colistin and Acute-Kidney-Injury

Limited data are available to guide colistin use in older adults (>65 years old). We aimed to assess the effectiveness and safety of colistin in this population.. Systematic review and meta-analysis of original data from randomized control trials, cohort studies and case-control studies assessing colistin regimens with various comparisons for any infection. Original data were obtained from corresponding authors of original studies. The primary outcome was all-cause 1 month mortality; secondary outcomes included clinical and microbiological outcomes and adverse events, including acute kidney injury. Two independent reviewers screened citations, extracted data and assessed risk of bias. ORs with 95% CIs were pooled.. We included 38 publications (41 comparisons) reporting 2857 elderly individuals: 29 studies compared a colistin-based regimen versus another regimen (comparison 1) and 10 compared colistin monotherapy versus colistin combination (comparison 2). No significant difference in 1 month mortality was demonstrated between colistin and comparator (comparison 1, OR 1.13, 95% CI 0.80-1.60; comparison 2, OR 0.99, 95% CI 0.78-1.27). Clinical failure was significantly more likely with colistin-based therapy versus comparator (OR 1.52, 95% CI 1.13-2.06). Acute kidney injury was also significantly more common with colistin-based combinations versus other drugs (OR 3.81, 95% CI 2.14-6.77).. For older adults, colistin-based therapy resulted in no mortality difference, compared with other regimens, for any infection. Clinical failure and acute kidney injury were significantly more common with colistin-based regimens. Close renal function monitoring is needed while using colistin in older adults.

Topics: Acute Kidney Injury; Aged; Case-Control Studies; Cohort Studies; Colistin; Humans

Colistin is the last-resort antimicrobial agent against infections caused by multidrug-resistance Gram-negative bacteria (MDR-GNB). However, a differing risk of colistin-associated acute kidney injury (CA-AKI) has been demonstrated without affecting mortality, thus the association and its importance needs to be questioned. To assess the impact of this adverse effect, a meta-analysis comparing colistin with other antibiotics in treating MDR-GNB infections was conducted. The PubMed, Embase and Cochrane Library electronic databases were searched up to 31 December 2018 for cohort studies and randomised controlled trials with at least two arms with one arm containing colistin-based treatment. The primary endpoint was the incidence of AKI. The secondary endpoint was 30-day all-cause mortality. A total of 34 studies, including 26 regarding colistin-based therapy versus other antibiotics and 9 regarding colistin monotherapy versus combination therapy, were included. The incidence of CA-AKI was 32.3%. Colistin was associated with an 82% higher incidence of AKI than other antibiotics [odd ratio (OR) = 1.82, 95% confidence interval (CI) 1.13-2.92; P = 0.01]. Most CA-AKI events were mild and reversible without a higher rate of mortality or the requirement for renal replacement therapy (RRT). Only 1.0% of patients required RRT for > 4 weeks. Compared with colistin monotherapy, combination therapy was associated with a significantly lower incidence of AKI (OR = 1.46, 95% CI 1.10-1.94; P = 0.009), particularly in combination with a carbapenem (OR = 1.97, 95% CI 1.30-2.99; P = 0.001). In conclusion, CA-AKI might not be an important limitation of colistin in MDR-GNB therapy.

Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Carbapenems; Cohort Studies; Colistin; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Incidence; Renal Replacement Therapy

This review comprehensively assessed the safety and efficacy of colistin alone or in combination in adults with Acinetobacter baumannii infection. PubMed, Embase and the Cochrane Library were searched from inception to March 2018 for studies evaluating colistin monotherapy compared with other antibiotic therapy or colistin-based combination therapy for the treatment of A. baumannii infection in adults. Efficacy outcomes were clinical response and microbiological cure. Safety outcomes were mortality and nephrotoxic adverse events. A total of 4 randomised controlled trials (RCTs) and 14 observational studies were identified, including 7 reporting colistin versus other antibiotics and 12 reporting colistin monotherapy versus colistin-based combination therapy. Overall clinical response, microbiological response and mortality did not differ significantly between colistin monotherapy versus other antibiotics. However, the incidence of nephrotoxicity was significantly higher in colistin monotherapy (OR = 2.50, 95% CI 1.05-5.98; P = 0.04). No significant differences were detected in clinical response and >28-day mortality between colistin monotherapy and combination therapy. However, colistin-based combination therapy showed an increased microbiological response (OR = 0.49, 95% CI 0.32-0.74; P = 0.0009) and decreased incidence of nephrotoxicity (OR = 1.66, 95% CI 0.99-2.78; P =0.05). In conclusion, colistin alone is as effective as other antibiotics for the treatment of A. baumannii infection but has a higher risk of nephrotoxicity. Colistin-based combination therapy demonstrated a microbiological benefit and no higher risk of nephrotoxicity compared with monotherapy. High-quality RCTs are still needed to confirm the beneficial role of colistin-based combination therapy.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Acute Kidney Injury; Adult; Anti-Bacterial Agents; Colistin; Drug Therapy, Combination; Humans; Treatment Outcome

Colistin and polymyxin B are increasingly reintroduced in clinical practice due to the absence of effective antibiotics for the treatment of emerging infections caused by gram-negative bacteria. The synthesis of current evidence on the characteristics of polymyxins, especially regarding nephrotoxicity, is necessary. This study aims to conduct a systematic review and meta-analysis of cohort-type observational studies in order to identify the prevalence of nephrotoxicity in patients treated with either colistin or polymyxin B. PubMed, Scopus, and DOAJ electronic databases were searched, and manual searches were done. Cohort studies evaluating renal damage (nephrotoxicity) in adult patients caused by colistin or polymyxin B were included. Meta-analyses of the prevalence of nephrotoxicity as well as cumulative meta-analysis and meta-regression were conducted. After the systematic searches, 95 cohorts (n = 7911 patients) were included for analysis. The nephrotoxicity prevalence was 26.7% [confidence interval (CI) 95%: 22.8-30.9%] for colistin and 29.8% (CI 23.8-36.7%) for polymyxin B (P = 0.720). The publication year of the studies, the criteria used to classify renal damage, and the nephrotoxicity as primary or secondary outcome showed a significant influence on the adverse event rates.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Colistin; Humans; Observational Studies as Topic; Polymyxin B; Prevalence

The emergence of multidrug resistant (MDR) infections and the shortage of new therapeutic options have made colistin, a polymyxin antibiotic, the main option for the treatment of MDR Gram-negative bacterial infections in the last decade. However, the rapid onset of renal damage often prevents the achievement of optimal therapeutic doses and/or forces the physicians to interrupt the therapy, increasing the risk of drug resistance. The proper management of colistin-induced nephrotoxicity remains challenging, mostly because the investigation of the cellular and molecular pharmacology of this drug, off the market for decades, has been largely neglected. For years, the renal damage induced by colistin was considered a mere consequence of the detergent activity of this drug on the cell membrane of proximal tubule cells. Lately, it has been proposed that the intracellular accumulation is a precondition for colistin-mediated renal damage, and that mitochondria might be a primary site of damage. Antioxidant approaches (e.g., ascorbic acid) have shown promising results in protecting the kidney of rodents exposed to colistin, yet none of these strategies have yet reached the bedside. Here we provide a critical overview of the possible mechanisms that may contribute to colistin-induced renal damage and the potential protective strategies under investigation.

Topics: Acute Kidney Injury; Animals; Anti-Bacterial Agents; Antioxidants; Cell Membrane; Colistin; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacterial Infections; Humans; Kidney

Colistin is an old antibiotic, which is abandoned decades ago because of high nephrotoxicity rates. However, it is reintroduced to clinical medicine due to lack of newly discovered antibiotics and is still widely used for the treatment of resistant gram-negative infections. Discovering mechanisms to reduce nephrotoxicity risk is of significant importance since exposed patients may have many other factors that alter kidney functions. Several agents were evaluated in animal models of colistin nephrotoxicity as a means to prevent kidney injury. Considerable heterogeneity exists in terms of reporting colistin dosing and experimental designs. This issue leads clinicians to face difficulties in designing studies and sometimes may lead to report dosing strategies inadequately. Here, we present a review according to animal models of colistin nephrotoxicity using data gathered from previous experiments to draw attention on possible complexities that researchers may encounter.

Topics: Acute Kidney Injury; Animals; Anti-Bacterial Agents; Colistin; Disease Models, Animal; Dose-Response Relationship, Drug; Kidney; Rats; Rats, Sprague-Dawley; Rats, Wistar; Risk Factors; Toxicity Tests

Colistin and polymyxin B (PMB) have different pharmacokinetic profiles and minor differences in antimicrobial activities that may result in discrepancies in mortality and nephrotoxicity. A systematic review and meta-analysis was conducted. PubMed, Scopus and Cochrane Library databases were searched. There was no significant difference in unadjusted mortality between patients treated with colistin and PMB [risk ratio (RR) = 0.71, 95% confidence interval (CI) 0.45-1.13]. Adjusted data were not available. Unadjusted nephrotoxicity was more common in patients treated with colistin than PMB (RR = 1.55, 95% CI 1.36-1.78). According to the RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) criteria, there was no difference regarding risk, injury or failure between colistin and PMB. Although episodes of loss of renal function were few in general, they developed primarily in colistin-treated patients (RR = 8.55, 95% CI 1.48-49.49). Colistin was associated with more episodes of nephrotoxicity that also occurred sooner in the analysis of adjusted data (hazard ratio = 2.16, 95% CI 1.43-3.27). Colistin administration was an independent risk factor for nephrotoxicity in two studies. Future studies should evaluate in depth the factors associated with mortality and nephrotoxicity in patients treated with polymyxins and the impact of polymyxin-associated nephrotoxicity on mortality.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Polymyxin B; Survival Analysis; Treatment Outcome

Nephrotoxicity is a common adverse effect of the clinically used polymyxins, colistin and polymyxin B. This adverse effect is dose limiting for both polymyxins, as the plasma polymyxin concentrations associated with renal damage overlap those required for antibacterial effect. Since development of acute kidney injury (AKI) during therapy is highly undesirable, it is extremely important to know whether there is any difference between the nephrotoxic potential of colistin (administered as its inefficient prodrug, colistimethate) and polymyxin B (administered as the active form). Both polymyxins are cytotoxic to renal tubular cells and are prone to cause nephrotoxicity

Topics: Acute Kidney Injury; Animals; Anti-Bacterial Agents; Bacterial Infections; Biological Transport; Clinical Trials as Topic; Colistin; Humans; Kidney; Mice; Polymyxin B; Prodrugs; Rats; Survival Analysis

Colistin (polymyxin E) is a mainly concentration-dependent bactericidal antimicrobial active against multidrug-resistant Gram-negative bacteria. After being abandoned over the past 30 years due to its neuro- and nephrotoxicity, colistin has been reintroduced recently as a last-resort drug for the treatment of multidrug-resistant Gram-negative bacteria infections in combination with other antimicrobials. Unfortunately, although renal toxicity is a well-known dose-related adverse effect of colistin, relatively few studies are currently available on its peculiar pharmacodynamic/pharmacokinetic properties in clinical settings at high risk for drug accumulation, such as acute or chronic kidney disease. In these specific contexts, the risk for underdosing is also substantial because colistin can be easily removed by dialysis/hemofiltration, especially when the most efficient modalities of renal replacement therapy (RRT) are used in critically ill patients. For this reason, recent recommendations in patients undergoing RRT have shifted toward higher dosing regimens, and therapeutic drug monitoring is advised. This review aims to summarize the main issues related to chemical structure, pharmacodynamics/pharmacokinetics, and renal toxicity of colistin. Moreover, recent data and current recommendations concerning colistin dosing in patients with reduced kidney function, with special regard to those receiving RRT such as dialysis or hemofiltration, are also discussed.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Colistin; Drug Monitoring; Humans; Kidney; Kidney Diseases; Practice Guidelines as Topic; Renal Insufficiency, Chronic; Renal Replacement Therapy

The polymyxin antibiotics [colistin and polymyxin B (PMB)] are increasingly used as a last-line option for the treatment of infections caused by extensively drug-resistant Gram-negative bacteria. Despite having similar structures and antibacterial activity in vitro, the two clinically available polymyxins have very different pharmacological properties, as colistin (polymyxin E) is intravenously administered to patients in the form of an inactive prodrug colistin methanesulphonate (sodium). This review will discuss recent progress in the pharmacokinetics/pharmacodynamics and toxicity of colistin and PMB, the factors that affect their pharmacological profiles, and the challenges for the effective use of both polymyxins. Strategies are proposed for optimising their clinical utility based upon the recent pharmacological studies in vitro, in animals and patients. In the 'Bad Bugs, No Drugs' era, polymyxins are a critically important component of the antibiotic armamentarium against difficult-to-treat Gram-negative 'superbugs'. Rational approaches to the use of polymyxins must be pursued to increase their effectiveness and to minimise resistance and toxicity.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Colistin; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Polymyxin B

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

With the reintroduction of colistimethate and polymyxin B into clinical practice, a review of their individual and comparative nephrotoxicity attributes as reported in contemporary literature was undertaken. Given variability in definitions used for acute kidney injury, a particular focus was placed on studies utilizing the Risk-Injury-Failure-Loss-End Stage Kidney Disease (RIFLE) criteria of assessment to provide for standardized comparison. Primary risk factors examined included the influence of dosing and the receipt of concomitant nephrotoxins. The typical severity and time course of renal injury that develops were also analyzed. Nephrotoxicity rates with colistimethate appear to approach 50%, and could be of lower frequency and severity with polymyxin B based on limited literature. Acute kidney injury generally appears to be mild to moderate in magnitude and reversible in nature, though as many as 20% of patients experiencing it may require renal replacement therapy of some duration. The majority of studies showed some relationship with dosing- variably reported as being associated with daily dose or cumulative exposure. Traditional nephrotoxic agents did not appear to confer additional risk individually in the majority of investigations, though receipt of multiple concurrent nephrotoxins did yield a relationship in several. Further studies will be required to better characterize the renal adverse effect profile of these agents, particularly in the case of polymyxin B.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Colistin; Humans; Polymyxin B

Topics: Acute Kidney Injury; Ampicillin; Anti-Bacterial Agents; Cephalosporins; Chloramphenicol; Colistin; Erythromycin; Female; Humans; Kanamycin; Kidney Function Tests; Methicillin; Nitrofurantoin; Oxacillin; Penicillins; Peritoneal Dialysis; Renal Dialysis; Streptomycin; Sulfonamides; Tetracycline

Nephrotoxicity remains a major long-standing concern for colistin, and it is critical to find agents that can prevent it. The present study aims to investigate the effect of vitamin E on the prevention of colistin-induced nephrotoxicity based on its antioxidant and free radical scavenging properties.. A randomized clinical trial was designed for 52 patients taking colistin. These patients were categorized into two groups of equal size, receiving colistin or colistin plus vitamin E (α-Tocopherol). Vitamin E with doses of 400 units was administrated daily either orally or by a nasogastric tube if needed. The incidence of Acute Kidney Injury (AKI) and its duration was recorded based on RIFLE criteria.. The Incidence of AKI based on RIFLE criteria was 42.3% and 46.2% in intervention and control groups, respectively. The analysis showed no significant difference in the prevalence of AKI for the two groups (P = 0.78). There was no significant difference in the duration of AKI neither (P = 0.83).. Although vitamin E is a powerful biological antioxidant, the effects of Vitamin E prophylaxis on colistin-induced nephrotoxicity was not taken into consideration in this study.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Colistin; Gram-Negative Bacterial Infections; Humans; Pharmaceutical Preparations; Retrospective Studies; Risk Factors; Vitamin E

Nephrotoxicity has been a concern with new dosing regimens of colistin. This study was designed to compare nephrotoxicity of high dose and conventional dose of colistin and the ability of detecting it using neutrophil gelatinase-associated lipocalin (NGAL).. A randomized clinical trial was carried out on 40 patients with multidrug-resistant gram-negative infections assigned into 2 groups to receive high and conventional doses of colistin. Blood samples were taken 4 times for measuring serum NGAL. The incidence of acute kidney injury was also evaluated based on the risk, injury, failure, loss, end-stage renal disease (RIFLE) criteria.. Baseline levels of NGAL were not significantly different between the patients on the high dose and conventional dose of colistin. The mean NGAL levels on day 10 were 762.14 ± 415.44 pg/mL and 623.67 ± 272.61 pg/mL, respectively.  However, between-group analysis did not show a significant difference in the NGAL levels. The prevalence of acute kidney injury was 60% and 15% based on the RIFLE criteria, in the high-dose and conventional-dose groups, respectively (P = .003).. Although colistin-induced nephrotoxicity was not confirmed with NGAL levels, our findings, however, showed a higher incidence of acute kidney injury associated with high-dose colistin, defined by the RIFLE criteria. Higher levels of NGAL in the acute kidney injury patients were associated with high-dose regimen of colistin.

