colistin and Kidney-Failure--Chronic

Multidrug-resistant organisms cause significant morbidity and mortality. Infections due to resistant gram-negative bacilli are increasingly being reported. For years, carbapenem antibiotics have been successfully used to treat infections due to resistant Enterobacteriaceae, such as

Topics: Aged, 80 and over; Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Colistin; Enterobacteriaceae Infections; Female; Humans; Kidney Failure, Chronic; Peritoneal Dialysis; Peritonitis

Most significant side effect of colistin therapy which is used for the treatment of multi-drug resistant Gram-negative infections is nephrotoxicity. Our aim was to investigate the differences of colistin nephrotoxicity between the geriatric age group (≥65 years) and the younger age group (<65 years) in critically ill medical intensive care unit (ICU) patients.. The medical records of the 76 patients who were taken colistin therapy due to multi-resistant Gram-negative infections between January 2010 and June 2014 in the our medical ICU were retrospectively investigated. Demographic characteristics, reasons for colistin use, daily colistin dose, duration of colistin use were recorded. Colistin-dependent renal dysfunction was evaluated according to the risk, injury, failure, loss and end-stage renal failure (RIFLE) criterias.. The median age of the patients was 65 (65.8% male). Nephrotoxicity was developed in 36 (47.4%) patients. Thirty-nine (51.3%) patients were in geriatric age group, 37 (48.7%) were in younger age group. In geriatric age group, the rates of male gender (53.8 vs 78.4%, p = 0.031), pulmonary (48.7 vs 16.2%, p = 0.003) and cardiac diseases (71.8 vs 29.7%, p < 0.001), post-nephrotoxicity BUN levels (p = 0.023) and urine output during nephrotoxicity (p = 0.016) were higher than younger age group. Nephrotoxicity was developed in 22 (56.4%) patients of geriatric age group, and in 14 (37.8%) patients in younger age group (p = 0.115). The presence of cardiac disease, renal pathology and high creatinin value on admission, daily amount of colistin per body mass, total amount of colistin, use of colistin for pulmonary infection, use of amphotericin and vasopressor on admission were found as risk factors for colistin nephrotoxicity development in all study group; the daily amount of colistin per body mass (risk ratio:0.41; 95% CI 0.19-0.89) and vasopressor use during hospitalization were found independent risk factors (risk ratio:13.54; 95% CI 2.21-83.09).. In our study, in geriatric patient group colistin nephrotoxicity was not different from the younger age group. In the ICU, the age for nephrotoxicity does not appear to be a point to be considered for the initiation of colistin.

Topics: Aged; Anti-Bacterial Agents; Colistin; Critical Illness; Female; Humans; Intensive Care Units; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Retrospective Studies; Risk Factors

This study aimed to determine potential host-, pathogen-, infection- and treatment-related risk factors that might predict a fulminant fatal course of bacteraemia caused by extensively drug-resistant Acinetobacter baumannii (XDR-Aba).. Eighty-seven patients with monomicrobial growth of XDR-Aba in blood cultures within a 6-year period (2011-2016) were studied. Patients were divided into three groups according to ICU outcome: Group A (n=40) consisted of patients who survived; Group B (n=10) included patients with fulminant sepsis who died early (≤48h); and Group C (n=37) included patients who died later (>48h) after the onset of bacteraemia.. Regarding patient co-morbidities, patients who died from fulminant XDR-Aba bacteraemia had a significantly higher prevalence of chronic renal failure compared with patients who survived (40.0% vs. 7.5%; P=0.029). Patients with fulminant sepsis showed more severe organ dysfunction based on SOFA score compared with survivors (10.83±2.93 vs. 6.65±3.6; P=0.013). The primary to secondary bacteraemia ratio and appropriate treatment were similar among the three outcome groups. Patients with fulminant bacteraemia displayed higher rates of colistin-, tigecycline- and pandrug-resistant strains, although not statistically significant.. Patients suffering from a fulminant course of XDR-Aba bacteraemia showed significantly higher rates of chronic renal failure and multiple organ dysfunction. Resistance patterns of XDR-Aba isolates and receipt of appropriate treatment did not affect outcomes. Further studies including larger samples of patients along with investigation of specific virulence determinants of individual Aba strains are needed.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Intensive Care Units; Kidney Failure, Chronic; Male; Middle Aged; Retrospective Studies; Risk Factors; Sepsis

