Higher Risk Of Nephrotoxicity Research Articles

Machine learning algorithms to predict colistin-induced nephrotoxicity from electronic health records in patients with multidrug-resistant Gram-negative infection

ObjectivesColistin-induced nephrotoxicity prolongs hospitalisation and increases mortality. The study aimed to construct machine learning models to predict colistin-induced nephrotoxicity in patients with multidrug-resistant Gram-negative infection. MethodsPatients receiving colistin from three hospitals in the Clinical Research Database were included. Data were divided into a derivation cohort (2011–2017) and a temporal validation cohort (2018–2020). Fifteen machine learning models were established by categorical boosting, light gradient boosting machine and random forest. Classifier performances were compared by the sensitivity, F1 score, Matthews correlation coefficient (MCC), area under the receiver operating characteristic (AUROC) curve, and area under the precision-recall curve (AUPRC). SHapley Additive exPlanations plots were drawn to understand feature importance and interactions. ResultsThe study included 1392 patients, with 360 (36.4%) and 165 (40.9%) experiencing nephrotoxicity in the derivation and temporal validation cohorts, respectively. The categorical boosting with oversampling achieved the highest performance with a sensitivity of 0.860, an F1 score of 0.740, an MCC of 0.533, an AUROC curve of 0.823, and an AUPRC of 0.737. The feature importance demonstrated that the days of colistin use, cumulative dose, daily dose, latest C-reactive protein, and baseline haemoglobin were the most important risk factors, especially for vulnerable patients. A cutoff colistin dose of 4.0 mg/kg body weight/d was identified for patients at higher risk of nephrotoxicity. ConclusionsMachine learning techniques can be an early identification tool to predict colistin-induced nephrotoxicity. The observed interactions suggest a modification in dose adjustment guidelines. Future geographic and prospective validation studies are warranted to strengthen the real-world applicability.

In vitro activity of ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam alone or in combination with polymyxin B against carbapenem resistant Acinetobacter baumannii.

Nosocomial infection caused by Carbapenem-Resistant Acinetobacter baumannii (CR-A. baumannii) has become a challenge in clinical practice. Acting as the last resort antibacterial agents for the treatment of CR-A. baumannii infection, polymyxins have high risk of nephrotoxicity and poor clinical efficacy. Ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam are three β-lactam/β-lactamase inhibitor combination complexes that newly approved by the Food and Drug Administration for the treatment of carbapenem-resistant Gram-negative bacterial infection. In this study, we analyzed the in vitro activity of those novel antibacterial agents alone or in combination with polymyxin B against the CR-A. baumannii obtained from a Chinese tertiary hospital. Our results suggest that those novel antibacterial agents should not be used alone for the treatment of CR-A. baumannii infection, as they cannot prevent the regrowth of bacteria at the clinical achievable blood concentration. Imipenem/relebactam and meropenem/vaborbactam should not be used as the substitutes of imipenem and meropenem for polymyxin B based combination therapy against CR-A. baumannii, since they have no edge over imipenem and meropenem on antibacterial activity when in combination with polymyxin B. Ceftazidime/avibactam may be more suitable than ceftazidime for polymyxin B based combination therapy against CR-A. baumannii, as it has a higher synergistic rate with polymyxin B, and the antibacterial activity of ceftazidime/avibactam is much higher than that of ceftazidime when tested in combination with polymyxin B. Ceftazidime/avibactam may also be the better choice than imipenem and meropenem for polymyxin B based combination therapy against CR-A. baumannii, as it has a higher synergistic rate with polymyxin B.

Investigation of Effect of the Colistin Loading Dosage on the clinical, Microbiological, and Laboratory Results in Acinetobacter baumannii Ventilator-Associated Pneumonia /Pneumonia.