Topics: Acute Kidney Injury; Adult; Aged; Anti-Bacterial Agents; APACHE; Biomarkers; Colistin; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Incidence; Iran; Lipocalin-2; Male; Middle Aged; Predictive Value of Tests; Prevalence; Risk Factors; Time Factors; Treatment Outcome

The study aimed to prospectively assess incidence and risk factors for colistin-associated nephrotoxicity. This is a secondary analysis of a multicentre, randomized clinical trial, comparing efficacy and safety of colistin versus the combination of colistin plus rifampicin in severe infections due to extensively drug-resistant (XDR) Acinetobacter baumannii. The primary end point was acute kidney injury (AKI) during colistin treatment, assessed using the AKI Network Criteria, and considering death as a competing risk. A total of 166 adult patients without baseline kidney disease on renal replacement therapy were studied. All had life-threatening infections due to colistin-susceptible XDR A. baumannii. Patients received colistin intravenously at the same initial dose (2 million international units (MIU) every 8 h) with predefined dose adjustments according to the actual renal function. Serum creatinine was measured at baseline and at days 4, 7, 11, 14 and 21 (or last day of therapy when discontinued earlier). Outcomes assessed were 'time to any kidney injury' (AKI stages 1-3) and 'time to severe kidney injury' (considering only AKI stages 2-3 as events). When evaluating overall mortality, AKI occurrence was modelled as a time-dependent variable. AKI was observed in 84 patients (50.6%, stage 1 in 40.4%), with an incidence rate of 5/100 person-days (95% CI 4-6.2). Risk estimates of AKI at 7 and 14 days were 30.6% and 58.8%. Age and previous chronic kidney disease were significantly associated with any AKI in multivariable analysis. Neither 'any' nor 'severe AKI' were associated with on-treatment mortality (p 0.32 and p 0.54, respectively). AKI occurs in one-third to one-half of colistin-treated patients and is more likely in elderly patients and in patients with kidney disease. As no impact of colistin-associated AKI on mortality was found, this adverse event should not represent a reason for withholding colistin therapy, whenever indicated.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Acute Kidney Injury; Adult; Aged; Anti-Bacterial Agents; Colistin; Creatinine; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Endpoint Determination; Female; Humans; Incidence; Male; Middle Aged; Multivariate Analysis; Prospective Studies; Rifampin; Risk Assessment

Twenty-one patients who received intravenous colistimethate sodium (CMS) for at least 7 days for the treatment of multidrug-resistant Gram-negative bacterial infections were included in a prospective cohort study at 'Henry Dunant' Hospital in Athens, Greece. The mean (+/- standard deviation) and median daily doses, cumulative doses and duration of treatment of intravenous CMS were, respectively, 5.5 (+/- 1.9) and 6 million IU, 90.2 (+/- 52.0) and 72 million IU, and 17.7 (+/- 11.7) and 15 days (range 7-54 days). Three patients (14.3%) developed nephrotoxicity during treatment with CMS. The cumulative dose of administered CMS was statistically correlated with the difference in values of serum creatinine between the end and start of CMS treatment (r = 0.6, P = 0.004 by Spearman's test).

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cohort Studies; Colistin; Creatinine; Female; Gram-Negative Bacterial Infections; Greece; Humans; Injections, Intravenous; Kidney Function Tests; Male; Middle Aged; Nephrotic Syndrome; Prospective Studies; Treatment Outcome

In this retrospective cohort study, we aimed to evaluate the incidence, risk factors and outcomes of amikacin-induced acute kidney injury (AKI) in critically ill patients with sepsis. A total of 311 patients were included in the study. Of them, 83 (26.7%) had amikacin-induced AKI. In model 1, the multivariable analysis demonstrated concurrent use of colistin (OR 25.51, 95%CI 6.99-93.05, p< 0.001), presence of septic shock during amikacin treatment (OR 4.22, 95%CI 1.76-10.11, p=0.001), and Charlson Comorbidity Index (OR 1.14, 95%CI 1.02-1.28, p=0.025) as factors independently associated with an increased risk of amikacin-induced AKI. In model 2, the multivariable analysis demonstrated concurrent use of at least one nephrotoxic agent (OR 1.95, 95%CI 1.10-3.45; p=0.022), presence of septic shock during amikacin treatment (OR 3.48, 95%CI 1.61-7.53; p=0.002), and Charlson Comorbidity Index (OR 1.12, 95%CI 1.01-1.26; p=0.037) as factors independently associated with an increased risk of amikacin-induced AKI. In conclusion, before amikacin administration, the risk of AKI should be considered, especially in patients with multiple complicated comorbid diseases, septic shock, and those receiving colistin therapy.

Topics: Acute Kidney Injury; Amikacin; Colistin; Critical Illness; Humans; Intensive Care Units; Respiration, Artificial; Retrospective Studies; Risk Factors; Sepsis; Shock, Septic

Colistin is considered as a last resort therapy for multidrug-resistant gram-negative organisms. It is widely used despite the significant risk of nephrotoxicity. Experimental studies showed the nephroprotective effect of dexmedetomidine, a sedative agent, against colistin toxicity. This study was performed to show the possible nephroprotective effect of dexmedetomidine among critically ill patients who received colistin.. Adult (>17 years) patients who were admitted to our surgical and medical intensive care unit (ICU) from March 2018 through March 2021, and who received colistin were included. Patients who receive Colistin therapy or intensive care unit follow-up of <72 h (discharge or death) and Acute kidney injury (AKI) or need hemodialysis prior to colistin therapy at the same hospitalization were excluded. AKI risk factors were examined by grouping patients with and without AKI. Patients, receiving colistin concomitantly with dexmedetomidine were also evaluated.. Of the 139 patients included, 27 (17.8%) patients received dexmedetomidine. Sixty-five patients (47%) had AKI, at a median 5 (4-7) days after the initiation of colistin. Older age, lower baseline estimated glomerular filtration rate, and vasopressor use were associated with a higher risk of AKI, while dexmedetomidine use was associated with a lower risk. In the multivariate regression model, dexmedetomidine use was independently associated with a lower risk of AKI development (OR 0.20 95% CI 0.07-0.59, p = 0.003).. In respect to these findings, dexmedetomidine may provide protection against AKI during colistin therapy in critically ill patients.

Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Colistin; Critical Illness; Dexmedetomidine; Gram-Negative Bacteria; Humans; Intensive Care Units; Retrospective Studies; Risk Factors

Oxidative stress-mediated colistin's nephrotoxicity is associated with the diminished activity of nuclear factor erythroid 2-related factor 2 (Nrf2) that is primarily correlated with cellular PH domain and leucine-rich repeat protein phosphatase (PHLPP2) levels. This study investigated the possible modulation of PHLPP2/protein kinase B (Akt) trajectory as a critical regulator of Nrf2 stability by rosuvastatin (RST) to guard against colistin-induced oxidative renal damage in rats.. Colistin (300,000 IU/kg/day; i.p.) was injected for 6 consecutive days, and rats were treated simultaneously with RST orally at 10 or 20 mg/kg.. RST enhanced renal nuclear Nrf2 translocation as revealed by immunohistochemical staining to boost the renal antioxidants, superoxide dismutase (SOD) and reduced glutathione (GSH) along with a marked reduction in caspase-3. Accordingly, rats treated with RST showed significant restoration of normal renal function and histological features. On the molecular level, RST effectively decreased the mRNA expression of PHLPP2 to promote Akt phosphorylation. Consequently, it deactivated GSK-3β and reduced the gene expression of Fyn kinase in renal tissues.. RST could attenuate colistin-induced oxidative acute kidney injury via its suppressive effect on PHLPP2 to endorse Nrf2 activity through modulating Akt/GSK3 β/Fyn kinase trajectory.

Topics: Acute Kidney Injury; Animals; Antioxidants; Colistin; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Kidney; NF-E2-Related Factor 2; Oxidative Stress; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-fyn; Rats; Rosuvastatin Calcium; Signal Transduction

We aimed to determine the risk factors that may be associated with colistin-induced acute kidney injury (AKI) to promote the safer use of colistin in the treatment of nosocomial infections caused by multidrug-resistant Gram-negative bacteria in intensive care units.. This retrospective observational study was conducted among adult patients who received a minimum of 48 h of intravenous colistin from January 2020 to December 2020 at the intensive care unit of a tertiary care hospital. AKI diagnosis and staging were made based on the Kidney Disease Improving Global Outcome Criteria.. Of 148 patients who received intravenous colistin at a daily dose of 9 million IU, 54 (36%) developed AKI. In the univariate analysis, age, Charlson comorbidity index, APACHE II score, duration of colistin treatment, basal creatinine level, use of vasopressors, and vancomycin were significantly associated with AKI (p < 0.05). The multivariate analysis revealed that the independent predictor of AKI was the use of vasopressors (OR: 3.14; 95% confidence interval: 1.39-97.07; p = 0.06).. The use of vasopressors in critically ill patients was independently associated with AKI developing during colistin treatment.

Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Colistin; Critical Illness; Humans; Intensive Care Units; Retrospective Studies; Risk Factors; Vancomycin

Colistin is one of the last resort antibiotic options for resistant gram-negative pathogens. Renal injury is the most common side effect of colistin. Characteristics of nephrotoxicity are well described in adults. However, this data is sparse in children.. In this study we evaluated the incidence, severity, time course and risk factors of colistin nephrotoxicity in a pediatric population.. In a prospective study over a 9-month period, children who received intravenous colistin for at least 48 h were evaluated for renal side effect by utilizing Risk-Injury-Failure-Loss-End Stage Kidney Disease (RIFLE) criteria. Children receiving renal replacement therapy (RRT) or received a repeated course of colistin were excluded.. Thirty-seven children were included. Median age of participants was 4.5 months. Overall, 48.6% of the cases developed AKI and consisted 56% in the Risk, 33% in the Injury and 11% in the Failure categories of RIFLE criteria. AKI was reversible while colistin continued and no one required RRT. Mean ± SD time to AKI development was 10.94 ± 7.51 days. Multivariate logistic regression analysis demonstrated that total cumulative dose of colistin was an independent predictor of nephrotoxicity (standardized ß = 1.024, P = 0.034).. AKI is a common side effect of colistin therapy in critically ill children developing in nearly half of recipients. However, with the dosage range utilized in this study, in the majority of children, renal injury seemed to be mild to moderate in nature. Given the limited treatment options available in critically ill children with resistant gram-negative pathogens, colistin remains a marvelous therapeutic option. Further studies are required to fully elucidate the risk factors and clinical pictures of colistin-induced nephrotoxicity.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Colistin; Critical Illness; Humans; Infant; Prospective Studies; Risk Factors

The aim of this study was to compare the safety and effectiveness of ceftolozane-tazobactam (C-T) to colistin-based regimen for treating infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa.. This was a retrospective, multicentre, observational cohort study of inpatients who received either C-T or intravenous colistin for treating infections caused by MDR P. aeruginosa. The study was conducted in five tertiary care hospitals in Saudi Arabia. The main study outcomes included clinical cure at end of treatment, in-hospital mortality, and acute kidney injury (AKI). Univariate analysis and multivariate logistic regression model were conducted to evaluate the independent effect of C-T on the clinical outcome.. A total of 184 patients were included in the study: 82 patients received C-T, and 102 patients received colistin-based regimen. Clinical cure (77% vs. 57%; P = 0.005; OR, 2.52; 95% CI, 1.32-4.79) was significantly more common in patients who received C-T. After adjusting the difference between the two groups, treatment with C-T is independently associated with clinical cure (adjusted OR, 2.47; 95% CI, 1.16-5.27). In-hospital mortality (39% vs. 49%; P = 0.175; OR, 0.67; 95% CI, 0.37-1.20) was lower in patients who received C-T, but the difference was not significant. AKI (15% vs. 41%; P < 0.001; OR, 0.25; 95% CI, 0.12-0.51) was significantly less common in patients who received C-T.. C-T is associated with a higher rate of clinical cure and lower rate of AKI compared to colistin. Our findings support the preferential use of C-T over colistin-based regimen for treating these infections.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Cephalosporins; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Tazobactam

Colistimethate sodium and tobramycin are important systemic antibiotics for treatment of cystic fibrosis (CF) pulmonary exacerbations but can induce acute kidney injury (AKI). We characterize the rate of AKI in CF patients treated with systemic colistimethate sodium compared with tobramycin.. This single-centre, retrospective cohort study included hospitalized CF patients treated with IV colistimethate sodium or tobramycin. The primary outcome was AKI defined using the RIFLE criteria. Multivariate logistic regression using a mixed model was performed to identify variables that were independently associated with AKI.. Overall, 156 patients representing 507 care encounters were included. The OR of AKI was not increased with IV colistimethate sodium relative to IV tobramycin after adjusting for other potential predictor variables (aOR 1.00; 95% CI 0.16-6.03). The frequency of AKI was 9.5% across all encounters, 6.9% with IV colistimethate sodium and 9.9% with IV tobramycin, with RIFLE category R (risk) being the most common stage, accounting for 4.2% of encounters with IV colistimethate sodium and 9.2% with IV tobramycin. The concomitant use of another nephrotoxin (aOR 2.51; 95% CI 1.27-4.95) or the combination of vancomycin and piperacillin/tazobactam (aOR 5.95; 95% CI 2.05-17.3) were both associated with increased odds of AKI.. Systemic treatment with colistimethate sodium or tobramycin in the CF patient population is associated with a similar rate of nephrotoxicity. However, clinicians should be mindful of the increased risk for AKI in patients treated with either IV colistimethate sodium or IV tobramycin when used concurrently with other nephrotoxic agents, particularly the combination of vancomycin and piperacillin/tazobactam.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Colistin; Cystic Fibrosis; Drug Therapy, Combination; Humans; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Tobramycin; Vancomycin

Ventilator-associated events (VAEs) are major complications of mechanical ventilation (MV). Herein, we aimed to evaluate whether acute kidney injury (AKI) developed in patients who had been followed up with the diagnosis of Acinetobacter baumannii (AcB)-related VAE, the need for renal replacement therapy (RRT), and its relationship with mortality in patients who developed AKI due to colistin treatment.. A retrospective evaluation of 2,622 patients was conducted. Patients who developed AcB-based VAE and received parental colistin treatment were evaluated in terms of age, sex, diagnosis on intensive care unit (ICU) admission, Acute Physiology and Chronic Health Evaluation (APACHE) II score, colistin dose and treatment duration, duration of ICU stay, AKI staging according to Kidney Disease Improving Global Outcomes criteria, RRT requirement, and mortality.. Eighty-five patients (3.19%) had VAEs, of whom 28 (32.9%) had AcB-related VAE. Bacterial eradication was achieved in 14 patients (50%), clinical response was achieved in 14 patients (50%), the mean colistin dose was 298.2 ± 85.5 mg/d, and mean duration of colistin treatment was 14.3 ± 8.6 days. AKI was detected as stages I, II, and III in 28.6%, 14.3%, and 28.6% of the patients; respectively. There was no difference between patients requiring RRT and those who did not in terms of the APACHE II score, bacterial eradication, clinical response to therapy, a daily dose of colistin, treatment duration, and MV duration.. Colistin treatment of AcB-related VAE caused AKI in 71.5% of the patients and led to serious conditions in 25% of the patients requiring RRT.  DOI: 10.52547/ijkd.6694.

