Polymyxin-B and vancomycin-associated acute kidney injury in critically ill patients

Soares, Douglas de Sousa; Reis, André da Fonte; Silva, Geraldo Bezerra da; Leite, Tacyano Tavares; Filho, Sérgio Luiz Arruda Parente; Rocha, Camille Arraes; Daher, Elizabeth De Francesco

doi:10.1080/20477724.2017.1309338

Cited by 19 publications

(18 citation statements)

References 27 publications

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“…In fact, overall AKI rates were similar to the average rate of 40% found in previous studies of PMB (range, 20% to 60%) (27)(28)(29)(30)(31)(32)(33)(34). The proportion of patients with renal failure in our study might be considered higher (46.3% of patients with AKI) than that described in reports of previous studies, which presented an average proportion of patients with renal failure of approximately 22% (but the average proportion ranged widely from 4% to 50%) (27)(28)(29)(30)(31)(32)(33)(34), and the onset of failure may have occurred earlier in our sample than patients in previous studies. The number of patients requiring renal replacement therapy in our cohort may also be considered high, potentially indicating a higher risk for more severe kidney damage in patients receiving these high doses, although a definitive conclusion requires a proper control group exposed to lower doses.…”

Section: Discussionsupporting

confidence: 87%

Severe Infusion-Related Adverse Events and Renal Failure in Patients Receiving High-Dose Intravenous Polymyxin B

John

Falci

Rigatto

et al. 2018

Antimicrob Agents Chemother

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The use of very high doses of polymyxin B (PMB) against carbapenem-resistant Gram-negative bacilli has been addressed in experiments as a strategy to improve bacterial killing and suppress resistance emergence. However, the toxicities of very high doses in patients are unknown. We conducted a retrospective cohort study assessing patients receiving PMB at>3 mg/kg of body weight/day or a total dose of ≥250 mg/day. The main outcomes were severe infusion-related adverse events according to the Common Terminology Criteria for Adverse Events and the renal failure category of RIFLE criteria for acute kidney injury (AKI) during treatment. A total of 222 patients were included for analysis of infusion-related events. The mean PMB dose was 3.61 ± 0.97 mg/kg/day (median total dose/day = 268 mg). Severe infusion-related adverse events occurred in two patients, resulting in an incidence of 0.9% (95% confidence interval, 0.2 to 3.2%); one was classified as a life-threatening adverse event, and one was classified as a severe adverse event. Renal failure was analyzed in 115 patients, and 25 (21.7%) patients presented renal failure (54 [47.0%] developed any degree of AKI, categorized as risk [27.8%], injury [25.9%], and failure [46.3%]). Treatment with a vasoactive drug, concomitant treatment with nephrotoxic drugs, and baseline creatinine clearance were independent risk factors for renal failure. Neither the PMB daily dose scaled by body weight nor the total daily dose was associated with renal failure. The in-hospital mortality rate was 60% (134 patients): 26% of deaths (57 patients) occurred during treatment, and none occurred during infusion. Our data suggest that high-dose schemes have an acceptable safety profile and could be further tested in clinical trials assessing strategies to improve patient outcomes and minimize the emergence of PMB resistance.

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Section: Discussionsupporting

confidence: 87%

Severe Infusion-Related Adverse Events and Renal Failure in Patients Receiving High-Dose Intravenous Polymyxin B

John

Falci

Rigatto

et al. 2018

Antimicrob Agents Chemother

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“…This is consistent with the literature reports on polymyxin B nephrotoxicity. 9 , 11 , 12 The results showed that polymyxin B could also cause increases in SCr, BUN, and urinary protein. As the experiment is based on the clinical adult dose of polymyxin B, 2.5 mg/kg/q24 h, converted to a dose of 18 mg/kg/q24 h for rats, the SCr and BUN levels of rats in each administration group are not particularly high; moreover, there is a significant fluctuation during the day, and the values of SCr and BUN often fluctuate in the range of high values and normal values during 5 days of continuous administration.…”