Materials and Methods Adult patients administered colistin with and without LD for MDR Acinetobacter baumannii VAP/pneumonia in intensive care units (ICUs) in a tertiary teaching hospital between 1 January 2018 and 31 December 2019 were included in this retrospective cohort study. The primary endpoint was an assessment of clinical and microbiological success between treatment groups. Secondary endpoints included 14- and 30-day mortality and development of nephrotoxicity. Results A total of 101 patients were included (colistin with LD, n = 57; colistin without LD, n = 44). No significant difference in clinical success was observed between groups (73.7% versus 77.3%; p=0.670). In patients receiving colistin with LD, the microbiological success rate increased from 65.9% to 71.9%, but there was no statistically significantly difference (p=0.510). In terms of using combination therapies with carbapeneme and/or tigecycline, there was no significant difference between treatment groups (p=0.30). The rates of 14- and 30-day mortality were similar between groups. The colistin with LD group had a higher rate of nephrotoxicity compared to the other group (52.6% versus 20.5% p=0.001). The clinical and microbiological response times were found significantly higher in the colistin with LD group (p=0.001; p=0.017). Conclusion Colistin with LD was associated with a higher risk of nephrotoxicity and was not related to clinical success, microbiological success, and prolonged survival. Randomized comparative studies are needed to confirm the efficacy of LD colistin regimen on MDR Acinetobacter infection.

NGAL and KIM-1 – early urinary biomarkers of nephrotoxicity mediated by cisplatin: Observational study

Background. Cisplatin is widely used in modern oncological practice. Despite high efficacy treatment with cisplatin is conjugated with high risk of nephrotoxicity. Approximately one third of patients develop renal disfunction after first injection of cisplatin. In clinical practice serum creatinine elevation is used as a marker of renal damage, which is observed after failure of 50% of kidney function. That is why the finding of early biomarker of nephrotoxicity is still an issue. NGAL and KIM-1 are markers of renal damage, the predictive value of which has been described in cardiac surgery and resuscitation practice: an increase in the concentration of these markers in urine precedes the development of renal damage, both ischemic and direct toxic.
 Aim. To evaluate the role of NGAL and KIM-1 in urine as early markers of cisplatin nephrotoxicity.
 Materials and methods. The study included 50 patients treated with cisplatin in combination with fluoropyrimidines or paclitaxel. Prior to treatment and over a period of 8 weeks, the Friedman test was used to assess blood pressure, plasma creatinine, potassium, urea levels, daily proteinuria, urine NGAL and KIM-1 levels, and glomerular filtration rate (GFR). ROC analysis was used to assess the prognostic significance of NGAL and KIM-1 in the development of nephrotoxicity.
 Results. There was a statistically significant increase in the level of urea (=17.7; df 4, p=0.001), potassium (=42; df 4, p0.001), a decrease in GFR (=32.3; df 4, p0.001), the appearance of proteinuria (=50.4; df 4, p0.001). The concentration of NGAL and KIM-1 increased already one week after the start of cisplatin therapy, reaching a maximum by 8 weeks (=200; df 4, p0.001). The appearance of NGAL at a concentration of 10.743 ng/ml and KIM-1 at a concentration of 182.4 pg/ml in the first week after administration of cisplatin allows predicting the development of nephrotoxicity by the 8th week with high sensitivity (90.91%) and specificity (94.87%), AUC 0.96.
 Conclusion. The appearance of NGAL and KIM-1 in urine already in the first week of treatment allows predicting the development of nephrotoxicity a decrease in GFR of less than 60 ml/min by the 8th week of therapy with high sensitivity and specificity. Both biomarkers can be considered early prognostically significant.

Population Pharmacokinetics of Polymyxin B in Obese Patients for Resistant Gram-Negative Infections.

Polymyxin B is an effective but potentially nephrotoxic antibiotic that is commonly used to treat resistant Gram-negative infections. As a weight-based dosing drug, obese patients may be at a high risk of nephrotoxicity. However, the pharmacokinetics and dosing recommendations for this population are currently lacking. This study aimed to describe the polymyxin B population pharmacokinetics and to evaluate pharmacokinetic/pharmacodynamics (PK/PD) target attainment for obese patients. This study included 26 patients (body mass index, BMI >30) who received polymyxin B for ≥3 days. The total body weight (TBW) ranged from 75 to 125 kg, and the BMI ranged from 30.04 to 40.35. A two-compartment model adequately described the data using Phoenix NLME software. Monte Carlo simulation was used to assess polymyxin B exposure and the probability of target attainment (PTA). As a result, body weight had no significant effect on polymyxin B pharmacokinetics. According to model-based simulation, adjusted body weight (ABW)-based regimens had a high probability of achieving optimal exposure with minimal toxicity risk by comparing TBW and ideal body weight (IBW)-based regimens. The fixed dose of 125 mg or 150 mg q12h had a high toxicity risk. PTA results showed that TBW, IBW, and ABW-based regimens had similar PTA values. Therefore, for obese patients, ABW-based regimens but with a daily dose <250 mg have a high likelihood of achieving an AUCss,24h of 50–100 mg h/L and attaining PK/PD targets with the MIC ≤0.5 mg/L.