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

To describe the clinical and microbiological data of carbapenem-resistant Enterobacteriaceae (CRE) infections, the treatment used, hospital- and infection-related mortality, and risk factors for death.. A prospective cohort conducted from March 2011 to December 2012. Clinical, demographic, and microbiological data such as in vitro sensitivity, clonality, carbapenemase gene mortality related to infection, and overall mortality were evaluated. Data were analyzed using Epi Info version 7.0 (CDC, Atlanta, GA, USA) and SPSS (Chicago, IL, USA).. One hundred and twenty-seven patients were evaluated. Pneumonia, 52 (42 %), and urinary tract infections (UTI), 51 (40.2 %), were the most frequent sites of infection. The isolates were polyclonal; the Bla. CRE infection mortality was higher among patients with pneumonia. Infections caused by colistin-resistant isolates did not increase mortality. The use of more than two drugs on combination therapy did not show a protective effect on outcome. The isolates were polyclonal, and the bla

Topics: Adult; Age Factors; Aged; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Cohort Studies; Colistin; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Hospital Mortality; Humans; Kidney Failure, Chronic; Male; Microbial Sensitivity Tests; Middle Aged; Pneumonia; Polymerase Chain Reaction; Prospective Studies; Renal Dialysis; Risk Factors; Shock, Septic; Urinary Tract Infections

Topics: Adult; Anti-Bacterial Agents; Coinfection; Colistin; Combined Modality Therapy; Disease Susceptibility; Drug Substitution; Drug Therapy, Combination; Humans; Kidney Failure, Chronic; Male; Muscle Hypotonia; Osteomyelitis; Renal Dialysis; Reoperation; Respiration, Artificial; Respiratory Insufficiency; Shock, Septic; Spinal Dysraphism; Surgical Wound Infection

Colistin, administered intravenously as its inactive prodrug colistin methanesulphonate (CMS), is being increasingly used. However, there is very limited information available on the impact of haemodialysis (HD) on the pharmacokinetics of CMS and formed colistin.. A single 30 min intravenous dose of CMS (150 mg of colistin base activity) was administered to 10 patients undergoing HD. HD was performed from 1.5 to 5.5 h after the start of the CMS infusion. Serial blood samples were collected over 50 h, additional blood samples pre- and post-dialysis membrane at three timepoints during HD, dialysate samples at four timepoints during HD, and a cumulative urine sample over 24 h. CMS and colistin were determined by HPLC. Population modelling and determination of HD clearance by multiple methods was conducted.. The average amount of CMS recovered in the dialysate was 30.6% of the dose administered. The concentrations of CMS and colistin in the plasma and the amounts of CMS recovered in the dialysate were well described by the population disposition model. The clearance of CMS by dialysis as estimated by population analysis based on systemic plasma concentrations and amounts in the dialysate was 4.26 L/h (26% coefficient of variation). The dialysis clearance determined from the pre- and post-membrane plasma concentrations was 5.67 L/h (21%) for CMS and 3.99 L/h (44%) for colistin. Thus, CMS clearance by dialysis from trans-cartridge extraction was ∼30% higher than when calculated based on the amount in dialysate, suggesting adsorption to the membrane.. Due to the extensive removal of CMS by dialysis, HD should be conducted at the end of a dosing interval and a supplemental dose should be administered.

