A survey of the utilization of anti‐pseudomonal beta‐lactam therapy in cystic fibrosis patients

Zobell, Jeffery T.; Young, David C.; Waters, C. Dustin; Ampofo, Krow; Cash, Jared; Marshall, Bruce C.; Olson, Jared; Chatfield, Barbara A.

doi:10.1002/ppul.21467

Cited by 39 publications

(71 citation statements)

References 13 publications

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“…4 According to recent surveys, the most commonly used intravenous antipseudomonal antibiotic classes were beta-lactams (98%) and aminoglycosides (61%-94.3%). [5][6][7] These surveys also elicited interesting results regarding the dosage strategies currently used by care centers. [5][6][7] Previous surveys of CF centers revealed that recommended doses and dosage regimens are not used by a substantial number of CF centers despite CFF, European, and UK CF Trust Working Group recommendations, and literature confirming the efficacy and safety of larger than Food and Drug Administration-approved doses for beta-lactam agents and once-daily aminoglycosides.…”

Section: Introductionmentioning

confidence: 99%

“…[5][6][7] These surveys also elicited interesting results regarding the dosage strategies currently used by care centers. [5][6][7] Previous surveys of CF centers revealed that recommended doses and dosage regimens are not used by a substantial number of CF centers despite CFF, European, and UK CF Trust Working Group recommendations, and literature confirming the efficacy and safety of larger than Food and Drug Administration-approved doses for beta-lactam agents and once-daily aminoglycosides. [8][9][10] Possible explanations may include concern for dose-related adverse effects incurred from larger doses, lack of familiarity with dosage guidelines among CF practitioners, lack of understanding of fundamental pharmacokinetic/ pharmacodynamics principles, lack of a dedicated CF pharmacist, and the use of published dosage references which do not contain these doses.…”

Section: Introductionmentioning

confidence: 99%

“…[8][9][10] Possible explanations may include concern for dose-related adverse effects incurred from larger doses, lack of familiarity with dosage guidelines among CF practitioners, lack of understanding of fundamental pharmacokinetic/ pharmacodynamics principles, lack of a dedicated CF pharmacist, and the use of published dosage references which do not contain these doses. [5][6][7] These surveys suggest that additional education and implementation strategies are needed to assist CF practitioners in optimizing the treatment of APEs.…”

Section: Introductionmentioning

confidence: 99%

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Tobramycin and Beta-Lactam Antibiotic Use in Cystic Fibrosis Exacerbations: A Pharmacist Approach

Zobell

Epps

Kittell

et al. 2016

The Journal of Pediatric Pharmacology and Therapeutics

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OBJECTIVES: Survey suggests that recommended doses and dosage regimens for antipseudomonal antibiotics for the treatment of acute pulmonary exacerbations in cystic fibrosis (CF) patients are not used, and one way to address these disparities is the involvement of pharmacists who are dedicated to CF. This is the first survey specifically designed for pharmacists at Cystic Fibrosis Foundation (CFF)-accredited centers to identify how tobramycin and antipseudomonal beta-lactams are being used. The purpose of this survey is to quantify this information and to promote future study to allow for implementation of tobramycin and beta-lactam dosage and monitoring standardization. METHODS: An anonymous national cross-sectional survey of pharmacists that are affiliated with CFFaccredited programs was performed using Qualtrics.com. RESULTS: The survey had a 48.5% response rate. Most pediatric pharmacists (78.6%) report using extendedinterval tobramycin dosage. The most common reported starting dosage was 10 mg/kg every 24 hours; most centers aim for a maximum serum concentration (C max ) between 20 and 40 mg/L (78.6%). A total of 26 adult pharmacists reported using extended-interval dosage (96%), using an initial dosage of 10 mg/kg/ day. The most common parameters used to adjust dosage were C max and area under the curve (AUC; 31%); the C max goal was 20 to 40 mg/L (84.2%). Most respondents (79%) report using beta-lactams in combination with tobramycin. Extended-infusion and continuous-infusion beta-lactams were used more in adults than pediatric patients. CONCLUSIONS: Most CF pharmacists report using extended-interval tobramycin. With the information from this survey, the establishment of future consensus recommendations by pharmacists for optimal and consistent tobramycin and antipseudomonal beta-lactam dosage and monitoring strategies needs to be considered.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Tobramycin and Beta-Lactam Antibiotic Use in Cystic Fibrosis Exacerbations: A Pharmacist Approach

Zobell

Epps

Kittell

et al. 2016

The Journal of Pediatric Pharmacology and Therapeutics

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“…This major beta-lactam antibiotic, which has been on the market for many years, represents one of the main agents to treat acute pulmonary exacerbations (APE). In a recent survey, devoted to utilization of antipseudomonal beta-lactam antibiotics in the treatment of APE among Cystic Fibrosis Foundation-accredited care centers, ceftazidime appears as the most used beta-lactam analog, comprising 74/167 (44%) of all infusions, whether intermittent or extended (1).…”

mentioning

confidence: 99%

How To Minimize Toxic Exposure to Pyridine during Continuous Infusion of Ceftazidime in Patients with Cystic Fibrosis?

