Academic literature on the topic 'Polymyxin B administration'
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Journal articles on the topic "Polymyxin B administration"
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Vaara, Martti, Timo Vaara, Janis Kuka, Eduards Sevostjanovs, Solveiga Grinberga, Maija Dambrova, and Edgars Liepinsh. "Excretion of the Polymyxin Derivative NAB739 in Murine Urine." Antibiotics 9, no. 4 (March 27, 2020): 143. http://dx.doi.org/10.3390/antibiotics9040143.
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Extremely multiresistant strains of Enterobacteriaceae are emerging and spreading at a worrisome pace. Polymyxins are used as the last-resort therapy against such strains, in spite of their nephrotoxicity. We have previously shown that novel polymyxin derivatives NAB739 and NAB815 are less nephrotoxic in cynomolgus monkeys than polymyxin B and are therapeutic in murine Escherichia coli pyelonephritis at doses only one-tenth of that needed for polymyxin B. Here we evaluated whether the increased efficacy is due to increased excretion of NAB739 in urine. Mice were treated with NAB739 and polymyxin B four times subcutaneously at doses of 0.25, 0.5, 1, 2, and 4 mg/kg. In plasma, a clear dose–response relationship was observed. The linearity of Cmax with the dose was 0.9987 for NAB739 and 0.975 for polymyxin B. After administration of NAB739 at a dose of 0.25 mg/kg, its plasma concentrations at all tested time points were above 0.5 µg/mL while after administration at a dose of 0.5 mg/kg its plasma concentrations exceeded 1 µg/mL. The Cmax of NAB739 in plasma was up to 1.5-times higher after single (first) administration and up to two-times higher after the last administration when compared to polymyxin B. Polymyxin B was not detected in urine samples even when administered at 4 mg/kg. In contrast, the concentration of NAB739 in urine after single administration at a dose of 0.25 mg/kg was above 1 µg/mL and after administration of 0.5 mg/kg its average urine concentration exceeded 2 µg/mL. At the NAB739 dose of 4 mg/kg, the urinary concentrations were higher than 35 µg/mL. These differences explain our previous finding that NAB739 is much more efficacious than polymyxin B in the therapy of murine E. coli pyelonephritis.
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Iudin, Dmitrii, Natalia Zashikhina, Elena Demyanova, Viktor Korzhikov-Vlakh, Elena Shcherbakova, Roman Boroznjak, Irina Tarasenko, et al. "Polypeptide Self-Assembled Nanoparticles as Delivery Systems for Polymyxins B and E." Pharmaceutics 12, no. 9 (September 11, 2020): 868. http://dx.doi.org/10.3390/pharmaceutics12090868.
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Polymyxins are peptide antibiotics that are highly efficient against many multidrug resistant pathogens. However, the poor stability of polymyxins in the bloodstream requires the administration of high drug doses that, in turn, can lead to polymyxin toxicity. Consequently, different delivery systems have been considered for polymyxins to overcome these obstacles. In this work, we report the development of polymyxin delivery systems based on nanoparticles obtained from the self-assembly of amphiphilic random poly(l-glutamic acid-co-d-phenylalanine). These P(Glu-co-dPhe) nanoparticles were characterized in terms of their size, surface charge, stability, cytotoxicity, and uptake by macrophages. The encapsulation efficiency and drug loading into P(Glu-co-dPhe) nanoparticles were determined for both polymyxin B and E. The release kinetics of polymyxins B and E from nanoformulations was studied and compared in buffer solution and human blood plasma. The release mechanisms were analyzed using a number of mathematical models. The minimal inhibitory concentrations of the nanoformulations were established and compared with those determined for the free antibiotics.
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Dai, Chongshan, Yang Wang, Gaurav Sharma, Jianzhong Shen, Tony Velkov, and Xilong Xiao. "Polymyxins–Curcumin Combination Antimicrobial Therapy: Safety Implications and Efficacy for Infection Treatment." Antioxidants 9, no. 6 (June 9, 2020): 506. http://dx.doi.org/10.3390/antiox9060506.
