Duration of intravenous antibiotic therapy in people with cystic fibrosis

Plummer, Amanda; Wildman, Martin J; Gleeson, Tim

doi:10.1002/14651858.cd006682.pub5

Cited by 36 publications

(13 citation statements)

References 65 publications

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“…Studies have looked to find the optimal length of therapy222324 but potential treatment durations are based on empirical evidence. This study used a mathematical model as a way to determine the time to eradication of the infection and therefore the minimum duration of treatment required.…”

Section: Discussionmentioning

confidence: 99%

Optimising Antibiotic Usage to Treat Bacterial Infections

Paterson

Hoyle

Ochoa

et al. 2016

Sci Rep

104

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The increase in antibiotic resistant bacteria poses a threat to the continued use of antibiotics to treat bacterial infections. The overuse and misuse of antibiotics has been identified as a significant driver in the emergence of resistance. Finding optimal treatment regimens is therefore critical in ensuring the prolonged effectiveness of these antibiotics. This study uses mathematical modelling to analyse the effect traditional treatment regimens have on the dynamics of a bacterial infection. Using a novel approach, a genetic algorithm, the study then identifies improved treatment regimens. Using a single antibiotic the genetic algorithm identifies regimens which minimise the amount of antibiotic used while maximising bacterial eradication. Although exact treatments are highly dependent on parameter values and initial bacterial load, a significant common trend is identified throughout the results. A treatment regimen consisting of a high initial dose followed by an extended tapering of doses is found to optimise the use of antibiotics. This consistently improves the success of eradicating infections, uses less antibiotic than traditional regimens and reduces the time to eradication. The use of genetic algorithms to optimise treatment regimens enables an extensive search of possible regimens, with previous regimens directing the search into regions of better performance.

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Section: Discussionmentioning

confidence: 99%

Optimising Antibiotic Usage to Treat Bacterial Infections

Paterson

Hoyle

Ochoa

et al. 2016

Sci Rep

104

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“…Guidelines recommend that pulmonary exacerbations are treated aggressively with a combination of at least two intravenous anti-pseudomonal antibiotics for 14 days [12,13]. However, this practice is based on limited evidence [13].…”

Section: Introductionmentioning

confidence: 99%

Pyrosequencing reveals transient cystic fibrosis lung microbiome changes with intravenous antibiotics

et al. 2014

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Chronic airway infection in adults with cystic fibrosis (CF) is polymicrobial and the impact of intravenous antibiotics on the bacterial community composition is poorly understood. We employed culture-independent molecular techniques to explore the early effects of i.v. antibiotics on the CF airway microbiome.DNA was extracted from sputum samples collected from adult subjects with CF at three time-points (before starting treatment, and at day 3 and day 8-10 of i.v. antibiotics) during treatment of an infective pulmonary exacerbation. Microbial community profiles were derived through analysis of bacterial-derived 16S ribosomal RNA by pyrosequencing and changes over time were compared. 59 sputum samples were collected during 24 pulmonary exacerbations from 23 subjects. Between treatment onset and day 3 there was a significant reduction in the relative abundance of Pseudomonas and increased microbial diversity. By day 8-10, bacterial community composition was similar to pre-treatment. Changes in community composition did not predict improvements in lung function.The relative abundance of Pseudomonas falls rapidly in subjects with CF receiving i.v. antibiotic treatment for a pulmonary exacerbation and is accompanied by an increase in overall microbial diversity. However, this effect is not maintained beyond the first week of treatment. @ERSpublications Changes in the CF microbiome in response to i.v. antibiotics are not sustained despite ongoing antibiotic pressure

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“…Exposures below the TR can lead to therapeutic failure, increased antibiotic resistance, and poor patient outcomes (2,3). To help ensure optimal therapy, a therapeutic exposure must be achieved as quickly as possible (8,9), preferably after the first dose of a treatment course, which can last up to 14 days (10).…”

mentioning

confidence: 99%

Bayesian Estimation of Tobramycin Exposure in Patients with Cystic Fibrosis

Barras

Serisier

Hennig

et al. 2016

Antimicrob Agents Chemother

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cFixed tobramycin (mg/kg) dosing is often inappropriate in patients with cystic fibrosis (CF), as pharmacokinetics are highly variable. The area under the concentration-time curve (AUC) is an exposure metric suited to monitoring in this population. Bayesian strategies to estimate AUC have been available for over 20 years but are not standard practice in the clinical setting. To assess their suitability for use in clinical practice, three AUC estimation methods using limited sampling were compared to measured true exposure by using intensive sampling tobramycin data. Adults prescribed once daily intravenous tobramycin had eight concentrations taken over 24 h. An estimate of true exposure within one dosing interval was calculated using the trapezoidal method and compared to three alternate estimates determined using (i) a two-sample log-linear regression (LLR) method (local hospital practice); (ii) a Bayesian estimate using one concentration (AUC 1 ); and (iii) a Bayesian estimate using two concentrations (AUC 2 ). Each method was evaluated against the true measured exposure by a Bland-Altman analysis. Twelve patients with a median (range) age and weight of 25 (18 to 36) years and 66.5 (51 to 76) kg, respectively, were recruited. There was good agreement between the true exposure and the three alternate estimates of AUC, with a mean AUC bias of <10 mg/liter · h in each case, i.e., ؊8.2 (LLR), 3.8 (AUC 1 ), and 1.0 (AUC 2 ). Bayesian analysis-based and LLR estimation methods of tobramycin AUC are equivalent to true exposure estimation. All three methods may be suitable for use in the clinical setting; however, a one-sample Bayesian method may be most useful in ambulatory patients for which coordinating blood samples is difficult. Suitably powered, randomized clinical trials are required to assess patient outcomes.

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Duration of intravenous antibiotic therapy in people with cystic fibrosis

Cited by 36 publications

References 65 publications

Optimising Antibiotic Usage to Treat Bacterial Infections

Optimising Antibiotic Usage to Treat Bacterial Infections

Pyrosequencing reveals transient cystic fibrosis lung microbiome changes with intravenous antibiotics

Bayesian Estimation of Tobramycin Exposure in Patients with Cystic Fibrosis

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