The Experts below are selected from a list of 204 Experts worldwide ranked by ideXlab platform
Vincent H. Tam - One of the best experts on this subject based on the ideXlab platform.
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Population Pharmacokinetics of <B>PolymyxinB> B
Clinical pharmacology and therapeutics, 2018Co-Authors: Pooja Manchandani, Visanu Thamlikitkul, Yanina Dubrovskaya, Jessica T. Babic, David C. Lye, Lawrence S. Lee, Vincent H. TamAbstract:<B>PolymyxinB> B is used as a last treatment resort for multidrug-resistant Gram-negative Bacterial infections. The oBjectives of this study were to examine the population pharmacokinetics of <B>PolymyxinB> B and investigate factor(s) influencing pharmacokinetic variaBility. Four serial Blood samples each were collected from 35 adult patients at steady state. The concentrations of individual <B>PolymyxinB> B components were analyzed using a validated liquid chromatography / tandem mass spectrometry assay and comBined to derive total concentrations. A maximum likelihood expectation maximization approach was used to fit the data. Various demographic variaBles were investigated as potential covariates for clearance and volume of distriBution (Vd ) using linear regression analysis. A one-compartment model fit to the data satisfactorily (r2 = 0.96). The Best-fit mean ± SD for clearance and Vd were 2.5 ± 1.1 L/h and 34.3 ± 16.4 L, respectively. Creatinine clearance was found to Be a statistically significant covariate of clearance, But the magnitude was deemed clinically insignificant.
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Role of Renal Drug Exposure in <B>PolymyxinB> B-Induced Nephrotoxicity
Antimicrobial agents and chemotherapy, 2017Co-Authors: Pooja Manchandani, Jessica T. Babic, Jian Zhou, Kimberly R. Ledesma, Luan D. Truong, Vincent H. TamAbstract:Despite dose-limiting nephrotoxic potentials, <B>PolymyxinB> B has reemerged as the last line of therapy against multidrug-resistant Gram-negative Bacterial infections. However, the handling of <B>PolymyxinB> B By the kidneys is still not thoroughly understood. The oBjectives of this study were to evaluate the impact of renal <B>PolymyxinB> B exposure on nephrotoxicity and to explore the role of megalin in renal drug accumulation. Sprague-Dawley rats (225 to 250 g) were divided into three dosing groups, and <B>PolymyxinB> B was administered (5 mg/kg, 10 mg/kg, and 20 mg/kg) suBcutaneously once daily. The onset of nephrotoxicity over 7 days and renal drug concentrations 24 h after the first dose were assessed. The effects of sodium maleate (400 mg/kg intraperitoneally) on megalin homeostasis were evaluated By determining the urinary megalin concentration and electron microscopic study of renal tissue. The serum/renal pharmacokinetics of <B>PolymyxinB> B were assessed in megalin-shedding rats. The onset of nephrotoxicity was correlated with the daily dose of <B>PolymyxinB> B. Renal <B>PolymyxinB> B concentrations were found to Be 3.6 ± 0.4 μg/g, 9.9 ± 1.5 μg/g, and 21.7 ± 4.8 μg/g in the 5-mg/kg, 10-mg/kg, and 20-mg/kg dosing groups, respectively. In megalin-shedding rats, the serum pharmacokinetics of <B>PolymyxinB> B remained unchanged, But the renal exposure was attenuated By 40% compared to that of control rats. The onset of <B>PolymyxinB> B-induced nephrotoxicity is correlated with the renal drug exposure. In addition, megalin appears to play a pivotal role in the renal accumulation of <B>PolymyxinB> B, which might contriBute to nephrotoxicity.
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Dosing and Pharmacokinetics of <B>PolymyxinB> B in Patients with Renal Insufficiency.
