Problems: 4: The Aminoglycoside Antibiotics
Problems: 4: The Aminoglycoside Antibiotics
Problems: 4: The Aminoglycoside Antibiotics
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Applied Clinical Pharmacokinetics, 3e
4: The Aminoglycoside Antibiotics
PROBLEMS
The following problems are intended to emphasize the computation of initial and individualized doses using clinical pharmacokinetic techniques.
Clinicians should always consult the patient’s chart to confirm that antibiotic therapy is appropriate for current microbiologic cultures and
sensitivities. Also, it should be confirmed that the patient is receiving other appropriate concurrent antibiotic therapy, such as βlactam or anaerobic
agents, when necessary to treat the infection.
1. PQ is a 75yearold, 62kg (height = 5 ft 9 in) male with gramnegative sepsis. His current serum creatinine is 1.3 mg/dL, and it has been stable since
admission. Compute a gentamicin dose for this patient to provide a steadystate peak concentration of 8 μg/mL and a steadystate trough
concentration of 1.5 μg/mL using conventional dosing.
2. Patient PQ (see problem 1) was prescribed gentamicin 110 mg every 12 hours. Steadystate gentamicin concentrations were obtained before and
after the fourth dose, and the peak concentration (obtained ½ hour after a ½hour infusion of gentamicin) was 9.5 μg/mL while the trough
concentration (obtained within ½ hour before dosage administration) was 3.0 μg/mL. Compute a revised gentamicin dose for this patient to
provide a steadystate peak concentration of 8 μg/mL and a steadystate trough concentration of 1 μg/mL using conventional dosing.
3. ZW is a 35yearold, 75kg (height = 5 ft 7 in) female with gramnegative pneumonia and chronic renal failure. Her current serum creatinine is 3.7
mg/dL, and it has been stable since admission. Compute a gentamicin dose for this patient to provide a steadystate peak concentration of 10
μg/mL and a steadystate trough concentration of 1.0 μg/mL using conventional dosing.
4. Patient ZW (see problem 3) was prescribed gentamicin 120 mg every 24 hours. Steadystate gentamicin concentrations were obtained before and
after the fourth dose, and the peak concentration (obtained ½ hour after a ½hour infusion of gentamicin) was 7 μg/mL while the trough
concentration (obtained within ½ hour before dosage administration) was less than 0.5 μg/mL. Compute a revised gentamicin dose for this patient
to provide a steadystate peak concentration of 10 μg/mL and a steadystate trough concentration of less than 2 μg/mL using conventional dosing.
5. JK is a 55yearold, 140kg (height = 5 ft 8 in) male with an intraabdominal infection secondary to a knife wound. His current serum creatinine is 0.9
mg/dL, and it has been stable since admission. Compute a gentamicin dose for this patient to provide a steadystate peak concentration of 6 μg/mL
and a steadystate trough concentration of 0.5 μg/mL using conventional dosing.
6. Patient JK (see problem 5) was prescribed gentamicin 120 mg every 8 hours. Steadystate gentamicin concentrations were obtained before and
after the fourth dose, and the peak concentration (obtained ½ hour after a ½hour infusion of gentamicin) was 5.9 μg/mL while the trough
concentration (obtained within ½ hour before dosage administration) was 2.5 μg/mL. Compute a revised gentamicin dose for this patient to
provide a steadystate peak concentration of 6 μg/mL and a steadystate trough concentration of less than 1 μg/mL using conventional dosing.
7. AF is a 45yearold, 140kg (5 ft 2 in) female with an S. viridans endocarditis. Her current serum creatinine is 2.4 mg/dL and is stable. Compute a
tobramycin dose for this patient to provide a steadystate peak concentration of 4 μg/mL, and a steadystate trough concentration of 0.5 μg/mL
using conventional dosing.
8. Patient AF (see problem 7) was prescribed tobramycin 100 mg every 12 hours. Steadystate tobramycin concentrations were obtained before and
after the fourth dose, and the peak concentration (obtained ½ hour after a ½hour infusion of tobramycin) was 6.2 μg/mL while the trough
concentration (obtained within ½ hour before dosage administration) was 1.5 μg/mL. Compute a revised tobramycin dose for this patient to
provide a steadystate peak concentration of 4 μg/mL and a steadystate trough concentration of 1 μg/mL or less using conventional dosing.
9. FH is a 24yearold, 60kg (5 ft 7 in) male with cystic fibrosis and Pseudomonas aeruginosa cultured from a sputum culture. He was hospitalized due
to worsening pulmonary function tests. His current serum creatinine is 0.7 mg/dL. Compute a tobramycin dose for this patient to provide a steady
state peak concentration of 10 μg/mL, and a steadystate trough concentration of less than 2 μg/mL using conventional dosing.
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10. Patient FH (see problem 9) was prescribed tobramycin 250 mg every 8 hours. Steadystate tobramycin concentrations were obtained before and
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after the fourth dose, and the peak concentration (obtained ½ hour after a ½hour infusion of tobramycin) was 7.9 μg/mL while the trough
concentration (obtained within ½ hour before dosage administration) was 1 μg/mL. Compute a revised tobramycin dose for this patient to provide
concentration (obtained within ½ hour before dosage administration) was 1.5 μg/mL. Compute a revised tobramycin dose for this patient to
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provide a steadystate peak concentration of 4 μg/mL and a steadystate trough concentration of 1 μg/mL or less using conventional dosing.
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9. FH is a 24yearold, 60kg (5 ft 7 in) male with cystic fibrosis and Pseudomonas aeruginosa cultured from a sputum culture. He was hospitalized due
to worsening pulmonary function tests. His current serum creatinine is 0.7 mg/dL. Compute a tobramycin dose for this patient to provide a steady
state peak concentration of 10 μg/mL, and a steadystate trough concentration of less than 2 μg/mL using conventional dosing.