Bourget¹,

Amin

Dupont³

et al. 2014

Antimicrob Agents Chemother

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Ceftazidime is particularly efficient against Pseudomonas aeruginosa in cystic fibrosis patients. Thus, the spontaneous production of pyridine, which is a toxic product, raises some concern. Our aim was to examine the kinetics of degradation of ceftazidime in portable infusion pumps either at 4°C, 22°C, or 33°C and to propose some recommendations in order to reduce the pyridine exposure. Two administration models were studied in vitro. In model 1, we administered 12 g of ceftazidime infused over 23 h (once-daily infusion) compared to 6 g infused over 11.5 h in model 2 (twice-daily regimen). Samples were collected at 0 h and then every 4 and 2 h after the shaping of portable infusion pumps in models 1 and 2, respectively. Both ceftazidime and pyridine were analyzed using an ultraviolet high-performance liquid chromatograph. Production of pyridine is highly depending on the temperature. The in situ production of pyridine per day of treatment decreases at a ratio close to 1/6 and 1/3 between 33°C and 4°C in models 1 and 2, respectively. Regardless of the conditions, the production of pyridine is significantly lower in model 2, whereas the total delivery amount of ceftazidime is significantly higher at 4°C and 33°C compared to that in model 1. According to a the precautionary principle, these findings lead to three major recommendations: (i) exposing a solution of ceftazidime to over 22°C should be strictly avoided, (ii) a divided dose of 6 g over 11.5 h instead of a once-daily administration is preferred, and (iii) infusion should be administered immediately after reconstitution.

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“…Additionally, the device is not limited to the one-compartment pharmacokinetic model described in the present study but can also accommodate arbitrary pharmacokinetic profiles and alternative dosing strategies, such as extended or continuous infusions as well as multiple-antibiotic dosing. Meropenem, a carbapenem antibiotic, was chosen for the initial studies because of its clinical application in the treatment of multidrugresistant P. aeruginosa, particularly P. aeruginosa infections in the lungs of cystic fibrosis patients, and the human PK profile and planktonic cell PD parameters of meropenem have already been well described (10,11,24,(36)(37)(38). Future studies will include additional antibiotic classes targeting P. aeruginosa, including aminoglycosides and fluoroquinolones, as well as combination drug therapy targeting different spatial regions of the biofilm.…”

Section: Discussionmentioning

confidence: 99%

New In Vitro Model To Study the Effect of Human Simulated Antibiotic Concentrations on Bacterial Biofilms

Haagensen

Verotta

Huang

et al. 2015

Antimicrob Agents Chemother

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A new in vitro pharmacokinetic/pharmacodynamic simulator for bacterial biofilms utilizing flow cell technology and confocal laser scanning microscopy is described. The device has the ability to simulate the changing antibiotic concentrations in humans associated with intravenous dosing on bacterial biofilms grown under continuous culture conditions. The free drug concentrations of a single 2-g meropenem intravenous bolus dose and first-order elimination utilizing a half-life of 0.895 h (elimination rate constant, 0.776 h ؊1 ) were simulated. The antibacterial activity of meropenem against biofilms of Pseudomonas aeruginosa PAO1 and three clinical strains isolated from patients with cystic fibrosis was investigated. Additionally, the effect of meropenem on PAO1 biofilms cultured for 24 h versus that on biofilms cultured for 72 h was examined. Using confocal laser scanning microscopy, rapid biofilm killing was observed in the first hour of the dosing interval for all biofilms. However, for PAO1 biofilms cultured for 72 h, only bacterial subpopulations at the periphery of the biofilm were affected, with subpopulations at the substratum remaining viable, even at the conclusion of the dosing interval. The described model is a novel method to investigate antimicrobial killing of bacterial biofilms using human simulated concentrations.

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A survey of the utilization of anti‐pseudomonal beta‐lactam therapy in cystic fibrosis patients

Cited by 39 publications

References 13 publications

Tobramycin and Beta-Lactam Antibiotic Use in Cystic Fibrosis Exacerbations: A Pharmacist Approach

Tobramycin and Beta-Lactam Antibiotic Use in Cystic Fibrosis Exacerbations: A Pharmacist Approach

How To Minimize Toxic Exposure to Pyridine during Continuous Infusion of Ceftazidime in Patients with Cystic Fibrosis?

New In Vitro Model To Study the Effect of Human Simulated Antibiotic Concentrations on Bacterial Biofilms

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