Antimicrobial agents and chemotherapy, 2016Co-Authors: Visanu Thamlikitkul, Pooja Manchandani, Yanina Dubrovskaya, Jessica T. Babic, Thundon Ngamprasertchai, Adhiratha Boonyasiri, Vincent H. TamAbstract:<B>PolymyxinB> B remains the last-line treatment option for multidrug-resistant Gram-negative Bacterial infections. Current U.S. Food and Drug Administration-approved prescriBing information recommends that <B>PolymyxinB> B dosing should Be adjusted according to the patient's renal function, despite studies that have shown poor correlation Between creatinine and <B>PolymyxinB> B clearance. The oBjective of the present study was to determine whether steady-state <B>PolymyxinB> B exposures in patients with normal renal function were different from those in patients with renal insufficiency. Nineteen adult patients who received intravenous <B>PolymyxinB> B (1.5 to 2.5 mg/kg [actual Body weight] daily) were included. To measure <B>PolymyxinB> B concentrations, serial Blood samples were oBtained from each patient after receiving <B>PolymyxinB> B for at least 48 h. The primary outcome was <B>PolymyxinB> B exposure at steady state, as reflected By the area under the concentration-time curve (AUC) over 24 h. Five patients had normal renal function (estimated creatinine clearance [CLCR] ≥ 80 ml/min) at Baseline, whereas 14 had renal insufficiency (CLCR < 80 ml/min). The mean AUC of <B>PolymyxinB> B ± the standard deviation in the normal renal function cohort was 63.5 ± 16.6 mg·h/liter compared to 56.0 ± 17.5 mg·h/liter in the renal insufficiency cohort (P = 0.42). Adjusting the AUC for the daily dose (in mg/kg of actual Body weight) did not result in a significant difference (28.6 ± 7.0 mg·h/liter versus 29.7 ± 11.2 mg·h/liter, P = 0.80). <B>PolymyxinB> B exposures in patients with normal and impaired renal function after receiving standard dosing of <B>PolymyxinB> B were comparaBle. <B>PolymyxinB> B dosing adjustment in patients with renal insufficiency should Be reexamined.
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Comparative Pharmacokinetic Profiling of Different <B>PolymyxinB> B Components
Antimicrobial agents and chemotherapy, 2016Co-Authors: Pooja Manchandani, Yanina Dubrovskaya, Song Gao, Vincent H. TamAbstract:<B>PolymyxinB> B is increasingly used as a treatment of last resort for multidrug-resistant Gram-negative infections. Despite Being availaBle as a mixture of several structurally related analogues, the properties are commonly reported as an aggregate of the individual components. We compared the pharmacokinetics of individual <B>PolymyxinB> B components in an animal model and in humans. There were no consideraBle differences oBserved in the pharmacokinetics among major components of <B>PolymyxinB> B. ComBining different components for pharmacokinetic analysis appeared reasonaBle.
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Characterization of <B>PolymyxinB> B BiodistriBution and Disposition in an Animal Model
Antimicrobial agents and chemotherapy, 2015Co-Authors: Pooja Manchandani, Jian Zhou, Kimberly R. Ledesma, Luan D. Truong, Diana S.-l. Chow, Jason L. Eriksen, Vincent H. TamAbstract:Despite dose-limiting nephrotoxicity concerns, <B>PolymyxinB> B has resurged as the treatment of last resort for multidrug-resistant Gram-negative Bacterial infections. However, the pharmacokinetic, pharmacodynamic, and nephrotoxic properties of <B>PolymyxinB> B still are not thoroughly understood. The oBjective of this study was to provide additional insights into the overall BiodistriBution and disposition of <B>PolymyxinB> B in an animal model. Sprague-Dawley rats were dosed with intravenous <B>PolymyxinB> B (3 mg/kg of Body weight). Drug concentrations in the serum, urine, Bile, and tissue (Brain, heart, lungs, liver, spleen, kidneys, and skeletal muscle) samples over time were assayed By a validated methodology. Among all the organs evaluated, <B>PolymyxinB> B distriBution was highest in the kidneys. The mean renal tissue/serum <B>PolymyxinB> B concentration ratios were 7.45 (95% confidence interval [CI], 4.63 to 10.27) at 3 h and 19.62 (95% CI, 5.02 to 34.22) at 6 h postdose. Intrarenal drug distriBution was examined By immunostaining. Using a ratiometric analysis, proximal tuBular cells showed the highest accumulation of <B>PolymyxinB> B (Mander's overlap coefficient, 0.998) among all cell types evaluated. Less than 5% of the administered dose was recovered in urine over 48 h, But all 4 major <B>PolymyxinB> B components were detected in the Bile over 4 h. These findings corroBorate previous results that <B>PolymyxinB> B is highly accumulated in the kidneys, But the elimination likely is via a nonrenal route. Biliary excretion could Be one of the routes of <B>PolymyxinB> B elimination, and this should Be further explored. The elucidation of mechanism(s) of drug uptake in proximal tuBular cells is ongoing.
