Effectiveness and Tolerability of A Polymyxin B Dosing Protocol

Esaian, Diana; Dubrovskaya, Yanina; Phillips, Michael; Papadopoulos, John

doi:10.1345/aph.1q294

Cited by 19 publications

(24 citation statements)

References 5 publications

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“…The rate of nephrotoxicity reported in our study is comparable to those from other studies. Previous studies reported overall rates of nephrotoxicity as assessed by RIFLE criteria of between 23% and 60% (5)(6)(7)(9)(10)(11)(12)(13). Studies by Esaian et al (9) and Lam et al (11) reported the rates of nephrotoxicity with PMB once-versus twice-daily dosing as 80% versus 66% and 58% versus 20%, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies reported overall rates of nephrotoxicity as assessed by RIFLE criteria of between 23% and 60% (5)(6)(7)(9)(10)(11)(12)(13). Studies by Esaian et al (9) and Lam et al (11) reported the rates of nephrotoxicity with PMB once-versus twice-daily dosing as 80% versus 66% and 58% versus 20%, respectively. Of note, Esaian et al (9) and Lam et al (11) identified nephrotoxicity as a secondary endpoint and defined it as a 1.5-fold increase in one SCr value within 24 h, in contrast to this study, in which those who were identified in the risk category had at least two consecutive SCr values 1.5 times that of the baseline.…”

Section: Discussionmentioning

confidence: 99%

“…Available data related to the pharmacokinetic/pharmacodynamics (PK/PD) index to predict efficacy indicate that bacterial killing of PMB correlates with the ratio of the area under the concentration-time curve for the free, unbound fraction to the MIC (fAUC/MIC) (3, 4). Since PMB displays linear PK, the dosing schedule appeared to have little impact on PMB bactericidal activity, as the total daily dose (exposure) remained the same.Prior studies used risk, injury, failure, loss, and end-stage renal disease (RIFLE) criteria to access PMB nephrotoxicity and reported overall incidences in the range from 23% up to 60% (1,(5)(6)(7)(8)(9)(10)(11)(12)(13). While the majority of these studies commented on the overall rate of nephrotoxicity, only two studies directly compared the rates of nephrotoxicity with once-versus twice-daily dosing.…”

mentioning

confidence: 99%

“…Prior studies used risk, injury, failure, loss, and end-stage renal disease (RIFLE) criteria to access PMB nephrotoxicity and reported overall incidences in the range from 23% up to 60% (1,(5)(6)(7)(8)(9)(10)(11)(12)(13). While the majority of these studies commented on the overall rate of nephrotoxicity, only two studies directly compared the rates of nephrotoxicity with once-versus twice-daily dosing.…”

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confidence: 99%

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Nephrotoxicity Associated with Intravenous Polymyxin B Once- versus Twice-Daily Dosing Regimen

Okoduwa

Ahmed

Guo

et al. 2018

Antimicrob Agents Chemother

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Nephrotoxicity is a known adverse effect of polymyxin B (PMB). Animal data suggest that once-daily dosing may reduce the rate and delay the onset of acute kidney injury (AKI). In a multicenter retrospective study, we evaluated adult patients with a creatinine clearance (CrCl) of ≥30 ml/min who received ≥48 h of PMB therapy. The primary endpoint was the difference in rate of AKI comparing once- and twice-daily PMB dosing. The secondary endpoints included the time to AKI and the recovery of renal function. Of 273 eligible patients, 100 from each group were matched on the basis of propensity scores. In the matched groups, nephrotoxicity, defined according to risk, injury, failure, loss, and end-stage renal disease (RIFLE) criteria, was more frequent with once- than with twice-daily dosing (47% versus 17%, respectively; = 0.0005). After adjusting for residual differences by multivariate conditional logistic regression, once-daily dosing was more likely to result in nephrotoxicity (adjusted odds ratio, 2.5; 95% confidence interval [CI], 1.413 to 4.541; = 0.002). Among 64 patients who developed AKI, the median onsets were similar between the groups (7 days with once versus 6 days with twice-daily dosing, = 0.095). Of 37 patients who had their serum creatinine evaluated subsequently, 29/37 (78%) had recovery of renal function. No patient required renal replacement therapy. Our findings suggest that AKI is significantly more common with PMB once daily than with twice-daily dosing with no difference in time to AKI. A prospective randomized study is warranted to validate these results.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Nephrotoxicity Associated with Intravenous Polymyxin B Once- versus Twice-Daily Dosing Regimen

Okoduwa

Ahmed

Guo

et al. 2018

Antimicrob Agents Chemother

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“…From January 2009 onwards, polymyxin B dosing was based on the hospital protocol established by our antimicrobial stewardship program: a loading dose of 25,000 units/kg was given on day 1, followed by 25,000 units/kg given every 24 h in patients with normal renal function. Subsequent doses and the dosing interval were adjusted based on CL CR (9).…”