Topics: Acinetobacter baumannii; Acute Kidney Injury; Colistin; Humans; Intensive Care Units; Retrospective Studies; Ventilators, Mechanical

Colistin use has increased because of the emergence of infections caused by resistant gram-negative bacteria. Acute kidney injury (AKI) remains a treatment-limiting factor for widespread colistin clinical use. This study aimed at determining the incidence and the factors associated with the development of colistin-induced AKI.. A retrospective observational study was conducted by reviewing files of adult patients with normal kidney function between January 2015 to March 2019 at a university hospital located in Beirut city. AKI was defined based on KDIGO criteria. Independent variables associated with colistin-induced AKI were also tested.. In this study, a total of 113 patients were included. AKI occurred in 53 patients (46.9%). The Charlson Comorbidity Index (CCI) was found to be significantly greater in the AKI group (2.26, P-value = 0.026). In the multivariate analysis, low serum albumen was found as an independent significant predictor for AKI (OR=.065, 95%CI: .013-.337, P-value=0.001). Moreover, the risk for AKI increased by 2 folds (OR=2.019, 95%CI: 1.094-3.728, P-value: 0.025), when two or more nephrotoxic agents were administered simultaneously with colistin. The patient's age was also found as a significant predictor for AKI (OR=1.034, 95%CI:1-1.07), with a cut-off value of 58.5-year-old.. This study demonstrated that the concomitant use of two or more nephrotoxic drugs, patient's age of 58.5 or above, and the presence of hypoalbuminemia were independent factors for the development of colistin-induced AKI. These factors should be therefore taken into consideration when prescribing colistin in clinical practice to decrease the risk of AKI.

Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Colistin; Humans; Incidence; Middle Aged; Retrospective Studies; Risk Factors

Background Colistin is a potentially nephrotoxic antibiotic used for the management of multidrug-resistant bacterial infections in critically ill patients. Co-administration with other nephrotoxins was reported as a potentially modifiable risk factor of colistin acute kidney injury. Objective To establish the role of colistin dosing and co-medications in development of colistin kidney injury. Setting Community teaching hospital in Latvia. Method Adult patients from intensive care units with diagnosed Gram-negative bacterial infections, undergoing colistin treatment for longer than 72 h, and not receiving renal replacement therapy were included in this retrospective study. Main outcome measure Colistin nephrotoxicity was defined as an increase in the serum creatinine level by at least 50% from the baseline after ≥ 48 h. Results In 73 of 87 cases, Acinetobacter baumannii pneumonia was diagnosed. The nephrotoxicity rate was 27.6% with a median onset of 8 days. In 79% of the cases, colistin was co-administrated with at least one potentially nephrotoxic agent. The most used nephrotoxins were loop diuretics (44 cases), non-steroidal anti-inflammatory drugs (19 cases) and vancomycin (11 cases). The use of nephrotoxins was similar in patients with colistin nephrotoxicity (group-1) and without it (group-2). Carbapenems were more common in group-2 (37% vs 62%, p = 0.004) and a colistin loading dose of 9 MU in group-1 (87% vs 62%, p = 0.027). However, in the multifactor regression analysis, the protective role of carbapenems was not confirmed. Conclusion Potentially nephrotoxic agents are commonly co-administrated with colistin. This study failed to prove their role in the development of acute kidney injury.

Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Hospitals, Teaching; Humans; Latvia; Retrospective Studies

Topics: Acute Kidney Injury; Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Age Distribution; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Polymyxin B; Retrospective Studies; United States; United States Food and Drug Administration; Young Adult

Colistin is a potent antibiotic which is mainly preferred in the treatment of multidrug-resistant (MDR) gram-negative bacilli. However, due to the increased risk of acute kidney injury following its use, the clinical application is limited. This nephrotoxicity is known to be induced by oxidative stress and related inflammation. In this study on rats, potent antioxidants Dexpanthenol (DEX) and Ascorbic acid (Vit C) have been administered in combination with Colistin to find out whether they would weaken Colistin's nephrotoxic effects.. Inflammation biomarkers were studied with enzyme-linked immunosorbent assay (ELISA) kits, and oxidative stress biomarkers were studied with different photometric methods in blood and tissue samples taken after treatment with DEX and Vit C in rats with colistin nephrotoxicity. In addition, inflammation and necrosis in the kidney tissues were examined pathologically.. It has been observed in the serum and tissue samples that DEX and Vit C decrease oxidative stress and inflammation biomarkers, therefore acting as nephroprotective agents.. These compounds have been found to ameliorate the nephrotoxic effects of Colistin, which were demonstrated in the rats treated with Colistin, as well as the combinations.

Topics: Acute Kidney Injury; Animals; Ascorbic Acid; Colistin; Disease Models, Animal; Inflammation; Injections, Intraperitoneal; Male; Neuroprotective Agents; Oxidative Stress; Pantothenic Acid; Rats; Rats, Sprague-Dawley

Colistin is an, antibiotic used to treat carbapenem-resistant

Topics: Acinetobacter baumannii; Acinetobacter Infections; Acute Kidney Injury; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Kidney Function Tests; Male; Middle Aged; Organ Dysfunction Scores; Risk Factors

A colistin loading dose is required to achieve adequate drug exposure for the treatment of multidrug-resistant Gram-negative bacteria. However, data on acute kidney injury (AKI) rates associated with this approach in children have been unavailable. The aim of this study was to examine AKI rates in children who were prescribed a colistin loading dose.. A retrospective study was conducted in patients aged 1 month to 18 years who had received intravenous colistin for ≥48 h. Loading dose (LD) was defined as colistin methanesulfonate at 4-5 mg of colistin base activity/kg/dose. AKI was defined according to KDIGO serum creatinine (SCr) criteria - SCr ≥ 1.5 times the baseline, measured 3-7 days after colistin initiation. Augmented renal clearance (ARC) was defined as an estimated glomerular filtration rate (eGFR) >150 mL/min/1.73 m. In total, 181 children were enrolled. The mean age was 4.3 years (95% confidence interval [CI], 3.6-4.9 years). Ninety-five of the subjects (52.5%) were male. There were 157 children with a baseline eGFR of ≥ 80 mL/min/1.73 m. AKI rate was not different among children who received an intravenous colistin loading dose. This approach should be implemented to ensure the necessary drug exposure required for good treatment outcomes.

Topics: Acute Kidney Injury; Administration, Intravenous; Aged; Child; Child, Preschool; Colistin; Creatinine; Drug Resistance, Multiple; Female; Glomerular Filtration Rate; Humans; Male; Middle Aged; Retrospective Studies; Risk Factors; Treatment Outcome

Infections by carbapenem-resistant Klebsiella pneumoniae (CRKp) are an increasing global threat with limited therapeutic options. Our objective was to evaluate clinical and microbiological outcomes of patients treated with amikacin for CRKp infections. We did a retrospective cohort of patients > 18 years old, with CRKp infections treated with amikacin in two tertiary care hospitals in Porto Alegre, Brazil. The impact of clinical factors, antibiotic treatment, and amikacin minimum inhibitory concentration (MIC) on patients' 30-day mortality was assessed. Microbiological clearance and nephrotoxicity (assessed by RIFLE score) were evaluated as secondary outcomes. A Cox regression analysis was done for mortality. We included 84 patients for analysis. Twenty-nine (34.5%) patients died in 30 days. Amikacin MIC values ranged from 0.125 to 8 μg/mL and did not influence on mortality, regardless of the prescribed dose of this antibiotic (P = 0.24). Bacterial clearance occurred in 17 (58.6%) of 29 patients who collected subsequent cultures. Two (16.6%) of the 12 persistently positive cultures changed the amikacin susceptibility profile from susceptible to intermediate. Twenty-nine (37.2%) patients developed acute kidney injury (AKI): risk 13, injury 11, and failure 5. Risk factors for AKI were higher baseline eGFR (P < 0.01) and combination therapy with colistin (P = 0.02). Comparing patients who received combination with colistin vs polymyxin B, AKI occurred in 60.0% vs 20.6%, respectively, P < 0.01. Fifteen of the 16 (16.6%) patients who developed renal injury or failure were receiving colistin. In conclusion, amikacin was an effective treatment for CRKp infections. Within susceptible range, amikacin MIC values did not influence on clinical outcomes. Combination therapy of amikacin and colistin was highly nephrotoxic and should be used with caution.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Amikacin; Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Treatment Outcome; Young Adult

Colistin is widely used in the treatment of nosocomial infections caused by carbapenem-resistant gram-negative bacilli (CR-GNB). Colistin-induced nephrotoxicity is one of the major adverse reactions during colistin treatment. Comparisons of colistin-induced nephrotoxicity between different formulations of colistin are rarely reported.. In this retrospective cohort study, we enrolled intensive care unit-admitted patients if they had culture isolates of CR-GNB and underwent intravenous treatment with colistin. The occurrence of acute kidney injury (AKI) during intravenous treatment with colistin was recorded. The occurrence of colistin-induced nephrotoxicity was compared between two formulations of colistin, Locolin®, and Colimycin®. Treatment outcomes associated with the occurrence of colistin-induced nephrotoxicity were also investigated.. Among 195 patients, 95 who were treated with Locolin® and 100 who were treated with Colimycin® were included for analysis. Patients treated with Locolin® had a higher rate of occurrence of stage 2 (46.3% vs. 32%, p = 0.040) and stage 3 (29.5% vs. 13%, p = 0.005) AKI than did those treated with Colimycin®. In multivariate analysis, the presence of septic shock (adjusted odds ratio [aOR] 2.17, 95% confidence interval [CI] 1.10-4.26) and inappropriate colistin dosage (aOR 2.52, 95% CI 1.00-6.33) were clinical factors associated with colistin-induced nephrotoxicity. Treatment with Colimycin® was an independent factor associated with a lower risk of colistin-induced nephrotoxicity (aOR 0.37, 95% CI 0.18-0.77). The mortality rate was comparable between patients with and without colistin-induced nephrotoxicity.. The risk of colistin-induced nephrotoxicity significantly varied in different formulations of colistin in critically ill patients. Colistin-induced nephrotoxicity was not associated with increased mortality rate.

Topics: Acute Kidney Injury; Administration, Intravenous; Aged; Aged, 80 and over; Colistin; Critical Illness; Drug Compounding; Drug Resistance, Bacterial; Female; Hospital Mortality; Humans; Male; Middle Aged; Retrospective Studies; Risk Factors; Taiwan

Colistimethate sodium (CMS) has been postulated as the principal cause of high incidence of clinical acute kidney injury (AKI) in multidrug-resistance (MDR) septic patients with normal baseline serum creatinine (sCr) who were treated with CMS. This prospective observational study was conducted to examine the incidence and clinical outcomes of clinical and subclinical AKI in MDR septic patients receiving CMS.. Forty-two MDR septic patients with normal sCr who required CMS were included. Clinical AKI was diagnosed by increased sCr levels according to the KDIGO2012 criteria while subclinical AKI was identified by elevated levels of urinary neutrophil gelatinase-associated lipocalin (uNGAL > 150 ng/mL) or urinary liver-type fatty-acid-binding protein (uL-FABP > 10.5 ng/mL).. Clinical AKI was noted in 47.6% of patients on day 5 and 38.1% on day 7 after initiating CMS. By using uL-FABP, subclinical AKI was observed in 45.2% and 54.8% on day 5 and 7, respectively. At baseline prior to CMS treatment, subclinical AKI was already present in 90%. The baseline uL-FABP was superior to the baseline uNGAL in early prediction of clinical AKI on day 5. The subclinical AKI patients had comparable worse outcomes as clinical AKI patients.. The incidence of subclinical AKI in MDR septic patients before CMS treatment was extremely high. The baseline uL-FABP provided the best predictive capacity of clinical AKI. The causes of clinical AKI might include the persistence of sepsis process, subclinical AKI and CMS nephrotoxicity. Proper management of subclinical AKI patients before CMS initiation should be concerned to prevent further renal damage and improve patient and renal outcomes.

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Anti-Bacterial Agents; Asymptomatic Diseases; Biomarkers; Colistin; Creatinine; Drug Resistance, Multiple, Bacterial; Fatty Acid-Binding Proteins; Female; Humans; Incidence; Lipocalin-2; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Risk Assessment; Risk Factors; Sepsis; Time Factors; Treatment Outcome

Nephrotoxicity is the most important adverse effect of colistin therapy. We investigated the frequency of nephrotoxicity, risk factors related to nephrotoxicity, and its relationship with mortality in patients who received intravenous colistin in intensive care units (ICUs).. We retrospectively reviewed the data of patients who received intravenous colistin in ICUs between 2011 and 2017. Acute kidney injury (AKI) diagnosis and staging were made based on the Kidney Disease Improving Global Outcome criteria.. Higher AKI and mortality rates are observed in patients with diabetes, heart failure, advanced age and the hemodynamically impaired. However, it is a fact that there are no alternative therapies other than colistin in the treatment of multidrug-resistant Gram-negative bacterial infections. Therefore, the development of AKI in this patient group should not be considered a sufficient reason for discontinuing colistin treatment. Understanding the risk factors in this potential nephrotoxic treatment can provide a more careful patient follow-up.

Topics: Acute Kidney Injury; Administration, Intravenous; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; APACHE; Colistin; Critical Illness; Female; Humans; Intensive Care Units; Male; Middle Aged; Prognosis; Retrospective Studies; Risk Factors; Time Factors; Turkey

Cystic fibrosis (CF) patients, with Pseudomonas aeruginosa infection, often require repeated aminoglycoside courses for the management of acute pulmonary exacerbations (APEs). Acute kidney injury (AKI) due to aminoglycosides has been reported; little data exist regarding long-term nephrotoxicity with repeated exposure. The objective of this study was to describe the incidence of acute and chronic nephrotoxicity due to cumulative intravenous (IV) aminoglycoside exposure. This is a retrospective, observational study of pediatric and adult CF patients admitted to an academic medical center between January 1, 2006 and October 1, 2018 for APE management. Patients were eligible for inclusion if they received at least five courses of an IV aminoglycoside for at least 7 days each. Cumulative weight-based aminoglycoside dose was reported in milligrams per kilogram. For each admission, baseline and highest serum creatinine were collected to assess the incidence of AKI. The baseline and final estimated glomerular filtration rate (eGFR) were calculated to assess long-term effects on renal function. Sixty-six patients, representing greater than 700 courses, were included in the final analysis. The median cumulative weight-based aminoglycoside dose was 1183 mg/kg of tobramycin or tobramycin equivalent. Twenty percent of courses resulted in AKI; 86% were Stage 1. A repeated measure multivariate model showed colistin, piperacillin/tazobactam, vancomycin, and age were significant AKI risk factors. There was no correlation between cumulative aminoglycoside dose and change in eGFR. AKI from IV aminoglycoside exposure occurred in 20% of courses. Cumulative exposure to IV aminoglycosides in APE management was not correlated with long-term renal dysfunction.

Topics: Acute Kidney Injury; Adolescent; Adult; Age Factors; Anti-Bacterial Agents; Child; Child, Preschool; Colistin; Cystic Fibrosis; Female; Humans; Incidence; Infant; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination; Pseudomonas Infections; Retrospective Studies; Risk Factors; Tobramycin; Vancomycin; Young Adult

The objectives of the present study were to identify risk factors for development of acute kidney injury (AKI) during the treatment of bacteraemia due to carbapenem non-susceptible Gram-negative bacteria (CnS-GNB) and its role on mortality. Data of all patients with bacteraemia by CnS-GNB in the intensive care unit of a tertiary hospital from 2012 to 2016 were included. AKI was defined by AKIN criteria. Secondary outcomes were AKI development in patients treated with colistin and predictors of 14-day mortality. Among 285 episodes of bacteraemia due to CnS-GNB, 84 (29.5%) developed AKI. Multivariate analysis revealed that obesity, septic shock, maximum noradrenaline dose and eGFR<60 mL/min/1.73m² upon bacteraemia onset were independently associated with development of AKI. Out of 228 patients receiving colistin, 64 (28.1%) developed AKI. Multivariate analysis found the same factors as before in addition to voriconazole administration. Fourteen-day mortality was 34.2% and was independently associated with bacteraemia by Pseudomonas aeruginosa, AKI during bacteraemia treatment, maximum noradrenaline dose, SAPS II and SOFA scores upon bacteraemia onset, whereas appropriate combination therapy and catheter-related bacteraemia were independently associated with better survival. AKI was a frequent complication of bacteraemia by CnS-GNB and was associated with septic shock and baseline renal function impairment. Mortality was higher among patients that developed AKI due to bacteraemia. Colistin should be considered a safe therapeutic option for treating such infections.

Topics: Acute Kidney Injury; Adult; Aged; Anti-Bacterial Agents; Bacteremia; Carbapenems; Colistin; Critical Illness; Drug Resistance, Bacterial; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Retrospective Studies; Risk Assessment; Risk Factors

Intravenous colistin is increasingly used to treat multidrug-resistant Gram-negative infections. Highly variable nephrotoxicity rates have been reported. Recent PK/PD studies propose a loading dose and a maintenance dose for better efficacy, but data on the renal toxicity of such regimens are rare. This study aimed to evaluate the incidence and risk factors for nephrotoxicity related to colistin after implementation of a new dosing regimen including a loading dose.. This was a prospective observational study that was made between adult patients who received a minimum of 48 hours of intravenous colistin from December 2012 to January 2014 at the medical and surgical intensive care units (ICU) of a university hospital. The severity of acute kidney injury (AKI) was defined by the RIFLE criteria.. Fifty-nine patients met the inclusion criteria, and 31 (52.5%) developed nephrotoxicity. The APACHE-II score was > 15 in 81% of patients. The median time to nephrotoxicity was 7 days. Patients with AKI were in risk (10.2%), injury (16.9%), failure (25.4%), and none of the patients developed permanent renal insufficiency. A logistic regression model identified three predictors of colistin-associated nephrotoxicity: age; the number of days that estimated target plasma concentrations of colistin were ≥ 3.5 mg/L in the first week of therapy; and baseline creatinine level.. In this cohort of severely ill ICU patients, colistin led to a relatively high rate of nephrotoxicity. Further studies are needed to identify the optimal dose for both efficacy and safety.

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Critical Illness; Dose-Response Relationship, Drug; Female; Humans; Intensive Care Units; Male; Middle Aged; Prospective Studies; Young Adult

Polymyxin B and colistin are nephrotoxic drugs used in the treatment of carbapenem-resistant Enterobacteriaceae. The aim of this study is to evaluate the burden of costs due to polymyxin associated AKI and propose a simulated break-even price for new therapies.. The pharmacoeconomic model is based on two large cross-sectional studies of polymyxin nephrotoxicity. Total direct costs in patients with and without renal failure were compared. The direct cost of each hemodialysis section (USD82.94) and daily hospital charges (USD934.85) were based on the values used in a major public hospital in the city where the clinical study was performed. The break-even price of new drugs was simulated considering eventual new drugs as effective as polymyxins, but less nephrotoxic in different percentages. Outcomes of patients after hospital discharge were not evaluated.. Total direct cost of the group of patients who survived without AKI was significantly lower than total direct cost of the groups either with AKI or the group who died without AKI. There was a tendency of even higher costs in those who died with AKI and dialysis. Direct cost of hemodialysis was not as important as the longer hospitalization after sepsis. Considering daily cost of polymyxin is USD60, drugs with 50% less AKI could be considered cost-beneficial if the daily cost is lower than USD160.. AKI in patients with carbapenem-resistant Enterobacteriaceae treated with polymyxin increases both length of stay in hospital and total costs.

Topics: Acute Kidney Injury; Adult; Aged; Anti-Bacterial Agents; Brazil; Carbapenem-Resistant Enterobacteriaceae; Colistin; Cost of Illness; Cross-Sectional Studies; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae Infections; Female; Health Expenditures; Humans; Length of Stay; Male; Middle Aged; Models, Econometric; Polymyxin B; Renal Dialysis; Risk Factors

Owing to the emerging problem of MDR bacteria, interest in 'old' antibiotics such as colistin has re-emerged. However, research on the dosing of colistin in patients undergoing renal replacement therapy (RRT), such as prolonged intermittent renal replacement therapy (PIRRT), is scarce.. The aim of this study was to evaluate single- and multiple-dose pharmacokinetics of colistin and its prodrug colistin methanesulfonate in ICU patients with acute kidney injury (AKI) undergoing PIRRT.. We performed a prospective clinical pharmacokinetic single- and multiple-dose study. Eight ICU patients with AKI undergoing treatment with PIRRT and receiving intravenous colistin were studied on day 1 and days 5-9 of treatment, depending on the timing of dialysis. Six million IU (MIU) of colistin methanesulfonate was administered 8 h prior to the PIRRT session followed by 3 MIU every 8 h. The study was registered under clinicaltrails.gov (NCT02556190).. PIRRT removed a considerable amount of colistin and colistin methanesulfonate with a median dialyser plasma CL of 70.1 mL/min (IQR 36.6-96.2) for colistin and 69.3 mL/min (IQR 56.3-318.7) for colistin methanesulfonate. The median amount of colistin in the total collected dialysate was 154 mg (IQR 105-175), corresponding to about 50% of the daily dose. Median colistin peak concentrations accumulated from 5.79 mg/L (IQR 4.14-8.79) on day 1 to 9.49 mg/L (IQR 8.39-10.41) on days 5-9. Cmax was significantly and inversely correlated with body weight.. PIRRT eliminates about half of the daily administered colistin dose. Even a 6 MIU loading dose of colistin methanesulfonate may not ensure immediate sufficient colistin plasma levels in all critically ill patients. However, we measured significant colistin accumulation, suggesting that the dose of colistin methanesulfonate should be adjusted according to body weight and RRT intensity.

Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Bacterial Infections; Colistin; Critical Illness; Drug Administration Schedule; Drug Monitoring; Female; Humans; Intermittent Renal Replacement Therapy; Male; Middle Aged

Topics: Acute Kidney Injury; Adult; Aged; Anti-Bacterial Agents; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Hospitals, University; Humans; Intensive Care Units; Kidney; Latvia; Male; Middle Aged; Renal Dialysis; Retrospective Studies; Tertiary Healthcare

The use of colistin in the treatment of multidrug-resistant Gram-negative bacterial infections is restricted due to nephrotoxicity. We investigated the effects of aged black garlic extract (ABGE) on colistin-induced kidney injury in rats. Rats were assigned to four groups. Normal saline was intraperitoneally and intragastrically injected for control group. ABGE was intragastrically injected for garlic group. Ten mg/kg of colistin was intraperitoneally injected for 6 consecutive days for colistin group. One percent of ABGE was done 30 min prior to colistin injection for treatment group. Rats were sacrificed on the next day after last colistin injection. Colistin injection increased the serum levels of blood urea nitrogen and creatinine; however, ABGE prevented deterioration of these serum levels. ABGE also alleviated tubular damage, including vacuolation and necrosis. TUNEL-positive cells were observed less frequently for the ABGE-treated groups. CD68 positive cells were significantly decreased by pretreatment with ABGE. Levels of oxidative stress biomarkers such as 8-hydroxydeoxyguanosine and malondialdehyde were lower in the ABGE-treated groups. Levels of NF-κB, inducible NO synthase, COX-2, and TGF-β1 were lower in rats that had been treated with ABGE injection. Renal levels of IL-1β and TNF-α were increased by colistin administration whereas renal SOD, catalase, and GSH levels were restored by ABGE administration. These results suggest that ABGE, which has antioxidant and anti-inflammatory properties, might be a potential therapeutic agent to prevent renal toxicity of colistin.

Topics: Acute Kidney Injury; Animals; Antioxidants; Colistin; Disease Models, Animal; Garlic; Gram-Negative Bacterial Infections; Humans; Kidney; Male; Oxidative Stress; Plant Extracts; Rats; Rats, Sprague-Dawley; Treatment Outcome; Water

Nonclinical studies have suggested that oxidative damage, caspase-mediated apoptosis, and inducible nitric oxide synthase levels may be involved in the pathogenesis of colistin (CST)-associated acute renal failure. MIN inhibits caspase 1, caspase 3, and inducible nitric oxide synthase, leading to the hypothesis that coadministration of CST with MIN (CST-MIN) may reduce the incidence of acute renal failure as well as produce additive or synergistic antimicrobial effects. A multicenter retrospective cohort study was conducted using the Premier Research database to examine the impact of CST-MIN on acute renal failure. Inclusion criteria were as follows: age of ≥18 years, intensive care unit admission at CST initiation, primary International Classification of Diseases 9 (ICD-9) diagnosis of pneumonia or sepsis, nondialysis at hospital admission, and discharge between January 2010 and December 2015. ICD-9 code 584.XX or ICD-10 code N17 was used to define acute renal failure. Baseline comparisons, 1:8 propensity score matching, and confirmatory logistic regression analyses were conducted. In total, 4,817 patients received CST and met inclusion criteria; 93 received CST-MIN. Unadjusted frequency of acute renal failure was significantly lower in patients receiving CST-MIN than CST (11.8% versus 23.7%,

Topics: Acute Kidney Injury; Adult; Aged; Cohort Studies; Colistin; Critical Illness; Female; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Minocycline; Patient Readmission; Protective Agents; Retrospective Studies; Treatment Outcome

The use of colistin for multi-drug resistant (MDR) infections has led to an increase of colistin-associated acute kidney injury (AKI). Nevertheless, information on long-term renal prognosis is scarce. We aimed to determine the predictors of chronic kidney disease (CKD) in survivors of MDR-infections with colistin-associated AKI.. A retrospective cohort of patients with colistin-associated AKI was compared with controls (survivors of severe infections who developed AKI matched by age, sex, diabetes, vancomycin exposure, and baseline kidney function). The primary outcome was the development of CKD after 6months of follow-up.. From 2011 to 2015, 122 patients with MDR infections received colistin. Among 72 survivors, 29 (40%) had colistin-associated AKI. After 6months, 22 of them (75%) progressed to CKD (G3 in 21/22) compared with 16 (27%) in 58 controls (P<0.001). Independent predictors of progression to CKD were colistin use [odds ratio (OR): 8.86; 95% CI: 2.8-27.8] and age (OR: 1.04, 95% CI: 1.01-1.07). In patients exposed to colistin, a total dose of colistin >5g was an independent predictor of progression to CKD (OR: 14.1, 95% CI: 2.6-75.7).. Colistin-associated AKI had a substantial risk for the latter development CKD, and consequently, these patients should be tightly monitored.

Topics: Acute Kidney Injury; Adult; Aged; Anti-Bacterial Agents; Cohort Studies; Colistin; Female; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Mexico; Middle Aged; Prevalence; Renal Insufficiency, Chronic; Retrospective Studies; Risk Factors; Staphylococcal Infections; Survivors; Young Adult

Topics: Acute Kidney Injury; Aged; Anti-Bacterial Agents; Colistin; Communicable Diseases; Drug Administration Schedule; Drug Resistance, Multiple, Bacterial; Female; Humans; Kidney; Male; Middle Aged; Retrospective Studies; Treatment Outcome

Colistin (polymyxin E) is an important constituent of the polymyxin class of cationic polypeptide antibiotics. Intrarenal oxidative stress can contribute to colistin-induced nephrotoxicity. Nicotinamide adenine dinucleotide 3-phosphate oxidases (Noxs) are important sources of reactive oxygen species. Among the various types of Noxs, Nox4 is predominantly expressed in the kidney.. We investigated the role of Nox4 and benefit of Nox4 inhibition in colistin-induced acute kidney injury using in vivo and in vitro models.. Human proximal tubular epithelial (HK-2) cells were treated with colistin with or without NOX4 knockdown, or GKT137831 (most specific Nox1/4 inhibitor). Effects of Nox4 inhibition on colistin-induced acute kidney injury model in Sprague-Dawley rats were examined.. Nox4 expression in HK-2 cells significantly increased following colistin exposure. SB4315432 (transforming growth factor-β1 receptor I inhibitor) significantly inhibited Nox4 expression in HK-2 cells. Knockdown of NOX4 transcription reduced reactive oxygen species production, lowered the levels of pro-inflammatory markers (notably mitogen-activated protein kinases) implicated in colistin-induced nephrotoxicity and attenuated apoptosis by altering Bax and caspase 3/7 activity. Pretreatment with GKT137831 replicated these effects mediated by downregulation of mitogen-activated protein kinase activities. In a rat colistin-induced acute kidney injury model, administration of GKT137831 resulted in attenuated colistin-induced acute kidney injury as indicated by attenuated impairment of glomerulus function, preserved renal structures, reduced expression of 8-hydroxyguanosine and fewer apoptotic cells.. Collectively, these findings identify Nox4 as a key source of reactive oxygen species responsible for kidney injury in colistin-induced nephrotoxicity and highlight a novel potential way to treat drug-related nephrotoxicity.

Topics: Acute Kidney Injury; Animals; Anti-Bacterial Agents; Cell Line; Colistin; Disease Models, Animal; Epithelial Cells; Humans; Models, Biological; NADPH Oxidase 4; Oxidative Stress; Rats, Sprague-Dawley; Transforming Growth Factor beta

Colistin is a last resort antibiotic to treat multidrug-resistant Gram-negative bacteria infections. Colistin is administered intravenously in the form of its inactive prodrug colistin methanesulfonate (CMS). For patients with acute kidney impairment and continuous renal replacement therapy high extracorporeal clearance may cause a substantial removal of active colistin from the bloodstream, eventually decreasing its antibacterial efficacy. Currently recommended doses of CMS may therefore be inadequate for these patients. We report on the potential value of a modified regimen that adopts a loading dose of CMS (bolus of 9 MU vs. conventional 3 MU every 8 h), followed by maintenance (3 MU every 8 h). Preliminary pharmacokinetic evidence for the feasibility and efficacy of this regimen is described for 2 patients.

Topics: Acute Kidney Injury; Aged; Anti-Bacterial Agents; Area Under Curve; Colistin; Critical Illness; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Prognosis; Pseudomonas aeruginosa; Renal Dialysis; Renal Replacement Therapy; ROC Curve

Background Colistin is used to treat gram-negative infections but it's highly associated with nephrotoxicity. Objectives To determine the incidence and risk factors as well as mortality in patients on colistin. Setting Sultan Qaboos University Hospital, Muscat, Oman. Methods This was a retrospective cohort study of patients admitted and who received colistin for ≥ 48 h. The exclusion criteria included inhaled colistin therapy, cystic fibrosis, or pregnancy. The study period was from January 2010 to June 2016. Main outcome measures Nephrotoxicity using the Risk, Injury, Failure, Loss and Endstage kidney disease (RIFLE) criteria. The secondary outcomes were incidence, risk factors and mortality in patients on colistin. Results A total of 123 patients were included. Colistin-associated nephrotoxicity (CAN) occurred in 57 (46%) patients after colistin therapy. As per the RIFLE criteria, 22 (18%) patients were classified as 'at risk', 17 (14%) as 'injury', and 18 (15%) as 'failure'. Multivariate analysis indicated that increasing age (adjusted odds ratio (aOR), 1.03; 95% confidence interval (CI) 1.01-1.06; p = 0.004) and higher APACHE II score (aOR 1.08; 95% CI 1.01-1.16; p = 0.040) were significant predictors for the development of nephrotoxicity. Factors associated with mortality included ICU admission (aOR 23.3; 95% CI 5.04-106; p < 0.001), vasopressin use (aOR 5.54; 95% CI 1.56-19.6; p = 0.008) and higher APACHE II score (aOR 1.15; 95% CI 1.03-1.30; p = 0.027). Conclusions The incidence of CAN was 46%. Increasing age and higher APACHE II score were the risk factors for CAN. Factors associated with mortality at 28 days included ICU admission and higher APACHE II score.

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cohort Studies; Colistin; Female; Humans; Incidence; Male; Middle Aged; Oman; Retrospective Studies; Risk Factors; Young Adult

Despite colistin's longstanding reported association with nephrotoxicity, the attributable risk and timing of toxicity onset are still unknown. Whether substantial toxicity occurs during the initial 72 hours of exposure has important implications for early treatment decisions. The objective of this study was to compare colistin-exposed patients with a matched control group given other broad spectrum antibiotics.. We conducted a retrospective cohort study in patients treated for multidrug-resistant. The study included 150 propensity-matched pairs with similar types of infection, similar delays to effective treatment, and similar baseline characteristics. Incidence of AKI was 77 of 150 (51%) in the colistin group versus 33 of 150 (22%) in matched controls (risk difference, 29%; 95% confidence interval, 19 to 39), corresponding to a number needed to harm of 3.5. Early toxicity was apparent, because AKI risk was higher in colistin-exposed patients at 72 hours of exposure (incidence rate ratio, 1.9; 95% confidence interval, 1.1 to 3.5). In both groups, hospital mortality in patients who experienced AKI was lower if kidney function returned to baseline during hospitalization. The effect of colistin exposure on AKI risk varied inversely according to baseline hemoglobin concentration.. Colistin is associated with substantial excess AKI that is apparent within the first 72 hours of treatment. Colistin's toxicity varied according to baseline hemoglobin concentration.. This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_03_15_CJASNPodcast_18_4_M.mp3.

Topics: Acute Kidney Injury; Aged; Anti-Bacterial Agents; Case-Control Studies; Colistin; Female; Hemoglobins; Hospital Mortality; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Propensity Score; Recovery of Function; Retrospective Studies; Risk Factors; Time Factors

The most important concern with polymyxins (Colistin and Polymyxin B) use is nephrotoxicity. There is no prospective data comparing nephrotoxicity of these two drugs, when administered in high doses and as per current recommendations. We conducted a prospective study to compare their trend of nephrotoxicity in our patient population.. Our study included adult ICU patients who received more than 48 h of Colistin or Polymyxin B and had no confounding factors for nephrotoxicity. Loading and maintenance doses were given as per a uniform protocol. Nephrotoxicity was defined as twofold increase in serum creatinine, or 50% decrease in estimated baseline creatinine clearance. Patients were followed up for 1 week after therapy. Statistical analysis was performed using SPSS version 20.0.. 61 patients were included in Colistin group, and 51 patients in Polymyxin B group. Median Colistin dose was 233.3 (IQR 150-300) mg/day and median Polymyxin B dose was 200 (IQR 180-240) mg/day. Median duration of Colistin and Polymyxin B use was 7 (IQR 5-7) days and 7 (IQR 7-9) days respectively. Nephrotoxicity developed in 39.3% patients in Colistin group compared to 11.8% patients in Polymyxin B group. Mean onset of nephrotoxicity was 3.8 ± 0.8 days with Colistin, and 4.2 ± 0.7 days with Polymyxin B therapy. In bivariate analysis, Colistin daily dose ≥ 300 mg was found to be associated with nephrotoxicity. There was no effect of age or BMI on Colistin toxicity. Mean duration of renal failure was 4.9 ± 3.1 days with Colistin use, and 5.0 ± 2.4 days with Polymyxin B use. 75% patients in Colistin group and 83.3% patients in Polymyxin B group who developed nephrotoxicity recovered their renal function by 1 week.. Colistin in currently recommended doses is significantly more nephrotoxic than Polymyxin B. Colistin toxicity is dose-dependent, mostly mild to moderate, and is reversible in most cases.

Topics: Acute Kidney Injury; Age Factors; Aged; Aged, 80 and over; Anti-Bacterial Agents; Body Mass Index; Colistin; Creatinine; Drug Combinations; Female; Humans; Intensive Care Units; Kidney; Male; Middle Aged; Nephrons; Polymyxin B; Prospective Studies; Treatment Outcome

Topics: Acute Kidney Injury; Colistin; Critical Illness; Humans; Minocycline; Retrospective Studies

To investigate the molecular mechanisms of colistimethate sodium-induced nephrotoxicity and the protective effect of N-acetylcysteine (NAC) against nephrotoxicity.. Twenty-eight Wistar rats were divided into four groups comprised of control, colistin, NAC, and colistin-NAC co-treatment, respectively. Serum creatinine and urine N-acetyl-β-d-glucosaminidase (NAG) levels were measured at different time intervals. Histological changes, apoptosis, total oxidant and antioxidant status, and the expression levels of endothelial nitric oxide synthase (eNOS), superoxide dismutase 2 (SOD2), and matrix metalloproteinase 3 (MMP3) were evaluated in renal tissue.. In the colistin group, post-treatment creatinine levels were higher than pretreatment levels (p = .001). There was a significant increase in urine NAG level following colistin treatment on day 10, compared to the baseline value and the first day of treatment (p = .001 and .0001, respectively). Urine NAG levels were higher in the colistin group on the 10th day of treatment than in the other groups (p < .01). Colistin treatment increased the apoptosis index and renal histological damage score (RHDS) significantly and these changes were reversed in NAC co-treatment (RHSD and apoptosis index were 45 and 0 for sterile saline group, 29 and 2 for NAC group, 122 and 7 for colistin group, and 66 and 2 for colistin + NAC group). We observed no difference between groups regarding total antioxidant and total oxidant status in the kidneys. The expression levels of eNOS, SOD2, and MMP3 decreased significantly in the kidneys of colistin-treated rats; these changes were reversed in the kidneys of NAC co-treated rats.. N-acetylcysteine prevented colistin-induced nephrotoxicity through activation of expression levels of SOD2, eNOS, and MMP3.

Topics: Acetylcysteine; Acetylglucosaminidase; Acute Kidney Injury; Animals; Colistin; Creatinine; Disease Models, Animal; Free Radical Scavengers; Humans; Kidney; Male; Matrix Metalloproteinase 3; Nitric Oxide Synthase Type III; Rats; Rats, Wistar; Reactive Oxygen Species; Superoxide Dismutase

Given the severity and high mortality of multidrug-resistant Gram-negative bacilli (MDR-GNB) infections, the use of colistin will increase in patients with MDR-GNB infection.. This study aims to assess the efficacy and safety of intravenous colistin in very low birth weight (VLBW; birth weight < 1500 g) preterm infants.. We retrospectively analyzed the medical records of patients who received colistin between June 2016 and December 2017. The patients were assigned to two groups: the VLBW group and the non-VLBW group. Both groups were evaluated for response to treatment and adverse effects.. In total, 66 infants who received colistin therapy were included; of these, 28 infants were VLBW. All of our patients received standard colistin treatment of 5 mg/kg per day in three doses and the median duration of colistin treatment was 14 days. No significant differences were observed between the groups with respect to the efficacy of colistin (defined as showing microbiological clearance in control cultures and the absence of mortality during treatment) (89.3 vs 86.8%, p > 0.99). Serum magnesium and potassium levels were significantly lower in the VLBW group than in the non-VLBW group during colistin therapy (magnesium, 1.30 vs 1.70 mg/dL, p < 0.001; potassium, 3.6 vs 4.6 mEq/L, p < 0.001). Acute kidney injury was observed in four infants in the VLBW group and one in the non-VLBW group, without significant differences (p = 0.15).. Colistin administration appears to be efficacious in VLBW infants; however, renal function tests and serum electrolytes should be monitored more closely in these infants during treatment.

Topics: Acute Kidney Injury; Administration, Intravenous; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Male; Retrospective Studies; Treatment Outcome

This study aimed to assess the predictors of acute kidney injury (AKI) during colistin therapy in a cohort of patients with bloodstream infections (BSI) due to colistin-susceptible Gram-negative bacteria, focusing on the role of serum albumin levels. The study consisted of two parts: (1) a multicentre retrospective clinical study to assess the predictors of AKI during colistin therapy, defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria; and (2) bioinformatic and biochemical characterization of the possible interaction between human serum albumin and colistin. Among the 170 patients included in the study, 71 (42%), 35 (21%), and 11 (6%) developed KDIGO stage 1 (K1-AKI), KDIGO stage 2 (K2-AKI), and KDIGO stage 3 (K3-AKI), respectively. In multivariable analyses, serum albumin <2.5 g/dL was independently associated with K1-AKI (subdistribution hazard ratio [sHR] 1.85, 95% confidence interval [CI] 1.17-2.93, p = 0.009) and K2-AKI (sHR 2.37, 95% CI 1.15-4.87, p = 0.019). Bioinformatic and biochemical analyses provided additional information nurturing the discussion on how hypoalbuminemia favors development of AKI during colistin therapy. In conclusion, severe hypoalbuminemia independently predicted AKI during colistin therapy in a large cohort of patients with BSI due to colistin-susceptible Gram-negative bacteria. Further study is needed to clarify the underlying causal pathways.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Colistin; Computational Biology; Female; Humans; Hypoalbuminemia; Incidence; Male; Models, Molecular; Molecular Conformation; Retrospective Studies; Sepsis; Serum Albumin, Human; Severity of Illness Index; Structure-Activity Relationship

This study aimed to investigate whether hesperidin and chrysin antioxidants have protective effects on renal injury induced by colistin in rats. Renal lipid peroxidation, total glutathione (GSH) levels, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) enzyme activities, serum urea and creatinine levels, as well as tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) levels were determined. Injuries to the proximal and distal tubules were determined using histopathological and double immunohistochemistry examinations. The results showed that hesperidin and chrysin significantly decreased the levels of MDA and inflammatory parameters and significantly increased GSH, SOD, CAT, and GSH-Px levels against colistin-induced renal injury. The results also showed that cystatin C and calbindin D28K immunopositivities significantly increased through hesperidin and chrysin treatment. Hesperidin and chrysin alleviated the renal injury induced by colistin via anti-oxidant and anti-inflammatory activities. Thus, hesperidin and chrysin could attenuate colistin-induced nephrotoxicity via antioxidant and anti-inflammatory activities. Addition of hesperidin or chrysin to the treatment protocol of colistin treatment might benefit patient treatment in terms of the prevention of colistin-induced renal injury.

Topics: Acute Kidney Injury; Animals; Anti-Bacterial Agents; Colistin; Drug Therapy, Combination; Flavonoids; Hesperidin; Inflammation Mediators; Male; Rats; Rats, Sprague-Dawley; Treatment Outcome

Nephrotoxicity of intravenous (IV) colistin has impeded its clinical use; aerosolized (AS) colistin may be an alternative, but safety data are lacking. Therefore, this study aimed to evaluate the incidence of acute kidney injury (AKI) and risk factors associated with IV and AS colistin administration.. A retrospective study was performed in a tertiary referral hospital. Data were collected before and after colistin administration between October 2012 and April 2016. Exclusion criteria were as follows: age less than 18 years, previous colistin administration, concurrent use of IV and AS colistin, dialysis before colistin use, and colistin use for less than 3 days. We compared AKI incidence following administration of IV versus AS colistin and analyzed risk factors for colistin-associated nephrotoxicity.. A total of 464 patients were enrolled (n = 311, IV group; n = 153, AS group). Incidence of AKI was significantly higher in the IV group (IV vs AS, 20.26% vs 7.84%, p-value < 0.001). Duration of colistin use (OR 1.033, 95% CI 1.009-1.058, p-value 0.008) and presence of chronic kidney disease (OR 2.710, 95% CI 1.348-5.448, p-value 0.005) were associated with nephrotoxicity. There were no significant risk factors associated with AS colistin.. Although AS colistin was not associated with any significant risk factors for nephrotoxicity, duration of colistin use and baseline kidney function may affect AS colistin-associated nephrotoxicity.

Topics: Acute Kidney Injury; Administration, Inhalation; Administration, Intravenous; Aerosols; Aged; Aged, 80 and over; Colistin; Female; Humans; Incidence; Male; Middle Aged; Retrospective Studies; Risk Factors; Tertiary Care Centers

Intravenous colistimethate sodium (CMS) use in burn center patients is increasing due to the emergence of multidrug-resistant gram-negative bacteria. However, optimal dosing strategies and factors that may contribute to treatment failure are limited. The purpose of this study was to determine factors that may contribute to treatment failure in colistin-treated burn center patients.. This retrospective, observational study included burn center patients that received ≥48h of intravenous CMS between June 1, 2009 and June 30, 2014. Data was collected utilizing the institution's electronic medical record system. Statistical analysis included demographic, univariable, and multivariable analysis to determine factors that may predict clinical failure of burn center patients requiring intravenous CMS.. Eighty-one patients were included in this study, with 55 patients (68%) achieving clinical success. A total daily dose (TDD) of >5mg/kg ideal body weight (IBW) was associated with significantly less clinical failure (odds ratio=0.21; 95% CI, 0.05, 0.91). Additionally, clinical failure was significantly higher in patients with wounds as the primary source of infection, creatinine clearances of 91-120mL/min, and those receiving renal replacement therapy. No difference was observed in nephrotoxicity when comparing TDD >5mg/kg IBW and TDD ≤5mg/kg IBW.. Clinical success was significantly higher with larger intravenous CMS doses in burn center patients. Higher CMS doses were not found to be associated with increased nephrotoxicity within this patient group.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Acute Kidney Injury; Adult; Aged; Anti-Bacterial Agents; Burn Units; Burns; Colistin; Creatinine; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Outcome Assessment, Health Care; Pseudomonas aeruginosa; Pseudomonas Infections; Renal Replacement Therapy; Retrospective Studies; Treatment Failure

The increasing trend of extensively drugresistant gram negative bacteria responsible for nosocomial infections has prompted resurgence colistin usage. Colistin-induced nephrotoxicity is a concern with disparity in the reported rates between previous studies. This study aims to evaluate colistin-induced nephrotoxicity among Malaysian population.. The medical records of ICU patients receiving colistin therapy in Hospital Serdang and Hospital Sungai Buloh from 2010 to 2012 were retrospectively reviewed. Demographics data, treatment characteristic as well as culture result and creatinine level were documented. Nephrotoxicity was determined based on RIFLE criteria.. A total of 100 patients were included. Median daily dose, cumulative dose and duration of colistin therapy were 3.0 MIU (IQR: 4, range 1-12), 17.8 MIU (IQR: 31.5, range 2-180) and seven days (IQR: 4, range 1-30). Nephrotoxicity was found in 23% of the study population. All cases were reversible but marginally associated with higher mortality. No statistical association exist between age, gender and race as well as administration routes with nephrotoxicity by univariable analysis. The association of dose and duration with nephrotoxicity was also not significant by univariable analysis. After adjustment for confounders, statistical association between the independent variables and dependent variable remains not significant.. Lower dose and shorter duration in local settings contribute to lack of association between colistin therapy and nephrotoxicity in this study. Higher dosing regimen with loading dose application has been introduced in the latest National Antibiotic Guideline. Further evaluation of colistin-induced nephrotoxicity and potential risk factors is therefore warranted.

Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Colistin; Cross Infection; Female; Humans; Intensive Care Units; Malaysia; Male; Middle Aged; Retrospective Studies; Risk Factors

The aim of this study was to assess the safety and efficacy of colistin use in critically ill neonates.. This was a case-control study that included newborn infants with proven or suspected nosocomial infections between January 2012 and October 2015, at two centers in Diyarbakir, Turkey. The clinical and laboratory characteristics and outcomes of patients who received colistin therapy were reviewed and compared to patients who were treated with antimicrobial agents other than colistin during the same period.. Forty-seven cases who received intravenous colistin (colistin group) and 59 control patients (control group) were included. There were no significant differences between the groups regarding outcomes and nephrotoxicity, including acute renal failure. Colistin therapy was associated with significantly reduced serum magnesium (1.38 ± 0.39 mg/dL vs. 1.96 ± 0.39 mg/dL, p < 0.001) and hypokalemia (46.8% vs. 25.4%, p = 0.026). The patients who received colistin also had longer hospital stays (43 (32-70) days vs. 39 (28-55) days, p = 0.047), a higher rate of previous carbapenem exposure (40.4% vs. 11.9%, p = 0.001), and a higher age at the onset of infection (13 (10-21) days vs. 11 (9-15) days, p = 0.03).. This study showed that colistin was both effective and safe for treating neonatal infections caused by multidrug-resistant gram-negative bacteria. However, intravenous colistin use was significantly associated with hypomagnesemia and hypokalemia.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Case-Control Studies; Colistin; Critical Illness; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Humans; Infant, Newborn; Male

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Bacteriophages; Colistin; Humans; Male; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis

Acute kidney injury (AKI) occurs in a substantial proportion of critically ill patients receiving intravenous colistin. In the pharmacokinetic/toxicodynamic analysis reported here, the relationship of the occurrence of AKI to exposure to colistin and a number of potential patient factors was explored in 153 critically ill patients, none of whom were receiving renal replacement therapy. Tree-based modeling revealed that the rates of AKI were substantially higher when the average steady-state plasma colistin concentration was greater than ∼2 mg/liter.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Creatinine; Critical Illness; Female; Humans; Male; Middle Aged

Colistimethate sodium (CMS) is frequently used in the treatment of nosocomial multidrug-resistant gram-negative infections. Nephrotoxicity is the most important side effect. The aim of this study is to evaluate the effect of colistin on nephrotoxicity and to assess prognosis in patients treated with CMS due to hospital-acquired pneumonia (HAP).. Patients treated with CMS for HAP due to multidrug-resistant Pseudomonas aeruginosa or Acinetobacter baumannii were included in this cohort study.. We evaluated 281 patients treated with two different brands of CMS whose administration dose is different: imported (n= 58, low dose/kg) and domestic (n= 223, high dose/kg). Nephrotoxicity developed in 175 patients (62.3%). The median age (73 vs. 66 years, p= 0.004) and mortality rates were higher (66.9% vs. 52.8%, p= 0.022) in patients having nephrotoxicity. The patients receiving high dose/kg had higher nephrotoxicity rate (67.7% vs. 41.4%, p< 0.001). The clinical, bacteriological response and mortality rates of the whole group were 52.0%, 61.0%, 61.6%, respectively. The clinical and bacteriological response rates were similar in the different dose groups. Multivariate analysis showed that nephrotoxicity was associated with domestic brand depending on use of high dose (OR= 3.97), advanced age (β= 0.29, p= 0.008), male gender (OR= 2.60), hypertension (OR= 2.50), red blood cells transfusion (OR= 2.54), absence of acute kidney injury (OR= 10.19), risk stage of RIFLE (OR= 11.9).. Nephrotoxicity is associated with the use of high dose colistin, age, gender, hypertension, red blood cells replacement and RIFLE stage. The mortality rate is higher in patients developing nephrotoxicity.

Topics: Acute Kidney Injury; Adult; Aged; Anti-Bacterial Agents; Cohort Studies; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Pneumonia; Prognosis; Renal Insufficiency

Emergence of multidrug-resistant (MDR) gram-negative (GN) pathogens and lack of novel antibiotics have increased the use of colistin, despite unknown optimal dosing. This study aimed to evaluate the safety and efficacy of a colistin loading dose, high-dose (LDHD) maintenance regimen in patients with MDR-GN pneumonia.. A retrospective cohort analysis was performed comparing critically ill patients with MDR-GN pneumonia pre- and postimplementation of a colistin LDHD guideline with a primary outcome of clinical cure. Safety was assessed using incidence of acute kidney injury (AKI) based on RIFLE (risk, injury, failure, loss, end-stage renal disease) criteria.. Seventy-two patients met the inclusion criteria (42 preimplementation and 30 postimplementation). Clinical cure was achieved in 23 (55%) patients in the preimplementation group and 20 (67%) patients in the postimplementation group ( P = .31). AKI occurred in 50% of the patients during the preimplementation period and 58% during the postimplementation period ( P = .59) with no difference in initiation rates of renal replacement therapy.. The increased clinical cure rate after implementation of the colistin LDHD guideline did not reach statistical significance. The LDHD guideline, however, was not associated with an increased incidence of AKI, despite higher intravenous colistin doses. Opportunity exists to optimize colistin dosage while balancing toxicity, but larger studies are warranted.

Topics: Acute Kidney Injury; Adult; Aged; Anti-Bacterial Agents; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Pneumonia; Retrospective Studies

Acute kidney injury (AKI) remains a treatment-limiting toxicity of colistin. Recently developed clinical practice guidelines from the Kidney Disease: Improving Global Outcomes (KDIGO) group have harmonized definitions of AKI, but have not been widely applied to patients receiving colistin.. We retrospectively defined AKI by KDIGO definitions among adult patients receiving intravenous colistin for ≥ 3 days. Risk factors for AKI within 48 hours and 7 days of initiating colistin were determined by multivariable logistic regression.. Among 249 patients treated with colistin, rates of AKI were 12% and 29% at 48 hours and 7 days, respectively. At 48 hours, patients in the intensive care unit were at increased risk for AKI. Within 7 days, colistin daily doses >5mg/kg, chronic liver disease, and concomitant vancomycin were independent predictors. Seven percent of patients required renal replacement therapy at a median of 5 days (range: 3-7) following colistin initiation.. Safe use of colistin is promoted by early detection of AKI with KDIGO criteria, avoiding nephrotoxins, and limiting duration of therapy.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Comorbidity; Humans; Incidence; Middle Aged; Retrospective Studies; Risk Factors; Severity of Illness Index; Time Factors; Young Adult

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 aim of this study was to investigate the incidence of acute kidney injury (AKI) and risk factors due to colistin use in patients infected with multidrug-resistant pathogens. This multicenter, retrospective, observational study was conducted in Turkey, at 5 different research and university hospitals. Cox regression analyses were performed, to determine independent predictors of AKI. From April 2012 to July 2014, a total of 216 patients aged between 18-94 years, treated with colistimethate sodium (CMS) were included in the study. The mean age of the patients was 60.3 ± 20.1 years. The overall incidence of AKI was 34.3% (74/216) at any time during treatment. Concomitant use of loop diuretics, baseline creatinine level, and CMS dosage were independently associated with AKI. According to our results, patients with higher baseline creatinine levels, or patients who had to use concomitant loop diuretics may need to be monitored more closely, and dose adjustment should be done promptly. More comprehensive studies are, however, still needed to evaluate the efficacy of low-dose colistin since higher doses tend to increase the risk of AKI.

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Drug Interactions; Female; Hospitals, University; Humans; Incidence; Male; Middle Aged; Retrospective Studies; Risk Factors; Sodium Potassium Chloride Symporter Inhibitors; Turkey; Young Adult

The increasing prevalence of multidrug-resistant (MDR) nosocomial infections accounts for increased morbidity and mortality of such infections. Infections with MDR Gram-negative isolates are frequently treated with colistin. Based on recent pharmacokinetic studies, current colistin dosing regimens may result in a prolonged time to therapeutic concentrations, leading to suboptimal and delayed effective treatment. In addition, studies have demonstrated an association between an increased colistin dose and improved clinical outcomes. However, the specific dose at which these outcomes are observed is unknown and warrants further investigation. This retrospective study utilized classification and regression tree (CART) analysis to determine the dose of colistin most predictive of global cure at day 7 of therapy. Patients were assigned to high- and low-dose cohorts based on the CART-established breakpoint. The secondary outcomes included microbiologic outcomes, clinical cure, global cure, lengths of intensive care unit (ICU) and hospital stays, and 7- and 28-day mortalities. Additionally, safety outcomes focused on the incidence of nephrotoxicity associated with high-dose colistin therapy. The CART-established breakpoint for high-dose colistin was determined to be >4.4 mg/kg of body weight/day, based on ideal body weight. This study evaluated 127 patients; 45 (35%) received high-dose colistin, and 82 (65%) received low-dose colistin. High-dose colistin was associated with day 7 global cure (40% versus 19.5%; P = 0.013) in bivariate and multivariate analyses (odds ratio [OR] = 3.40; 95% confidence interval [CI], 1.37 to 8.45; P = 0.008). High-dose colistin therapy was also associated with day 7 clinical cure, microbiologic success, and mortality but not with the development of acute kidney injury. We concluded that high-dose colistin (>4.4 mg/kg/day) is independently associated with day 7 global cure.

Topics: Acute Kidney Injury; Aged; Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; Carbapenems; Colistin; Drug Administration Schedule; Drug Dosage Calculations; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Intensive Care Units; Length of Stay; Male; Microbial Sensitivity Tests; Middle Aged; Multivariate Analysis; Retrospective Studies; Survival Analysis; Treatment Outcome

Colistin is increasingly used as a last option for the treatment of severe infections due to Gram-negative bacteria in critically ill patients requiring intermittent hemodialysis (HD) for acute renal failure. Our objective was to characterize the pharmacokinetics (PK) of colistin and its prodrug colistin methanesulfonate (CMS) in this population and to suggest dosing regimen recommendations. Eight intensive care unit (ICU) patients who were under intermittent HD and who were treated by CMS (Colimycine) were included. Blood samples were collected between two consecutive HD sessions. CMS and colistin concentrations were measured by a specific chromatographic assay and were analyzed using a PK population approach (Monolix software). Monte Carlo simulations were conducted to predict the probability of target attainment (PTA). CMS nonrenal clearance was increased in ICU-HD patients. Compared with that of ICU patients included in the same clinical trial but with preserved renal function, colistin exposure was increased by 3-fold in ICU-HD patients. This is probably because a greater fraction of the CMS converted into colistin. To maintain colistin plasma concentrations high enough (>3 mg/liter) for high PTA values (area under the concentration-time curve for the free, unbound fraction of a drug [fAUC]/MIC of >10 and fAUC/MIC of >50 for systemic and lung infections, respectively), at least for MICs lower than 1.5 mg/liter (nonpulmonary infection) or 0.5 mg/liter (pulmonary infection), the dosing regimen of CMS should be 1.5 million international units (MIU) twice daily on non-HD days. HD should be conducted at the end of a dosing interval, and a supplemental dose of 1.5 MIU should be administered after the HD session (i.e., total of 4.5 MIU for HD days). This study has confirmed and complemented previously published data and suggests an a priori clear and easy to follow dosing strategy for CMS in ICU-HD patients.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Critical Illness; Drug Administration Schedule; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Lung; Male; Microbial Sensitivity Tests; Middle Aged; Renal Dialysis; Respiratory Tract Infections

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

Colistimethate sodium (CMS) is the commercialized form of colistin that is effective against multiresistant Gram-negative bacilli. Its main side effects are nephrotoxicity and neurotoxicity. Pharmacodynamic dosages showed that they were infratherapeutic. Therefore, strategies with higher doses were proposed. The aim of this study was to assess the efficiency and toxicity of higher-dose CMS by comparing two treatment strategies: high-dose CMS versus standard-dose CMS.. A prospective and comparative study of two matched groups was conducted. Fourty-six patients in each group were matched for age, severity and nature of infection. In the high-dose colistin group, CMS was administered at a loading dose of 9 MIU followed by a maintenance dose of 4.5 MIU/12 h. In the second group, retrospectively analyzed, colistin was administered at 6 MIU/day. For each group, clinical results, bacteriological eradication and daily creatinine clearance were recorded. Primary outcome measures were clinical cure defined as disappearance of infectious signs and eradication of microorganisms in all the follow-up cultures. Secondary outcome measures were incidence of acute renal failure and mortality.. Ninety-two patients were analyzed by matching. There was a higher cure rate in the high-dose group (63 vs. 41.3%, p = 0.04). No higher risk of nephrotoxicity was found by increasing daily doses of colistin (32.2 versus 26%, p = 0.64). Similarly, there was no significant difference in the time to onset of renal failure (8.32 vs. 11 days, p = 1) or in the requirement of hemodialysis (26.6 vs. 41%, p = 1).. The high-dose colistin regimen is more efficient, without significant renal or neurological toxicity.

Topics: Acute Kidney Injury; Adult; Aged; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Prospective Studies; Severity of Illness Index

With increasing rates of infections caused by MDR Gram-negative organisms, clinicians resort to older agents such as colistimethate sodium (CMS) despite a significant risk of nephrotoxicity. Several risk factors for CMS-associated nephrotoxicity have been reported, but they have yet to be validated. We compared the performance of published mathematical models in predicting the risk of CMS-associated nephrotoxicity.. In a multicentre, retrospective, cohort study, adult patients (≥18 years of age) were evaluated from five large academic medical centres in the USA. Patients with normal renal function (baseline serum creatinine ≤1.5 mg/dL) who received intravenous CMS for ≥72 h were followed for up to 30 days. The development of nephrotoxicity was as defined by the RIFLE criteria. Each published model was conditioned using patient-specific variables to predict the risk of nephrotoxicity. The predictive performance of the models was evaluated using the observed-to-expected (O/E) ratio. The most significant cut-off threshold for stratifying patients into high and low risk of nephrotoxicity was identified using classification and regression tree analysis.. A total of 106 patients were examined (mean age 53.3 ± 14.9 years, 66% male); the overall observed nephrotoxicity rate was 52.8%. We identified a simple model demonstrating reasonable overall nephrotoxicity risk assessment [O/E ratio of 1.07 (95% CI = 0.81-1.39)] and high sensitivity (92.9%) in predicting nephrotoxicity development in patients on CMS therapy.. We identified a model that could be incorporated into patient management strategies to reduce the risk of nephrotoxicity in patients requiring CMS therapy.

Topics: Academic Medical Centers; Acute Kidney Injury; Administration, Intravenous; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Decision Support Techniques; Female; Humans; Male; Middle Aged; Models, Theoretical; Retrospective Studies; Risk Assessment; United States; Young Adult

Colistin pharmacokinetics data are scarce regarding patients undergoing renal replacement therapy (RRT), or even absent as in patients treated with sorbent technologies potentially capable of removing colistin by extensive absorption on many polymeric materials.. Twelve septic shock patients with acute kidney injury (AKI) undergoing RRT [continuous venovenous hemodiafiltration (CVVHDF) n = 7, coupled-plasma filtration adsorption-HF (CPFA-HF) n = 4, hemoperfusion n = 1] treated with colistin methanesulfonate at a dose of 4.5 × 10(6) U bid were studied. Colistin A (Col-A) and colistin B (Col-B) concentrations on plasma and effluent at time 0, 0.2, 1, 3, 6, 12, 24 and 48 h were determined by the liquid chromatography-tandem mass spectrometry method.. With CVVHDF the sieving coefficient was lower for Col-A, peaked early (0.40 for Col-A at 10 min, and 0.59 for Col-B at 3 h) and declined after 48 h (0.22 and 0.30 for Col-A and Col-B, respectively). Colistin's filter clearance showed a similar pattern, with the highest clearance value of 18.7 ml/min for Col-B at 1 h. With CPFA-HF after the cartridge the Col-A and Col-B levels were negligible (<0.2 mg/l) or not detectable. The sum of the effluent and cartridge clearances reached values of 30 and 40 ml/min for Col-A and Col-B, respectively. With hemoperfusion the postcartridge concentrations for Col-A and Col-B were about 30 % lower than those determined precartridge.. During CPFA-HF and CVVHDF, the extent of colistin removal is high, and patients should receive an unreduced dosage. However, due to risk of accumulation in long-term administration colistin plasma levels determination is recommended.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Chromatography, Liquid; Colistin; Critical Illness; Female; Follow-Up Studies; Hemodiafiltration; Humans; Male; Mass Spectrometry; Middle Aged; Shock, Septic; Sorption Detoxification

Nephrotoxicity is an important adverse effect of colistin methanesulfonate (CMS) therapy. No data exist on rates and risk factors for colistin-related nephrotoxicity in Saudi Arabia (SA). We conducted a prospective cohort study to identify rates and risk factors for CMS nephrotoxicity in our patient population.. We prospectively included adult patients who received ≥48 hours of intravenous CMS therapy. Pregnant patients and those on renal replacement were excluded. Patients received 9 million units (mU) loading dose followed by 3 mU 8 hourly. In renal impairment, CMS dosing was adjusted according to calculated creatinine clearance (CrCl). Nephrotoxicity was defined as per RIFLE criteria (Risk, Injury, Failure, Loss and End-stage renal disease). Statistical analysis was performed using SPSS version 20.0 (IBM, Armonk, New York, USA). The study was approved by the institution's Research Ethics Committee.. A total of 67 patients were included in the study. Mean (±standard deviation) age was 57.5 (±24.0) years, Charlson Co-morbidity Score 2.88 (±2.39), CrCl 133.60 (±92.54) mL/min and serum albumin 28.65 (±4.45) g/L. Mean CMS dose was 0.11 (±0.04) mU/kg/day and mean total CMS dose received was 101.21 (±47.37) mU. Fifty-one (76.1%) patients developed RIFLE-defined nephrotoxicity. Mean total CMS dose and duration of therapy before onset of nephrotoxicity were 66.71 (±43.45) mU and 8.70 (±6.70) days, respectively. In bivariate analysis, patients with nephrotoxicity were significantly older (P 0.013) and had lower baseline serum albumin (P 0.008). Multivariate logistic regression identified serum albumin [odds ratio (OR) 0.72; 95% confidence interval (CI) 0.57-0.93; P 0.010] and intensive care admission (OR 16.38; 95% CI 1.37-195.55; P 0.027) as independent risk factors for CMS nephrotoxicity.. High dose intravenous CMS therapy is associated with high rates of nephrotoxicity in SA. Independent risk factors for colistin nephrotoxicity were baseline hypoalbuminemia and intensive care admission.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Female; Gram-Negative Bacterial Infections; Humans; Male; Mesylates; Middle Aged; Pregnancy; Prospective Studies; Retrospective Studies; Saudi Arabia; Young Adult

To observe the safety and efficacy of Colistimethate sodium in children infected with gram-negative bacteria, susceptible only to colistimethate sodium.. This prospective observational study done over 2 years observed children who received colistin for >48 h, for renal failure as defined by p-RIFLE criteria.. Out of 68 children, 52 (76.5%) survived. There were three children with evidence of acute kidney injury and none had neurotoxicity. Serum creatinine significantly decreased at 48 h and at end of treatment, from that at beginning of therapy (P=0.007).. Colistimethate sodium is effective against carbapenem-resistant Gram-negative bacteria, and is safe in children.