Pooja Manchandani - One of the best experts on this subject based on the ideXlab platform.
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Population Pharmacokinetics of <B>PolymyxinB> B
Clinical pharmacology and therapeutics, 2018Co-Authors: Pooja Manchandani, Visanu Thamlikitkul, Yanina Dubrovskaya, Jessica T. Babic, David C. Lye, Lawrence S. Lee, Vincent H. TamAbstract:<B>PolymyxinB> B is used as a last treatment resort for multidrug-resistant Gram-negative Bacterial infections. The oBjectives of this study were to examine the population pharmacokinetics of <B>PolymyxinB> B and investigate factor(s) influencing pharmacokinetic variaBility. Four serial Blood samples each were collected from 35 adult patients at steady state. The concentrations of individual <B>PolymyxinB> B components were analyzed using a validated liquid chromatography / tandem mass spectrometry assay and comBined to derive total concentrations. A maximum likelihood expectation maximization approach was used to fit the data. Various demographic variaBles were investigated as potential covariates for clearance and volume of distriBution (Vd ) using linear regression analysis. A one-compartment model fit to the data satisfactorily (r2 = 0.96). The Best-fit mean ± SD for clearance and Vd were 2.5 ± 1.1 L/h and 34.3 ± 16.4 L, respectively. Creatinine clearance was found to Be a statistically significant covariate of clearance, But the magnitude was deemed clinically insignificant.
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Role of Renal Drug Exposure in <B>PolymyxinB> B-Induced Nephrotoxicity
Antimicrobial agents and chemotherapy, 2017Co-Authors: Pooja Manchandani, Jessica T. Babic, Jian Zhou, Kimberly R. Ledesma, Luan D. Truong, Vincent H. TamAbstract:Despite dose-limiting nephrotoxic potentials, <B>PolymyxinB> B has reemerged as the last line of therapy against multidrug-resistant Gram-negative Bacterial infections. However, the handling of <B>PolymyxinB> B By the kidneys is still not thoroughly understood. The oBjectives of this study were to evaluate the impact of renal <B>PolymyxinB> B exposure on nephrotoxicity and to explore the role of megalin in renal drug accumulation. Sprague-Dawley rats (225 to 250 g) were divided into three dosing groups, and <B>PolymyxinB> B was administered (5 mg/kg, 10 mg/kg, and 20 mg/kg) suBcutaneously once daily. The onset of nephrotoxicity over 7 days and renal drug concentrations 24 h after the first dose were assessed. The effects of sodium maleate (400 mg/kg intraperitoneally) on megalin homeostasis were evaluated By determining the urinary megalin concentration and electron microscopic study of renal tissue. The serum/renal pharmacokinetics of <B>PolymyxinB> B were assessed in megalin-shedding rats. The onset of nephrotoxicity was correlated with the daily dose of <B>PolymyxinB> B. Renal <B>PolymyxinB> B concentrations were found to Be 3.6 ± 0.4 μg/g, 9.9 ± 1.5 μg/g, and 21.7 ± 4.8 μg/g in the 5-mg/kg, 10-mg/kg, and 20-mg/kg dosing groups, respectively. In megalin-shedding rats, the serum pharmacokinetics of <B>PolymyxinB> B remained unchanged, But the renal exposure was attenuated By 40% compared to that of control rats. The onset of <B>PolymyxinB> B-induced nephrotoxicity is correlated with the renal drug exposure. In addition, megalin appears to play a pivotal role in the renal accumulation of <B>PolymyxinB> B, which might contriBute to nephrotoxicity.