Vancomycin in adult prescribing: is it time to move on from trough-based dosing in the UK?

Vancomycin remains a useful agent in the infection doctor's toolkit, particularly for Staphylococcus aureus and MRSA infections. Therapeutic drug monitoring (TDM) is essential to maintain efficacy and avoid toxicity. Until recently, trough-based dosing has been the recommended method but in recent years the reliability of this has been questioned. The 2020 Infectious Diseases Society of America (IDSA) vancomycin guideline update has sent a clear message that trough-based dosing is not to be relied on, instead recommending dosing via 24 h AUC/MIC. The UK, however, has yet to follow suit in this, despite the wealth of evidence showing that trough-based dosing puts patients at higher risk of nephrotoxicity. Clearly, it is time to incorporate AUC/MIC-based dosing to utilize this effective antibiotic safely.

Amikacin Liposome Inhalation Suspension for Mycobacterium avium Complex Lung Disease

OBJECTIVE: To review the pharmacology, pharmacokinetics, pharmacodynamics, clinical efficacy, safety, administration, and role of amikacin liposome inhalation suspension (ALIS) in treatment of Mycobacterium avium complex (MAC) lung disease.<br/> DATA SOURCES: A PubMed search using the terms "amikacin inhaled," "nebulized," and "liposome suspension" was performed. Selected infectious diseaseconference posters were also examined for relevant information. In addition, pertinent guidelines were reviewed.<br/> STUDY SELECTION/DATA EXTRACTION: Guidelines for the management of nontuberculous mycobacterial infections from the American Thoracic Society/ Infectious Diseases Society of America and the British Thoracic Society were used to summarize guidelinebased therapy (GBT). A phase II and a phase III clinical trial were reviewed to evaluate the role of ALIS in the treatment of MAC lung disease.<br/> DATA SYNTHESIS: ALIS is a new formulation of inhaled amikacin (AMK) indicated for the treatment of MAC lung disease refractory to GBT in adults who are not candidates for intravenous AMK. An ongoing clinical trial has demonstrated that once-daily ALIS plus GBT results in higher rates of culture conversion compared with GBT alone by month 6 among patients with a mean age of 65 years. The most common adverse reactions associated with ALIS were dysphonia, cough, bronchospasm, hemoptysis, and ototoxicity. Nephrotoxicity was uncommon.<br/> CONCLUSION: ALIS has been shown to increase culture conversion rates when added to GBT in adults with difficult-to-treat MAC lung disease. ALIS is associated with high rates of pulmonary and auditory adverse reactions and a low risk of renal adverse reactions. ALIS may be an attractive treatment option for older adults who are at high risk for nephrotoxicity.

Amikacin Liposome Inhalation Suspension for Mycobacterium avium Complex Lung Disease.

OBJECTIVE: To review the pharmacology, pharmacokinetics, pharmacodynamics, clinical efficacy, safety, administration, and role of amikacin liposome inhalation suspension (ALIS) in treatment of Mycobacterium avium complex (MAC) lung disease.<br/> DATA SOURCES: A PubMed search using the terms "amikacin inhaled," "nebulized," and "liposome suspension" was performed. Selected infectious diseaseconference posters were also examined for relevant information. In addition, pertinent guidelines were reviewed.<br/> STUDY SELECTION/DATA EXTRACTION: Guidelines for the management of nontuberculous mycobacterial infections from the American Thoracic Society/ Infectious Diseases Society of America and the British Thoracic Society were used to summarize guidelinebased therapy (GBT). A phase II and a phase III clinical trial were reviewed to evaluate the role of ALIS in the treatment of MAC lung disease.<br/> DATA SYNTHESIS: ALIS is a new formulation of inhaled amikacin (AMK) indicated for the treatment of MAC lung disease refractory to GBT in adults who are not candidates for intravenous AMK. An ongoing clinical trial has demonstrated that once-daily ALIS plus GBT results in higher rates of culture conversion compared with GBT alone by month 6 among patients with a mean age of 65 years. The most common adverse reactions associated with ALIS were dysphonia, cough, bronchospasm, hemoptysis, and ototoxicity. Nephrotoxicity was uncommon.<br/> CONCLUSION: ALIS has been shown to increase culture conversion rates when added to GBT in adults with difficult-to-treat MAC lung disease. ALIS is associated with high rates of pulmonary and auditory adverse reactions and a low risk of renal adverse reactions. ALIS may be an attractive treatment option for older adults who are at high risk for nephrotoxicity.

