Infectious Diseases Pharmacotherapy for Children With Cystic Fibrosis

Molloy, Leah; Nichols, Kristen R.

doi:10.1016/j.pedhc.2015.07.010

Cited by 12 publications

(12 citation statements)

References 93 publications

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“…The 30 mg −1 kg −1 day −1 every 24 hours regimen has also been suggested by other authors and our data support that this regimen may be a valid option for patients with pediatric CF. 40 These results support the fundamental role of TDM, since this ratio was not enough for one-third of our patients, and close monitoring may be useful to optimize the amikacin regimen (Table 4). In addition, all our patients had a satisfactory clinical response and manageable adverse events, which shows that the therapeutic ranges may still have to be better studied.…”

Section: Discussionsupporting

confidence: 74%

“…This is based on the Cmax/MIC ratio (40‐60 mg/L/4 mg/L = 10‐15) for most of our patients. The 30 mg −1 kg −1 day −1 every 24 hours regimen has also been suggested by other authors and our data support that this regimen may be a valid option for patients with pediatric CF . These results support the fundamental role of TDM, since this ratio was not enough for one‐third of our patients, and close monitoring may be useful to optimize the amikacin regimen (Table ).…”

Section: Discussionmentioning

confidence: 99%

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Population pharmacokinetics of amikacin in patients with pediatric cystic fibrosis

Guido

Pérez

Halac

et al. 2019

Pediatric Pulmonology

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Introduction Amikacin is commonly used in patients with pediatric cystic fibrosis (CF) for the treatment of pulmonary exacerbations. Amikacin efficacy is related to maximum plasma concentration/minimum inhibitory concentration (Cmax/MIC) ratio >8. Pharmacokinetic data in patients with pediatric CF are scarce. The aim of this study was to develop a population pharmacokinetic (PopPK) model describing amikacin disposition in patients with pediatric CF. Methods CF patients under 18 years of age with pulmonary exacerbation who received amikacin were enrolled. Patients received different amikacin regimens (30 mg−1 kg−1 day−1 every 8, 12, or 24 hours) depending on the patient's status and hospital protocols. Amikacin serum levels were obtained for therapeutic drug monitoring. PopPK model was developed using MONOLIX Suite‐2018R1 (Lixoft). Results A total of 39 patients (114 amikacin concentrations) were included in this study. Population estimates for the elimination rate constant (k) and the volume of distribution (V) were 0.541 hours−1 and 0.451 L/kg, respectively. Between‐subject and between‐occasion variability were 53% and 16.5% for k and 31% and 22% for V, respectively. Bodyweight was a significant covariate associated with V. Based on simulations, almost 70% of the patients receiving 30 mg−1 kg−1 day−1 every 24 hours would achieve a Cmax/MIC ratio >8 which is an appropriate therapeutic goal while no patient in the other two groups (Q8 and Q12) would achieve that objective. Conclusions The regimen of 30 mg−1 kg−1 day−1 every 24 hours more adequately fulfilled the therapeutic target for amikacin. Although all our patients had good clinical results and a good adverse‐events profile, further studies are necessary to redefine the optimal treatment strategy.

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Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Population pharmacokinetics of amikacin in patients with pediatric cystic fibrosis

Guido

Pérez

Halac

et al. 2019

Pediatric Pulmonology

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“…3 Pediatric CF patients are at a high risk of AG toxicities due to altered membrane permeability and increased lean body mass, causing greater drug distribution throughout the body. 4 Persistent use of high-dose IV AG therapies has been reported to cause ototoxicity in numerous studies, ranging from 8% to 47%. [5][6][7][8][9][10] Hearing loss can significantly influence language and speech development in children, and earlier detection is needed to prevent long-term effects of ototoxicity.…”

Section: What This Study Addsmentioning

confidence: 99%

Cost-effectiveness of implementing routine hearing screening using a tablet audiometer for pediatric cystic fibrosis patients receiving high-dose IV aminoglycosides

Huang

McKinzie

Tak

2021

JMCP

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“…However, the epidemiological cut-off is determined using the susceptibility data from the wild-type population and does not take into consideration any mutant strains [ 13 ], which are commonly encountered in the mucus-obstructed airways of CF patients. Therefore, people with CF bronchiectasis often receive antibiotics in higher doses and for longer duration, compared to non-CF bronchiectasis [ 14 ]. So clinicians cannot rely only on such data for prescribing empirical therapy to the CF patients.…”

Section: Introductionmentioning

confidence: 99%

Comparison of respiratory pathogen colonization and antimicrobial susceptibility in people with cystic fibrosis bronchiectasis versus non-cystic fibrosis bronchiectasis: a protocol for a systematic review

2021

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Background Both cystic fibrosis (CF) and non-cystic fibrosis bronchiectasis are characterized by permanent bronchial dilation, impaired mucociliary clearance, and development of chronic colonization and infection. Although the major airway microbiota in both CF and non-CF bronchiectasis may be similar, there are some differences in clinical and microbiologic features. There may also be differences in antibiotic susceptibility patterns between the CF and non-CF populations. Therefore, analysis and comparison of the microbiota and antibiotic susceptibility pattern in CF bronchiectasis versus non-CF bronchiectasis would help to improve the management of both conditions. Methods Two authors will independently search the electronic databases PubMed, EMBASE, the Cochrane Library, and LIVIVO, for studies reporting bacterial colonization of the respiratory tract in adults and children diagnosed with bronchiectasis in either CF or non-CF. We will include studies examining any respiratory tract specimen, using conventional bacterial culture or other specialized techniques such as molecular methods. We will also examine the antimicrobial susceptibility patterns in people with CF bronchiectasis versus non-CF bronchiectasis. The authors will independently assess the risk of bias in each included study using the Newcastle Ottawa Scale (NOS). We will present the data with descriptive statistics and provide pooled estimates of outcomes, wherever it is feasible to perform meta-analysis. Heterogeneity in studies will be explored by visual inspection of forest plots as well as using the Higgins and Thompson I2 method. We will contact the corresponding authors of studies where data is/are missing and try to obtain the missing data. We will undertake sensitivity analysis to explore the impact of study quality and subgroup analysis based on pre-set criteria. We will prepare a summary of findings’ table and assess the confidence in the evidence using the GRADE methodology. Discussion To date, there are no locally applicable evidence-based guidelines for antimicrobial treatment of non-CF bronchiectasis patients. In general, treatment is based on extrapolation of evidence in people with CF bronchiectasis. An insight into the microbiota and antimicrobial susceptibility patterns in the two conditions would facilitate appropriate rather than empiric antimicrobial therapy and hopefully reduce the burden of antimicrobial resistance created by rampant usage of antibiotics. Systematic review registration The protocol has been registered in PROSPERO on July 26, 2020 (PROSPERO registration number: CRD42020193859).

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Infectious Diseases Pharmacotherapy for Children With Cystic Fibrosis

Cited by 12 publications

References 93 publications

Population pharmacokinetics of amikacin in patients with pediatric cystic fibrosis

Population pharmacokinetics of amikacin in patients with pediatric cystic fibrosis

Cost-effectiveness of implementing routine hearing screening using a tablet audiometer for pediatric cystic fibrosis patients receiving high-dose IV aminoglycosides

Comparison of respiratory pathogen colonization and antimicrobial susceptibility in people with cystic fibrosis bronchiectasis versus non-cystic fibrosis bronchiectasis: a protocol for a systematic review

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