Extended-Interval Aminoglycoside Use in Cystic Fibrosis Exacerbation in Children and Young Adults

Safi, Khalid H.; Damiani, Justina M.; Sturza, Julie; Nasr, Samya Z.

doi:10.1177/2333794x16635464

Cited by 3 publications

(3 citation statements)

References 34 publications

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“…In the pediatric and adult literature, concerns with extended interval dosing have also been raised about possible bacterial regrowth during the drug-free interval. 32,33 Although there are several different neonatal empiric gentamicin regimens proposed in the literature, the optimal regimen has not been identified. Efficacy of gentamicin has most commonly been associated with a peak to MIC ratio of 8 to 10:1.…”

Section: Discussionmentioning

confidence: 99%

Development of Gentamicin Resistance During Treatment of Escherichia coli Ventilator-Associated Pneumonia in a Neonate

Newby

2020

Journal of Pharmacy Practice

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A neonate born at 25 + 1/7 weeks developed ventilator-associated pneumonia at 29 + 3/7 weeks post-menstrual age with Escherichia coli that was originally sensitive to gentamicin. After 3 days of treatment with gentamicin, the minimum inhibitory concentration (MIC) changed from less than 1 mg/L to more than 16 mg/L. It appears that suboptimal gentamicin dosing led to the development of gentamicin resistance. As the patient was not improving clinically, the antibiotics were changed once the gentamicin resistance was identified. To minimize resistance and treatment failure, clinicians should consider the patient-specific pharmacokinetic parameters, achieved peak level, and the amount of time the gentamicin level will remain below the MIC of the organism being treated.

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Section: Discussionmentioning

confidence: 99%

Development of Gentamicin Resistance During Treatment of Escherichia coli Ventilator-Associated Pneumonia in a Neonate

Newby

2020

Journal of Pharmacy Practice

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“…While the study demonstrated that aminoglycoside clearance was higher in younger patients, its limitations including study design and small sample size limit its applicability to practice. 29 The TOPIC study was the largest study area. 34 The NINJA program was implemented at multiple centers to reduce AKI in hospitalized children related to nephrotoxic medication exposure.…”

Section: Dosing Strategiesmentioning

confidence: 99%

“…However, there was no discussion on how the change impacted efficacy via FEV 1 or the incidence of nephrotoxicity. While the study demonstrated that aminoglycoside clearance was higher in younger patients, its limitations including study design and small sample size limit its applicability to practice 29 . The TOPIC study was the largest study conducted in both adult and pediatric patients with CF in which PK data was collected systematically.…”

Section: Dosing Strategiesmentioning

confidence: 99%

Aminoglycoside dosing and monitoring for Pseudomonas aeruginosa during acute pulmonary exacerbations in cystic fibrosis

Ochs

Dillman

Caverly

et al. 2021

Pediatric Pulmonology

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Aminoglycosides are commonly used for the treatment of Pseudomonas aeruginosa (PsA) in the setting of acute pulmonary exacerbations (PEx) in pediatric patients with cystic fibrosis (CF). There are controversies and practice differences between institutions related to aminoglycoside dosing and monitoring strategies. The purpose of this review article is to summarize the currently available literature and identify gaps in the literature related to pharmacokinetic parameter goals, aminoglycoside dosing strategies, and methods for monitoring serum aminoglycoside concentrations for treatment of PsA in CF PEx, and throughout will discuss anticipated changes with the increasing availability of highly effective CF transmembrane conductance regulator modulators. This review focuses on tobramycin, as it is the most commonly used aminoglycoside in CF PEx, and will briefly discuss special circumstances surrounding use of amikacin and gentamicin.

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Impact of Patient-Specific Aminoglycoside Monitoring for Treatment of Pediatric Cystic Fibrosis Pulmonary Exacerbations

Hemmann

Woods

Makhlouf

et al. 2022

The Journal of Pediatric Pharmacology and Therapeutics

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OBJECTIVE Aminoglycosides are frequently used for empiric and definitive treatment of cystic fibrosis (CF) pulmonary exacerbations. Various methods have been described for aminoglycoside therapeutic drug monitoring. The objective of this study is to evaluate the effect of patient-specific pharmacokinetic calculations for aminoglycosides used to treat CF pulmonary exacerbations. METHODS Ambidirectional cohort study of patients admitted to a children's hospital from June 1, 2018, through February 28, 2019, and June 1, 2019, through February 8, 2021. The primary outcome was the occurrence of dosing changes after analysis of initial serum concentrations in either group. Secondary outcomes included occurrence of nephrotoxicity, duration of antibiotics, and length of stay. RESULTS Twenty-four patients (75%) in the intervention group versus zero in the control group required dosing adjustments after initial analysis of serum concentrations were completed (p < 0.001). There was not a statistically significant between-group difference for duration of antibiotics in days (median, 14 vs 13.5; Z, 1.07; p = 0.29) or length of stay (median, 11 vs 11; Z, −0.31; p = 0.76). There was also not a statistically significant between-group difference in forced expiratory volume in one second (FEV1) change from admission to discharge (11.4% vs 13.9%; t, 0.61; Degrees of Freedom, 39; p = 0.55). Two patients (6.25%) in the intervention group experienced nephrotoxicity compared with zero patients in the control group (risk difference, 6.25%; 95% CI, −2.14 to 14.64; number needed to harm, 16). CONCLUSIONS Patient-specific pharmacokinetic monitoring led to significantly more dosing changes and was associated with similar patient outcomes as trough-only monitoring. Further studies are needed to identify methods to optimize aminoglycoside dosing and monitoring for these patients with the goal of reducing toxicities while maximizing efficacy.

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Extended-Interval Aminoglycoside Use in Cystic Fibrosis Exacerbation in Children and Young Adults

Cited by 3 publications

References 34 publications

Development of Gentamicin Resistance During Treatment of Escherichia coli Ventilator-Associated Pneumonia in a Neonate

Development of Gentamicin Resistance During Treatment of Escherichia coli Ventilator-Associated Pneumonia in a Neonate

Aminoglycoside dosing and monitoring for Pseudomonas aeruginosa during acute pulmonary exacerbations in cystic fibrosis

Impact of Patient-Specific Aminoglycoside Monitoring for Treatment of Pediatric Cystic Fibrosis Pulmonary Exacerbations

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