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The emergence of antimicrobial resistance in Gram-negative bacteria poses a huge health challenge. The therapeutic use of polymyxins (i.e., colistin and polymyxin B) is commonplace due to high efficacy and limiting treatment options for multidrug-resistant Gram-negative bacterial infections. Nephrotoxicity and neurotoxicity are the major dose-limiting factors that limit the therapeutic window of polymyxins; nephrotoxicity is a complication in up to ~60% of patients. The emergence of polymyxin-resistant strains or polymyxin heteroresistance is also a limiting factor. These caveats have catalyzed the search for polymyxin combinations that synergistically kill polymyxin-susceptible and resistant organisms and/or minimize the unwanted side effects. Curcumin—an FDA-approved natural product—exerts many pharmacological activities. Recent studies showed that polymyxins–curcumin combinations showed a synergistically inhibitory effect on the growth of bacteria (e.g., Gram-positive and Gram-negative bacteria) in vitro. Moreover, curcumin co-administration ameliorated colistin-induced nephrotoxicity and neurotoxicity by inhibiting oxidative stress, mitochondrial dysfunction, inflammation and apoptosis. In this review, we summarize the current knowledge-base of polymyxins–curcumin combination therapy and discuss the underlying mechanisms. For the clinical translation of this combination to become a reality, further research is required to develop novel polymyxins–curcumin formulations with optimized pharmacokinetics and dosage regimens.
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Nation, Roger, Maria Rigatto, Diego Falci, and Alexandre Zavascki. "Polymyxin Acute Kidney Injury: Dosing and Other Strategies to Reduce Toxicity." Antibiotics 8, no. 1 (March 14, 2019): 24. http://dx.doi.org/10.3390/antibiotics8010024.
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Polymyxins are valuable antimicrobials for the management of multidrug-resistant Gram-negative bacteria; however, nephrotoxicity associated with these drugs is a very common side effect that occurs during treatment. This article briefly reviews nephrotoxic mechanisms and risk factors for polymyxin-associated acute kidney injury (AKI) and discusses dosing strategies that may mitigate kidney damage without compromising antimicrobial activity. Polymyxins have a very narrow therapeutic window and patients requiring treatment with these drugs are frequently severely ill and have multiple comorbidities, which increases the risk of AKI. Notably, there is a significant overlap between therapeutic and toxic plasma polymyxin concentrations that substantially complicates dose selection. Recent dosing protocols for both colistin and polymyxin B have been developed and may help fine tune dose adjustment of these antibiotics. Minimizing exposure to modifiable risk factors, such as other nephrotoxic agents, is strongly recommended. The dose should be carefully selected, particularly in high-risk patients. The administration of oxidative stress-reducing drugs is a promising strategy to ameliorate polymyxin-associated AKI, but still requires support from clinical studies.
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Hajimohammadi, Ali, Khalil Badiei, Parviz Kheibari, Meherdad Pourjafar, and Aliasghar Chalmeh. "Effects of polymyxin B on clinical signs, serum TNF-α, haptoglobin and plasma lactate concentrations in experimental endotoxaemia in sheep." Journal of Veterinary Research 62, no. 1 (March 30, 2018): 79–85. http://dx.doi.org/10.2478/jvetres-2018-0011.
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AbstractIntroductionThe experiment evaluated the effects of intravenous administration of polymyxin B on experimental endotoxaemia in sheep.Material and MethodsTwenty clinically healthy fat-tailed sheep were randomly divided into: a group treated with 6,000 U/kg of polymyxin B, a group at 12,000 U/kg, and positive and negative controls. Endotoxaemia was induced by intravenous administration of lipopolysaccharide (LPS) fromE.coliserotype O55:B5 at 0.5 μg/kg. polymyxin was infused intravenously along with 2.5 L of isotonic intravenous fluids at 20 mL/kg/h. The positive control group received LPS and 2.5 L of isotonic fluids, the negatives receiving just 2.5 L of isotonic fluids. Clinical signs were evaluated before and at 1.5, 3, 4.5, 6, 24, and 48 h after LPS administration. Blood was also sampled at the denoted hours and serum haptoglobin, tumour necrosis factor-α (TNF-α), and plasma lactate concentrations were assayed.ResultsThe serum concentration of TNF-α in the positive control group increased significantly up to 48 h after LPS administration. The concentration of TNF-α was significantly different from those of the polymyxin B and positive control groups from 3 to 48 h; also, the concentrations of haptoglobin at different times in the polymyxin groups were lower than those of the positive control group and were significant at hours 3 to 48 (P < 0.05). Following the LPS administration, haptoglobin and TNF-α concentrations changed without significant difference between the two polymyxin B groups.ConclusionPolymyxin B (6,000 U/kg) restrained blood lactate concentrations. Furthermore, it significantly improved the clinical signs in endotoxaemic animals, including rectal temperature and heart and respiratory rates. Polymyxin B may be an antiendotoxic in fat-tailed sheep.
