin or other antibacterial agents. Mechanical ventilation was adopte.Treatment failure was defined as no improvement or worse of clinical symptoms, laboratory data, requiring change of teicoplanin therapy.
Group B; Group B (40 mL/min≤CLcr<60mL/min) : Teicoplanin was intravenously administered 3 times at the loading dose of 400 mg at 12h intervals, followed by maintenance dosing 400 mg/d.	Device: other antibacterial agents，breathing machine; If treatment failure for patients in group A，group B，group C and group D，change dose of teicoplanin or other antibacterial agents. Mechanical ventilation was adopte.Treatment failure was defined as no improvement or worse of clinical symptoms, laboratory data, requiring change of teicoplanin therapy.
Group C; Group C (CLcr<40mL/min) : Teicoplanin was intravenously administered 2 times at the loading dose of 400 mg at 12h intervals, followed by maintenance dosing 200 mg/d.	Device: other antibacterial agents，breathing machine; If treatment failure for patients in group A，group B，group C and group D，change dose of teicoplanin or other antibacterial agents. Mechanical ventilation was adopte.Treatment failure was defined as no improvement or worse of clinical symptoms, laboratory data, requiring change of teicoplanin therapy.
Group D; Group D (standard regimen) : Teicoplanin was intravenously administered 1-3 times at the loading dose of 400 mg at 12h intervals, followed by maintenance dosing 200 mg/d.	Device: other antibacterial agents，breathing machine; If treatment failure for patients in group A，group B，group C and group D，change dose of teicoplanin or other antibacterial agents. Mechanical ventilation was adopte.Treatment failure was defined as no improvement or worse of clinical symptoms, laboratory data, requiring change of teicoplanin therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum teicoplanin trough concentrations	Teicoplanin trough samples were taken immediately 30 minutes before teicoplanin administration on the fourth day. Blood samples for 2-3 mL were collected in blood-collection tubes without any additives and centrifuged at 3500 rpm for 10min. Serum teicoplanin trough concentrations (Cmin) were determined by a high-performance liquid chromatography method as previously described. The detections were completed in Translational Medicine Center of Zhengzhou Central Hospital affiliated to Zhengzhou University.	0.5 hour before teicoplanin administration on the fourth day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
White blood cell count (WBC)	It was completed before initiation and after completion of teicoplanin therapy in Zhengzhou city clinical inspection center.	2 years
C-reaction protein (CRP)	It was completed before initiation and after completion of teicoplanin therapy in Zhengzhou city clinical inspection center.	2 years
Asparttate aminotransferase (AST)	It is an indicator of liver function.It was completed before initiation and after completion of teicoplanin therapy in Zhengzhou city clinical inspection center.	2 years
Alanine aminotransferase (ALT)	It is an indicator of liver function.It was completed before initiation and after completion of teicoplanin therapy in Zhengzhou city clinical inspection center.	2 years
Serum creatinine (Scr)	It is an indicator of renal function.It was completed before initiation and after completion of teicoplanin therapy in Zhengzhou city clinical inspection center.	2 years
CLcr	It is an indicator of renal function.It was completed before initiation and after completion of teicoplanin therapy in Zhengzhou city clinical inspection center.	2 years

Collaborators and Investigators

• Sponsor: People's Hospital of Zhengzhou University

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2015
• Primary Completion (Actual): August 20, 2016
• Study Completion (Actual): October 30, 2016

Study Registration Dates

• First Submitted: July 19, 2017
• First Submitted That Met QC Criteria: July 21, 2017
• First Posted (Actual): July 25, 2017

Study Record Updates

• Last Update Posted (Actual): July 25, 2017
• Last Update Submitted That Met QC Criteria: July 21, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia; Anti-Infective Agents; Anti-Bacterial Agents
• Other Study ID Numbers: LZhou

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes