A Vancomycin Dosage Regimen Developed for Obese Patients
A Vancomycin Dosage Regimen Developed for Obese Patients
All cases in which patients received vancomycin from January 2008 through July 2010 at Orlando Health were screened; 170 cases met the inclusion criteria. Thirty-two cases were excluded from the final data analysis because the treated patients had an estimated CLcr of <60 mL/min at baseline (n = 13) or unstable renal function at the time of vancomycin initiation (n = 11) or had received a total daily dose of <15 mg/kg/day (n = 8). In the 11 cases involving unstable renal function, records indicated that 6 of the patients had an acute improvement and 5 had an acute decline in SCr of ≥0.3 mg/dL during the first 48 hours of vancomycin administration.
Of the remaining 138 cases, 74 and 64 cases were stratified into the revised-and original-protocol dosing groups, respectively. A comparison of baseline patient characteristics is presented in Table 1 . The two groups were similar with respect to age, sex, and renal function. Patients in the revised-protocol group had a greater TBW, BMI, and TBW:IBW ratio. In all cases included in the analysis, the patients had a BMI of ≥30 kg/m. The mean ± S.D. duration of vancomycin therapy (6.3 ± 4.3 days) did not differ significantly between the groups (p = 0.608).
Vancomycin Dosing Vancomycin loading doses were administered to 57% of all patients. Similar percentages of patients in the revised-and original-protocol groups received loading doses (57% and 58%, respectively; p = 0.901). The mean ± S.D. loading dose was 20 ± 2 mg/kg in the revised-protocol group and 21 ± 3 mg/kg in the original-protocol group (p = 0.343); in contrast, the mean ± S.D. vancomycin maintenance dosage was 19 ± 2 mg/kg/day with the revised protocol and 34 ± 7 mg/kg/day with the original protocol (p < 0.001). In the revised-protocol group, all but two patients received vancomycin at a dosage of 10 mg/kg every 12 hours.
Time to Attainment of Vancomycin Trough Levels The median time from the first dose of vancomycin to the collection of a blood sample for measurement of the first trough concentration was 61.1 hours in the revised-protocol group (interquartile range [IQR], 47.5–83.2 hours) and 54.9 hours in the original-protocol group (IQR, 38.1–78.1 hours) (p = 0.129). The number of estimated elapsed half-lives before obtaining the first vancomycin trough was similar between the two groups ( Table 2 ). Of note, similarly high percentages of patients in the revised-protocol and original-protocol groups (69% and 66%, respectively; p = 0.681) were at an estimated steady state by the time the first trough concentration was obtained.
Vancomycin Trough LevelsTable 3 shows the mean trough values for each vancomycin dosing group and patient subset. The revised-protocol group had a significantly higher frequency of vancomycin troughs within the target range as compared with the original-protocol group (59% versus 36%, p = 0.006). The prevalence of above-target troughs was significantly lower in the revised-protocol group than in the original-protocol group (18% versus 55%, p < 0.001), with a mean ± S.D. trough value of 29.1 ± 7.5 μg/mL in the original-protocol group. Among the 31 ICU cases evaluated, 6 (50%) in the revised-protocol group and 2 (11%) in the original-protocol group had vancomycin trough levels within the target range (p = 0.032). In 15 (79%) of the 19 ICU cases involving use of the original protocol, patients had above-target trough levels, with a mean ± S.D. trough value of 30.5 ± 9.2 μg/mL. Among the 48 cases in the combined study cohort in which patients had a vancomycin trough of >20 μg/mL, the vancomycin dosage was reduced in 37 cases, discontinued in 9 cases, and maintained in 2 cases (those 2 patients both had trough values of 22 μg/mL).
Although it was associated with a higher frequency of target vancomycin-trough attainment, the revised protocol also was associated with a clinically relevant higher frequency of below-target troughs than the original protocol (23% versus 9%, p = 0.033).
Overall, nephrotoxicity occurred in a total of 4 (2.9%) of the evaluated cases; the mean ± S.D. baseline and maximum SCr values in those 4 patients were 0.8 ± 0.1 and 3.0 ± 1.2 mg/dL. Elevated SCr values were noted on days 6–13 of vancomycin therapy. In all cases involving nephrotoxicity, the first vancomycin trough was >15 μg/mL. The frequency of nephrotoxicity did not differ significantly with the revised and original dosing protocols (2.7% and 3.1%, respectively; p = 1). Due to the low rate of nephrotoxicity, patient comorbidities and alternative risk factors for nephrotoxicity could not be statistically evaluated. Of note, 28 (20%) of the patients had received a maintenance vancomycin dosage of >4 g per day (range, 4–6 g per day) and nephrotoxicity was not observed in any case; the median length of therapy in those 28 cases was 5.5 days.
