colistin and Drug-Related-Side-Effects-and-Adverse-Reactions

Polymyxins have been available since the 1960s, however, because of their adverse effects, their use has been reserved for the treatment of infections caused by multiresistant bacteria. The increase in the clinical experience acquired in recent years and the published medical literature have raised doubts about the information provided by the product, indicating the need to update dosage recommendations, pharmacokinetics and pharmacokinetic/pharmacodynamic information (PK/PD). In addition, differences in concentration and dose between the different products of colistin may lead to errors of indication/administration and pose a risk to patients. In 2013, the European Medicines Agency (EMA) commissioned the Committee for Medicinal Products for Human Use (CHPM) to review available data and to make updated recommendations on the use of colistin. This procedure yielded a first report in 2014. This review highlights critical safety and efficacy aspects, reviews the recent pharmacokinetic and stability advances, the available pharmaceutical forms in Chile, providing the schemes currently recommended by health care agencies and experts in the field.

Topics: Anti-Bacterial Agents; Chile; Colistin; Drug-Related Side Effects and Adverse Reactions; Humans

Polymyxins are 'old' antimicrobials which were abandoned for almost 30 years because of significant renal and neurological toxicity. However, the alarming rise in multiresistant Gram-negative bacterial infections worldwide has revived interest in these 'forgotten' agents. Colistin (polymyxin E) is one of the main antibiotics of this class. It is most often administered as the prodrug colistimethate sodium. Doses for treatment of systemic infections in adults range between 3 and 9 million IU per day. Colistin is increasingly used to treat pneumonia and bacteremia in critically ill patients. During their intensive care unit stay, many of these patients will need continuous renal replacement therapy (CRRT) because of acute kidney injury or an unstable hemodynamic condition. Based on recent pharmacological data and our own experience, we postulate that patients undergoing CRRT may receive substantially higher doses of colistin (i.e. a high loading dose, followed by a maintenance dose of up to 4.5 million IU t.i.d.). Treatment can be continued for a prolonged time period without increasing toxicity. CRRT counteracts colistin accumulation because the drug is continuously filtered and also significantly adsorbed in the bulk of the dialysis membrane. Implementing such a 'CRRT rescue' therapy does require the strict use of highly adsorptive dialysis membranes in association with citrate anticoagulation to increase membrane performance.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Colistin; Drug-Related Side Effects and Adverse Reactions; Gram-Negative Bacterial Infections; Humans; Kidney; Renal Replacement Therapy; Treatment Outcome

Infections due to multidrug-resistant Gram-negative bacteria (including Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae) are being reported with increasing frequency from various parts of the world.. To share personal perspectives on the clinical use of colistin based on the available evidence reported in the literature as well as on knowledge obtained through our clinical experience with the use of colistin in a considerable number of patients during the past 7 years.. Literature review and personal experience.. During the last decade, clinicians in several countries have resorted to colistin (polymyxin E), an antibiotic that has been shown to be clinically effective and acceptably safe for intravenous, aerosolized, and intrathecal/intraventricular administration. However, more data are needed to answer important clinical questions, including the appropriate colistin dosage, comparison of colistin monotherapy with combination therapy, and the possible preventive and therapeutic role of aerosolized colistin.

Topics: Animals; Chemistry, Pharmaceutical; Colistin; Drug Resistance, Multiple; Drug Tolerance; Drug-Related Side Effects and Adverse Reactions; Humans; Polymyxins

Topics: Adrenal Cortex Hormones; Aminohippuric Acids; Antidepressive Agents; BCG Vaccine; Cardiac Glycosides; Chloramphenicol; Chloroquine; Colistin; Drug-Related Side Effects and Adverse Reactions; Eye Diseases; Humans; Myopia; Nalidixic Acid; Neuritis; Phenothiazines; Streptomycin; Tetanus Toxoid; Tetracycline; Vision Disorders