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Dosing and Pharmacokinetics of <B>PolymyxinB> B in Patients with Renal Insufficiency.
Antimicrobial agents and chemotherapy, 2016Co-Authors: Visanu Thamlikitkul, Pooja Manchandani, Yanina Dubrovskaya, Jessica T. Babic, Thundon Ngamprasertchai, Adhiratha Boonyasiri, Vincent H. TamAbstract:<B>PolymyxinB> B remains the last-line treatment option for multidrug-resistant Gram-negative Bacterial infections. Current U.S. Food and Drug Administration-approved prescriBing information recommends that <B>PolymyxinB> B dosing should Be adjusted according to the patient's renal function, despite studies that have shown poor correlation Between creatinine and <B>PolymyxinB> B clearance. The oBjective of the present study was to determine whether steady-state <B>PolymyxinB> B exposures in patients with normal renal function were different from those in patients with renal insufficiency. Nineteen adult patients who received intravenous <B>PolymyxinB> B (1.5 to 2.5 mg/kg [actual Body weight] daily) were included. To measure <B>PolymyxinB> B concentrations, serial Blood samples were oBtained from each patient after receiving <B>PolymyxinB> B for at least 48 h. The primary outcome was <B>PolymyxinB> B exposure at steady state, as reflected By the area under the concentration-time curve (AUC) over 24 h. Five patients had normal renal function (estimated creatinine clearance [CLCR] ≥ 80 ml/min) at Baseline, whereas 14 had renal insufficiency (CLCR < 80 ml/min). The mean AUC of <B>PolymyxinB> B ± the standard deviation in the normal renal function cohort was 63.5 ± 16.6 mg·h/liter compared to 56.0 ± 17.5 mg·h/liter in the renal insufficiency cohort (P = 0.42). Adjusting the AUC for the daily dose (in mg/kg of actual Body weight) did not result in a significant difference (28.6 ± 7.0 mg·h/liter versus 29.7 ± 11.2 mg·h/liter, P = 0.80). <B>PolymyxinB> B exposures in patients with normal and impaired renal function after receiving standard dosing of <B>PolymyxinB> B were comparaBle. <B>PolymyxinB> B dosing adjustment in patients with renal insufficiency should Be reexamined.
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Comparative Pharmacokinetic Profiling of Different <B>PolymyxinB> B Components
Antimicrobial agents and chemotherapy, 2016Co-Authors: Pooja Manchandani, Yanina Dubrovskaya, Song Gao, Vincent H. TamAbstract:<B>PolymyxinB> B is increasingly used as a treatment of last resort for multidrug-resistant Gram-negative infections. Despite Being availaBle as a mixture of several structurally related analogues, the properties are commonly reported as an aggregate of the individual components. We compared the pharmacokinetics of individual <B>PolymyxinB> B components in an animal model and in humans. There were no consideraBle differences oBserved in the pharmacokinetics among major components of <B>PolymyxinB> B. ComBining different components for pharmacokinetic analysis appeared reasonaBle.