Clinical and Laboratory Standards Institute and European Committee on Antimicrobial Susceptibility Testing Position Statements on Polymyxin B and Colistin Clinical Breakpoints.

Recent data on polymyxin pharmacokinetics, pharmacodynamics, toxicity, and clinical outcomes suggest these agents have limited clinical utility. Pharmacokinetics-pharmacodynamics data show a steady-state concentration of 2 μg/mL is required for killing bacteria with colistin minimum inhibitory concentrations of 2 μg/mL. Less than 50% of patients with normal renal function achieve this exposure, and it is associated with high risk of nephrotoxicity. This exposure does not achieve bacterial stasis in pneumonia models. Randomized and observational studies consistently demonstrate increased mortality for polymyxins compared with alternative agents. The Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) are 2 global organizations that establish interpretive criteria for in vitro susceptibility data. CLSI has recently taken the step to eliminate the "susceptible" interpretive category for the polymyxins, whereas EUCAST maintains this interpretive category. This viewpoint describes the opinions of these organizations and the data that were used to inform their perspectives.

Colistin-induced Nephrotoxicity in a Tertiary Teaching Hospital.

Colistin-induced nephrotoxicity is a well-known major adverse event, which may occur within seven days [early acute kidney injury (AKI)] with a high mortality rate of 70% or after seven days (late AKI). The main objective of this retrospective study is to assess the severity and associated risk factors for the development of colistin-related nephrotoxicity. An observational retrospective cohort study was conducted over 12 months (January-December 2017). All patients with a baseline normal renal function, who received intravenous colistin for >72 h, were included. Nephrotoxicity was defined using the RIFLE criteria (Risk, Injury, Failure, Loss, and End-stage renal disease). The demographic and clinical variables were retrieved from the hospital's electronic medical record system and compiled in an electronic database. All the statistical analysis was carried out by SAS JMP from SAS Institute Inc., Cary, NC. Seventy patients met the inclusion criteria. Colistin-induced nephrotoxicity occurred in 45.71% of the patients, of whom 40.6% were at Risk, 21.9% at Injury, and 37.5% at Failure according to RIFLE criteria. In patients who developed AKI, the average total colistin dose received before AKI was 4.4 mg/kg/day. More than half of the AKI group (53.13%) received an inappropriate total dose of colistin. Age, 65 years and older, was significantly associated with a high risk of nephrotoxicity (P <0.05), which developed within 6.8 ± 0.44 days from receiving a colistin dose. Clinical pharmacy services were consulted in 28.13% of the cases, and the dose was adjusted in 37.5% of the patients. Colistin nephrotoxicity is common and is associated more with older age group and inappropriate dosing.

