Follow-up survey of the utilization of anti-pseudomonal beta-lactam antibiotics at U.S. cystic fibrosis centers

Fischer, Diana; Namanny, Halee; Zobell, Jeffery T.

doi:10.1002/ppul.23350

Cited by 6 publications

(11 citation statements)

References 3 publications

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“…The use of US Food and Drug Administration (FDA) versus CFF or European consensus approved dosing guidelines (CF dosing) for antipseudomonal β-lactam antibiotics (n = 38) and whether they achieved therapeutic PD indices are shown in Table 4. [18][19][20] For 3 commonly used β-lactam antibiotics, the CF dosing guidelines are much larger than the FDA recommendations. The CF dosing for ceftazidime is 300 mg/kg/day (pediatric) or 3 to 4 g every 6 to 8 hours (adult), whereas FDA dosing guidelines recommend 150 mg/kg/day (pediatric) or 2 g every 8 hours (adult).…”

Section: Resultsmentioning

confidence: 99%

“…17 Although updated Cystic Fibrosis Foundation (CFF) and European consensus guidelines suggest larger dosing regimens to overcome more rapid renal clearance, recent surveys on antipseudomonal β-lactam use found that the dosing regimens used in 38% to 53% of the CF centers are actually below these guidelines. 7,[18][19][20] Prior studies have shown that some CF patients improve with antibacterial therapy, even when treating antibiotic-resistant organisms. 3 This affects clinical practice, because some providers may choose to continue antibiotics despite reported resistance, if the patient shows clinical improvement.…”

Section: Introductionmentioning

confidence: 99%

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Relationship of Pulmonary Outcomes, Microbiology, and Serum Antibiotic Concentrations in Cystic Fibrosis Patients

Hahn¹,

Jensen²,

Fanous³

et al. 2018

The Journal of Pediatric Pharmacology and Therapeutics

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OBJECTIVES To determine the frequency of subtherapeutic exposure to intravenously administered β-lactam antibiotics in a cohort of cystic fibrosis (CF) patients who were treated for a pulmonary exacerbation, and its impact on pulmonary function. METHODS Nineteen CF patients between the ages of 5 and 21 years treated at Children's National Health System for a pulmonary exacerbation were followed between March 2015 and August 2016 in a prospective, longitudinal study. Pharmacokinetic modeling and minimum inhibitory concentrations (MICs) of the involved pathogens were used to determine therapeutic or subtherapeutic β-lactam antibiotic exposure based on the time the antibiotic concentration was above the MIC. Clinical outcomes were measured by spirometry values. RESULTS The 19 participants were treated with a total of 29 courses of antibiotics. The most common β-lactam antibiotics used in a treatment course were ceftazidime (62%) and meropenem (45%). There was no difference in age, CF genotype, or creatinine clearance between the 9 participants (47%) who reached therapeutic concentrations versus the 10 (53%) who did not. Those who achieved sufficiently high antibiotic exposure had more significant improvement of their pulmonary function tests. CONCLUSIONS We found that sufficient antibiotic exposure during treatment of CF pulmonary exacerbations was associated with improved pulmonary function. Moreover, it was impossible to predict, solely from the dosing regimen used, which patients were going to reach therapeutic β-lactam antibiotic serum concentrations. This suggests that CF patients may benefit from closer monitoring of their β-lactam exposure and bacterial MIC for optimal clinical outcomes.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Relationship of Pulmonary Outcomes, Microbiology, and Serum Antibiotic Concentrations in Cystic Fibrosis Patients

Hahn¹,

Jensen²,

Fanous³

et al. 2018

The Journal of Pediatric Pharmacology and Therapeutics

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“…Due to higher beta-lactam antibiotic clearance in CF persons, the CF Foundation (CFF) and the European consensus guidelines recommend higher dosing regimens to achieve the needed serum concentrations 25,26 . However, surveys of CF centers in the US found that IV anti-pseudomonal beta-lactams were dosed below these guidelines 38-53% of the time 18,27 . No studies have evaluated IV beta-lactam antibiotic pharmacokinetics (PK) and pharmacodynamics (PD), specifically T > MIC, on relative bacterial abundance and alpha diversity.…”

mentioning

confidence: 99%

Changes in microbiome diversity following beta-lactam antibiotic treatment are associated with therapeutic versus subtherapeutic antibiotic exposure in cystic fibrosis