Topics: Acute Kidney Injury; Administration, Intravenous; Adolescent; Anti-Bacterial Agents; Child; Child, Preschool; Colistin; Creatinine; Drug Resistance, Bacterial; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Infant; Infant, Newborn; Male; Microbial Sensitivity Tests; Prospective Studies; Sepsis

To investigate the development of nephrotoxicity associated with colistin dose, and whether this relationship differs depending on renal function.. A retrospective cohort study of patients who received intravenous colistin to treat infections caused by extensively drug-resistant Gram-negative microorganisms. Adult patients receiving colistin for 72 hours or longer were included in this study. Patients who received renal replacement therapy at baseline or were administered colistin for less than 3 days were excluded. Colistin-induced nephrotoxicity was defined as a doubling of baseline serum creatinine. Colistin dosing was evaluated based on both actual body weight and ideal body weight.. Single general hospital between 2010 and 2013.. A total number of 475 patients received colistin therapy. Of these patients, 329 met the inclusion criteria and were included in the analysis.. None.. One hundred forty-three patients (43.5%) experienced nephrotoxicity during colistin treatment. The median onset time of nephrotoxicity was 6 days (interquartile range, 4-8 days). The patients with nephrotoxicity were older. Hematocrit and serum albumin levels were lower in patients with nephrotoxicity. Median daily dosing of colistin based on ideal body weight was significantly higher in patients with nephrotoxicity than in those without nephrotoxicity (4.55 vs 4.43 mg/kg/d, respectively; p=0.021). The cumulative dose was not different between patients with and without nephrotoxicity. In multiple logistic regression analysis, daily colistin dosing based on ideal body weight was only significantly associated with the development of nephrotoxicity in patients with an estimated glomerular filtration rate<60 mL/min/1.73 m2 (odds ratio, 2.34; 95% CI, 1.22-4.5). In these affected patients, based on a receiver operating characteristic plot, the optimal predictive cutoff of colistin dose for the development of nephrotoxicity was 2.87 mg/kg/d of colistin, with a sensitivity of 92.3% and a specificity of 76.7%. In patients with estimated glomerular filtration rate≥60 mL/min/1.73 m, age, serum albumin, hematocrit, and use of glycopeptide were associated with the development of nephrotoxicity.. Development of nephrotoxicity was significantly more strongly associated with the dose of colistin, but only in patients with an estimated glomerular filtration rate<60 mL/min/1.73 m2 and not in those with normal renal function.

Topics: Acute Kidney Injury; Age Factors; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Creatinine; Dose-Response Relationship, Drug; Drug Resistance, Bacterial; Female; Glomerular Filtration Rate; Gram-Negative Bacterial Infections; Hematocrit; Humans; Male; Middle Aged; Retrospective Studies; Risk Factors; Serum Albumin; Time Factors

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Colistin; Critical Illness; Drug Resistance, Multiple; Female; Humans; Kidney; Male; Pseudomonas Infections

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Colistin; Critical Illness; Drug Resistance, Multiple; Female; Humans; Kidney; Male; Pseudomonas Infections

Critically ill patients with severe sepsis or septic shock may need relatively high colistin daily doses for efficacy against multidrug-resistant and extensively drug-resistant gram-negative rods. However, acute kidney injury (AKI) may represent a major dose-limiting adverse effect of colistin. We sought to determine AKI occurrence and to identify factors influencing AKI risk in severely ill patients receiving colistin according to a recently proposed dosing strategy.. A prospective, observational, cohort study involving patients with severe sepsis or septic shock who received colistin was performed. AKI was defined according to Acute Kidney Injury Network criteria. Colistin administration was driven by a modified pharmacokinetics-pharmacodynamics (PK/PD)-based dosing approach.. Of 70 patients who received colistin at a median daily dose of 9 million IU (MIU; interquartile range, 5.87-11.1 MIU), 31 (44%) developed AKI. In univariate analysis, age, Acute Physiology and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA), score and baseline renal impairment were significantly associated with AKI. Moreover, patients with AKI were less frequently treated with adjuvant ascorbic acid (P = .003). In multivariate analysis, independent predictors of AKI were baseline renal impairment (adjusted hazard ratio, 4.15; 95% confidence interval, 1.9-9.2; P < .001) and age (1.03; 1.0-1.05; P = .028), whereas a strong independent renal-protective role emerged for ascorbic acid (0.27; .12-.57; P < .001).. In severely ill patients receiving colistin according to a PK/PD-driven dosing approach, baseline renal impairment and older age strongly predict AKI occurrence, but concomitant administration of ascorbic acid markedly reduces AKI risk, allowing safer use of colistin.

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antidotes; Ascorbic Acid; Blighia; Colistin; Critical Illness; Female; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Prospective Studies; Risk Factors; Sepsis; Young Adult

Colistin has been revived, in the era of extensively drug-resistant (XDR) Gram-negative infections, as the last-resort treatment in critically ill patients. Recent studies focusing on the optimal dosing strategy of colistin have demonstrated the necessity of a loading dose at treatment initiation (D. Plachouras, M. Karvanen, L. E. Friberg, E. Papadomichelakis, A. Antoniadou, I. Tsangaris, I. Karaiskos, G. Poulakou, F. Kontopidou, A. Armaganidis, O. Cars, and H. Giamarellou, Antimicrob Agents Chemother 53:3430-3436, 2009, http://dx.doi.org/10.1128/AAC.01361-08; A. F. Mohamed, I. Karaiskos, D. Plachouras, M. Karvanen, K. Pontikis, B. Jansson, E. Papadomichelakis, A. Antoniadou, H. Giamarellou, A. Armaganidis, O. Cars, and L. E. Friberg, Antimicrob Agents Chemother 56:4241- 4249, 2012, http://dx.doi.org/10.1128/AAC.06426-11; S. M. Garonzik, J. Li, V. Thamlikitkul, D. L. Paterson, S. Shoham, J. Jacob, F. P. Silveira, A. Forrest, and R. L. Nation, Antimicrob Agents Chemother 55:3284-3294, 2011, http://dx.doi.org/10.1128/AAC.01733-10). In 19 critically ill patients with suspected or microbiologically documented infections caused by XDR Gram-negative strains, a loading dose of 9 MU colistin methanesulfonate (CMS) (∼ 270 mg colistin base activity) was administered with a maintenance dose of 4.5 MU every 12 h, commenced after 24 h. Patients on renal replacement were excluded. CMS infusion was given over 30 min or 1 h. Repeated blood sampling was performed after the loading dose and after the 5th or 6th dose. Colistin concentrations and measured CMS, determined after hydrolization to colistin and including the partially sulfomethylated derivatives, were determined with a liquid chromatography-tandem mass spectrometry assay. Population pharmacokinetic analysis was conducted in NONMEM with the new data combined with data from previous studies. Measured colistimethate concentrations were described by 4 compartments for distribution and removal of sulfomethyl groups, while colistin disposition followed a 1-compartment model. The average observed maximum colistin A plus B concentration was 2.65 mg/liter after the loading dose (maximum time was 8 h). A significantly higher availability of the measured A and B forms of colistimethate and colistin explained the higher-than-expected concentrations in the present study compared to those in previous studies. Creatinine clearance was a time-varying covariate of colistimethate clearance. The incidence of acute renal injury was

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Chromatography, Liquid; Colistin; Creatinine; Critical Illness; Drug Administration Schedule; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Infusions, Intravenous; Male; Middle Aged; Models, Statistical; Tandem Mass Spectrometry

Polymyxin B (PMB) and colistin, administered as the prodrug colistin methanesulfonate sodium (CMS), are increasingly used to treat carbapenem-resistant Gram-negative bacteria. Nephrotoxicity is the major dose-limiting adverse effect of both polymyxins. A retrospective cohort study of 132 patients was conducted to evaluate risk factors for acute kidney injury (AKI), classified according to Acute Kidney Injury Network criteria, in patients treated with ≥48h of intravenous PMB or CMS, with particular focus on potential differences between each polymyxin. The overall incidence of AKI was 25.8% (34/132) [20.8% (20/96) and 38.9% (14/36) in patients treated with PMB and CMS, respectively; P=0.06]. In the Cox regression model, doses ≥2million International Units (MIU) of PMB or >9MIU of CMS were the only variable independently associated with AKI [adjusted hazard ratio (aHR)=2.11, 95% confidence interval (CI) 1.01-4.41; P=0.04]. Vancomycin co-administration was strongly associated with AKI, although this was not statistically significant (aHR=2.22, 95% CI 0.98-5.04; P=0.058). There was no statistically significant difference in the incidence of AKI between patients treated with PMB or CMS in the multivariate model (aHR=1.74, 95% CI 0.82-3.69; P=0.15). High dose was the main risk factor for AKI regardless of the polymyxin administered. Vancomycin co-administration likely increases the risk of AKI. Although there was a higher overall incidence of AKI in patients treated with CMS compared with PMB, CMS was not significantly associated with this outcome after adjusting for the above variables.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Acute Kidney Injury; Anti-Bacterial Agents; Cohort Studies; Colistin; Female; Hospital Mortality; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Polymyxin B; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Risk Factors; Vancomycin

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Colistin; Critical Illness; Female; Humans; Kidney; Male

To describe the efficacy of intravenous colistin on clinical and microbiological outcomes in preterm infants with nosocomial sepsis in neonatal intensive care unit (NICU) and define adverse events observed with this treatment.. The records of preterm infants who received colistin with or without positive cultures in the NICU were retrospectively reviewed. Patients were evaluated for response to therapy and side effects.. A total of 21 preterm infants with medians of 28 weeks (23-36) gestational age and 870 g (620-2,650) birth weight were included. The median duration and dose of colistin therapy were 9 days (3-26) and 3 mg/kg/d (2-5). Recovery rate in patients including all with/without positive culture was 81% (17/21). Microbiological clearance by colistin was 69% (9/13). The major side effect observed was acute kidney injury (19%). At least 24% of infants required electrolyte supplementation during the colistin therapy. Magnesium levels were significantly lower at the end of the colistin therapy (p < 0.001). Acute kidney injury and electrolyte disturbances including hypomagnesemia were reversible in all surviving patients.. We suggest that renal function tests and serum electrolytes should be monitored closely and replaced in case of any need during the colistin therapy in preterm infants.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Acute Kidney Injury; Administration, Intravenous; Anti-Bacterial Agents; Colistin; Cross Infection; Electrolytes; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Intensive Care, Neonatal; Magnesium; Male; Microbial Sensitivity Tests; Retrospective Studies; Sepsis; Water-Electrolyte Imbalance

Infections due to multidrug-resistant gram-negative bacteria (MDR-GNB) are a significant burden to the healthcare system globally. Colistin is the drug of choice for MDR-GNB and recent studies recommend high doses. This study investigated the safety of low-dose colistin and the relationship of minimum inhibitory concentration (MIC) of colistin with bacterial cure in the treatment for MDR-GNB infections.. Computerized dispensing records identified all patients who received colistin during January 2010 and December 2011. Patients who were aged < 12 years old, who received colistin for < 72 h or had moderate to severe renal impairment were excluded. Medical records of the remaining patients were reviewed for the necessary data to determine the bacterial cure and nephrotoxicity of colistin. Multivariate logistic regression analysis was used to determine the predictors of bacterial cure.. A total of 125 evaluable patients received colistin during the study period. Ninety-four of 125 (75·2%) patients achieved bacterial cure. No statistically significant differences were observed between patients who achieved and failed to achieve bacterial cure with regards to age, gender, site of infection, mg/kg dose or duration of colistin use. The average MIC in the bacterial cure group was significantly lower than the MIC in the bacterial failure group (P = 0·002). Similarly, 30-day mortality from the last dose of colistin was significantly lower in the bacterial cure group (P = 0·002). Nephrotoxicity occurred in 12·8% of patients and was not associated with the dose of colistin or concomitant use of nephrotoxic medications. MIC of <1 μg/mL was the only significant independent predictor of bacterial cure in the multivariate logistic regression analysis (P = 0·015), whereas infection caused by MDR Klebsiella pneumonia was an independent risk factor for bacterial failure (P = 0·049).. Low-dose colistin is an effective option in the treatment for infections caused by MDR-GNB with a low incidence of nephrotoxicity. Patients who achieved bacterial cure had significantly lower MIC values of colistin against MDR-GNB than those who failed to achieve it. Colistin dose should be based on the MIC data of a given patient or local antimicrobial sensitivity data to maximize its efficacy.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Male; Microbial Sensitivity Tests; Middle Aged

Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Colistin; Humans; Plasma; Renal Dialysis

Colistin (COL) has become the backbone of the treatment of infections due to extensively drug-resistant (XDR) Gram-negative bacteria. The most common restriction to its use is acute kidney injury (AKI).. We conducted a retrospective cohort study to evaluate risk factors for new-onset AKI in patients receiving COL. The cohort consisted of 198 adults admitted to 9 referral hospitals between January 2010 and October 2012 and treated with intravenous COL for ≥ 72 h. Patients with no pre-existing kidney dysfunction were compared in terms of risk factors and outcomes of AKI graded according to the RIFLE criteria. Logistic regression analysis was used to identify associated risk factors.. A total of 198 patients met the inclusion criteria, of whom 167 had no pre-existing kidney dysfunction; the mean patient age was 58.77 (± 18.98) y. Bloodstream infections (34.8%) and ventilator-associated pneumonia (32.3%) were the 2 most common indications for COL use. New-onset AKI developed in 46.1% of the patients, graded as risk (10%), injury (15%), and failure (21%). Patients with high Charlson co-morbidity index (CCI) scores (p = 0.001) and comparatively low initial glomerular filtration rate (GFR) estimations (p < 0.001) were more likely to develop AKI, but older age (p = 0.001; odds ratio 5.199, 95% confidence interval 2.684-10.072) was the major predictor in the multivariate analysis. In-hospital recovery from AKI occurred in 58.1%, within a median of 7 days.. COL-induced nephrotoxicity occurred significantly more often in patients older than 60 y of age and was related to low initial GFR estimations and high CCI scores, which were basically determined by age.

Topics: Acute Kidney Injury; Administration, Intravenous; Adult; Age Factors; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cohort Studies; Colistin; Comorbidity; Female; Glomerular Filtration Rate; Humans; Male; Middle Aged; Retrospective Studies; Risk Factors; Young Adult

Nephrotoxicity was assessed in 173 critically ill patients receiving intravenous colistin or polymyxin B; it occurred in 60.4% and 41.8%, respectively. Further investigation is necessary to elucidate the reason for the difference in nephrotoxicity observed between the groups and to assess the impact of severity of illness and dosing/administration.

