colistin and Body-Weight

A double-blind study was conducted to test the prophylactic effect of a non-absorbable broad-spectrum antimicrobial (oral colistin sulfate) against acute diarrhea in Apache children. Children 1 to 6 months old had over twice the morbidity from diarrhea if assigned to the antimicrobial group as compared to placebo, while the toddler group (7-30 months) taking the antimicrobial had somewhat less diarrhea. Enteropathogenic E. coli were significantly more often isolated from the antimicrobial group (but only in well children). No special effect on the children's growth by the antimicrobial was discerned.

Topics: Age Factors; Arizona; Body Weight; Child Nutritional Physiological Phenomena; Child, Preschool; Clinical Trials as Topic; Colistin; Diarrhea, Infantile; Drug Evaluation; Escherichia coli; Feces; Female; Humans; Indians, North American; Infant; Male; Placebos; Salmonella; Shigella

The objective of this study was to evaluate effects of zinc oxide nanoparticles (nano-ZnOs) as a substitute for colistin sulfate (CS) and/or zinc oxide (ZnO) on growth performance, serum enzymes, zinc deposition, intestinal morphology and epithelial barrier in weaned piglets. A total of 216 crossbred Duroc×(Landrace×Yorkshire) piglets weaned at 23 days were randomly assigned into 3 groups, which were fed with basal diets supplemented with 20 mg/kg CS (CS group), 20mg/kg CS+3000 mg/kg ZnO (CS+ZnO group), and 1200 mg/kg nano-ZnOs (nano-ZnO group) for 14 days. Results indicated that compared to CS group, supplementation of 1200 mg/kg nano-ZnOs (about 30 nm) significantly increased final body weight and average daily gain, and 3000 mg/kg ZnO plus colistin sulfate significantly increased average daily gain and decreased diarrhea rate in weaned piglets. There was no significant difference in growth performance and diarrhea rate between nano-ZnO and CS+ZnO groups. Supplementation of nano-ZnOs did not affect serum enzymes (glutamic oxalacetic transaminase, glutamic-pyruvic transaminase, and lactate dehydrogenase), but significantly increased plasma and tissue zinc concentrations (liver, tibia), improved intestinal morphology (increased duodenal and ileal villus length, crypt depth, and villus surface), enhanced mRNA expression of ZO-1 in ileal mucosa, and significantly decreased diamine oxidase activity in plasma, total aerobic bacterial population in MLN as compared to CS group. Effects of nano-ZnOs on serum enzymes, intestinal morphology, and mRNA expressions of tight junction were similar to those of high dietary ZnO plus colistin sulfate, while nano-ZnOs significantly reduced zinc concentrations of liver, tibia, and feces, and decreased total aerobic bacterial population in MLN as compared to CS+ZnO group. These results suggested that nano-ZnOs (1200 mg/kg) might be used as a substitute for colistin sulfate and high dietary ZnO in weaned piglets.

Topics: Animals; Biomarkers; Body Weight; Colistin; Diarrhea; Dietary Supplements; Intestinal Mucosa; Nanoparticles; Random Allocation; Swine; Weaning; Zinc Oxide

Nephrotoxicity is the main adverse effect of colistin and polymyxin B (PMB). It is not clear whether these two antibiotics are associated with different nephrotoxicity rates. We compared the incidences of renal failure (RF) in patients treated with colistimethate sodium (CMS) or PMB for ≥48 h. A multicenter prospective cohort study was performed that included patients aged ≥18 years. The primary outcome was renal failure (RF) according to Risk, Injury, Failure, Loss, and End-stage renal disease (RIFLE) criteria. Multivariate analysis with a Cox regression model was performed. A total of 491 patients were included: 81 in the CMS group and 410 in the PMB group. The mean daily doses in milligrams per kilogram of body weight were 4.2 ± 1.3 and 2.4 ± 0.73 of colistin base activity and PMB, respectively. The overall incidence of RF was 16.9% (83 patients): 38.3% and 12.7% in the CMS and PMB groups, respectively (P< 0.001). In multivariate analysis, CMS therapy was an independent risk factor for RF (hazard ratio, 3.35; 95% confidence interval, 2.05 to 5.48;P< 0.001) along with intensive care unit admission, higher weight, older age, and bloodstream and intraabdominal infections. CMS was also independently associated with a higher risk of RF in various subgroup analyses. The incidence of RF was higher in the CMS group regardless of the patient baseline creatinine clearance. The development of RF during therapy was not associated with 30-day mortality in multivariate analysis. CMS was associated with significantly higher rates of RF than those of PMB. Further studies are required to confirm our findings in other patient populations.