Topics: Administration, Intravenous; Adult; Aged; Anti-Bacterial Agents; Blood Chemical Analysis; Chromatography, High Pressure Liquid; Colistin; Female; Humans; Kidney Failure, Chronic; Male; Metabolic Clearance Rate; Middle Aged; Models, Statistical; Prodrugs; Renal Dialysis; Time Factors; Urinalysis

A 74-year-old female patient with end-stage renal disease, undergoing periodic hemodialysis, was hospitalized due to infection by multidrug-resistant Acinetobacter baumannii after hip replacement surgery. She was treated with tigecycline, a glycylcycline agent. Subsequently she developed coagulation disorders as substantiated by increased international normalized ratio (INR), prolonged partial thromboplastin time (aPTT), and severe hypofibrinogenemia, followed by transaminasemia, cholestasis, and anemia. Ultrasonography and computed tomography revealed no underlying pathological entities. Tigecycline was discontinued and the patient underwent daily hemodialysis and received multiple fresh frozen plasma transfusions. Additionally, she was treated with colistin. Her clinical and laboratory status improved. We suggest that patients treated with tigecycline should be monitored for changes in INR, aPTT, and fibrinogen levels to avoid severe, life-threatening coagulation disturbances.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Blood Coagulation Disorders; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; International Normalized Ratio; Kidney Failure, Chronic; Minocycline; Partial Thromboplastin Time; Renal Dialysis; Tigecycline

Immunocompromised patients, such as those with multiple myeloma on peritoneal dialysis, are particularly susceptible to the occurrence of peritonitis.. We presented a 56-year-old female patient with a 10-year history of multiple myeloma. The patient was on peritoneal dialysis since 2010. During 2012 the patient had the first episode of peritonitis that was successfully managed, but in 2013 the second episode of peritonitis occured. Analysis of dialysate culture and exit site swab revealed the presence of multiresistant Acinetobacter spp., which was susceptible only to colistin. Prompt colistin therapy was administered at the doses of 100,000 units/day during six days, which resulted in complete recovery of the patient, as well as improvement of local abdominal findings. Gram-negative bacteria (genus Acinetobacter) are common causative agents in hospital-acquired infections. Studies confirmed susceptibility of Acinetobacter to colistin, which was also the case with the presented patient. Intravenous administration of colistin resulted in a complete remission of this severe, life-threatening peritonitis.. Patients with multiple myeloma and renal failure are highly prone to severe life-threatening infections.

Topics: Acinetobacter; Anti-Bacterial Agents; Colistin; Cross Infection; Female; Humans; Immunocompromised Host; Kidney Failure, Chronic; Middle Aged; Multiple Myeloma; Peritoneal Dialysis; Peritonitis; Treatment Outcome

Colistin use has reemerged for the treatment of infections caused by multidrug-resistant Gram-negative bacteria. However, the information on its pharmacokinetics is limited, especially in patients with end-stage renal disease, in which dosage adjustments are contradictory, and evidences the need to investigate the removal of colistin through renal replacement therapies like haemodialysis. This case study showed efficient removal of colistin methanesulphonate and formed colistin during intermittent haemodialysis in a patient infected by polymyxin-only-susceptible Pseudomonas aeruginosa. These results suggest the importance to monitor colistin plasma concentrations in these patients to minimize treatment failure due to suboptimal exposure to antibacterial colistin.

Topics: Aged; Anti-Bacterial Agents; Colistin; Humans; Kidney Failure, Chronic; Male; Polymyxins; Pseudomonas aeruginosa; Pseudomonas Infections; Renal Dialysis

