The Combined Antibiotic Therapy for Carbapenem Resistant Klebsiella Pneumoniae

How to Optimize the Combined Antibiotic Therapy for Carbapenem Resistant Klebsiella Pneumoniae

The infection of carbapenem resistant klebsiella pneumoniae (CRKP) is increasingly serious.Based on the early experimental basis and relevant research background,this study intends to separate and purify the CRKP from the bronchoalveolar lavage fluid (BALF) of the clinical patients.Designed by checkerboard assay and time-kill assay(TKA)，this study can explore the best combination therapy based on carbapenems.

Study Overview

• Status: Unknown
• Conditions: Antibiotic Resistant Infection
• Intervention / Treatment: Drug: Fosfomycin; Drug: Tigecycline; Drug: Polymyxin B

Detailed Description

1. Collect the BALF from patients diagnosed with CRKP infection in surgical intensive care unit（SICU）of Shanghai 10th people's hospital.
2. Separate and purify the BALF. Divide each CRKP into four treatment groups based on meropenem.

3.1 By checkerboard method and microdilution broth method,get the minimal inhibitory concentration (MICS) of two antibiotics,then calculate the fractional inhibitory concentration (FIC) index according to MIC results.

3.2 Observe the effect of two antibiotics on the growth of CRKP by TKA.

4.By the above two invitro experiments, analyze the data of the experimental results and get the best combination therapy based on carbapenems.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 201300
      • Recruiting
      • Shanghai 10th People's Hospital
      • Contact: Huanlong Qin, director; Phone Number: 18917683138; Email: wangsheng@tongji.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age from 18 to 90.
• infected with CRKP firstly .

Exclusion Criteria:

• APACHE II score > 35
• Vital signs are unstable
• Unable to tolerate fiberoptic bronchoscopy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: only meropenem therapy,; this group is only meropenem therapy as a single antibiotic treatment	Drug: Fosfomycin; Fosfomycin and meropenem; Other Names: meropenem; Drug: Tigecycline; Tigecycline and meropenem; Other Names: meropenem; Drug: Polymyxin B; Polymyxin B and meropenem; Other Names: meropenem

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the fractional inhibitory concentration index (FICI)	By checkerboard method and microdilution broth method,get the minimal inhibitory concentration (MICS) of two antibiotics,then calculate the fractional inhibitory concentration (FIC) index according to MIC results. Evaluation index: FIC=0.5 , coordinating effect. 0.5 < FIC <1, adding effect; 1 < FIC <2, irrelevant.	24hours-36hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the time-kill assay (TKA)	According to the Clinical and Laboratory Standards Institute,observe the changes of bacterial growth over time after different combination therapy.	36hours-48hours

Collaborators and Investigators

• Sponsor: Shanghai 10th People's Hospital
• Investigators: Principal Investigator: Li Hua, master, Shanghai 10th People's Hospital

Publications and helpful links

General Publications

• Du Y, Mu S, Liu Y, Yuan Y, Zhu Y, Ma L, Wang Q, Zhu Z, Liu Y, Wang S. The Genomic Characterization of KPC-Producing Klebsiella pneumoniae from the ICU of a Teaching Hospital in Shanghai, China. Infect Drug Resist. 2022 Jan 11;15:69-81. doi: 10.2147/IDR.S343673. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2019
• Primary Completion (Anticipated): August 31, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: October 30, 2018
• First Submitted That Met QC Criteria: May 11, 2019
• First Posted (Actual): May 15, 2019

Study Record Updates

• Last Update Posted (Actual): May 15, 2019
• Last Update Submitted That Met QC Criteria: May 11, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Tigecycline; Meropenem; Polymyxins; Polymyxin B; Fosfomycin
• Other Study ID Numbers: STPH-ICU-002

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: No
• product manufactured in and exported from the U.S.: No