colistin and Liver-Diseases

Topics: Adolescent; Adrenergic beta-Agonists; Adult; Advance Care Planning; Anti-Bacterial Agents; Anti-Inflammatory Agents; Bone Density; Bronchodilator Agents; Career Choice; Child; Colistin; Cystic Fibrosis; Diabetes Complications; Diabetes Mellitus; Education; Employment; Energy Intake; Exercise; Expectorants; Family Planning Services; Gastrointestinal Diseases; Humans; Insurance, Disability; Liver Diseases; Nutritional Support; Oxygen Inhalation Therapy; Palliative Care; Patient Care Team; Physical Fitness; Respiration, Artificial; United States

To investigate whether selective intestinal decontamination from oral administration of poorly absorbable antibiotics is effective in preventing bacterial infection in patients with acute liver failure, the incidence of nosocomial infection in 34 patients consecutively admitted to hospital between 1985-1990 and treated with either neomycin + colistin + nystatin or norfloxacin + nystatin (group I) was compared to the incidence of infection in 57 patients who did not receive oral, poorly absorbable antibiotics and who were consecutively admitted between 1972-1984 (group II). Patients from groups I and II had similar clinical and laboratory data at hospital admission. Twelve patients from group I and 33 from group II developed bacterial infection during the study period. The probability of infection was significantly different (p = 0.0083) in the two groups: 19% vs. 39% at the 3rd day of admission, 33% vs. 74% at the 7th day, and 48% vs. 78% at the 14th day, respectively. This difference was due to a different rate of infection from enterobacteria. Enterobacteria caused one infectious episode in group I and 24 in group II (p less than 0.001). The incidence of infections caused by other organisms, however, was similar in both groups (15 and 19 episodes, respectively). These results suggest that selective intestinal decontamination is useful in reducing the risk of infection from enterobacteria in patients with acute liver failure.

Topics: Adult; Bacterial Infections; Colistin; Enterobacteriaceae; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Hepatic Encephalopathy; Humans; Liver Diseases; Male; Neomycin; Norfloxacin; Nystatin; Pregnancy

Increasing evidence suggests that colistin monotherapy is suboptimal at currently recommended doses. We hypothesized that front-loading provides an improved dosing strategy for polymyxin antibiotics to maximize killing and minimize total exposure. Here, we utilized an in vitro pharmacodynamic model to examine the impact of front-loaded colistin regimens against a high bacterial density (10(8) CFU/ml) of Pseudomonas aeruginosa. The pharmacokinetics were simulated for patients with hepatic (half-life [t1/2] of 3.2 h) or renal (t1/2 of 14.8 h) disease. Front-loaded regimens (n=5) demonstrated improvement in bacterial killing, with reduced overall free drug areas under the concentration-time curve (fAUC) compared to those with traditional dosing regimens (n=14) with various dosing frequencies (every 12 h [q12h] and q24h). In the renal failure simulations, front-loaded regimens at lower exposures (fAUC of 143 mg · h/liter) obtained killing activity similar to that of traditional regimens (fAUC of 268 mg · h/liter), with an ∼97% reduction in the area under the viable count curve over 48 h. In hepatic failure simulations, front-loaded regimens yielded rapid initial killing by up to 7 log10 within 2 h, but considerable regrowth occurred for both front-loaded and traditional regimens. No regimen eradicated the high bacterial inoculum of P. aeruginosa. The current study, which utilizes an in vitro pharmacodynamic infection model, demonstrates the potential benefits of front-loading strategies for polymyxins simulating differential pharmacokinetics in patients with hepatic and renal failure at a range of doses. Our findings may have important clinical implications, as front-loading polymyxins as a part of a combination regimen may be a viable strategy for aggressive treatment of high-bacterial-burden infections.

Topics: Anti-Bacterial Agents; Colistin; Humans; In Vitro Techniques; Kidney Diseases; Liver Diseases; Models, Biological; Pseudomonas Infections

Topics: Amphotericin B; Ampicillin; Animals; Anti-Bacterial Agents; Azaguanine; Cephaloridine; Chloramphenicol; Colistin; Cyclophosphamide; Cycloserine; Erythromycin; Female; Kanamycin; Liver Diseases; Mice; Mitomycins; Penicillins; Polymyxins; Streptomycin; Tetracycline; Viomycin

Topics: Animals; Anti-Bacterial Agents; Antibiotics, Antitubercular; Chloramphenicol; Colistin; Cortisone; Encephalitis; Erythromycin; Kanamycin; Liver Diseases; Mice; Penicillins; Pharmacology; Protein Synthesis Inhibitors; Research; Rodent Diseases; Streptomycin; Sulfonamides; Tetracycline