Topics: Acute Kidney Injury; Adult; Age Factors; Aged; Aged, 80 and over; Anti-Bacterial Agents; Body Weight; Colistin; Drug Administration Schedule; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Intensive Care Units; Intraabdominal Infections; Kidney Failure, Chronic; Male; Middle Aged; Multivariate Analysis; Polymyxin B; Prospective Studies; Respiratory Tract Infections; Risk Factors; Survival Analysis

Colistin (polymixin E) is an antibiotic prescribed with resurging frequency for multidrug resistant gram negative bacterial infections. It is associated with nephrotoxicity in humans in up to 55% of cases. Little is known regarding genes involved in colistin nephrotoxicity. A murine model of colistin-mediated kidney injury was developed. C57/BL6 mice were administered saline or colistin at a dose of 16 mg/kg/day in 2 divided intraperitoneal doses and killed after either 3 or 15 days of colistin. After 15 days, mice exposed to colistin had elevated blood urea nitrogen (BUN), creatinine, and pathologic evidence of acute tubular necrosis and apoptosis. After 3 days, mice had neither BUN elevation nor substantial pathologic injury; however, urinary neutrophil gelatinase-associated lipocalin was elevated (P = 0.017). An Illumina gene expression array was performed on kidney RNA harvested 72 h after first colistin dose to identify differentially expressed genes early in drug treatment. Array data revealed 21 differentially expressed genes (false discovery rate < 0.1) between control and colistin-exposed mice, including LGALS3 and CCNB1. The gene signature was significantly enriched for genes involved in cell cycle proliferation. RT-PCR, immunoblot, and immunostaining validated the relevance of key genes and proteins. This murine model offers insights into the potential mechanism of colistin-mediated nephrotoxicity. Further studies will determine whether the identified genes play a causative or protective role in colistin-induced nephrotoxicity.

Topics: Animals; Body Weight; Cell Cycle Checkpoints; Cluster Analysis; Colistin; Disease Models, Animal; Galectin 3; Gene Expression Profiling; In Situ Nick-End Labeling; Kidney; Kidney Tubules; Male; Mice; Mice, Inbred C57BL; Necrosis; Proliferating Cell Nuclear Antigen; Reproducibility of Results

Thirty adult patients who received intravenous colistin (5.1 ± 2.4 mg/kg/day) were reviewed to evaluate dosing with respect to nephrotoxicity, which occurred in 10 (33%) patients within the first 5 days of treatment. Excessive colistin dosing was frequent (47%), often (71%) resulted from the use of actual body weight in obese patients, and was associated with higher rates of nephrotoxicity (80% versus 30%, P = 0.019).

Topics: Adult; Aged; Anti-Bacterial Agents; Body Weight; Colistin; Drug Administration Schedule; Female; Hospitals, Community; Hospitals, Teaching; Humans; Injections, Intravenous; Kidney; Male; Middle Aged; Retrospective Studies

The role of T-2 toxin-induced gastrointestinal lesions in T-2 toxin-enhanced resistance to listeriosis in mice was evaluated. The T-2 toxin-induced lesions did not cause a starvation effect sufficient to enhance resistance to listeriosis. Administration of polymyxin E markedly reduced the gram-negative intestinal microflora and did not eliminate the toxin-induced resistance to listeriosis. The T-2 toxin did not cause an increased expression of Ia surface antigens on peritoneal macrophages. Thus, toxin-induced anorexia and starvation or absorption of gram-negative intestinal bacteria and endotoxins through toxin-induced gastrointestinal lesions did not account for the enhancing effect of T-2 toxin on resistance to Listeria monocytogenes infection in mice.

Topics: Animals; Body Weight; Colistin; Digestive System; Female; Gram-Negative Bacteria; Histocompatibility Antigens Class II; Immunity, Cellular; Listeria monocytogenes; Listeriosis; Macrophages; Mice; Mice, Inbred ICR; Sesquiterpenes; Spleen; Starvation; T-2 Toxin

Topics: Acute Kidney Injury; Adolescent; Adult; Age Factors; Aged; Apnea; Body Weight; Colistin; Drug Hypersensitivity; Female; Follow-Up Studies; Humans; Kidney Diseases; Kidney Function Tests; Male; Middle Aged; Nausea; Nervous System Diseases; Paresthesia; Pneumonia; Prospective Studies; Pyelonephritis; Respiratory Insufficiency; Sepsis; Sex Factors; Statistics as Topic; Time Factors; Vomiting