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Tarnate, Paul Sherwin. "Rational Use of Polymyxins Against Multi-Drug Resistant Gram-Negative Bacteria." Pediatric Infectious Disease Society of the Philippines Journal 22, no. 1 (May 21, 2021): 3–13. http://dx.doi.org/10.56964/pidspj2021220102.
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The current strategy in treating multi-drug resistant gram-negative bacterial (MDR-GNB) infections is salvage therapy by using polymyxins. However, the beginning emergence of polymyxin resistance should enforce strict antimicrobial stewardship programs to preserve polymyxin efficacy. Knowledge of structural characteristics, pharmacodynamic, and pharmacokinetic profiles of polymyxins, as well as consideration of efficacy, safety, suitability, and cost, will help in the choice of the appropriate polymyxin for therapy. Polymyxin B is the recommended polymyxin for systemic use, while colistin is recommended for lower urinary tract infections, intraventricular, and intrathecal use. Either polymyxin can be used for hospital-acquired and ventilator-associated pneumonia. Combination therapy over monotherapy remains to be advantageous due to synergism and decreased resistance development. The choice of the second drug to be used should be based on full susceptibility, or if unavailable, a drug with the least minimum inhibitory concentration relative to the breakpoint set by the Clinical and Laboratory Standards Institute. Using the mnemonic ESCAPE can also guide physicians in their polymyxin prescription process: (1) Checking if the pathogen is Extensively resistant or multi-drug resistant; (2) checking the patient’s clinical status if compatible with Significant infection; (3) using Combination therapy; (4) ensuring Adequate dosing; (5) Proper preparation and administration of drug; and (6) keeping an Eye for response and adverse effects.
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Young, J. C., T. G. Kurowski, A. M. Maurice, R. Nesher, and N. B. Ruderman. "Polymyxin B inhibits contraction-stimulated glucose uptake in rat skeletal muscle." Journal of Applied Physiology 70, no. 4 (April 1, 1991): 1650–54. http://dx.doi.org/10.1152/jappl.1991.70.4.1650.
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Glucose transport in muscle is activated by contractile activity, an effect that persists in the postexercise state. Polymyxin B, a cyclic decapeptide antibiotic, inhibits the stimulation of glucose uptake in isolated muscle by contractile activity but also decreases tension development in electrically stimulated muscle. The purpose of this study was to determine whether polymyxin B also inhibits contraction-stimulated glucose uptake after in vivo administration of the drug and to examine the relationship between the effects of polymyxin B on tension development and its effects on contraction-stimulated glucose uptake. When polymyxin B was administered to rats in vivo, glucose uptake in muscle after electrical stimulation was decreased, despite the same amount of tension developed as in control rats, indicating an effect of polymyxin B on glucose transport independent of tension development. Our results also indicate that the postexercise increase in glucose uptake is a function of the tension developed by prior contractions. When muscles were perfused with medium containing polymyxin B, this relationship was disrupted. These results provide evidence that polymyxin B causes a decrease in muscle glucose uptake independent of its effects on tension development. The extent to which its effects on glucose uptake are also the result of a diminution in contractile force is uncertain.
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Alvarado Reyes, Yarelis, Raquel Cruz, Julia Gonzalez, Yeiry Perez, and William R. Wolowich. "Incidence of Acute Kidney Injury in Intermittent Versus Continuous Infusion of Polymyxin B in Hospitalized Patients." Annals of Pharmacotherapy 53, no. 9 (April 11, 2019): 886–93. http://dx.doi.org/10.1177/1060028019841898.
