Efficacy and Safety of Colistimethate Sodium for Injection in The Treatment of Carbapenem-Resistant Enterobacteriaceae Infection

Inclusion Criteria:

1. Patients who can provide written informed consent or their informed consent can beprovided by legal guardian

2. Patients who are hospitalized

3. Adults ≥18 years and ≤85 years of age

4. Patients suspected of or diagnosed with hospital-acquired pneumonia (HAP, in apatient hospitalised for more than 48 hours or developing within 7 days afterdischarge from a hospital) or bloodstream infection caused carbapenem-resistantenterobacteriaceae (CRE) based on the culture results of the sample collected 5 daysbefore the randomization or rapid diagnostic detection. Rapid testing of respiratory or blood specimens should be used to enable earlyidentification of CRE infection pneumonia. Patients can be randomized based on theresults of the rapid test while awaiting results of cultures from the locallaboratory. However, if the sample does not grow CRE in the local microbiologylaboratory culture, these patients will be withdrawn from the study drug treatment. Patients with HAP should fulfil one of the following systemic signs: 1)Fever (temperature >38°C) or hypothermia (rectal/core temperature <35°C);2)White bloodcell (WBC) count >10,000 cells/mm3, or WBC count <4500 cells/mm3, or >15% band formsand fulfil at least two of the following respiratory signs or symptoms:1)a new onsetof cough (or worsening of cough);2)production of purulent sputum or endotrachealsecretions;3)auscultatory findings consistent with pneumonia/pulmonary consolidation (e.g., rales, rhonchi, bronchial breath sounds, dullness to percussion,egophony);4)dyspnoea, tachypnoea or hypoxaemia (O2 saturation <90% or pO2 <60 mmHgwhile breathing room air). Patients with bloodstream infection should fulfil one of the followingcriterion:1)fever(≥38 ℃);2)chills;3)hypotension(systolic <90 mmHg, requiringvasopressors to maintain mean arterial pressure ≥60 mmHg,decreased by 30mmHg frombaseline) ,and isolation of CRE from at least two blood culture collected from twodifferent sites.

5. Respiratory or blood specimen obtained for culture within 5 days prior torandomization, and after the onset of signs and symptoms of HAP or bloodstreaminfection (ideally before receipt of any systemic antibiotics).

6. Patients whose APACHE II score is between 10 and 30.

Exclusion Criteria:

1. Patients who received polymyxin for more than 48 hours in the 72 hours prior torandomization.

2. Patients who received antibiotics more than 24 hours in the 72 hours prior torandomization, and after treatment，conditions of patients improved.

3. Patient with history of serious allergy, hypersensitivity (eg, anaphylaxis), or anyserious reaction to Colistimethate Sodium for Injection or other ingredients of it.

4. Evidence of active concurrent pneumonia requiring additional antimicrobialstreatment caused by Streptococcus pneumoniae，Haemophilusinfluenzae，Methicillin-resistant staphylococcus aureus，Vancomycin-resistantenterococcus，Mycoplasma pneumonia，Legionella pneumophila, respiratory syncytialvirus, influenza virus, parainfluenza virus, Middle East Respiratory Virus,Mycobacteria, Aspergillus, Mucormycosis, Candida,etc. If these organisms areidentified but it is deemed by the Investigator that no treatment is warranted andtheir presence does not significantly change the prognosis of the patient, then thepatient may be considered for this study.

5. Patients who are diagnosed with primary lung cancer (including small cell lungcancer/non-small cell lung cancer patients) or other malignancy transferred to thelungs or other known post obstructive pneumonia. Patients who is known or suspectedof active tuberculosis, cystic fibrosis, lung abscess, pyothorax or obstructivepneumonia.

6. Patients with hematological malignancy such as leukemia, lymphoma and multiplemyeloma.

7. Patients with lung/heart transplantation or stem cell transplantation.

8. Patient was immunocompromised and at risk of infection by opportunistic pathogensincluding, but not limited to the following:1) HIV (AIDS or CD4 <200). 2)chemoradiotherapy within 3 months prior to randomisation. 3) Immunosuppressivetherapy including maintenance corticosteroids (0.5 mg/kg prednisone per day or otherequivalent glucocorticoid). 4) Absolute neutrophil count <500/mm3.

9. Patients with chronic liver failure with portal hypertension, acute hepatic failureor acute decompensation of chronic hepatic failure.

10. Patients who participated in other clinical trials within three months.

11. Patient was pregnant or breastfeeding. If either urine or serum β-hCG test waspositive, the patient was excluded.

12. Patient who have been previously enrolled in this study.

13. Patients who have condionts that may affect the trial.

14. Other conditions exist researchers thought are not suitable.