Section: Resultsmentioning

confidence: 99%

Risk Factors for Treatment Failure of Polymyxin B Monotherapy for Carbapenem-Resistant Klebsiella pneumoniae Infections

Dubrovskaya

Chen

Scipione

et al. 2013

Antimicrob Agents Chemother

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I nfections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) have been associated with poor outcomes. An overall mortality rate of 48% is reported for patients with CRKP, compared to 26% for those with carbapenem-susceptible K. pneumoniae infections (1). CRKP isolates confer resistance through the production of K. pneumoniae carbapenemases (KPCs), which are able to hydrolyze all currently available ␤-lactams, including carbapenems (2). Due to additional mechanisms of resistance commonly found in KPC-producing isolates, they often demonstrate resistance to other antimicrobial classes, including fluoroquinolones and aminoglycosides (2, 3). This limits therapeutic choices, as polymyxins (polymyxin B or colistin) and tigecycline may be the only antibiotics that retain in vitro and in vivo microbiological activity.CRKP infections are often treated with combination therapy (4, 5); however, the choice of agents is both limited and challenging. Combination therapy with aminoglycosides, if susceptibility is preserved, carries an increased risk of nephrotoxicity. Due to a high volume of distribution, low blood levels, and high MIC, tigecycline is a "last resort" option, particularly for bloodstream infections. High MICs of carbapenems preclude achieving therapeutic levels even with pharmacodynamically optimized dosing strategies. Although in vitro synergy against CRKP has been observed when polymyxin B is used in combination with rifampin, cefepime, aminoglycosides, carbapenems, or tigecycline, testing methods are nonstandardized, and therefore the clinical effect of synergy remains unclear (3,(6)(7)(8). Limited data have demonstrated survival benefits of combination therapy using polymyxin B or colistin with carbapenems and/or tigecycline for patients with CRKP bacteremia (4, 5). Given the frequently encountered challenges of combination therapy, we aimed to describe the outcomes for patients with CRKP infections treated with polymyxin B monotherapy and to identify risk factors for treatment failure. MATERIALS AND METHODSStudy design. This was a retrospective study in a tertiary care academic medical center in New York City. The study population included adult patients (aged Ն18 years) with CRKP infections who received polymyxin B monotherapy for Ն72 h. Only the first treatment course was included.Microbiology. Cases were identified from a microbiology lab report of CRKP isolates from 1 January 2007 to 15 August 2011 and by review of medical records. The Vitek-2 system (bioMérieux) used by our microbiology laboratory has built-in analysis software (version R05.01) that enables it to identify resistance phenotypes. Isolates were included if the ertapenem/imipenem MIC was reported as resistant by Vitek-2. For tigecycline and polymyxin B, susceptibility was defined as an MIC of Յ2 mg/liter by Etest, according to Food and Drug Administration (FDA) breakpoints for Enterobacteriaceae and Clinical and Laboratory Standards Institute (CLSI) breakpoints for Acinetobacter baumannii, respectively. Data collection. Patient...

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Mid‐dosing interval concentration is important for polymyxin B exposure and acute kidney injury in critically ill patients

Wang,

Li,

Huang

et al. 2023

CPT Pharmacom & Syst Pharma

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This study aimed to evaluate the association between polymyxin B (PMB) exposure and acute kidney injury (AKI) and analyze the risk factors for PMB‐induced AKI in critically ill patients. Plasma concentrations of PMB were determined using an ultra‐performance liquid chromatography‐tandem mass spectrometer in intensive care unit patients who were administered PMB. Univariate and multivariate analyses were conducted to identify risk factors. A receiver operating characteristic curve was constructed to assess the discriminant power of the factors and to identify the cut‐off value for AKI. The white blood cell count and estimated area under the concentration–time curve (AUC) of patients administered PMB were independent risk factors for PMB‐induced AKI, where AUC were calculated using a first‐order pharmacokinetic equation based on the mid‐dosing interval concentration (C1/2t) and peak concentration. The area under the receiver operating characteristic curve of the final model was 0.805 (95% confidence interval 0.690–0.921). The cut‐off value for the combined predictor was 0.57. Alternatively, when using C1/2t, which was strongly correlated with AUC, as the only independent risk factor, the analysis showed that the 3.47 μg/mL threshold provides favorable differentiation between the AKI and non‐AKI groups. These results provide insightful information for TDM‐guiding PMB dosing in the clinical practice.

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Effectiveness and Tolerability of A Polymyxin B Dosing Protocol

Cited by 19 publications

References 5 publications

Nephrotoxicity Associated with Intravenous Polymyxin B Once- versus Twice-Daily Dosing Regimen

Nephrotoxicity Associated with Intravenous Polymyxin B Once- versus Twice-Daily Dosing Regimen

Risk Factors for Treatment Failure of Polymyxin B Monotherapy for Carbapenem-Resistant Klebsiella pneumoniae Infections

Mid‐dosing interval concentration is important for polymyxin B exposure and acute kidney injury in critically ill patients

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