Clinical features and mortality of patients on renal replacement therapy receiving polymyxin B

Rigatto, Maria Helena; Falci, Diego Rodrigues; Lopes, Natane Tenedini; Zavascki, Alexandre Prehn

doi:10.1016/j.ijantimicag.2015.11.007

Cited by 23 publications

(26 citation statements)

References 18 publications

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“…Schemes of high-dose PMB to overcome the emergence of resistance to this antibiotic during exposure have been evaluated in in vitro infection models, with promising results (14)(15)(16)(17). Moreover, few observational studies have suggested that increased doses might be associated with improved clinical outcomes (8)(9)(10)18). Nonetheless, toxicity, particularly that related to the infusion of such high doses, has not been addressed so far.…”

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

“…Some clinical studies with PMB have shown that higher doses, most within the upper limit of the recommended range, have been associated with lower rates of mortality (8)(9)(10). Despite this, unfavorable clinical outcome rates are still considered unacceptably high (8)(9)(10). In addition, resistance to both polymyxins has increasingly been reported, and in vitro studies have shown that the emergence of resistance is relatively common even by isolates exposed to polymyxin concentrations similar to those expected in vivo after the administration of an adequate dose of polymyxins (11)(12)(13).…”

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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: Discussionmentioning

confidence: 99%

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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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“…Clinical data also suggest that dose reductions in patients on CVVHD can potentially lead to underexposure and increased risk of poor outcomes . Higher total daily doses were associated with lower 30‐day mortality in bivariate analysis (p=0.04), and a total daily dose of 200 mg or more (equivalent to 2 million IU or more) was associated with a lower risk of 30‐day mortality in multivariate analysis (p=0.02) . Thus dose reductions for patients receiving renal replacement therapy are not only unwarranted based on the limited amount of PK data, but the clinical evidence suggests they might potentially be harmful to patients.…”

Section: Clinical Questions and Recommendationsmentioning

confidence: 99%

International Consensus Guidelines for the Optimal Use of the Polymyxins: Endorsed by the American College of Clinical Pharmacy (ACCP), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of America (IDSA), International Society for Anti‐infective Pharmacology (ISAP), Society of Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP)

et al. 2019

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The polymyxin antibiotics colistin (polymyxin E) and polymyxin B became available in the 1950s and thus did not undergo contemporary drug development procedures. Their clinical use has recently resurged, assuming an important role as salvage therapy for otherwise untreatable gram‐negative infections. Since their reintroduction into the clinic, significant confusion remains due to the existence of several different conventions used to describe doses of the polymyxins, differences in their formulations, outdated product information, and uncertainties about susceptibility testing that has led to lack of clarity on how to optimally utilize and dose colistin and polymyxin B. We report consensus therapeutic guidelines for agent selection and dosing of the polymyxin antibiotics for optimal use in adult patients, as endorsed by the American College of Clinical Pharmacy (ACCP), Infectious Diseases Society of America (IDSA), International Society of Anti‐Infective Pharmacology (ISAP), Society for Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP). The European Society for Clinical Microbiology and Infectious Diseases (ESCMID) endorses this document as a consensus statement. The overall conclusions in the document are endorsed by the European Committee on Antimicrobial Susceptibility Testing (EUCAST). We established a diverse international expert panel to make therapeutic recommendations regarding the pharmacokinetic and pharmacodynamic properties of the drugs and pharmacokinetic targets, polymyxin agent selection, dosing, dosage adjustment and monitoring of colistin and polymyxin B, use of polymyxin‐based combination therapy, intrathecal therapy, inhalation therapy, toxicity, and prevention of renal failure. The treatment guidelines provide the first ever consensus recommendations for colistin and polymyxin B therapy that are intended to guide optimal clinical use.

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“…Correcting these abnormalities might help lower the incidence of renal injury with polymyxin B. In view of this, Rigatto et al [56] studied mortality outcomes in patients of renal replacement therapy (RRT). In 88 RRT patients receiving polymyxin B (1.5 to 3 mg/kg/day) for over 48 hours, 30-day mortality was 51.1%.…”

Section: Efficacy Of Polymyxin B: Combination Therapymentioning

confidence: 99%

Resurgence of Polymyxin B for MDR/XDR Gram-Negative Infections: An Overview of Current Evidence

Garg

Singh

Juneja

et al. 2017

Critical Care Research and Practice

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Clinical features and mortality of patients on renal replacement therapy receiving polymyxin B

Cited by 23 publications

References 18 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

Resurgence of Polymyxin B for MDR/XDR Gram-Negative Infections: An Overview of Current Evidence

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