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Characterization of <B>PolymyxinB> B BiodistriBution and Disposition in an Animal Model
Antimicrobial agents and chemotherapy, 2015Co-Authors: Pooja Manchandani, Jian Zhou, Kimberly R. Ledesma, Luan D. Truong, Diana S.-l. Chow, Jason L. Eriksen, Vincent H. TamAbstract:Despite dose-limiting nephrotoxicity concerns, <B>PolymyxinB> B has resurged as the treatment of last resort for multidrug-resistant Gram-negative Bacterial infections. However, the pharmacokinetic, pharmacodynamic, and nephrotoxic properties of <B>PolymyxinB> B still are not thoroughly understood. The oBjective of this study was to provide additional insights into the overall BiodistriBution and disposition of <B>PolymyxinB> B in an animal model. Sprague-Dawley rats were dosed with intravenous <B>PolymyxinB> B (3 mg/kg of Body weight). Drug concentrations in the serum, urine, Bile, and tissue (Brain, heart, lungs, liver, spleen, kidneys, and skeletal muscle) samples over time were assayed By a validated methodology. Among all the organs evaluated, <B>PolymyxinB> B distriBution was highest in the kidneys. The mean renal tissue/serum <B>PolymyxinB> B concentration ratios were 7.45 (95% confidence interval [CI], 4.63 to 10.27) at 3 h and 19.62 (95% CI, 5.02 to 34.22) at 6 h postdose. Intrarenal drug distriBution was examined By immunostaining. Using a ratiometric analysis, proximal tuBular cells showed the highest accumulation of <B>PolymyxinB> B (Mander's overlap coefficient, 0.998) among all cell types evaluated. Less than 5% of the administered dose was recovered in urine over 48 h, But all 4 major <B>PolymyxinB> B components were detected in the Bile over 4 h. These findings corroBorate previous results that <B>PolymyxinB> B is highly accumulated in the kidneys, But the elimination likely is via a nonrenal route. Biliary excretion could Be one of the routes of <B>PolymyxinB> B elimination, and this should Be further explored. The elucidation of mechanism(s) of drug uptake in proximal tuBular cells is ongoing.
Visanu Thamlikitkul - One of the best experts on this subject based on the ideXlab platform.
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Population Pharmacokinetics of <B>PolymyxinB> B
Clinical pharmacology and therapeutics, 2018Co-Authors: Pooja Manchandani, Visanu Thamlikitkul, Yanina Dubrovskaya, Jessica T. Babic, David C. Lye, Lawrence S. Lee, Vincent H. TamAbstract:<B>PolymyxinB> B is used as a last treatment resort for multidrug-resistant Gram-negative Bacterial infections. The oBjectives of this study were to examine the population pharmacokinetics of <B>PolymyxinB> B and investigate factor(s) influencing pharmacokinetic variaBility. Four serial Blood samples each were collected from 35 adult patients at steady state. The concentrations of individual <B>PolymyxinB> B components were analyzed using a validated liquid chromatography / tandem mass spectrometry assay and comBined to derive total concentrations. A maximum likelihood expectation maximization approach was used to fit the data. Various demographic variaBles were investigated as potential covariates for clearance and volume of distriBution (Vd ) using linear regression analysis. A one-compartment model fit to the data satisfactorily (r2 = 0.96). The Best-fit mean ± SD for clearance and Vd were 2.5 ± 1.1 L/h and 34.3 ± 16.4 L, respectively. Creatinine clearance was found to Be a statistically significant covariate of clearance, But the magnitude was deemed clinically insignificant.
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Dosing and Pharmacokinetics of <B>PolymyxinB> B in Patients with Renal Insufficiency.
