Once-daily versus multiple-daily dosing with intravenous aminoglycosides for cystic fibrosis

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

“…Similar to previous studies, patients within our study who received IV tobramycin dosed multiple times daily had a significantly increased risk of AKI in comparison to patients receiving IV tobramycin dosed at least every 24 h, with 50% versus 28.7% developing AKI, respectively ( p = 0.047). Our findings correlate with one Cochrane analysis comparing once versus multidaily dosing of aminoglycoside therapy in pediatric and adult patients with CF, which found a significantly lower rise in creatinine with once‐daily aminoglycoside therapy in children, perpetuating the recommendation to utilize once daily dosing of aminoglycosides, whenever possible, in pediatric patients 18 . Additionally, as each of the aforementioned studies found no difference in clinical efficacy between once daily and three times daily dosing, it may be concluded that multidaily dosing of IV tobramycin offers no demonstratable clinical benefit, but results in a significantly increased risk of nephrotoxicity in both pediatric and adult patients.…”

“…Although not statistically different, there was an observed increase in rate of AKI in patient encounters who did not achieve a therapeutic AUC 24 or C max when compared to those with a therapeutic AUC 24 or C max. This finding may be explained by the overall increased incidence of multi‐daily dosing in the patients who did not achieve a therapeutic AUC 24 or C max, and is supported by previous literature denoting a decreased likelihood of obtaining a therapeutic C max with IV aminoglycoside therapy dosed multiple times daily, rather than once daily 15–21 . Given the lack of correlation between time undetectable and efficacy found within this study, institution guidelines should be modified to discourage multidaily dosing of IV tobramycin, thereby mitigating AKI incidence, in pediatric patients.…”

“…The results of this study unexpectedly demonstrated an increased incidence of AKI in the pediatric cohort, when compared to the adult cohort (45.5% vs. 25.9%), which was likely secondary to the increased incidence of multidaily dosing of IV tobramycin in pediatric patients. Once‐daily dosing of IV aminoglycoside therapy has previously been demonstrated to reduce nephrotoxicity, without sacrificing efficacy, in both pediatric and adult patients with CF 15–21 . In one large randomized control study, Smyth et al noted a significant increase in incidence of nephrotoxicity in pediatric patients receiving IV tobramycin dosed three times daily, when compared to once daily dosing, with a mean percent change in creatinine of 3.7% versus −4.5%, respectively (adjusted mean difference −8%, 95% confidence inteval: [−15.7–0.4]; p = 0.04) 21 .…”

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

“…Similar to previous studies, patients within our study who received IV tobramycin dosed multiple times daily had a significantly increased risk of AKI in comparison to patients receiving IV tobramycin dosed at least every 24 h, with 50% versus 28.7% developing AKI, respectively ( p = 0.047). Our findings correlate with one Cochrane analysis comparing once versus multidaily dosing of aminoglycoside therapy in pediatric and adult patients with CF, which found a significantly lower rise in creatinine with once‐daily aminoglycoside therapy in children, perpetuating the recommendation to utilize once daily dosing of aminoglycosides, whenever possible, in pediatric patients 18 . Additionally, as each of the aforementioned studies found no difference in clinical efficacy between once daily and three times daily dosing, it may be concluded that multidaily dosing of IV tobramycin offers no demonstratable clinical benefit, but results in a significantly increased risk of nephrotoxicity in both pediatric and adult patients.…”

“…Although not statistically different, there was an observed increase in rate of AKI in patient encounters who did not achieve a therapeutic AUC 24 or C max when compared to those with a therapeutic AUC 24 or C max. This finding may be explained by the overall increased incidence of multi‐daily dosing in the patients who did not achieve a therapeutic AUC 24 or C max, and is supported by previous literature denoting a decreased likelihood of obtaining a therapeutic C max with IV aminoglycoside therapy dosed multiple times daily, rather than once daily 15–21 . Given the lack of correlation between time undetectable and efficacy found within this study, institution guidelines should be modified to discourage multidaily dosing of IV tobramycin, thereby mitigating AKI incidence, in pediatric patients.…”