Topics: Acute Kidney Injury; Administration, Intravenous; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cohort Studies; Colistin; Critical Illness; Female; Humans; Incidence; Male; Middle Aged; Polymyxin B; Retrospective Studies; Tertiary Care Centers

Use of colistin methanesulfonate (CMS) was abandoned in the 1970s because of excessive nephrotoxicity, but it has been reintroduced as a last-resort treatment for extensively drug-resistant infections caused by gram-negative bacteria (Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumonia). We conducted a retrospective cohort study to evaluate risk factors for new-onset acute kidney injury (AKI) in critically ill patients receiving high intravenous doses of colistin methanesulfonate and/or other nephrotoxic antibiotics.. The cohort consisted of 279 adults admitted to two general ICUs in teaching hospitals between 1 April 2009 and 30 June 2011 with 1) no evidence on admission of acute or chronic kidney disease; and 2) treatment for more than seven days with CMS and/or other nephrotoxic antimicrobials (NAs, that is, aminoglycosides, glycopeptides). Logistic regression analysis was used to identify risk factors associated with this outcome.. The 279 cases that met the inclusion criteria included 147 patients treated with CMS, alone (n = 90) or with NAs (n = 57), and 132 treated with NAs alone. The 111 (40%) who developed AKI were significantly older and had significantly higher Simplified Acute Physiology Score II (SAPS II) scores than those who did not develop AKI, but rates of hypertension, diabetes mellitus and congestive heart failure were similar in the two groups. The final logistic regression model showed that in the 147 patients who received CMS alone or with NAs, onset of AKI during the ICU stay was associated with septic shock and with SAPS II scores ≥43. Similar results were obtained in the 222 patients treated with CMS alone or NAs alone.. In severely ill ICU patients without pre-existing renal disease who receive CMS high-dose for more than seven days, CMS therapy does not appear to be a risk factor for this outcome. Instead, the development of AKI was strongly correlated with the presence of septic shock and with the severity of the patients as reflected by the SAPS II score.

Topics: Acute Kidney Injury; Adult; Aged; Anti-Bacterial Agents; Cohort Studies; Colistin; Critical Illness; Female; Humans; Infusions, Intravenous; Kidney; Male; Middle Aged; Prospective Studies; Retrospective Studies; Risk Factors; Sepsis

Colistin (polymyxin E) was developed ~ 60 years ago but was rarely used in clinical practice during the last 20 years because of concerns related to high rates of nephrotoxicity. However, it was recently reintroduced to clinical practice in many parts of the world for the treatment of multi-drug resistant gram-negative bacilli. In the current study, we evaluated the predictive capacity of urine neutrophil gelatinase-associated lipocalin (NGAL) for early diagnosis of acute kidney injury (AKI) in geriatric patients with urinary tract infection (UTI) receiving colistin therapy.. We studied 116 patients aged 80.7 ± 12 treated with colistin who suffered from UTI. Urinary NGAL was measured at baseline and 1 - 2 hours after the second dose of colistin. The primary outcome was AKI. Secondary outcome was in-hospital morbidity and mortality.. 52 patients (44.8%) developed acute tubular necrosis (ATN) (14% of these had underlying CKD), 8 (7%) had prerenal azotemia, 8 (7%) had stable CKD without changes in renal function during hospitalization and the remaining 48 patients (41%) had normal kidney function. The mean duration of colistin therapy was 9.1 ± 4.8 days. At baseline, urine NGAL was 405 ± 452 g/l in ATN, 285 ± 256 g/l in prerenal azotemia, 390 ± 468 g/l in CKD and 347 ± 877 g/l in normal kidney function patients (difference non-significant). We were unable to demonstrate statistically significant increments of urine NGAL following colistin administration in either ATN or non-ATN patient groups. Urine NGAL was not correlated with urinary leukocyte or erythrocyte counts or baseline comorbidities such as CKD, heart failure, or diabetes. For primary outcome (ATN), receiver operating characteristics curve revealed AUC 0.59 (95% CI 0.49 - 0.7) sensitivity 0.65, and specificity 0.62 for a cutoff value of urinary NGAL 140 g/l. Similar results were obtained for secondary outcomes.. Our data suggest limited predictive capacity of urinary NGAL for early diagnosis of AKI in a large clinical setting of geriatric patients hospitalized for UTI and receiving the potentially nephrotoxic colistin. This finding is likely due to the powerful influence of UTI on NGAL levels in both patients with normal kidney function and those with a wide spectrum of acute or chronic kidney diseases.

Topics: Acute Kidney Injury; Acute-Phase Proteins; Aged; Aged, 80 and over; Anti-Bacterial Agents; Biomarkers; Colistin; Early Diagnosis; Female; Humans; Lipocalin-2; Lipocalins; Male; Prospective Studies; Proto-Oncogene Proteins; Urinary Tract Infections

The aim of this study was to investigate the efficacy and safety of colistin therapy in pediatric patients with severe nosocomial infections in pediatric intensive care unit.. The medical records of patients treated with colistin at a 200-bed university children hospital were reviewed.. Thirty-one patients (male/female = 22/9; median age, 3 years; range, 3 months-17 years) received forty-one courses of colistin. The average dose of colistin was 4.9 ± 0.5 mg/kg/day and average treatment duration was 19.8 ± 10.3 days. Three patients who received concomitant nephrotoxic agent with colistin developed nephrotoxicity. Colistin treatment was well tolerated in other patients, and neurotoxicity was not seen in any patient. Favourable outcome was achieved in 28 (68.3%) episodes. Twelve patients died during the colistin therapy. Six of these patients died because of primary underlying disease. The infection-related mortality rate was found 14.6% in this study.. In our study, colistin therapy was found to be acceptable treatment option for the severe pediatric nosocomial infections caused by multi-drug resistant bacteria. However, the use of concomitant nephrotoxic drugs with colistin must be avoided and renal function test should be closely monitored.

Topics: Acute Kidney Injury; Adolescent; Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Colistin; Cross Infection; Female; Hospitals, University; Humans; Infant; Intensive Care Units, Pediatric; Male; Treatment Outcome

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

The nephrotoxicity of colistin has been reported in the literature. A previous report has shown that acute kidney injury (AKI) occurred after an average of 13.5 days, but we have experienced that AKI developed with colistin administration earlier. We investigated clinical features of patients who developed AKI according to the time of AKI development after colistin use. We retrospectively collected the data of the patients who were admitted to 4 hospitals between January 2007 and May 2009. This study included 119 patients who had received intravenous colistin for over 72 h. We compared the early AKI group (AKI developed within 7 days) with the late AKI group. The patients' age was 64.1 ± 14.0 years. AKI occurred in 65 of the 119 patients (54.6%). The duration of colistin use was 7.7 ± 6.4 days. AKI occurred in 46 patients within 7 days after colistin treatment and in 19 patients after 7 days. The patients with early AKI had a higher mortality rate than those with late AKI (OR: 4.37, 95% CI: 1.34, 14.18). In conclusion, clinicians might be cautioned that the mortality rate is higher for the patients with early occurrence of AKI than that for the patients with late occurrence of AKI.

Topics: Acute Kidney Injury; Aged; Anti-Bacterial Agents; Colistin; Female; Follow-Up Studies; Hospital Mortality; Humans; Male; Middle Aged; Predictive Value of Tests; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome

A rise in infections with multidrug-resistant Pseudomonas aeruginosa (MDR-PA) is a significant contributor to increased morbidity and mortality of patients with hematologic malignancies. The aim of this study was to determine the efficacy and safety of colistin (colistimethate sodium) in the treatment of serious infections caused by MDR-PA in these patients.. A matched pair analysis of renal function, toxicities, and outcome of 26 patients receiving colistin and control subjects was done. All patients had clinical signs of sepsis; P. aeruginosa was isolated from blood in 69% of patients in colistin group and 84% in control group. Patients treated with colistin received 3 million units every 8 hours for a median duration of 13 days. Additionally, patients received at least two additional antimicrobial or antifungal drugs.. Resolution of infection was achieved in twenty patients (76.9%) receiving colistin and in 17 (65.4%) control subjects. Mortality rate was 11% in both groups. There was no statistically significant difference in the level of serum creatinine, creatinine clearance, or potassium levels before and after treatment between groups. Only one patient receiving colistin developed de novo renal failure and one displayed transient neurologic toxicity.. Our results suggest that in patients with hematologic malignancies, colistin is effective in treating severe infections caused by MDR-PA while maintaining an acceptable toxicity profile. Prospective randomized studies comparing efficacy and safety of colistin with those of other antipseudomonal drugs are needed.

Topics: Acute Kidney Injury; Adolescent; Adult; Anti-Bacterial Agents; Case-Control Studies; Colistin; Croatia; Drug Resistance, Multiple, Bacterial; Female; Hematologic Neoplasms; Humans; Male; Matched-Pair Analysis; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Treatment Outcome; Young Adult

A retrospective cohort study evaluated the effectiveness and nephrotoxicity of intravenous colistin monotherapy vs. colistin-meropenem combination therapy for patients with multidrug-resistant Gram-negative bacterial infections. Fourteen patients received intravenous colistin monotherapy and 57 received colistin-meropenem. No significant differences were found concerning clinical response of the infection (12/14 (85.7%) vs. 39/57 (68.4%), p 0.32) and development of nephrotoxicity (0/14 (0%) vs. 4/57 (7%), p 0.58). A favourable association was revealed between survival and treatment with colistin monotherapy compared to colistin-meropenem (0/14 (0%) vs. 21/57 (36.8%) deaths, p 0.007), even after adjusting for the variables for which significant differences were found.

Topics: Acute Kidney Injury; Adult; Aged; Anti-Bacterial Agents; Cohort Studies; Colistin; Drug Resistance, Multiple; Drug Therapy, Combination; Female; Gram-Negative Bacterial Infections; Humans; Male; Meropenem; Middle Aged; Retrospective Studies; Thienamycins; Treatment Outcome

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Colistin; Creatinine; Humans; Male; Middle Aged

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Colistin; Dose-Response Relationship, Drug; Humans; Infusions, Intravenous

Topics: Acute Kidney Injury; Ampicillin; Child, Preschool; Cholera; Colistin; Diarrhea; Disease Outbreaks; Drug Therapy, Combination; Feces; Female; Fluid Therapy; Gentamicins; Humans; Infant, Newborn; Male; Thailand; Vibrio cholerae

Topics: Acute Kidney Injury; Adult; Aged; Colistin; Contrast Media; Gentamicins; Hemoglobinuria; Humans; Male; Methicillin; Myoglobinuria

Clearance techniques were used to evaluate renal tubular sodium and water excretion in 4 patients with antibiotic-induced acute renal failure (ARF). Creatinine clearances and maximal urine flow rates of patients with ARF (22.6 and 5.23 ml/min, respectively) were significantly lower than control values during hypotonic volume expansion (125.5 and 13.71 ml/min, respectively, both p less than 0.01). During the period of maximal hydration, fractional sodium excretion (CNa/Ccr) and maximal urine osmolality (11.4% and 171 mosm/kg H2O, respectively) were increased compared to controls (1.04% and 53 mosm/kg H2O, respectively, both p less than 0.05). The increased CNa/Ccr observed in patients with ARF was consistent with reduced proximal sodium reabsorption as reflected by increased (CH2O + CNa)/Ccr and reduced fractional distal sodium reabsorption as indicated by decreased CH2O/(CH2O + CNa). The reduction in proximal and distal sodium reabsorption cannot be explained on the basis of an osmotic effect of urea as fractional clearances of BUN (CBUN/Ccr) were similar in patients with ARF and controls.

Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Body Water; Cephalothin; Colistin; Female; Gentamicins; Humans; Kanamycin; Kidney Tubules; Male; Middle Aged; Sodium

Topics: Acute Kidney Injury; Aged; Anti-Bacterial Agents; Burns; Cephalothin; Colistin; Drug Therapy, Combination; Gentamicins; Humans; Male; Middle Aged; Peritonitis; Postoperative Complications; Pseudomonas Infections

Topics: Acute Kidney Injury; Alcuronium; Colistin; Diuresis; Drug Synergism; Female; Humans; Middle Aged; Muscle Spindles; Nerve Block; Neuromuscular Blocking Agents; Sepsis; Time Factors

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Child; Colistin; Drainage; Female; Gentamicins; Humans; Hypotension; Male; Middle Aged; Peritoneal Dialysis; Postoperative Complications; Renal Dialysis; Sepsis

Topics: Acute Kidney Injury; Adolescent; Adult; Colistin; Female; Humans; Neuromuscular Diseases; Renal Dialysis

Topics: Acute Kidney Injury; Adolescent; Adult; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Colistin; Deafness; Endocarditis, Bacterial; Female; Humans; Kanamycin; Kidney; Kidney Function Tests; Male; Middle Aged; Pseudomonas Infections; Sepsis; Staphylococcal Infections; Streptococcal Infections; Urea; Vancomycin

Topics: Acute Kidney Injury; Aged; Blood Urea Nitrogen; Cephalothin; Colistin; Creatinine; Drug Synergism; Glomerular Filtration Rate; Humans; Kidney; Male; Middle Aged; Sulfonic Acids

Topics: Acute Kidney Injury; Adult; Apnea; Colistin; Humans; Male; Neurologic Manifestations

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Angiography; Blood Flow Velocity; Carbon Tetrachloride Poisoning; Cephaloridine; Cephalothin; Colistin; Diuretics; Glomerular Filtration Rate; Hemodynamics; Humans; Kanamycin; Kidney; Kidney Glomerulus; Mercury Poisoning; Middle Aged; Radioisotope Dilution Technique; Radioisotopes; Shock; Xenon

Topics: Acute Kidney Injury; Aged; Colistin; Humans; Kanamycin; Male; Middle Aged; Renal Dialysis

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

Topics: Acute Kidney Injury; Adult; Colistin; Humans; Kidney Tubules; Male; Renal Dialysis

High doses of colistin were used in the treatment of severely ill patients with refractory klebsiella chest and urinary tract infections. At the same time renal function was monitored to determine possible nephrotoxicity. In all patients it produced acute renal failure and in some acute tubular necrosis. Though renal failure contributed to the final cause of death in some cases, in the majority death was due to the primary neurological illness.

Topics: Acute Kidney Injury; Adult; Aged; Colistin; Creatinine; Female; Humans; Kidney; Kidney Function Tests; Klebsiella Infections; Male; Metabolic Clearance Rate; Middle Aged; Respiratory Tract Infections; Urea; Urinary Tract Infections

Topics: Accidents, Home; Acute Kidney Injury; Colistin; Exchange Transfusion, Whole Blood; Humans; Infant; Male; Peritoneal Dialysis

Topics: Acute Kidney Injury; Adult; Aged; Anti-Bacterial Agents; Colistin; Female; Humans; Infections; Lung Diseases; Male; Middle Aged; Sepsis

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Air Microbiology; Ampicillin; Ascitic Fluid; Bacteriocins; Benzalkonium Compounds; Catheterization; Cephaloridine; Chloramphenicol; Colistin; Cross Infection; Ethylene Oxide; Filtration; Gentamicins; Humans; Kanamycin; Lysogeny; Middle Aged; Nalidixic Acid; Peritoneal Dialysis; Pseudomonas aeruginosa; Pseudomonas Infections; Renal Dialysis; Sterilization; Streptomycin; Tetracycline; Ultraviolet Rays; Urinary Tract Infections

Topics: Acute Kidney Injury; Child; Colistin; Humans; Male; Peritoneal Dialysis

Topics: Acute Kidney Injury; Appendicitis; Child, Preschool; Colistin; Female; Humans; Kidney Tubules; Paralysis; Postoperative Complications

Topics: Acute Kidney Injury; Amphotericin B; Anti-Bacterial Agents; Bacitracin; Cephaloridine; Colistin; Drug Hypersensitivity; Gentamicins; Griseofulvin; Humans; Kanamycin; Kidney Function Tests; Methicillin; Penicillin G; Polymyxins; Streptomycin; Sulfonamides; Tetracycline

Topics: Acute Kidney Injury; Adult; Aged; Ascites; Blood Transfusion; Blood Urea Nitrogen; Blood Volume Determination; Colistin; Coma; Diuretics; Drinking Behavior; Female; Furosemide; Humans; Hypokalemia; Injections, Intravenous; Liver Cirrhosis; Male; Middle Aged; Natriuresis; Sodium; Spironolactone; Triamterene; Urea; Water Intoxication; Water-Electrolyte Balance

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Chloramphenicol; Colistin; Gentamicins; Humans; Nitrofurantoin

Topics: Acute Kidney Injury; Anuria; Colistin; Humans; Infections; Renal Dialysis

Topics: Acute Kidney Injury; Adult; Ampicillin; Cephalothin; Chloramphenicol; Chronic Disease; Colistin; Humans; Male; Pyelonephritis; Urinary Tract Infections

Topics: Acute Kidney Injury; Adult; Aged; Blood Pressure Determination; Blood Urea Nitrogen; Colistin; Electroencephalography; Female; Humans; Hypertension; Injections, Intramuscular; Male; Obesity; Proteinuria; Urography