Antimicrobial agents and chemotherapy, 2016Co-Authors: Visanu Thamlikitkul, Pooja Manchandani, Yanina Dubrovskaya, Jessica T. Babic, Thundon Ngamprasertchai, Adhiratha Boonyasiri, Vincent H. TamAbstract:<B>PolymyxinB> B remains the last-line treatment option for multidrug-resistant Gram-negative Bacterial infections. Current U.S. Food and Drug Administration-approved prescriBing information recommends that <B>PolymyxinB> B dosing should Be adjusted according to the patient's renal function, despite studies that have shown poor correlation Between creatinine and <B>PolymyxinB> B clearance. The oBjective of the present study was to determine whether steady-state <B>PolymyxinB> B exposures in patients with normal renal function were different from those in patients with renal insufficiency. Nineteen adult patients who received intravenous <B>PolymyxinB> B (1.5 to 2.5 mg/kg [actual Body weight] daily) were included. To measure <B>PolymyxinB> B concentrations, serial Blood samples were oBtained from each patient after receiving <B>PolymyxinB> B for at least 48 h. The primary outcome was <B>PolymyxinB> B exposure at steady state, as reflected By the area under the concentration-time curve (AUC) over 24 h. Five patients had normal renal function (estimated creatinine clearance [CLCR] ≥ 80 ml/min) at Baseline, whereas 14 had renal insufficiency (CLCR < 80 ml/min). The mean AUC of <B>PolymyxinB> B ± the standard deviation in the normal renal function cohort was 63.5 ± 16.6 mg·h/liter compared to 56.0 ± 17.5 mg·h/liter in the renal insufficiency cohort (P = 0.42). Adjusting the AUC for the daily dose (in mg/kg of actual Body weight) did not result in a significant difference (28.6 ± 7.0 mg·h/liter versus 29.7 ± 11.2 mg·h/liter, P = 0.80). <B>PolymyxinB> B exposures in patients with normal and impaired renal function after receiving standard dosing of <B>PolymyxinB> B were comparaBle. <B>PolymyxinB> B dosing adjustment in patients with renal insufficiency should Be reexamined.
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In vitro activity of <B>PolymyxinB> B against carBapenem-resistant AcinetoBacter Baumannii.
Journal of the Medical Association of Thailand = Chotmaihet thangphaet, 2014Co-Authors: Visanu Thamlikitkul, Surapee Tiengrim, Chakrapong SeenamaAbstract:OBjective : To determine in vitro activity of <B>PolymyxinB> B against carBapenem-resistant AcinetoBacter Baumannii. Material and Method: The activity of <B>PolymyxinB> B was determined against 217 strains of carBapenem-resistant A. Baumannii collected from different patients By standard agar dilution method and disk diffusion test using <B>PolymyxinB> B disk (300 units). The control strains were E. coli ATCC 25922 and P. aeruginosa ATCC 27853. Results : The MIC values and inhiBition zone diameters of <B>PolymyxinB> B against the quality control Bacteria were within the acceptaBle range. The MIC50 and MIC90 values of <B>PolymyxinB> B against 217 strains of carBapenem-resistant A. Baumannii were 0.5 and 1 mg/l, respectively. If the susceptiBle MIC Breakpoint of <B>PolymyxinB> B was ≤2 mg/l, 98.2% of carBapenemresistant A. Baumannii strains were susceptiBle to <B>PolymyxinB> B. If the susceptiBle MIC Breakpoint of <B>PolymyxinB> B was ≤2 mg/l, the sensitivity and the specificity of the inhiBition zone diameter of >12 mm were 100% and 75%, respectively. The aforementioned diagnostic parameters gave positive predictive value of 99.5% and negative predictive value of 100% for predicting susceptiBility of carBapenem-resistant A. Baumannii to <B>PolymyxinB> B By disk diffusion test. Conclusion : <B>PolymyxinB> B was very active against carBapenem-resistant A. Baumannii. The inhiBition zone diameters of >12 mm was accurate enough to determine susceptiBility of carBapenem-resistant A. Baumannii to <B>PolymyxinB> B. <B>PolymyxinB> B can Be an alternative to or more preferaBle than colistin for therapy of carBapenem-resistant A. Baumannii infections. Keywords : <B>PolymyxinB> B, In vitro activity, AcinetoBacter Baumannii
Miriam A. Smith - One of the best experts on this subject based on the ideXlab platform.