Results
Patient Selection
All cases in which patients received vancomycin from January 2008 through July 2010 at Orlando Health were screened; 170 cases met the inclusion criteria. Thirty-two cases were excluded from the final data analysis because the treated patients had an estimated CLcr of <60 mL/min at baseline (n = 13) or unstable renal function at the time of vancomycin initiation (n = 11) or had received a total daily dose of <15 mg/kg/day (n = 8). In the 11 cases involving unstable renal function, records indicated that 6 of the patients had an acute improvement and 5 had an acute decline in SCr of ≥0.3 mg/dL during the first 48 hours of vancomycin administration.
Comparison of the Revised and Original Protocols
Of the remaining 138 cases, 74 and 64 cases were stratified into the revised-and original-protocol dosing groups, respectively. A comparison of baseline patient characteristics is presented in Table 1 . The two groups were similar with respect to age, sex, and renal function. Patients in the revised-protocol group had a greater TBW, BMI, and TBW:IBW ratio. In all cases included in the analysis, the patients had a BMI of ≥30 kg/m. The mean ± S.D. duration of vancomycin therapy (6.3 ± 4.3 days) did not differ significantly between the groups (p = 0.608).
Vancomycin Dosing Vancomycin loading doses were administered to 57% of all patients. Similar percentages of patients in the revised-and original-protocol groups received loading doses (57% and 58%, respectively; p = 0.901). The mean ± S.D. loading dose was 20 ± 2 mg/kg in the revised-protocol group and 21 ± 3 mg/kg in the original-protocol group (p = 0.343); in contrast, the mean ± S.D. vancomycin maintenance dosage was 19 ± 2 mg/kg/day with the revised protocol and 34 ± 7 mg/kg/day with the original protocol (p < 0.001). In the revised-protocol group, all but two patients received vancomycin at a dosage of 10 mg/kg every 12 hours.
Time to Attainment of Vancomycin Trough Levels The median time from the first dose of vancomycin to the collection of a blood sample for measurement of the first trough concentration was 61.1 hours in the revised-protocol group (interquartile range [IQR], 47.5–83.2 hours) and 54.9 hours in the original-protocol group (IQR, 38.1–78.1 hours) (p = 0.129). The number of estimated elapsed half-lives before obtaining the first vancomycin trough was similar between the two groups ( Table 2 ). Of note, similarly high percentages of patients in the revised-protocol and original-protocol groups (69% and 66%, respectively; p = 0.681) were at an estimated steady state by the time the first trough concentration was obtained.
Vancomycin Trough LevelsTable 3 shows the mean trough values for each vancomycin dosing group and patient subset. The revised-protocol group had a significantly higher frequency of vancomycin troughs within the target range as compared with the original-protocol group (59% versus 36%, p = 0.006). The prevalence of above-target troughs was significantly lower in the revised-protocol group than in the original-protocol group (18% versus 55%, p < 0.001), with a mean ± S.D. trough value of 29.1 ± 7.5 μg/mL in the original-protocol group. Among the 31 ICU cases evaluated, 6 (50%) in the revised-protocol group and 2 (11%) in the original-protocol group had vancomycin trough levels within the target range (p = 0.032). In 15 (79%) of the 19 ICU cases involving use of the original protocol, patients had above-target trough levels, with a mean ± S.D. trough value of 30.5 ± 9.2 μg/mL. Among the 48 cases in the combined study cohort in which patients had a vancomycin trough of >20 μg/mL, the vancomycin dosage was reduced in 37 cases, discontinued in 9 cases, and maintained in 2 cases (those 2 patients both had trough values of 22 μg/mL).
Although it was associated with a higher frequency of target vancomycin-trough attainment, the revised protocol also was associated with a clinically relevant higher frequency of below-target troughs than the original protocol (23% versus 9%, p = 0.033).
Nephrotoxicity
Overall, nephrotoxicity occurred in a total of 4 (2.9%) of the evaluated cases; the mean ± S.D. baseline and maximum SCr values in those 4 patients were 0.8 ± 0.1 and 3.0 ± 1.2 mg/dL. Elevated SCr values were noted on days 6–13 of vancomycin therapy. In all cases involving nephrotoxicity, the first vancomycin trough was >15 μg/mL. The frequency of nephrotoxicity did not differ significantly with the revised and original dosing protocols (2.7% and 3.1%, respectively; p = 1). Due to the low rate of nephrotoxicity, patient comorbidities and alternative risk factors for nephrotoxicity could not be statistically evaluated. Of note, 28 (20%) of the patients had received a maintenance vancomycin dosage of >4 g per day (range, 4–6 g per day) and nephrotoxicity was not observed in any case; the median length of therapy in those 28 cases was 5.5 days.
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