This multicenter, real-world study was conducted from 14 hospitals in Henan province during the period of October 2018 to June 2019. The institutional research ethics committee of the First Affiliated Hospital of Zhengzhou University approved the study.
Patients aged more than 14 years who received PMB therapy for CRGNB infection for at least 7 days were randomly included in the study. Patients were excluded if they receive less than 7 days intravenous PMB.
Data was collected from electronic patients register and follow-up. The database was generated by the clinician through the electronics medical records query. The following variables were recorded: age, gender, underlying disease, hospitalization date, dates of admission and discharge from ICU, vital signs, Acute Physiology and Chronic Health Evaluation II (APACHEII) and the Sequential Organ Failure Assessment (SOFA) score, any major surgeries performed, ventilator care, site of isolation of organisms, and exposure to antimicrobial therapies, clinical features, biochemical indices, microbiological data on admission and on the day of introduction of PMB.
The dose and duration of PMB therapy, renal function, and clinical and microbiological outcomes, adverse reactions of PMB were noted. Patients were followed-up until the end treatment 28-days.
All bacterial were identified in the microbiology laboratory. The biological samples include blood, vein catheter, urine, sputum, tracheal secretions, bronchial-alveolar lavage fluid, intraperitoneal and pleural drainage fluids. Bacterial identification and drug sensitivity tests were performed using Vitek2 automatized system. Susceptibility was interpreted according to Clinical and Laboratory Standards Institute criteria. Isolates with a MIC ≤ 2 mg/L was considered susceptible to PMB (colistin breakpoint for Enterobacteriaceae).
However, the pathogen culture of the site patients were negative. The clinician judges the pathogen according to the characteristics of pathogen distribution in the department and his experience.
All patients were treated with intravenous PMB, to which all strains remained sensitive. All patients who require intravenous PMB should receive dose of 1.25–1.5 mg/kg (equivalent to 12,500–15,000 IU/kg) PMB every 12 hours is infused over 1 hour. In this study clinicians decide that combination therapy with at least two in vitro active agents as the definitive treatment was associated with higher effective. On isolation of strains of CRGNB that were resistant to carbapenem, intravenous antibiotic regimen were initiated at the discretion of the attending physician.
Diagnosis of infection was based on clinical features and isolation of bacteria from areas that normally sterile. Severe sepsis was defined as sepsis associated with organ dysfunction, or hypoperfusion. Septic shock was defined as sepsis 3.0. Pulmonary infection include hospital-associated pneumonia (HAP) and ventilator-associated pneumonia (VAP). HAP was defined as a pneumonia occurring 48 h or more after admission. VAP was defined as a pneumonia develops 48 h or more after tracheal intubation. Chronic diseases include heart disease, hypertension, stroke, cancer, diabetes mellitus and chronic obstructive pulmonary disease.
The primary outcome of this analysis was the 28-day mortality, and the secondary outcomes included all-cause hospital mortality, ICU mortality, occurrence of adverse events during PMB therapy. The clinical outcomes of this study were based on the recovery of patients following PMB therapy. 28-day mortality refers to patient deaths occurring within 28 days from the start of treatment, even if the death related to other important comorbidities, not the infectious condition.
Treatment success was defined as the complete disappearance or improvement of signs and symptoms of infection whereas. We also monitored the empirical treatment, in which PMB was prescribed empirically because biological sample cultures results were reported before or negative. Finally, cases in which they were impossible to evaluate the response to the PMB treatment because no culture test was performed at the end of PMB therapy to assess the outcome of the treatment were evaluated by physicians based on clinical symptoms.
Statistical analyses were carried out using the statistical software package IBM SPSS Statistics 21.0 (SPSS, Chicago, IL). The binary variables are described as counts and percentages and were evaluated by the Chi-squared test or Fisher’s exact test. Continuous variables of each group are presented as the mean ± SEM. Student’s t-test was used to compare the normally distributed continuous variables; otherwise, the Mann–Whitney U test was used. Associations between these significantly statically variables and 28-day mortality or all-cause hospital mortality were explored through multivariable logistic regression. A p-value < 0.05 was considered statistically significant.