Work

399Urinary NGAL is Elevated in Hospitalized Cystic Fibrosis Patients with Increased Tobramycin Exposure

Year: 2014

Type: article

Abstract: Background. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is a sensitive marker of kidney injury. It is reabsorbed via the same kidney receptor as tobramycin (tobra) and values could potentially predict changes in drug clearance/exposure during tobra therapy. We examined the relationship between individual tobra pharmacokinetic (PK) parameter estimates and uNGAL values during once daily tobra therapy in CF patients. Methods. Observational study in CF patients receiving once daily IV tobra for exacerbation of bronchopneumonia from October 2012-January 2014. uNGAL and SCr were measured daily. uNGAL was normalized for urine creatinine (UCr) and natural log transformed for comparisons. Tobra PK parameter estimates (AUC0-24, Cmax, CL) were determined using population model-based Bayesian estimation on days on which tobra levels were obtained (N = 141) using clinical PK software (MW/Pharm). We examined the association of log uNGAL concentrations and PK estimates by ordinary least squares regression accounting for subject clustering while adjusting for the time of day of urine collection and the time between tobra dose and urine sampling. We constructed nonparametric ROC curves to determine the optimal uNGAL cutoff which identifies increased tobra exposure (AUC > 125 mg*h/L). Finally, the slope of each subject's log uNGAL values over therapy was calculated using simple regression and correlated with their median PK parameter estimates. Results. 29 patients received 44 tobra courses. Median age was 15.3y (IQR 12.5-19.1) and tobra duration was 10 days (range 5-22). Tobra AUC was associated with increased log uNGAL values (beta = .008, p = .04). Cmax (p = .98) and CL (p = .45) were not associated with log uNGAL. The optimal uNGAL cutoff to identify tobra AUC > 125 mg*h/L by Youden's index was 64.5 ng/mg UCr: sensitivity 76%, specificity 65% (Figure). There was a positive correlation between the slope of log uNGAL during therapy and an individual's median tobra AUC (r = .28, p = .07) but not Cmax (p = .60) or CL (p = .80). Conclusion. Urinary NGAL concentrations are associated with tobramycin exposure (AUC) in patients with CF. Elevated uNGAL may detect increased and supra-therapeutic tobramycin exposure and could be used to augment therapeutic drug management in CF patients at risk for renal injury. Disclosures. All authors: No reported disclosures.

Source: Open Forum Infectious Diseases

DOI: 10.1093/ofid/ofu052.265

Authors: Kevin Downes, Marepalli Rao, Alexander Vinks, Michael Bennett, Stuart Goldstein

Institutions: Cincinnati Children's Hospital Medical Center, University of Cincinnati

Language: English

Topic: Antibiotics Pharmacokinetics and Efficacy

Subfield: Pharmacology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $4,053