Clinical analysis of colistin sulfate in the treatment of pneumonia caused by carbapenem-resistant Gram-negative bacteria

BACKGROUND Multidrug-resistant Gram-negative bacteria,exacerbated by excessive use of antimicrobials and immunosuppressants,are a major health threat.AIM To study the clinical efficacy and safety of colistin sulfate in the treatment of carbapenem-resistant Gram-negative bacilli-induced pneumonia,and to provide theoretical reference for clinical diagnosis and treatment.METHODS This retrospective analysis involved 54 patients with Gram-negative bacilli pneumonia admitted to intensive care unit of The General Hospital of the Northern Theater Command of the People's Liberation Army of China from August 2020 to June 2022.After bacteriological culture,the patients'airway secretions were collected to confirm the presence of Gram-negative bacilli.The patients were divided into the experimental and control groups according to the medication used.The research group consisted of 28 patients who received polymyxin sulfate combined with other drugs through intravenous,nebulization,or intravenous combined with nebulization,with a daily dosage of 1.5–3.0 million units.The control group consisted of 26 patients who received standard dosages of other antibiotics(including sulbactam sodium for injection,cefoperazone sodium sulbactam for injection,tigecycline,meropenem,or vaborbactam).RESULTS Of the 28 patients included in the research group,26 patients showed improvement,treatment was ineffective for two patients,and one patient died,with the treatment efficacy rate of 92.82%.Of the 26 patients in the control group,18 patients improved,treatment was ineffective for eight patients,and two patients died,with the treatment efficacy rate of 54.9%;significant difference was observed between the two groups(P<0.05).The levels of white blood cell(WBC),procalcitonin(PCT),and C-reactive protein(CRP)in both groups were significantly lower after treatment than before treatment(P<0.05),and the levels of WBC,PCT,and CRP in the research group were significantly lower than those in the control group(P<0.05).Compared with before treatment,there were no significant changes in aspartate aminotransferase,creatinine,and glomerular filtration rate in both groups,while total bilirubin and alanine aminotransferase decreased after treatment(P<0.05)with no difference between the groups.In patients with good clinical outcomes,the sequential organ failure assessment(SOFA)score was low when treated with inhaled polymyxin sulfate,and specific antibiotic treatment did not improve the outcome.Sepsis and septic shock as well as a low SOFA score were independent factors associated with good clinical outcomes.CONCLUSION Polymyxin sulfate has a significant effect on the treatment of patients with multiple drug-resistant Gram-negative bacilli pneumonia and other infections in the lungs and is safe and reliable.Moreover,the administration route of low-dose intravenous injection combined with nebulization shows better therapeutic effects and lower adverse reactions,providing new ideas for clinical administration.

Baicalin inhibits colistin sulfate-induced apoptosis of PC12 cells

Baicalin, a type of flavonoid extracted from the dried root of Scutellaria baicalensis georgi, has been shown to effectively inhibit cell apoptosis. Therefore, we assumed that baicalin would suppress colistin sulfate-induced neuronal apoptosis. PC12 cells exposed to colistin sulfate （62.5-500 μg/mL） for 24 hours resulted in PCl2 cell apoptosis. In addition, caspase-3 activity, lactate dehydrogenase level and free radical content increased in a dose-dependent manner. Subsequently, PC12 cells were pretreated with baicalin （25, 50 and 100 pg/mL）, and exposed to 125 pg/mL colistin sulfate. Cell morphology markedly changed, and cell viability increased. Moreover, caspase-3 activity, lac- tate dehydrogenase level and free radical content decreased. Results indicated that baicalin inhib- ited colistin sulfate-induced PC12 cell apoptosis by suppressing free radical injury, and reducing caspase-3 activity and lactate dehydrogenase activity.

Studies on the Injectable Solution of Colistin Sulfate and Its Pharmacokinetics

The present studies were conducted to compose an injectable solution of colistin sulfate containing local anaesthesia, antioxidant and other additions. Results showed that the novel preparation was stable either to heat or to light. The term of validity of the preparation was 2 years at room temperature.The preparation containing 25. 0 mg ml-1 colistin sulfate showed no local tissue irritation, but the concentration of 50. 0 mg ml-1 colistin sulfate showed obvious local tissue irritation. Result of acute toxicity test showed that the LD50 of intramuscular injection in mice was 38. 72 mg kg-1, and oral LD50 was 431. 39 mg kg-1. The evidence of neurotoxicity was observed in mice in the acute toxicity test. A dose of 10.0 mg kg-1 b. w. or 15:0 mg kg-1b. w. was administered intramuscularly to piglet once daily for 5 days. No changes were detected in the piglet body except for the slight epithelial tissue's granular degenerations in the kidney and liver at the dose of the 10.0 mg kg-1. While at the dose of 15. 0 mg kg-1, the obvious neurotoxicity was observed at 4-5 days. The epithelial tissues in the kidney and liver showed moderate granular degenerations, especially in the tubuli renales cells. Blood cell's morphosis indexes were normal. With relation to liver's function, the indexes went beyond the normal scope. But with relation to kidney's function, the indexes showed mostly normal.When the preparation was separately administered into muscle(i. m.) in piglets with the dose of 2. 5 and 5. 0 mg kg-1 b. w, whose Cmax were 3.73±0. 28 and 6. 40±0.18 Abstract:g ml-1; Tmax were 32±1. 5 and 34±1.8min; t1/2β were 256±14 min and 264±29 min, respectively. t1/2βt was 251±13 min for the injection given into aural vein( i. v.) with the dose of 2.5 mg kg1-1 b. w.. Samples of the experimentally determined plasma concentration of colistin sulfate generated two-exponential model with first-order absorption. The mean absolute bioavail-ability coefficient of 2.5 and 5. 0 mg kg-1 b. w. (i. m.) were 98. 30 and 88. 54%, respectively. The high bio-availability and the long maintaining time of the valid blood-drug concentration showed that the injectable solution was suitable for i. m. in pigs, whose recommended dose was 2.5 mg kg-1 b. w. , twice daily.