Clinical considerations for optimal use of the polymyxins: A focus on agent selection and dosing

Pogue, Jason M.; Ortwine, Jessica; Kaye, Keith S.

doi:10.1016/j.cmi.2017.02.023

Cited by 63 publications

(43 citation statements)

References 22 publications

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“…The dose of colistin was 5 mg/kg colistin base activity loading, followed by 5 mg/kg/day colistin base activity divided over 8 or 12 h in patients with normal renal function. For those with impaired renal function, the dosage was adjusted according to renal function, as previously described (25,26). The loading dose of tigecycline was 100 mg, followed by a maintenance dose of 50 mg every 12 h. The all-cause 14-day and 30-day mortality rates were used as the endpoints and were defined as death occurring within 14 and 30 days after the date of bacteremia onset, respectively.…”

Section: Methodsmentioning

confidence: 99%

Multicenter Study of Clinical Features of Breakthrough Acinetobacter Bacteremia during Carbapenem Therapy

Lee

Wang

Kuo

et al. 2017

Antimicrob Agents Chemother

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Breakthrough bacteremia during carbapenem therapy is not uncommon, and it creates therapeutic dilemmas for clinicians. This study was conducted to evaluate the clinical and microbiological characteristics of breakthrough bacteremia during carbapenem therapy and to assess the efficacy of various antimicrobial therapies. We analyzed 100 adults who developed breakthrough bacteremia during carbapenem therapy at 4 medical centers over a 6-year period. Their 30-day mortality rate was 57.0%, and the carbapenem resistance rate of their isolates was 87.0%. Among patients with carbapenem-resistant bacteremia, breakthrough bacteremia during carbapenem therapy was associated with a significantly higher 14-day mortality (51.7% versus 37.4%, respectively; = 0.025 by bivariate analysis) and a higher 30-day mortality ( = 0.037 by log rank test of survival analysis) than in the nonbreakthrough group. For the treatment of breakthrough bacteremia during carbapenem therapy, tigecycline-based therapy was associated with a significantly higher 30-day mortality (80.0%) than those with continued carbapenem therapy (52.5%) and colistin-based therapy (57.9%) by survival analysis ( = 0.047 and 0.045 by log rank test, respectively). Cox regression controlling for confounders, including severity of illness indices, demonstrated that treatment with tigecycline-based therapy for breakthrough bacteremia was an independent predictor of 30-day mortality (hazard ratio, 3.659; 95% confidence interval, 1.794 to 7.465; < 0.001). Patients with breakthrough bacteremia during carbapenem therapy posed a high mortality rate. Tigecycline should be used cautiously for the treatment of breakthrough bacteremia that develops during carbapenem therapy.

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Section: Methodsmentioning

confidence: 99%

Multicenter Study of Clinical Features of Breakthrough Acinetobacter Bacteremia during Carbapenem Therapy

Lee

Wang

Kuo

et al. 2017

Antimicrob Agents Chemother

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“…Although weight‐based dosing algorithms were proposed as alternatives in the U.S. package insert, such as those in a current RCT of colistin, https://clinicaltrials.gov/ct2/show/NCT01597973?term=NCT01597973&rank=1 . PK data do not support the need for weight‐based dosing.…”

Section: Clinical Questions and Recommendationsmentioning

confidence: 99%

“…Even with the daily doses proposed for patients with Cl cr greater than 90 mL/minute (Table 2), only 30-40% of patients are expected to achieve a plasma colistin C ss,avg of 2 mg/L or more, 6, 61 although almost 80% of such patients may achieve a C ss,avg of 1 mg/L or greater. 6 Although weight-based dosing algorithms were proposed as alternatives in the U.S. package insert, 69 PK data do not support the need for weight-based dosing.…”

Section: What Should My Initial Daily Maintenance Dose Of Cms Be mentioning

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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“…The colistin loading dose was 5 mg/kg colistin base activity, followed by 5 mg/kg/d colistin base activity divided over 8 or 12 hours in patients with normal renal function. For those with impaired renal function, the dosage was adjusted according to renal function as previously described [19,20]. The loading dose of tigecycline was 100 mg, followed by a maintenance dose of 50 mg every 12 hours.…”

Section: Study Variables and De Nitionsmentioning

confidence: 99%

Influence of Severity of Infection on the Effect of Appropriate Antimicrobial Therapy for Acinetobacter baumannii Bacteremic Pneumonia

Kang

How

Wang

et al. 2020

Preprint

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BackgroundThe impact of appropriate antimicrobial therapy for A. baumannii bacteremic pneumonia has not been well established due to the inclusion of the three phenotypically indistinguishable Acinetobacter species and confounding factors including underlying diseases and severity of infection. This retrospective study aimed to evaluate the impact of appropriate antimicrobial therapy on 14-day mortality in A. baumannii bacteremic pneumonia patients after adjusting for risk factors. MethodsThis study was conducted at five medical centers in Taiwan between July 2012 and June 2016. A. baumannii species identification was performed using reference molecular methods. Risk factors for 14-day mortality were analyzed via logistic regression. The interaction between the Acute Physiology and Chronic Health Evaluation (APACHE) II score and appropriate antimicrobial therapy was assessed using the logistic model. ResultsA total of 336 patients with monomicrobial A. baumannii bacteremic pneumonia were included in this study. The overall 14-day mortality rate was 47.3%. The crude mortality of appropriate antimicrobial therapy was 35.9% (57 of 151 patients). Appropriate antimicrobial therapy was associated with a lower mortality after multivariate adjustment (odds ratio [OR], 0.57; 95% confidence interval [CI], 0.34-0.97; p = 0.04), and the effect was influenced by APACHE II score (OR for interaction term, 0.0098; 95% CI, 0.0005-0.1885; p = 0.002). Further analysis demonstrated that appropriate antimicrobial therapy significantly reduced 14-day mortality among the patients with an APACHE II score >35 (OR 0.0098; 95% CI 0.0005-0.1885). ConclusionAppropriate antimicrobial therapy decreases 14-day mortality of the most severely ill patients with A. baumannii bacteremic pneumonia.

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Clinical considerations for optimal use of the polymyxins: A focus on agent selection and dosing

Cited by 63 publications

References 22 publications

Multicenter Study of Clinical Features of Breakthrough Acinetobacter Bacteremia during Carbapenem Therapy

Multicenter Study of Clinical Features of Breakthrough Acinetobacter Bacteremia during Carbapenem Therapy

Influence of Severity of Infection on the Effect of Appropriate Antimicrobial Therapy for Acinetobacter baumannii Bacteremic Pneumonia

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