The Combined Antibiotic Therapy for Carbapenem Resistant Klebsiella Pneumoniae

Study Overview
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Brief Summary
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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.

Detailed Description
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Collect the BALF from patients diagnosed with CRKP infection in surgical intensive care unit（SICU）of Shanghai 10th people's hospital. 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.

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

Conditions
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Antibiotic Resistant Infection

Intervention / Treatment
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* Drug: Fosfomycin
* Drug: Tigecycline
* Drug: Polymyxin B


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: only meropenem therapy,<br>this group is only meropenem therapy as a single antibiotic treatment | Drug: Fosfomycin<br>* Fosfomycin and meropenem<br>* Other names: meropenem;Drug: Tigecycline<br>* Tigecycline and meropenem<br>* Other names: meropenem;Drug: Polymyxin B<br>* Polymyxin B and meropenem<br>* Other names: meropenem;|

What is the study measuring?
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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 |