Pharmacokinetics in Patients with Cystic Fibrosis: A Systematic Review of Data Published Between 1999 and 2019

Sutter, Pieter-Jan De; Gasthuys, Elke; Braeckel, Eva Van; Schelstraete, Petra; Biervliet, S. Van; Bocxlaer, Jan Van; Vermeulen, An

doi:10.1007/s40262-020-00932-9

Cited by 25 publications

(51 citation statements)

References 161 publications

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“…Finally, drug bioavailability at the infection site is another important aspect to consider when evaluating (the lack of ) antibiotic efficacy. Pharmacokinetics for certain antibiotics administered to patients with CF through inhalation, orally or intravenously differ from that in healthy controls [170,171]. Focusing on the CF lung microenvironment, the most impactful factor is most likely the altered mucus rheology, which causes diffusion-limiting interactions with antibiotics, as described earlier.…”

Section: Mediators Of the Immune Responsementioning

confidence: 97%

The cystic fibrosis lung microenvironment alters antibiotic activity: causes and effects

et al. 2021

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Chronic airway colonisation by Pseudomonas aeruginosa, a hallmark of cystic fibrosis (CF) lung disease, is associated with increased morbidity and mortality and despite aggressive antibiotic treatment, P. aeruginosa is able to persist in CF airways. In vitro antibiotic susceptibility assays are poor predictors of antibiotic efficacy to treat respiratory tract infections in the CF patient population and the selection of the antibiotic(s) is often made on an empirical base. In the current review, we discuss the factors that are responsible for the discrepancies between antibiotic activity in vitro and clinical efficacy in vivo. We describe how the CF lung microenvironment, shaped by host factors (such as iron, mucus, immune mediators and oxygen availability) and the microbiota, influences antibiotic activity and varies widely between patients. A better understanding of the CF microenvironment and population diversity may thus help improve in vitro antibiotic susceptibility testing and clinical decision making, in turn increasing the success rate of antibiotic treatment.

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Section: Mediators Of the Immune Responsementioning

confidence: 97%

The cystic fibrosis lung microenvironment alters antibiotic activity: causes and effects

et al. 2021

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“…Additionally, previous studies have demonstrated the limitations of oropharyngeal sampling and the chal-lenges associated with this sampling method. 8 For the detection of PA, oropharyngeal sampling compared to bronchoalveolar lavage fluid was more specific than sensitive. For individuals unable to expectorate sputum, the false positive rate was consistently less than 10% resulting in a high negative predictive value for the presence of PA in oropharyngeal sampling.…”

Section: Discussionmentioning

confidence: 99%

“…13 However, sensitivity was variable between 44-75% thus there is a lower positive predictive value for PA in oropharyngeal sampling as well as in the identification of other respiratory isolates. 8,[12][13] Other considerations related to the concordance of sampling includes symptoms and the age of the individual. 8,14 Despite these limitations, the use of oropharyngeal swabs is standard practice among young, non-expectorating children in CF Care Centers.…”

Section: Discussionmentioning

confidence: 99%

“…8,[12][13] Other considerations related to the concordance of sampling includes symptoms and the age of the individual. 8,14 Despite these limitations, the use of oropharyngeal swabs is standard practice among young, non-expectorating children in CF Care Centers. This may become increasingly relevant in the era of highly effective CFTR modulator therapy, as more people with CF are healthier and unable to produce sputum.…”

Section: Discussionmentioning

confidence: 99%

“…7 Additionally, studies have demonstrated there are limitations of oropharyngeal sampling and the challenges associated with this sampling method compared to expectorated sputum. 8 This may contribute to variability with isolate surveillance and resistance trends over time. The combination of bacterial and host factors decreases the efficacy of treatments by impeding drug delivery, altering pharmacokinetics and increasing the risk of antimicrobial resistance.…”

Section: Introductionmentioning

confidence: 99%

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Development and Anaysis of a Cystic Fibrosis Specific Antibiogram

Elson¹,

Meier²,

Swanson³

et al. 2021

Preprint

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BACKGROUND: Antibiotic therapy is essential for the treatment of cystic fibrosis (CF) lung infections. CF-specific airway pathophysiology and frequent antimicrobial exposure increase the risk of resistant infections, creating challenges to antibiotic selection. Antibiotic selection is generally based on previous cultures or hospital-wide antibiograms (HWA); however, most HWA exclude CF isolates. We developed a multi-year CF antibiogram (CFA) to compare with HWA and inform antibiotic selection. METHODS: CF culture data were collected 2015 - 2019 at a single pediatric CF center. All sputum and oropharyngeal swab isolates are included in the CFA. Demographics, microorganism isolates, and susceptibility information are presented. Susceptibilities were reported for methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa (PA), Achromobacter species, Burkholderia species and Stenotrophomonas maltophilia. RESULTS: Over five years, the proportion of all SA isolates having methicillin-resistance was higher in the HWA (32%) than the CFA (28%). The most common gram-negative CF isolate was PA. Both gram-positive and gram-negative microorganisms were less susceptible in the CFA versus the HWA. CF isolates from sputum were less susceptible than oropharyngeal. MSSA and MRSA had significantly lower clindamycin susceptibility in the CFA compared to the HWA (MSSA 71% vs 79%, p<0.0001 and MRSA 39% vs 83%, p<0.0001). For every antimicrobial tested, PA isolates were less susceptible in the CFA compared to the HWA. There did not appear to be significant changes in susceptibility of CF isolates over time. CONCLUSIONS: These findings have clinical implications for empiric antimicrobial selection. A CFA will allow monitoring of resistance over time.

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Effects of Disease on Drug Disposition and Pharmacokinetics

2022

Drug Disposition and Pharmacokinetics

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Pharmacokinetics in Patients with Cystic Fibrosis: A Systematic Review of Data Published Between 1999 and 2019

Cited by 25 publications

References 161 publications

The cystic fibrosis lung microenvironment alters antibiotic activity: causes and effects

The cystic fibrosis lung microenvironment alters antibiotic activity: causes and effects

Development and Anaysis of a Cystic Fibrosis Specific Antibiogram

Effects of Disease on Drug Disposition and Pharmacokinetics

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