Colistin, administered intravenously as its inactive prodrug colistin methanesulfonate (CMS), is increasingly used as last-line therapy to combat multidrug-resistant Gram-negative bacteria. CMS dosing needs to be adjusted for renal function. The impact of continuous ambulatory peritoneal dialysis (CAPD) on the pharmacokinetics of both CMS and colistin has not been studied. No CMS dosing recommendations are available for patients receiving CAPD. Eight CAPD patients received a single intravenous CMS dose (150 mg colistin base activity [CBA]) over 30 min. Serial blood and dialysate samples, and cumulative urine where applicable, were collected over 25 h. CMS and colistin concentrations were determined by high-performance liquid chromatography. Population pharmacokinetic modeling and Monte Carlo simulations were conducted. The total body clearance of CMS (excluding CAPD clearance) was 1.77 liters/h (44%) [population mean (between-subject variability)], while CAPD clearance was 0.088 liter/h (64%). The population mean terminal half-life of CMS was 8.4 h. For colistin, the total clearance/fraction of CMS metabolized to colistin (fm) (excluding CAPD clearance) was 2.74 liters/h (50%), the CAPD clearance was 0.101 liter/h (34%), and the mean terminal half-life was 13.2 h. Monte Carlo simulations suggested a loading dose of 300 mg CBA on day 1 and a maintenance dose of either 150 mg or 200 mg CBA daily to achieve a target average steady-state plasma colistin concentration of 2.5 mg/liter. Clearance by CAPD was low for both CMS and formed colistin. Therefore, CMS doses should not be increased during CAPD. Modeling and simulation enabled us to propose the first evidence-based CMS dosage regimen for CAPD patients.

Topics: Anti-Bacterial Agents; Colistin; Humans; Kidney Failure, Chronic; Microbial Sensitivity Tests; Peritoneal Dialysis, Continuous Ambulatory

Recently, colistin has become a salvage therapy in the treatment of serious Intensive Care Unit infections owing to the emergence of extensively drug-resistant (XDR) bacterial isolates. This study aimed to show the effectiveness of colistin in critically ill patients with renal failure. A prospective case-control study of 94 patients admitted to medical intensive care units of a university hospital from December 2008 to June 2010 was conducted. All patients had infections with XDR Acinetobacter baumannii or Pseudomonas aeruginosa and received colistin. Cases comprised 39 patients with chronic renal failure (CRF) and controls were other patients without CRF. Apart from the male dominancy in the CRF group, there was no statistical difference between the two groups regarding demographic characteristics, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and site and type of infection. In patients who completed colistin therapy, bacteriological cure was seen in 87% of patients with CRF and 95% of patients without CRF (P=0.890). Mortality in patients with CRF was similar to that in patients without CRF (44% and 42%, respectively) (P=0.999). Nephrotoxicity developed in 23.6% of patients in the control group. Concomitant nephrotoxic agents and total defined daily dose of colistin did not affect the development of nephrotoxicity. The mortality rate was 38% in patients with nephrotoxicity, similar to the mortality rate in patients without nephrotoxicity (36%) (P=0.999). In conclusion, in critically ill patients with CRF, colistin therapy, although used at a reduced dosage, was as effective as in patients without CRF.

Topics: Acinetobacter baumannii; Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; APACHE; Bacterial Infections; Case-Control Studies; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Female; Hospitals, University; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Pseudomonas aeruginosa; Survival Analysis; Treatment Outcome

Intravenous colistin is used to treat resistant Gram-negative infections and is associated with nephrotoxicity. In overweight and obese adults, a paucity of data exists regarding the incidence and predictors of such toxicity. A retrospective nested case-control study was performed over 35 months for patients receiving intravenous colistin for ≥ 72 h with a body mass index (BMI) of ≥ 25 kg/m(2). The objective was to investigate the incidence and predictors of nephrotoxicity. Severity of acute kidney injury was defined by RIFLE (risk, injury, failure, loss, and end-stage kidney disease) criteria. Dosing and mortality were secondarily investigated. Forty-two patients met the inclusion criteria, and 20 (48%) developed nephrotoxicity. Patients with toxicity were in the risk (15%), injury (5%), and failure (80%) categories based on RIFLE criteria. A logistic regression model identified four predictors of colistin-associated nephrotoxicity: a BMI of ≥ 31.5 kg/m(2) (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.15 to 8.35), diabetes (OR, 2.11; 95% CI, 0.84 to 5.29), the length of hospitalization in days prior to receipt of colistin (OR, 1.04; 95% CI, 0.99 to 1.08), and age (OR, 1.08; 95% CI, 1.00 to 1.17). Among all of the patients, dosing based on the actual body weight and excessive dosing due to the use of the actual body weight were frequent at 64% and 92%, respectively. The 30-day all-cause in-hospital mortality rate was 40% in the toxicity group and 14% in the nontoxicity group (P = 0.14). Patients receiving intravenous colistin should be monitored for nephrotoxicity, especially when the BMI exceeds 31.5 kg/m(2). Prospective, randomized, controlled trials are warranted to further examine nephrotoxicity incidence and predictors and appropriate dosing strategies in this population.

