Experience with a once-daily dosing program of aminoglycosides in critically ill patients

Buijk, S. L. C. E.; Mouton, Johan W.; Gyssens, Inge C.; Verbrugh, Henri A.; Bruining, H. A.

doi:10.1007/s00134-002-1313-7

Cited by 150 publications

(87 citation statements)

References 28 publications

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“…The much smaller standard deviation for peak concentration of this group indicates that TDM allows more accurate dose determination, providing more predictable peak concentrations for specific patients. In human patients receiving aminoglycoside antimicrobials in intensive care units, TDM is considered essential because of decreased probability of these patients to achieve therapeutic concentrations at initial doses given 3, 6, 27, 28. The low proportion of peak concentrations >32 μg/mL in our study suggests this applies to our population of equine patients.…”

Section: Discussionmentioning

confidence: 66%

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Plasma Peak and Trough Gentamicin Concentrations in Hospitalized Horses Receiving Intravenously Administered Gentamicin

Bauquier

Boston

Sweeney

et al. 2015

Veterinary Internal Medicne

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BackgroundGentamicin is an aminoglycoside antimicrobial commonly used in horses at 6.6 mg/kg IV once daily. Therapeutic drug monitoring (TDM) can confirm desired peak concentration is reached for common bacterial isolates, and detect toxicosis associated with high trough values.ObjectivesDetermine the relationship between gentamicin dose and plasma concentration in hospitalized horses, and identify a starting dose range to achieve peaks > 32 μg/mL.AnimalsSixty‐five horses (2002–2010) receiving once‐daily gentamicin with TDM performed (N = 99 sets).MethodsRetrospective study. Data from hospitalized horses including weight, dose, plasma peak, and trough gentamicin concentration, creatinine concentrations and presence of focal or systemic disease were collected from medical records. Peak concentrations measured 25–35 minutes after administration were included (N = 77). Data were divided into low (<7.7 mg/kg), medium (7.7–9.7 mg/kg) and high (>9.7 mg/kg) dose groups, and were grouped by the horse having focal or systemic disease.ResultsPeak concentrations resulting from doses ≥7.7 mg/kg were 5.74 μg/mL (SE 2.1 μg/mL) greater than peaks from doses <7.7 mg/kg (P = .007). Peak concentrations was 3.6 times more likely to be >32 μg/mL if dose was ≥7.7 mg/kg (P = .04). There were no significant effects of dose on trough or creatinine concentration. At a given dose, horses with focal disease had higher peaks than those with systemic disease (P = .039).Conclusions and Clinical ImportanceThese data suggest gentamicin dosage should be individually determined in horses using TDM, but support an initial once‐daily dose of 7.7–9.7 mg/kg IV to achieve peaks >32 μg/mL and trough concentrations <2 μg/mL. Further studies evaluating the safety of doses >6.6 mg/kg are required.

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Section: Discussionmentioning

confidence: 66%

“…The need for TDM and dose adjustments in systemic illness is also emphasized in human medicine. As previously mentioned, TDM of aminoglycosides in human intensive care units is considered essential 3, 6, 27, 28, 33. Further, human studies have shown that volume of distribution in septic patients changes as disease state changes 33.…”

Section: Discussionmentioning

confidence: 98%

Plasma Peak and Trough Gentamicin Concentrations in Hospitalized Horses Receiving Intravenously Administered Gentamicin

Bauquier

Boston

Sweeney

et al. 2015

Veterinary Internal Medicne

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“…23 Aminoglycoside dosing is optimized via the administration of large (once daily) doses up to 7 mg/kg for gentamicin and tobramycin and up to 20 mg/kg for amikacin, aiming at a serum peak/MIC ratio of 8-12 (individual MIC or local data), which also minimizes nephrotoxicity. 28 Active therapeutic drug monitoring 29 should be performed to avoid toxic drug levels arising via accumulation. Optimization of vancomycin dosing is achieved by using a loading dose (up to 35 mg/kg) and ensuring optimal trough levels of approximately 15 mg/L, either by twice-daily administration or continuous infusion, in order to achieve an (AUC) 0-24 : MIC ratio of more than 400, which correlates with positive outcomes in patients with MRSA bacteremia.…”

Section: This Issue Of Haematologica 21mentioning

confidence: 99%

The role of antibiotic stewardship in limiting antibacterial resistance among hematology patients