The study aimed at evaluating the pharmacokinetics of colistin methanesulfonate sodium (CMS-Na) and describing observed safety findings in Japanese healthy male subjects.. A total of 22 Japanese healthy males were enrolled in this randomized double-blind, placebo controlled study. Dosing regimens of a single dose and twice-daily repeat doses of CMS-Na (2.5 mg/kg as colistin activity, 75,000 IU/kg) were employed. Safety variables included urinary N-acetyl-β-D-glucosaminidase, protein and β(2)-microblobulin. Concentrations of CMS and colistin were determined by LC-MS/MS. Pharmacokinetic parameters were obtained by noncompartmental analysis.. NCT01449838.. The urinary N-acetyl-β-D-glucosaminidase for the detection of early renal damage showed transient increases during the repeat dose period. Otherwise, no clinically significant findings related to study medication were observed. After 2.5-day twice-daily dosing, mean t(1/2) and CL(R) of colistin were 4.98 h and 0.0073 L/h/kg, respectively. Repeat dose C(max) and AUC(0-12) were increased by 72% and 63%, respectively, compared to single dose. The dosing regimen had little effect on renal excretion rate (fe) of both CMS and colistin. The previously reported area under the unbound concentration-time curve to minimum inhibitory concentration (MIC) ratio (fAUC/MIC) target values in mouse lung and thigh infection models compared with the distribution of fAUC/MIC in humans estimated by a Monte Carlo simulation indicated that a bacteriostatic effect was predicted in 84% and 96% of patients, respectively, whereas bactericidal effect was predicted in 65% and 78% of patients, respectively. As this study was conducted with a relatively small number of healthy subjects, safety and PK profiles in critically ill patient population may be different than was observed in this study.. CMS-Na was safely administered to healthy volunteers but resulted in transient increase of urinary N-acetyl-β-D-glucosaminidase (NAG) and protein. Based on this study, the highest recommended dose of CMS-Na had sufficient bacteriostatic effect.

Topics: Adult; Animals; Anti-Bacterial Agents; Asian People; Colistin; Dose-Response Relationship, Drug; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Humans; Infusions, Intraventricular; Japan; Male; Mice; Middle Aged

This study aims to evaluate the clinical pharmacist's contribution impact on the appropriate use of colistin. Our study was conducted prospectively in patients in the Internal Diseases Intensive Care Unit of Gazi University Medical Faculty Hospital for eight months. The first four months of the study were with the observation group, while the next four months were with the intervention group. The study determined how the active participation of clinical pharmacists had affected the appropriateness of colistin use. The results showed that the appropriate use of colistin was higher in the intervention group than in the observational group; furthermore, incidence of nephrotoxicity was lower. The difference between both groups was statistically significant (

Topics: Colistin; Drug-Related Side Effects and Adverse Reactions; Humans; Medication Errors; Pharmacists; Pharmacy Service, Hospital; Prospective Studies

Silymarin (Silybum marianum) has some protective effects against drug toxicity (cisplatin, acetaminophen, adriamycin, gentamicin etc.). Colistin is a strong antimicrobial, which is frequently used in the treatment of resistant gram-negative bacterial infections in recent years although it has nephrotoxic potential. This study was aimed to determine the role of silymarin against colistin-induced acute nephrotoxicity (CIN). Rats were randomly divided into four groups. The control group was treated with tap water whereas groups 2 and 3 received silymarin (orally, 100 mg/kg/day) and colistin (intraperitoneally, 750.000 IU/kg/day) for seven days, respectively. Group 4 received both 750,000 IU/kg/day colistin and 100 mg/kg/day silymarin for seven days. After euthanasia, histopathological and biochemical examinations were completed for the kidney tissue specimens and blood samples. All parameters of the control and silymarin groups were similar. Severe weight loss was seen in the groups receiving colistin (groups 3 and 4). Silymarin significantly increased glutathione peroxidase and superoxide dismutase levels when administered with colistin in group 4 only. Acute tubular injury, tubular necrosis, meduller congestion, interstitial inflammation and apoptotic indices of colistin group were significantly higher than the control group. The administration of colistin with silymarin (group 4) was able to make some improvements in tubular necrosis and significant increase in antioxidant capacity. Silymarin increased antioxidant enzyme activity only when used in combination with colistin. The effects of silymarin may become more pronounced when used at higher doses or with a longer duration of treatment and may prevent nephrotoxicity.

Topics: Animals; Antioxidants; Colistin; Drug-Related Side Effects and Adverse Reactions; Kidney; Oxidative Stress; Rats; Silybum marianum; Silymarin

Stenotrophomonas maltophilia-induced pulmonary haemorrhage is considered a fatal infection among haematological patients. The outcome can be explained by the patients' immunity status and late diagnosis and treatment.. We present the rare case of successful outcome in a 61-year-old female who developed alveolar haemorrhage and acute respiratory distress syndrome 8 days after a chemotherapy session for her acute lymphoblastic leukaemia, in the context of secondary bone marrow aplasia. Stenotrophomonas maltophilia was isolated in sputum culture. The patient benefitted from early empirical treatment with colistin followed by trimethoprim/sulfamethoxazole, according to the antibiogram. Despite a severe initial clinical presentation in need of mechanical ventilation, neuromuscular blocking agents infusion, and ventilation in prone position, the patient had a favourable outcome and was discharged from intensive care after 26 days.. Stenotrophomonas maltophilia severe pneumonia complicated with pulmonary haemorrhage is not always fatal in haematological patients. Empirical treatment of multidrug-resistant Stenotrophomonas maltophilia in an immunocompromised haematological patient presenting with hemoptysis should be taken into consideration.

