Comparison of the predictive value of area under the curve versus maximum serum concentration of intravenous tobramycin in cystic fibrosis patients treated for an acute pulmonary exacerbation

Abstract

Objectives The primary objective of this study was to compare the therapeutic predictive value of area under the curve (AUC24) versus maximum concentration (Cmax) in cystic fibrosis (CF) patients receiving intravenous (IV) tobramycin for a Pseudomonas aeruginosa (PsA) acute pulmonary exacerbation (APE). Acute kidney injury (AKI) incidence and the relationship between time undetectable and efficacy were also assessed. Methods A retrospective review was conducted in patients aged at least 1 month with a diagnosis of CF receiving IV tobramycin for treatment of a PsA APE and admitted to the University of Kentucky between August 2015 and August 2019. Patients were excluded if they had no growth of PsA on sputum culture or if two postdose tobramycin levels were not obtained following a dose adjustment of ≥20%. Results A total of 44 pediatric and 107 adult patient encounters met inclusion criteria. In patients with therapeutic success (n = 91), 75.8% had an AUC24 ≥80% and 80.3% had a Cmax ≥8 times the highest PsA minimal inhibitory concentration. There was a significant correlation between AUC24 and Cmax (r[149] = 0.727; p < 0.001). AKI incidence was significantly higher in patients receiving IV tobramycin dosed multiple times daily versus at least every 24 h (χ2[1, 151] = 3.9; p = 0.047). Conclusions The results of this study indicate that both AUC24 and Cmax serve as relatively accurate predictors of tobramycin efficacy. Additionally, given the significant increase in incidence of AKI, multidaily dosing of IV tobramycin should be avoided in pediatric and adult patients with CF.

New Recommendations of a Height-Based Dosing Regimen of Tobramycin for Cystic Fibrosis in Adults: A Population Pharmacokinetic Analysis

“…Both ratios have been reported as accurate predictors of tobramycin efficacy. 14 The daily AUC is a significant predictor of tobramycin nephrotoxicity, whereas C min has been largely linked to aminoglycoside nephrotoxicity. 37,38 In addition, the ratio of AUC (corrected for protein binding) to MIC has been found to significantly correlate with improvement in the forced expiratory volume in one-second FEV1.…”

“…12,13 Therefore, pharmacists, recommend an initial weight (WT)-based dosing regimen from ,10 mg/kg to 12.5 mg/kg of tobramycin accompanied by dose monitoring through maximal concentration (C max ) or area under the curve (AUC), as they are both identified as predictors of tobramycin efficacy. 14 Among the antibiotic classes, aminoglycosides exhibit increased total clearance (Cl) in patients with CF. 4 However, WT-based volume of tobramycin distribution has been reported to decrease in adult patients.…”

“…12,13 Therefore, pharmacists, recommend an initial weight (WT)-based dosing regimen from <10 mg/kg to 12.5 mg/kg of tobramycin accompanied by dose monitoring through maximal concentration (C max ) or area under the curve (AUC), as they are both identified as predictors of tobramycin efficacy. 14…”

Optimal Therapeutic Drug Monitoring Strategy for IV Aminoglycosides and IV Vancomycin in People with Cystic Fibrosis: A Systematic Review

“…Of the 4030 records identified in the initial search, 1 study 18 met the inclusion criteria (Figure 1); 2 additional studies were identified in the subsequent search. 19,20 The characteristics of included studies are summarized in Table 1.…”

“…18 The relationship between lung function improvement and Cmax/MIC was not dependent on dosing interval. 18 Landmesser and others 19 conducted a retrospective chart review comparing the predictive value of AUC24 and Cmax for change in absolute FEV1. Of patients who achieved an AUC24 of at least 80 mg*h/L, 75.8% had a return to baseline FEV1, compared with 61.5% of those with an AUC24 less than 80 mg*h/L (p = 0.147).…”