Gyssens¹,

Kern

Livermore

2013

Haematologica

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“…These aggressive doses could be responsible for a higher nephrotoxicity incidence. To date, a decrease in renal function has been observed in 5 to 14% of patients receiving AGs according to a wide definition (a Ͼ33% decrease in creatinine clearance [CL CR ] with or without an increase of creatinine in plasma of Ն0.3 mg/dl) or a more restrictive definition (a Ͼ50% decrease in CL CR with or without a plasma creatinine increase of Ն0.5 mg/dl) (11)(12)(13). Both definitions may overestimate AG-associated renal toxicity, and the addition of criteria for tubular damage to the definitions based on plasma creatinine levels lowers the incidence of AG-related nephrotoxicity by 2-or 3-fold (13,14).…”

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confidence: 99%

Propensity-Based Study of Aminoglycoside Nephrotoxicity in Patients with Severe Sepsis or Septic Shock

Picard

Bazin

Clouzeau

et al. 2014

Antimicrob Agents Chemother

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cTo assess the risk of acute kidney injury (AKI) attributable to aminoglycosides (AGs) in patients with severe sepsis or septic shock, we performed a retrospective cohort study in one medical intensive care unit (ICU) in France. Patients admitted for severe sepsis/septic shock between November 2008 and January 2010 were eligible. A propensity score for AG administration was built using day 1 demographic and clinical characteristics. Patients still on the ICU on day 3 were included. Patients with renal failure before day 3 or endocarditis were excluded. The time window for assessment of renal risk was day 3 to day 15, defined according to the RIFLE (risk, injury, failure, loss, and end-stage renal disease) classification. The AKI risk was assessed by means of a propensity-adjusted Cox proportional hazards regression analysis. Of 317 consecutive patients, 198 received AGs. The SAPS II (simplified acute physiology score II) score and nosocomial origin of infection favored the use of AGs, whereas a preexisting renal insufficiency and the neurological site of infection decreased the propensity for AG treatment. One hundred three patients with renal failure before day 3 were excluded. AGs were given once daily over 2.6 ؎ 1.1 days. AKI occurred in 16.3% of patients in a median time of 6 (interquartile range, 5 to 10) days. After adjustment to the clinical course and exposure to other nephrotoxic agents between day 1 and day 3, a propensity-adjusted Cox proportional hazards regression analysis showed no increased risk of AKI in patients receiving AGs (adjusted relative risk ‫؍‬ 0.75 [0.32 to 1.76]). In conclusion, in critically septic patients presenting without early renal failure, aminoglycoside therapy for less than 3 days was not associated with an increased risk of AKI.A minoglycosides (AGs) have bactericidal activity, which has been proven to be synergic with that of ␤-lactams. Although adding an AG to a standard antibiotic treatment did not translate into a reduction of mortality in Gram-negative-bacterial sepsis in subgroups of patients with globally moderate degrees of severity (1), a decrease in mortality was recently reported in a meta-analysis comparing a bitherapy to therapy with a ␤-lactam alone for patients with septic shock (2). In addition, AGs widen the spectrum of the antibiotic treatment, which should be advantageous in populations with an increased risk of resistant bacteria, such as intensive care unit (ICU) patients (3, 4). Empirical antibiotic treatments including AGs could be more appropriate in up to 15 to 20% of cases than a ␤-lactam alone (5, 6). In the ICU setting, modifications of the empirical antibiotic treatment or the addition of a new antibiotic occurs less frequently after bitherapy including an AG than after monotherapy (7).Unfortunately, nephrotoxicity is an important potential limitation of AGs. There is a consensus that AG-related nephrotoxicity has decreased over the years due to better consideration of both reduced duration of treatment and once-daily administration (8). However...

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Experience with a once-daily dosing program of aminoglycosides in critically ill patients

Cited by 150 publications

References 28 publications

Plasma Peak and Trough Gentamicin Concentrations in Hospitalized Horses Receiving Intravenously Administered Gentamicin

Plasma Peak and Trough Gentamicin Concentrations in Hospitalized Horses Receiving Intravenously Administered Gentamicin

The role of antibiotic stewardship in limiting antibacterial resistance among hematology patients

Propensity-Based Study of Aminoglycoside Nephrotoxicity in Patients with Severe Sepsis or Septic Shock

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