Topics: Acute Kidney Injury; Adult; Aged; Anti-Bacterial Agents; Biomarkers; Body Mass Index; Case-Control Studies; Colistin; Drug Dosage Calculations; Female; Gram-Negative Bacteria; Hospital Mortality; Humans; Injections, Intravenous; Kidney; Kidney Failure, Chronic; Logistic Models; Male; Middle Aged; Obesity; Overweight; Retrospective Studies; Risk Factors; Severity of Illness Index; United States

Acinetobacter baumannii are emerging as the causal agents of healthcare-associated infections. We describe arenal transplant recipient who developed bacteremia caused by multiresistant A. baumannii, which received a combination of tigecycline, colistin, and meropenem in continuous infusion. The clinical outcome was favorable. In this article we made a molecular study of this multiresistant strain. Our analysis reveals the presence of abla-OXA-72 gene,a class D of oxacillinase belonging to bla-OXA-40-like group,which constitutes the most disseminated familiy of carbapenemases in Spain. Thus, we found different susceptibility patterns of A. baumannii when we used different Mueller-Hinton agars with different manganese concentrations. Lastly, we explain the combination of these three antibiotics administered to increase microbiologic and pharmacodynamic yield.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Colistin; Drug Combinations; Drug Resistance, Multiple, Bacterial; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Meropenem; Microbial Sensitivity Tests; Minocycline; Reverse Transcriptase Polymerase Chain Reaction; Thienamycins; Tigecycline

Topics: Anti-Bacterial Agents; Bacterial Infections; Cephalosporins; Chloramphenicol; Colistin; Drug Therapy, Combination; Erythromycin; Gentamicins; Humans; Kidney Failure, Chronic; Lincomycin; Nalidixic Acid; Nitrofurantoin; Penicillin Resistance; Penicillins; Sulfamethoxazole; Sulfonamides; Tetracycline; Trimethoprim

Topics: Cephalothin; Colistin; Enterococcus faecalis; Escherichia coli Infections; Gentamicins; Humans; Kanamycin; Kidney Failure, Chronic; Kidney Function Tests; Male; Novobiocin; Postoperative Complications; Prostatectomy; Pseudomonas aeruginosa; Pseudomonas Infections; Streptococcal Infections; Urinary Tract Infections; Urologic Diseases

Topics: Adult; Colistin; Creatinine; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis; Renal Dialysis; Urea

Topics: Chloramphenicol; Colistin; Humans; Kanamycin; Kidney Failure, Chronic; Peritoneal Dialysis; Tetracycline

Topics: Biotransformation; Cephaloridine; Chloroquine; Chlortetracycline; Colistin; Creatinine; Doxycycline; Erythromycin; Glomerular Filtration Rate; Humans; Kidney; Kidney Failure, Chronic; Kidney Function Tests; Pharmacology; Streptomycin; Tetracycline

Topics: Adolescent; Anti-Bacterial Agents; Colistin; Drug Therapy; Geriatrics; Glomerulonephritis; Humans; Kidney Failure, Chronic; Kidney Function Tests; Pyelonephritis; Toxicology; Urinary Tract Infections