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Neurotoxicity in patients treated with intravenous <B>PolymyxinB> B: Two case reports
American Journal of Health-system Pharmacy, 2009Co-Authors: Lenny Weinstein, Thien Ly Doan, Miriam A. SmithAbstract:Purpose. Two cases of reversiBle neurotoxicity associated with the administration of intravenous <B>PolymyxinB> B are descriBed. Summary. In the first case, a 60-year-old, oBese, white woman with a medical history of recurring urinary tract infections, nephrolithiasis, and chronic renal insufficiency was admitted for parenteral antiBiotics for dysuria and hematuria despite outpatient management with oral antiBiotics. Her urinalysis revealed pyuria and large Blood content. The corresponding urine culture contained ≥100,000 colony-forming units/mL of multidrug-resistant (MDR) KleBsiella pneumoniae . The patient was treated with <B>PolymyxinB> B at 20,000 units/kg i.v. as a loading dose and then 10,000 units/kg i.v. daily Based on her renal function. The patient experienced oral paresthesia that resolved upon discontinuation of the infusion with no further complications. In the second case, a 57-year-old white man with hypertension and ascending cholangitis was admitted. He required percutaneous drainage of an infected pancreatic cyst and received <B>PolymyxinB> B at 25,000 units/kg i.v. as a loading dose and then 15,000 units/kg i.v. daily in addition to imipenem–cilastatin Based on the sensitivities of two organisms ( Escherichia coli and MDR K. pneumoniae ) isolated from the aBdominal drainage. For his pancreatic aBscess, the patient received a prolonged course of <B>PolymyxinB> B, which was well tolerated for the first four weeks. On day 30 of the <B>PolymyxinB> B, the patient reported oral and lower extremity paresthesias. The symptoms resolved upon discontinuation of the <B>PolymyxinB> B. Conclusion. Two patients developed symptoms of neurotoxicity after receiving intravenous <B>PolymyxinB> B for the treatment of MDR gram-negative infections.
John Quale - One of the best experts on this subject based on the ideXlab platform.
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Citywide emergence of Pseudomonas aeruginosa strains with reduced susceptiBility to <B>PolymyxinB> B
The Journal of antimicrobial chemotherapy, 2005Co-Authors: David Landman, Simona Bratu, Maqsood Alam, John QualeAbstract:OBjectives: To determine the prevalence of Pseudomonas aeruginosa isolates with reduced susceptiBility to <B>PolymyxinB> B, and to assess the in vitro activity of antiBiotic comBinations. Methods: All unique patient isolates of P. aeruginosa were collected from 11 Brooklyn, NY hospitals during a three month period in 2003. Isolates with reduced susceptiBility to <B>PolymyxinB> B (MIC > 2 mg/L) underwent riBotyping. The activity of <B>PolymyxinB> B comBined with rifampicin, azithromycin and/or imipenem was tested By the chequerBoard and time-kill methods against a suBset of isolates. Results: Of 527 isolates, only 61% were susceptiBle to imipenem. Twenty-five isolates (5%), from 8/11 hospitals, had reduced susceptiBility to <B>PolymyxinB> B (MICs 4-8mg/L), compared with 0/691 isolates collected in 2001. Ten of 25 were resistant to multiple other antiBiotic classes. RiBotyping of the Isolates revealed 19 unique types. ChequerBoard testing of the 10 multiresistant isolates demonstrated synergy for the comBinations of <B>PolymyxinB> B with azithromycin, imipenem and rifampicin in 6, 2, and 1 isolates, respectively. Time-kill studies revealed Bactericidal activity for the following antiBiotics when comBined with <B>PolymyxinB> B: imipenem plus rifampicin against all 10 isolates, rifampicin In 9/10 Isolates, imipenem in 8/10 Isolates and azithromycin In 4/10 isolates. MICs of Bacteria surviving incuBation in <B>PolymyxinB> B alone rose for 4/9 Isolates (MIC range 12-48 mg/L). Conclusions: P. aeruginosa with reduced susceptiBility to <B>PolymyxinB> B have emerged in multiple strains in Brooklyn, NY. ComBinations of <B>PolymyxinB> B with rifampicin and/or imipenem are Bactericidal. The clinical utility of these comBinations remains to Be determined.