2109. Liposomal Amphotericin B-associated Nephrotoxicity in Obese and Non-obese Patients

BackgroundLiposomal amphotericin B (L-amb) is an important antifungal agent which exhibits significant rates of dose-dependent nephrotoxicity. Animal studies demonstrate only small amounts of L-amb distribute into adipose tissue and obese animals show greater risk of nephrotoxicity with L-amb administration. This study aims to determine whether obese patients are at a higher risk of nephrotoxicity with weight-based doses of L-amb.MethodsWe performed a multi-center, retrospective cohort study of nephrotoxicity with L-amb in obese (BMI > 30) and non-obese adult patients at University of Utah Health and Intermountain Healthcare from January 1, 2014 through December 31, 2018. Our primary outcome was the rate of nephrotoxicity as determined by AKIN criteria. Patients receiving at least one dose of L-amb were identified for inclusion. Patients were excluded if they were already on a renal replacement at the time of L-amb initiation or they received L-amb prior to admission.ResultsWe included 221 patients, 47 (21%) were obese and 174 (79%) were non-obese. Median total body weight was 109 kg in obese patients compared with 70 kg in non-obese patients. Dosage based on ideal body weight was higher in the obese group (median 6.9 mg/kg vs. 4.9 mg/kg). Obese patients were significantly more likely to experience acute kidney injury (AKI) than non-obese patients (55% vs. 37%, P = 0.03). Patients who experienced nephrotoxicity received a higher average daily dose than those who did not (365 mg vs. 333 mg, P = 0.03), had a higher median cumulative dose (3,130 mg vs. 1,700 mg, P < 0.001), and had a higher median total body weight (79.6 kg vs. 71.9 kg, P = 0.04.). Additionally, daily dose normalized to total body weight was not associated with AKI (median 4.7 mg/kg in patients with AKI vs. 4.8 mg/kg in patients without AKI, P = 0.86). However, daily dose normalized to ideal body weight was associated with AKI (median 5.5 mg/kg in patients with AKI vs. 4.9 mg/kg in patients without AKI, P = 0.02).ConclusionWe identified a higher rate of nephrotoxicity among obese patients receiving L-amb compared with non-obese patients. These data suggest that dosing L-amb based on total body weight places obese patients at a higher risk of nephrotoxicity. This should be considered when assessing the risks and benefits of this dosing strategy in obese patients.Disclosures All authors: No reported disclosures.

Treatment of Ventilator-associated Pneumonia with High-dose Colistin Under Continuous Veno-venous Hemofiltration.

Background and ObjectivesHigh-dose colistin (COL) ensures adequate treatment of pneumonia caused by multidrug resistant gram-negative bacteria (MDR-GNB) but must be weighed against a higher risk of nephrotoxicity. Continuous veno-venous hemofiltration (CVVH) clears COL by filtering and membrane adsorption that permits to avoid dose accumulation and excessively high peak concentrations. We evaluated clinical/microbiological efficacy of the high-dose COL treatment under CVVH in patients with newly diagnosed MDR-GNB ventilator-associated pneumonia (VAP).MethodsObservational cohort study in critically ill adult patients with MDR-GNB VAP. Colistimethate sodium (CMS) was administered as a 9 million international units (MIU) of loading dose followed by 3 × 4.5 MIU daily. CVVH was performed over a highly adsorptive membrane. Clinical and microbiological efficacies were assessed at the end of therapy. In survivors, serum creatinine level was evaluated before and at the end of therapy.ResultsFourteen patients (8 male patients, aged 57 ± 14 years) were consecutively included. Isolated pathogens were Pseudomonas aeruginosa in 7, Klebsiella pneumoniae in 5, and other Enterobacteriaceae in 2 patients. A favorable clinical response was observed in 9 patients (64%). Full and presumed microbiological eradication was observed in 12 patients (86%). Two patients were diagnosed with Stage 1 acute kidney injury.ConclusionsIn patients with MDR-GNB VAP, CVVH may represent an interesting option to enable effective high-dose COL treatment.

Population pharmacokinetic analysis of high-dose methotrexate in pediatric and adult oncology patients.

High-dose methotrexate (HD-MTX) is widely used in pediatric and adult oncology treatment regimens. This study aimed to develop a population pharmacokinetic model to characterize pediatric and adult MTX exposure across various disease types and dosing regimens, and to evaluate exposure-toxicity relationships. MTX pharmacokinetic data from pediatric and adult patients were collected. A population pharmacokinetic model was developed to determine the effects of age, liver function, renal function, and demographics on MTX disposition. The final model was used in Monte Carlo simulations to generate expected exposures for different dosing regimens. The association of toxicity, determined through chart review, and MTX area under the curve (AUC) was modeled using logistic regression. The analysis included 5116 MTX concentrations from 320 patients (135 adult, age 19-79years; 185 pediatric, age 0.6-19years). Estimated glomerular filtration rate (eGFR) and treatment cycle number were independent predictors of clearance (CL). CL varied 2.1-fold over the range of study eGFR values and increased 14% for treatment cycle numbers greater than 7. Higher MTX AUC was associated with higher risk of nephrotoxicity in adults, and neurotoxicity and hepatotoxicity in pediatrics. This study represents one of the most comprehensive evaluations of HD-MTX PK across a wide range of ages and disease types. After accounting for differences in renal function, age did not impact CL, although toxicity patterns differed by age. The model allows for early identification of patients with slowed MTX clearance and at higher risk of toxicity.