Topics: Anti-Bacterial Agents; Colistin; Drug-Related Side Effects and Adverse Reactions; Female; Gram-Negative Bacterial Infections; Hemorrhage; Humans; Immunocompromised Host; Middle Aged; Pneumonia, Bacterial; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pulmonary Alveoli; Respiratory Distress Syndrome; Sputum; Stenotrophomonas maltophilia; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

To assess the effectiveness of additional risk minimization measures (aRMMs) implemented in Europe for colistimethate sodium (CMS) among healthcare professionals (HCPs) and patients/caregivers following safety concerns regarding incorrect use of CMS delivered via Turbospin inhaler.. A cross-sectional study was conducted among HCPs and patients/caregivers in Austria, Denmark, France, Germany, The Netherlands, and the United Kingdom between September 2016 and March 2018. Knowledge of the educational materials was assessed regarding common side effects, correct use of CMS and Turbospin inhaler, and capsule breakage. Awareness, receipt, and utilization of the aRMMs were also evaluated.. Among 124 HCPs surveyed, the majority acknowledged awareness (86.2%), receipt (91.0%), and utilization (81.6%) of the CMS educational materials and were knowledgeable about the common CMS side effects (93.2%). Most HCPs correctly answered most questions regarding the proper use of CMS (>90%), yet only half knew how to correctly use the Turbospin inhaler (53.2%). Knowledge about capsule breakage was moderate (67.5%). Of the 29 patients/caregivers surveyed, almost half were aware of the educational materials (48.1%); of these, 69.2% received and used the materials. Most patients/caregivers were knowledgeable about the common CMS side effects (81.5%) and proper CMS use (>85%); however, knowledge about correct Turbospin inhaler use and potential for capsule breakage was moderate to low (48.1% and 37.9%, respectively).. HCPs and patients/caregivers have good knowledge about the common side effects associated with CMS. However, knowledge of correct use of the Turbospin inhaler and capsule breakage was moderate to low.

Topics: Colistin; Cross-Sectional Studies; Drug-Related Side Effects and Adverse Reactions; Europe; Health Personnel; Humans; Inservice Training; Respiratory Therapy; Surveys and Questionnaires

The efficacy of ceftazidime-avibactam-a cephalosporin-β-lactamase inhibitor combination with in vitro activity against Klebsiella pneumoniae carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CRE)-compared with colistin remains unknown.. Patients initially treated with either ceftazidime-avibactam or colistin for CRE infections were selected from the Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE), a prospective, multicenter, observational study. Efficacy, safety, and benefit-risk analyses were performed using intent-to-treat analyses with partial credit and the desirability of outcome ranking approaches. The ordinal efficacy outcome was based on disposition at day 30 after starting treatment (home vs not home but not observed to die in the hospital vs hospital death). All analyses were adjusted for confounding using inverse probability of treatment weighting (IPTW).. Thirty-eight patients were treated first with ceftazidime-avibactam and 99 with colistin. Most patients received additional anti-CRE agents as part of their treatment. Bloodstream (n = 63; 46%) and respiratory (n = 30; 22%) infections were most common. In patients treated with ceftazidime-avibactam versus colistin, IPTW-adjusted all-cause hospital mortality 30 days after starting treatment was 9% versus 32%, respectively (difference, 23%; 95% bootstrap confidence interval, 9%-35%; P = .001). In an analysis of disposition at 30 days, patients treated with ceftazidime-avibactam, compared with those treated within colistin, had an IPTW-adjusted probability of a better outcome of 64% (95% confidence interval, 57%-71%). Partial credit analyses indicated uniform superiority of ceftazidime-avibactam to colistin.. Ceftazidime-avibactam may be a reasonable alternative to colistin in the treatment of K. pneumoniae carbapenemase-producing CRE infections. These findings require confirmation in a randomized controlled trial.