“…The results of this study unexpectedly demonstrated an increased incidence of AKI in the pediatric cohort, when compared to the adult cohort (45.5% vs. 25.9%), which was likely secondary to the increased incidence of multidaily dosing of IV tobramycin in pediatric patients. Once‐daily dosing of IV aminoglycoside therapy has previously been demonstrated to reduce nephrotoxicity, without sacrificing efficacy, in both pediatric and adult patients with CF 15–21 . In one large randomized control study, Smyth et al noted a significant increase in incidence of nephrotoxicity in pediatric patients receiving IV tobramycin dosed three times daily, when compared to once daily dosing, with a mean percent change in creatinine of 3.7% versus −4.5%, respectively (adjusted mean difference −8%, 95% confidence inteval: [−15.7–0.4]; p = 0.04) 21 .…”

Glomerular and Tubular Renal Function after Repeated Once-Daily Tobramycin Courses in Cystic Fibrosis Patients

“…Aminoglycoside antibiotics operate via a concentration dependent killing and a postantibiotic effect. Hence, once-daily dosing regimens were introduced that are considered less nephrotoxic [20]. This is the first study analysing renal function of CF patients exclusively treated with the once-daily regimen.…”

“…In particular children with CF have a higher volume of distribution for aminoglycoside antibiotics necessitating a higher dose compared to healthy children [26, 27]. The aminoglycoside courses applied in our study consisted exclusively of tobramycin, which is less nephrotoxic than gentamicin [28] and was applied in the once-daily dosing regimen that has reduced nephrotoxicity [20]. Due to higher patient weight and age, serum creatinine levels were higher in the patients who received tobramycin in this study.…”

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

“…Similar to previous studies, patients within our study who received IV tobramycin dosed multiple times daily had a significantly increased risk of AKI in comparison to patients receiving IV tobramycin dosed at least every 24 h, with 50% versus 28.7% developing AKI, respectively ( p = 0.047). Our findings correlate with one Cochrane analysis comparing once versus multidaily dosing of aminoglycoside therapy in pediatric and adult patients with CF, which found a significantly lower rise in creatinine with once‐daily aminoglycoside therapy in children, perpetuating the recommendation to utilize once daily dosing of aminoglycosides, whenever possible, in pediatric patients 18 . Additionally, as each of the aforementioned studies found no difference in clinical efficacy between once daily and three times daily dosing, it may be concluded that multidaily dosing of IV tobramycin offers no demonstratable clinical benefit, but results in a significantly increased risk of nephrotoxicity in both pediatric and adult patients.…”

“…Although not statistically different, there was an observed increase in rate of AKI in patient encounters who did not achieve a therapeutic AUC 24 or C max when compared to those with a therapeutic AUC 24 or C max. This finding may be explained by the overall increased incidence of multi‐daily dosing in the patients who did not achieve a therapeutic AUC 24 or C max, and is supported by previous literature denoting a decreased likelihood of obtaining a therapeutic C max with IV aminoglycoside therapy dosed multiple times daily, rather than once daily 15–21 . Given the lack of correlation between time undetectable and efficacy found within this study, institution guidelines should be modified to discourage multidaily dosing of IV tobramycin, thereby mitigating AKI incidence, in pediatric patients.…”

“…The results of this study unexpectedly demonstrated an increased incidence of AKI in the pediatric cohort, when compared to the adult cohort (45.5% vs. 25.9%), which was likely secondary to the increased incidence of multidaily dosing of IV tobramycin in pediatric patients. Once‐daily dosing of IV aminoglycoside therapy has previously been demonstrated to reduce nephrotoxicity, without sacrificing efficacy, in both pediatric and adult patients with CF 15–21 . In one large randomized control study, Smyth et al noted a significant increase in incidence of nephrotoxicity in pediatric patients receiving IV tobramycin dosed three times daily, when compared to once daily dosing, with a mean percent change in creatinine of 3.7% versus −4.5%, respectively (adjusted mean difference −8%, 95% confidence inteval: [−15.7–0.4]; p = 0.04) 21 .…”