Evaluation of Resveratrol in Cancer Patients and Experimental Models.

Cancer is one of the top three causes of death in the United States. The treatment regimen for controlling cancer includes a number of approaches depending on the classification of the tumor. Treatment may include radiation, surgery, and cancer chemotherapy agents as well as other interventions. Natural products have been identified for centuries to contain active pharmacologic activity and have been a starting point for numerous drugs which are currently on the market. Resveratrol (RES) is a natural product generated in plants in response to environmental stress and growing conditions. RES has been recognized since 1997 to possess anticancer activity. This review discusses the dietary sources of RES and the relative amounts present in the various food sources. A few limited clinical studies have explored RES effects in patients with prostate and colorectal cancer and have suggested some beneficial results. Future studies need to expand the sample size for clinical examination of RES in order to provide a better profile for the potential benefit of RES in cancer patients. This review also describes the potential mechanisms of RES as an antioxidant and in alteration of cell signaling. Another aspect for the role of RES in cancer may be in the interaction with cancer chemotherapy agents. Cisplatin is a cancer chemotherapy agent used for the treatment of bladder, testicular, ovarian, and many other cancers. Cisplatin usage is associated with a high risk of nephrotoxicity. Experimental studies suggest that RES may reduce cisplatin renal toxicity. The proposed mechanisms of protection are reviewed.

Combination of Ceftriaxone and Ampicillin for the Treatment of Enterococcal Endocarditis: A Qualitative Systematic Review

The aim of this systematic review is to review all human trials assessing the efficacy and safety of ampicillin and ceftriaxone for enterococcal endocarditis and to discuss the clinical implications of the findings. MEDLINE (1946-), EMBASE (1974-), CENTRAL, Google Scholar, and the World Health Organization Clinical Trials Registry Platform were searched through January 2017 using the search terms ampicillin, penicillin, ceftriaxone, cephalosporin, enterococ*, and endocarditis. Unpublished studies were eligible for inclusion. Additional references were identified from literature citations. Clinical trials in humans that reported on clinical efficacy or adverse outcomes with ceftriaxone and ampicillin therapy in patients with enterococcal endocarditis were included. Case reports, nonhuman, and non-English studies were excluded. Four observational clinical studies were identified. One examined the effects of ceftriaxone and ampicillin alone, and 3 compared the therapy to the current standard of care, ampicillin and gentamicin. The studies had small sample sizes and were not adequately designed or powered to establish noninferiority or equivalence to the current standard of care. Rates of clinical cure with ampicillin 2 g every 4 hours and ceftriaxone 2 g every 12 hours were similar to those of ampicillin and gentamicin. Ampicillin and ceftriaxone therapy was well tolerated with low rates of renal failure (0%-33%). The evidence to support the use of ampicillin and ceftriaxone for enterococcal endocarditis is not definitive. In the absence of compelling evidence, clinicians may consider ampicillin and ceftriaxone in patients with Enterococcus faecalis infection at high risk for nephrotoxicity or those with aminoglycoside-resistant pathogens.

Colistin Nephrotoxicity in Adults: Single Centre Large Series from India.