Topics: Aged; Anti-Bacterial Agents; Azabicyclo Compounds; beta-Lactamase Inhibitors; Carbapenem-Resistant Enterobacteriaceae; Ceftazidime; Colistin; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Enterobacteriaceae Infections; Female; Humans; Male; Middle Aged; Prospective Studies; Survival Analysis; Treatment Outcome

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug-Related Side Effects and Adverse Reactions; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Treatment Outcome

The aim of this study was to identify the predictors of acute renal injury associated with colistin treatment.. The patients who received treatment with colistin for more than 3 days were included in this retrospective cohort study. Acute renal injury was defined by the RIFLE (Risk Injury Failure Loss End stage renal disease) criteria. Patients whose serum creatinine levels increased at least 1.5-fold compared with baseline value were considered as cases with renal injury. The independent variables determining the development of acute renal injury were investigated by survival analysis.. A total of 112 cases [67 (59.8 %) were male, median age 64 (range: 18-93) years] were included in the study. Acute renal injury occurred in 66 (58.9 %) patients. Renal injury developed in first 7 days of the colistin therapy in 52 (78.8 %) cases and at day 8-23 in 14 (21.2 %) cases. On the day with highest levels of creatinine, 25 (22.3 %), 17 (15.2 %), and 33 (29.5 %) cases were in 'Risk', 'Injury', and 'Failure' group, respectively, according to RIFLE criteria. We identified three independent risk factors predicting acute colistin-induced renal injury: advanced age, low serum albumin levels, and high serum total bilirubin levels [odds ratio (confidence interval) = 1.022 (1.006-1.037), 0.643 (0.415-0.994), and 1.129 (1.014-1.257), respectively].. The advanced age, low serum albumin levels, and high serum total bilirubin levels are independent risk factors for colistin-induced nephrotoxicity.

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Cohort Studies; Colistin; Creatinine; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Middle Aged; Prevalence; Reproducibility of Results; Risk Factors; Sensitivity and Specificity; Survival Rate; Treatment Outcome; Turkey; Young Adult

The increasing incidence of infections caused by multidrug-resistant (MDR) or extremely drug-resistant (XDR) gram-negative organisms has led to the reemergence of colistin use. Clinical and demographic data were collected on 94 pediatric patients diagnosed with MDR or XDR gram-negative infections and treated with either a colistin-containing regimen (colistin group) or at least one antimicrobial agent other than colistin (noncolistin group). The overall clinical response rates were 65.8% in the colistin group and 70.0% in the noncolistin group (P = 0.33). The infection-related mortality rates were 11% in the colistin group and 13.3% in the noncolistin group (P = 0.74). There was no statistically significant difference in nephrotoxicity in the colistin and noncolistin groups. Colistin therapy was at least as effective and as safe as beta-lactam antibiotics or quinolones, with or without aminoglycosides, in the treatment of infections caused by gram-negative organisms and may be a therapeutic option in children.

Topics: Anti-Bacterial Agents; Child; Child, Preschool; Colistin; Drug Resistance, Multiple, Bacterial; Drug-Related Side Effects and Adverse Reactions; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Infant; Male; Renal Insufficiency; Retrospective Studies; Survival Analysis; Treatment Outcome

Topics: Anti-Bacterial Agents; Colistin; Drug-Related Side Effects and Adverse Reactions; Humans; Kidney

Topics: Adult; Aged; Anti-Bacterial Agents; Cohort Studies; Colistin; Drug Resistance, Multiple, Bacterial; Drug-Related Side Effects and Adverse Reactions; Female; France; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Infusions, Intravenous; Male; Middle Aged; Osteoarthritis; Retrospective Studies; Switzerland; Time Factors; Treatment Outcome

Topics: Ampicillin; Child, Preschool; Chloramphenicol; Colistin; Diagnosis, Differential; Drug Eruptions; Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Electroencephalography; Erythromycin; Female; Fever; Humans; Hydrocortisone; Infections; Kanamycin; Kidney Diseases; Male; Middle Aged; Penicillins; Pericarditis; Pertussis Vaccine; Pleural Diseases; Recurrence; Salicylates; Tetracycline; Tonsillectomy

Topics: Age Factors; Colistin; Drug-Related Side Effects and Adverse Reactions; Hospitalization; Humans; Massachusetts; Medical Records; Medical Staff, Hospital; Nitrofurantoin; Nursing Staff, Hospital; Penicillins; Sex Factors; Sulfamethoxazole; Sulfisoxazole