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Background: Studies evaluating the risk of developing acute kidney injury (AKI) with different dosing strategies of polymyxin B are limited. Objectives: To compare the incidence of AKI in patients treated with intermittent versus continuous polymyxin B therapy. Secondary objectives included time to onset of AKI, hospital length of stay (LOS), and all-cause hospital mortality. Variables associated with an increased risk of AKI were evaluated. Methods: A retrospective record review was conducted at a single center in Puerto Rico. Adult patients (≥18 years old) treated with polymyxin B (first course) for at least 48 hours from 2013-2015 were evaluated. Patients with a creatinine clearance <10 mL/min and/or on renal replacement were excluded. Results: A total of 69 patients were included: 42 in the continuous infusion and 27 in the intermittent dosing group. Incidence of AKI was not significantly different between the groups (intermittent 41% vs continuous 31%, P = 0.4). No difference was found in the onset of nephrotoxicity, hospital LOS, or all-cause hospital mortality. Variables associated with increased risk of AKI were baseline serum creatinine, age, and intensive care unit admission. Patients with a body mass index (BMI) >25 kg/m2 on polymyxin B via continuous infusion had a significantly higher cumulative incidence of AKI ( P = 0.016). Conclusion and Relevance: No difference in the risk of polymyxin B nephrotoxicity was found between intermittent and continuous infusion administration. Administration of polymyxin B via a continuous infusion may result in a higher risk of AKI in patients with a BMI >25 kg/m2.
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Neiva, Luciana Barros de Moura, Fernanda Teixeira Borges, Mirian Watanabe, Edson de Andrade Pessoa, Dulce Aparecida Barbosa, and Maria de Fatima Fernandes Vattimo. "Nephrotoxicity Of Polymyxin B: Experimental Study In Cells And Implications For Nursing Practice." Revista da Escola de Enfermagem da USP 48, no. 2 (April 2014): 272–77. http://dx.doi.org/10.1590/s0080-6234201400002000011.
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The aim of the study was to characterize the cell damage mechanisms involved in the pathophysiology of cytotoxicity of polymyxin B in proximal tubular cells (LLC - PK1) and discuss about the nurses interventions to identify at risk patients and consider prevention or treatment of nephrotoxicity acute kidney injury. This is a quantitative experimental in vitro study, in which the cells were exposed to 375μM polymyxin B sulfate concentration. Cell viability was determined by exclusion of fluorescent dyes and morphological method with visualization of apoptotic bodies for fluorescence microscopy. Cells exposed to polymyxin B showed reduced viability, increased number of apoptotic cells and a higher concentration of the enzyme lactate dehydrogenase. The administration of polymyxin B in vitro showed the need for actions to minimize adverse effects such as nephrotoxicity.
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Abdelraouf, Kamilia, Jie He, Kimberly R. Ledesma, Ming Hu, and Vincent H. Tam. "Pharmacokinetics and Renal Disposition of Polymyxin B in an Animal Model." Antimicrobial Agents and Chemotherapy 56, no. 11 (August 20, 2012): 5724–27. http://dx.doi.org/10.1128/aac.01333-12.
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ABSTRACTThe increasing prevalence of multidrug-resistant Gram-negative infections has led to the resurgence of systemic polymyxin B, but little is known about its pharmacokinetics. The objective of this study was to characterize the pharmacokinetics and renal disposition of polymyxin B. Eight female Sprague-Dawley rats (weight, 225 to 250 g) were administered a single intravenous polymyxin B dose (4 mg/kg of body weight). Serial serum samples were collected and assayed for major polymyxin B components using a validated ultraperformance liquid chromatography-tandem mass spectrometry method. The best-fit pharmacokinetic parameters of each component were derived and compared using one-way analysis of variance. Cumulative urine was also collected daily for 48 h and assayed for polymyxin B. Kidney drug concentrations were measured at 6 h (n= 3) and 48 h (n= 3) after the same dose. Additionally, three rats were administered 2 doses of intravenous polymyxin B (4 mg/kg) 7 days apart. Serial serum samples were collected pre- and post-renal insufficiency (induced by uranyl nitrate) and assayed for polymyxin B. The pharmacokinetic parameters of the major components did not appear to be significantly different (P> 0.05). Less than 1% of the dose was recovered unchanged in urine collected over 48 h following administration. Therapeutic drug concentrations persisted in kidney tissue at 48 h. The post-renal insufficiency to pre-renal insufficiency ratio of the area under the serum concentration-time curve from time zero to infinity was 1.33 ± 0.04. Polymyxin B components appear to have similar pharmacokinetics. Polymyxin B preferentially persists in kidneys, which suggests a selective uptake process in renal cells. A mechanism(s) other than renal excretion could be involved in polymyxin B elimination, and dosing adjustment in renal insufficiency may not be necessary.