Context:Limited Indian data are available on the rate of colistin nephrotoxicity and other risk factors contributing to the development of this important side effect.Aim:This study aims to generate data on colistin nephrotoxicity from a large cohort of Indian patients.Design:Retrospective cohort study.Materials and Methods:Case record analysis of patients who received colistin, in an oncology center in India, between January 2011 and December 2015. Nephrotoxicity was assessed using risk, injury, failure, loss, and end-stage (RIFLE) criteria.Statistical Analysis:P < 0.05 was considered as statistically significant.Results:Out of the 229 patients, 13.1% (30/229) developed abnormal RIFLE. Abnormal RIFLE group (n = 30), in comparison to the normal renal function group (n = 199), had higher number of patients in intensive care unit (ICU) (96% vs. 79%, P = 0.02), higher Acute Physiology and Chronic Health Evaluation (APACHE II) score (23 vs. 19 P = 0.0001), Charlson score (5.9 vs. 4.3, P = 0.001), mechanical ventilation (90% vs. 67%, P = 0.016), 28 days mortality (63% vs. 25%, P = 0.0001), and abnormal baseline creatinine (36% vs. 8%, P = 0.001). Coadministration of vancomycin had higher rates of nephrotoxicity (P = 0.039). There was no significant difference in nephrotoxicity between 6 and 9 MU/day dosing pattern (8.8% vs. 13.8%, P = 0.058).Conclusion:Nephrotoxicity rate in our retrospective single center large series of patients receiving colistin was 13.1%. Patients with abnormal baseline creatinine, ICU stay, and higher disease severity are at higher risk of nephrotoxicity while on colistin. A daily dose of 9 million does not significantly increase nephrotoxicity compared to the 6 million. Concomitant administration of vancomycin with colistin increases the risk of nephrotoxicity.

Efficacy and Toxicity of High-Dose Colistin in Multidrug-Resistant Gram-Negative Bacilli Infections: A Comparative Study of a Matched Series

Background: 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. Methods: 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. Results: 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). Conclusion: The high-dose colistin regimen is more efficient, without significant renal or neurological toxicity.

Rates of Renal Toxicity in Cancer Patients Receiving Cisplatin With and Without Mannitol

Cisplatin is a widely used antineoplastic. One of the major complications of cisplatin use is dose-limiting nephrotoxicity. There are many strategies to prevent this toxicity, including the use of mannitol as a nephroprotectant in combination with hydration. We aimed to evaluate the rates of cisplatin-induced nephrotoxicity in cancer patients receiving single-agent cisplatin with and without mannitol. This single-center retrospective analysis was a quasi experiment created by the national mannitol shortage. Data were collected on adult cancer patients receiving single-agent cisplatin as an outpatient from January 2011 to September 2012. The primary outcome was acute kidney injury (AKI). We evaluated 143 patients who received single-agent cisplatin; 97.2% of patients had head and neck cancer as their primary malignancy. Patients who did not receive mannitol were more likely to develop nephrotoxicity: odds ratio [OR] = 2.646 (95% CI = 1.008, 6.944; P = 0.048). Patients who received the 100 mg/m2 dosing and patients who had a history of hypertension also had a higher likelihood of developing nephrotoxicity: OR = 11.494 (95% CI = 4.149, 32.258; P < 0.0001) and OR = 3.219 (95% CI = 1.228, 8.439; P = 0.017), respectively. When limited quantities of mannitol are available, it should preferentially be given to patients at particularly high risk of nephrotoxicity. Our analysis suggests that those patients receiving the dosing schedule of 100 mg/m2 cisplatin every 3 weeks and those with hypertension are at the greatest risk of nephrotoxicity and would benefit from the addition of mannitol.

PS-096 Profile of onco-haematological patients susceptible to dose-adjustment to renal function

BackgroundRenal impairment can alter excretion of chemotherapeutic agents and increase systemic toxicity. For that reason dose adjustment is often required in cancer patients treated with these drugs. It is important...

Carbon Dioxide Contrast Enhancement for C-Arm CT Utility for Treatment Planning during Hepatic Embolization Procedures

A pilot study was performed to evaluate the use of carbon dioxide (CO2) as a contrast medium for C-arm computed tomography (CT). C-arm CT using CO2 was performed during embolization procedures in12 patients with hepatic malignancies and severe iodine allergy or high risk for nephrotoxicity. C-arm CT using gadolinium or iodinated contrast medium was performed for comparison. Of segmental arteries identified by conventional contrast enhancement, 96% were also seen with CO2 enhancement, but subsegmental arteries were not reliably depicted. CO2 enhancement identified 60% of tumors. Small, hypovascular, and infiltrative tumors were difficult to detect. CO2 is a promising alternative intraarterial contrast agent for C-arm CT.