Glomerular and Tubular Renal Function after Repeated Once-Daily Tobramycin Courses in Cystic Fibrosis Patients

“…Aminoglycoside antibiotics operate via a concentration dependent killing and a postantibiotic effect. Hence, once-daily dosing regimens were introduced that are considered less nephrotoxic [20]. This is the first study analysing renal function of CF patients exclusively treated with the once-daily regimen.…”

“…In particular children with CF have a higher volume of distribution for aminoglycoside antibiotics necessitating a higher dose compared to healthy children [26, 27]. The aminoglycoside courses applied in our study consisted exclusively of tobramycin, which is less nephrotoxic than gentamicin [28] and was applied in the once-daily dosing regimen that has reduced nephrotoxicity [20]. Due to higher patient weight and age, serum creatinine levels were higher in the patients who received tobramycin in this study.…”

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

“…Similar to previous studies, patients within our study who received IV tobramycin dosed multiple times daily had a significantly increased risk of AKI in comparison to patients receiving IV tobramycin dosed at least every 24 h, with 50% versus 28.7% developing AKI, respectively ( p = 0.047). Our findings correlate with one Cochrane analysis comparing once versus multidaily dosing of aminoglycoside therapy in pediatric and adult patients with CF, which found a significantly lower rise in creatinine with once‐daily aminoglycoside therapy in children, perpetuating the recommendation to utilize once daily dosing of aminoglycosides, whenever possible, in pediatric patients 18 . Additionally, as each of the aforementioned studies found no difference in clinical efficacy between once daily and three times daily dosing, it may be concluded that multidaily dosing of IV tobramycin offers no demonstratable clinical benefit, but results in a significantly increased risk of nephrotoxicity in both pediatric and adult patients.…”

“…Although not statistically different, there was an observed increase in rate of AKI in patient encounters who did not achieve a therapeutic AUC 24 or C max when compared to those with a therapeutic AUC 24 or C max. This finding may be explained by the overall increased incidence of multi‐daily dosing in the patients who did not achieve a therapeutic AUC 24 or C max, and is supported by previous literature denoting a decreased likelihood of obtaining a therapeutic C max with IV aminoglycoside therapy dosed multiple times daily, rather than once daily 15–21 . Given the lack of correlation between time undetectable and efficacy found within this study, institution guidelines should be modified to discourage multidaily dosing of IV tobramycin, thereby mitigating AKI incidence, in pediatric patients.…”

“…The results of this study unexpectedly demonstrated an increased incidence of AKI in the pediatric cohort, when compared to the adult cohort (45.5% vs. 25.9%), which was likely secondary to the increased incidence of multidaily dosing of IV tobramycin in pediatric patients. Once‐daily dosing of IV aminoglycoside therapy has previously been demonstrated to reduce nephrotoxicity, without sacrificing efficacy, in both pediatric and adult patients with CF 15–21 . In one large randomized control study, Smyth et al noted a significant increase in incidence of nephrotoxicity in pediatric patients receiving IV tobramycin dosed three times daily, when compared to once daily dosing, with a mean percent change in creatinine of 3.7% versus −4.5%, respectively (adjusted mean difference −8%, 95% confidence inteval: [−15.7–0.4]; p = 0.04) 21 .…”

Glomerular and Tubular Renal Function after Repeated Once-Daily Tobramycin Courses in Cystic Fibrosis Patients

“…Aminoglycoside antibiotics operate via a concentration dependent killing and a postantibiotic effect. Hence, once-daily dosing regimens were introduced that are considered less nephrotoxic [20]. This is the first study analysing renal function of CF patients exclusively treated with the once-daily regimen.…”

“…In particular children with CF have a higher volume of distribution for aminoglycoside antibiotics necessitating a higher dose compared to healthy children [26, 27]. The aminoglycoside courses applied in our study consisted exclusively of tobramycin, which is less nephrotoxic than gentamicin [28] and was applied in the once-daily dosing regimen that has reduced nephrotoxicity [20]. Due to higher patient weight and age, serum creatinine levels were higher in the patients who received tobramycin in this study.…”