Hahn

Fanous²,

Jensen

et al. 2019

Sci Rep

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In persons with cystic fibrosis (CF), decreased airway microbial diversity is associated with lower lung function. Conflicting data exist on the impact of short-term antibiotics for treatment of acute pulmonary exacerbations. However, whether differences in antibiotic exposure impacts airway microbiome changes has not been studied. We hypothesized that subtherapeutic beta-lactam antibiotic exposure, determined by the pharmacokinetics and pharmacodynamics (PK/PD) after intravenous (IV) antibiotic administration, would be associated with different patterns of changes in CF airway microbial diversity. eligible children were enrolled when well; study assessments were performed around the time of pulmonary exacerbation. plasma drug concentrations and bacterial minimum inhibitory concentrations (MICs) were used to determine therapeutic versus subtherapeutic beta-lactam antibiotic exposure. Respiratory samples were collected from children, and extracted bacterial DNA was amplified for the V4 region of the 16S rRNA gene. Twenty children experienced 31 APEs during the study; 45% (n = 14) of antibiotic courses were deemed therapeutic. Those in the therapeutic group had more significant decreases in alpha diversity at end of treatment and post-recovery compared to baseline than those in the subtherapeutic group. therapeutic and subtherapeutic beta-lactam use is associated with different patterns of changes in CF airway microbial diversity following antibiotic administration. More than 30,000 people in the United States are living with cystic fibrosis (CF), a severe autosomal recessive disease that leads to recurrent lung infections and chronic suppurative lung disease associated with significant morbidity and mortality 1,2. Children and adults frequently require hospitalization for severe recurrent lung infections, known as acute pulmonary exacerbations (APE) 3,4. Antibiotic use is typically directed at specific pathogens, such as Pseudomonas aeruginosa 5. However, prior studies have shown that in vitro susceptibilities do not correlate with clinical outcomes 6. This inconsistency may be due in part to the numerous other bacteria such as Prevotella spp., Veillonella spp., and Gemella spp. that have commonly been identified in CF airways by culture-independent sequencing 7-13 .

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“…According to the most recent utilization survey of anti‐pseudomonal beta‐lactams, no Cystic Fibrosis Foundation (CFF)‐accredited care centers reported use of ceftolozane‐tazobactam in the treatment of an APE . It was recently approved by the FDA in 2014 .…”

Section: Efficacy/tolerabilitymentioning

confidence: 99%

“…The PK parameters are listed in Table 1 reported use of ceftolozane-tazobactam in the treatment of an APE. 4 It was recently approved by the FDA in 2014. 2 The FDA-approved dose is 1.5 g IV every 8 h. 2 No efficacy data exists in CF and pediatric patients.…”

Section: Pharmacokinetics/ Pharmacodynamicsmentioning

confidence: 99%

Optimization of anti‐pseudomonal antibiotics for cystic fibrosis pulmonary exacerbations: II. Cephalosporins and penicillins update

Zobell

Epps

Young

2017

Pediatric Pulmonology

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Follow-up survey of the utilization of anti-pseudomonal beta-lactam antibiotics at U.S. cystic fibrosis centers

Cited by 6 publications

References 3 publications

Relationship of Pulmonary Outcomes, Microbiology, and Serum Antibiotic Concentrations in Cystic Fibrosis Patients

Relationship of Pulmonary Outcomes, Microbiology, and Serum Antibiotic Concentrations in Cystic Fibrosis Patients

Changes in microbiome diversity following beta-lactam antibiotic treatment are associated with therapeutic versus subtherapeutic antibiotic exposure in cystic fibrosis

Optimization of anti‐pseudomonal antibiotics for cystic fibrosis pulmonary exacerbations: II. Cephalosporins and penicillins update

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