Section: Discussionmentioning

confidence: 97%

Effect of Different Dosage Frequency of Polymyxin B on Rat Nephrotoxicity

Sun

Hu²,

Zhang

et al. 2021

DDDT

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Background Polymyxin B, as the final treatment against multidrug-resistant Gram-negative bacilli, is widely used in clinical practice. However, little is known about the nephrotoxicity of polymyxin B. The purpose of this study was to elucidate the relationship between polymyxin B nephrotoxicity and daily administration frequency. Methods Sprague–Dawley rats were randomly divided into three groups: 18 mg/kg/q24 h group (Group A, once daily), 9 mg/kg/q12 h group (Group B, twice daily), and normal saline control group (Group C). The rats were injected subcutaneously for 5 consecutive days with the same daily total dose and different frequency of administration. The serum creatinine (SCr) and blood urea nitrogen (BUN) of each group before administration (0 h), and 8 and 24 h after administration, were measured by tail vein blood sampling. On the sixth day, the rats in each group were killed, the left kidney was taken for pathological section observation, and the results of each group were compared. Results After 96 h of administrated polymyxin B, the total average level of SCr in Group A was 56.98±12.42 μmol/L, that of Group B was 52.02±8.68 μmol/L, and that of Group C was 34.36±5.39 μmol/L. BUN was 9.86±4.58, 10.54±4.08, and 3.55±0.73 mmol/L in Groups A, B, and C, respectively. The daily urinary protein excretion was 5004.45±1333.84 μg in Group A, 4608.04±1444.42 μg in Group B, and 2096.33±215.28 μg in Group C. In addition, according to the observation of pathological slices, compared with Group A, the number of exfoliated and necrotic cells of renal tubules in Group B was higher, and the morphological changes were more serious. Conclusion The experimental results showed that the renal toxicity in rats treated with a twice-daily subcutaneous dose of polymyxin B was higher than that in rats treated with once-daily dose of polymyxin B.

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“…An independent association between duration of polymyxin use and AKI has been reported ( p = 0.037; OR 1.06; 95% CI [1.00–1.12]). With respect to the combination of nephrotoxins, Soares et al. (2017) investigated the incidence of AKI in 115 ICU patients who used polymyxin B plus vancomycin (Group I) or polymyxin B alone (Group II), showing higher incidence of AKI in Group I than in Group II (62.7% vs. 28.5%, p = 0.005).…”

Section: Discussionmentioning

confidence: 99%

Drug therapy and other factors associated with the development of acute kidney injury in critically ill patients: a cross-sectional study

Soares

Mambrini

Botelho

et al. 2018

PeerJ

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BackgroundAcute kidney injury (AKI) is associated with a significant increase in morbidity, mortality, and health care costs. In intensive care units (ICU), AKI is commonly multifactorial and frequently involves diverse factors, such as hypovolemia, sepsis, and the use of nephrotoxic drugs. We aimed to investigate drug therapy and other factors associated with the development of AKI in a Brazilian public hospital.MethodsThis is a cross-sectional study involving critically ill patients at an ICU of a tertiary hospital. All data on sequential serum creatinine (SCr) level, glomerular filtration rate (GFR), and urine output were collected during ICU stay. The primary outcome was the occurrence of AKI assessed by the Acute Kidney Injury Network (AKIN) criterion. Sociodemographics, clinical data and drug therapy were considered as covariates. Factors associated with AKI were assessed using logistic regression.ResultsOverall, 122 participants were included in the study. Median age was 46.0 (interquartile range, IQ = 29.0–69.0) years, with a predominance of men (58.2%). Mean number of prescribed drugs throughout ICU stay was 22.0 ± 9.4. The number of potentially nephrotoxic drugs ranged from two to 24 per patient. A total of 29 (23.8%) ICU patients developed AKI. In the AKI-group, patients were older and showed higher Acute Physiology and Chronic Health Evaluation II (APACHE II) scores at admission, higher rates of sedation, mechanical ventilation, and infection. More drugs in general and specifically more vasoactive drugs were prescribed for AKI group. Patients who developed AKI tended to have extended stays in the ICU and a lower probability of being discharged alive than patients with no AKI development. Model adjustments of logistic regression showed that the number of medications (OR 1.15; 95% CI [1.05–1.27]) was the only factor associated with AKI in this study. This association was independent of drug nephrotoxicity.DiscussionIntensive care is characterized by its complexity that combines unstable patients, severe diseases, high density of medical interventions, and drug use. We found that typical risk factors for AKI showed statistical association on bivariate analysis. The contribution of drug therapy in the occurrence of AKI in medical ICUs reinforces the need for prevention strategies focused on early recognition of renal dysfunction and interventions in drug therapy. These actions would help improve the quality of patient care and ensure progress towards medication safety.

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Polymyxin-B and vancomycin-associated acute kidney injury in critically ill patients

Abstract: Although patients who received Polymyxin B plus vancomycin had more favorable clinical profile and higher previous GFR, they presented a higher AKI incidence than those patients who received Polymyxin B alone. Cumulative Polymyxin B dose > 10 million IU was independently associated to AKI.

Cited by 19 publications

References 27 publications

Severe Infusion-Related Adverse Events and Renal Failure in Patients Receiving High-Dose Intravenous Polymyxin B

Severe Infusion-Related Adverse Events and Renal Failure in Patients Receiving High-Dose Intravenous Polymyxin B

Effect of Different Dosage Frequency of Polymyxin B on Rat Nephrotoxicity

Drug therapy and other factors associated with the development of acute kidney injury in critically ill patients: a cross-sectional study

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