10. Patient FH (see problem 9) was prescribed tobramycin 250 mg every 8 hours. Steadystate tobramycin concentrations were obtained before and
after the fourth dose, and the peak concentration (obtained ½ hour after a ½hour infusion of tobramycin) was 7.9 μg/mL while the trough
concentration (obtained within ½ hour before dosage administration) was 1 μg/mL. Compute a revised tobramycin dose for this patient to provide
a steadystate peak concentration of 10 μg/mL and a steadystate trough concentration of 12 μg/mL using conventional dosing.
11. TY is a 66yearold, 65kg (5 ft 5 in) female with a suspected tuboovarian abscess secondary to hysterectomy surgery. While in the hospital, she
developed ascites due to preexisting liver cirrhosis and her current weight is 72 kg. Her current serum creatinine is 1.4 mg/dL. Compute a
gentamicin dose for this patient to provide a steadystate peak concentration of 6 μg/mL, and a steadystate trough concentration of less than 2
μg/mL using conventional dosing.
12. Patient TY (see problem 11) was prescribed gentamicin 120 mg every 12 hours. Steadystate gentamicin concentrations were obtained before and
after the fourth dose, and the peak concentration (obtained ½ hour after a ½hour infusion of gentamicin) was 4 μg/mL while the trough
concentration (obtained within ½ hour before dosage administration) was 0.8 μg/mL. Compute a revised gentamicin dose for this patient to
provide a steadystate peak concentration of 6 μg/mL and a steadystate trough concentration of 1 μg/mL using conventional dosing.
13. UQ is a 27yearold, 85kg (6 ft 2 in) male trauma patient with a gramnegative pneumonia and is currently on a respirator. He sustained multiple
injuries secondary to a motor vehicle accident 2 weeks ago and lost a large amount of blood at the accident site. He developed acute renal failure
because of prolonged hypotension and poor perfusion of his kidneys (current postdialysis serum creatinine is 5.3 mg/dL). He is receiving
hemodialysis on Mondays, Wednesdays, and Fridays from 0800 to 1200 H, using a lowflux dialysis filter. Recommend a gentamicin dosage regimen
that will achieve peak concentrations of 8 μg/mL and postdialysis concentrations of ∼2 μg/mL. The first dose of the regimen will be given
immediately after hemodialysis is finished on Wednesday at 1200 H.
14. Patient UQ (see problem 13) was prescribed gentamicin 180 mg loading dose and 130 mg after each dialysis. The following serum concentrations
were obtained:
Use these serum concentrations to compute the patient’s own pharmacokinetic parameters for gentamicin and a new dosage schedule that will
achieve peak concentrations of 8 μg/mL and postdialysis concentrations of less than 2 μg/mL.
15. LS is a 67yearold, 60kg (5 ft 2 in) female with a serum creatinine equal to 1.8 mg/dL placed on tobramycin for a hospitalacquired gramnegative
pneumonia. The prescribed dose was tobramycin 80 mg every 8 hours (infused over 1 hour) and two doses have been given at 0800 and 1600
hours. A trough concentration of 2.9 μg/mL was obtained at 1530 hours (½ hour before the second dose) and a peak concentration of 5.2 μg/mL
was obtained at 1705 hours (5 minutes after infusion of the second dose). Compute the dose to give Cssmax = 8 μg/mL and Cssmin = 1.5 μg/mL.
16. KK is a 52yearold, 87kg (6 ft 2 in) male status postappendectomy who developed a fever, elevated white blood cell count, and abdominal pain 24
hours after surgery. His current serum creatinine is 1.4 mg/dL and stable. (A) Compute an initial extendedinterval gentamicin dose for this patient.
(B) Nine hours after the second dose of gentamicin 610 mg every 24 hours, a gentamicin serum concentration equal to 8.2 μg/mL is measured.
Compute a revised gentamicin dose for this patient to provide steadystate peak concentrations of greater than 20 μg/mL and steadystate trough
concentrations of less than 1 μg/mL.
17. XS is a 45yearold, 65kg (5 ft 4 in) female bone marrow transplant recipient who develops a neutropenic fever. Her current serum creatinine is 1.1
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mg/dL. She is administered tobramycin 5 mg/kg daily (325 mg) as part of her antibiotic therapy. A tobramycin serum concentration was obtained 5
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hours after the first dose and equaled 19 μg/mL. Compute a revised tobramycin dose for this patient to provide steadystate peak concentrations of
greater than 25 μg/mL and steadystate trough concentrations of less than 1 μg/mL.
16. KK is a 52yearold, 87kg (6 ft 2 in) male status postappendectomy who developed a fever, elevated white blood cell count, and abdominal pain 24
hours after surgery. His current serum creatinine is 1.4 mg/dL and stable. (A) Compute an initial extendedinterval gentamicin dose for this patient.
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(B) Nine hours after the second dose of gentamicin 610 mg every 24 hours, a gentamicin serum concentration equal to 8.2 μg/mL is measured.
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Compute a revised gentamicin dose for this patient to provide steadystate peak concentrations of greater than 20 μg/mL and steadystate trough
concentrations of less than 1 μg/mL.
17. XS is a 45yearold, 65kg (5 ft 4 in) female bone marrow transplant recipient who develops a neutropenic fever. Her current serum creatinine is 1.1
mg/dL. She is administered tobramycin 5 mg/kg daily (325 mg) as part of her antibiotic therapy. A tobramycin serum concentration was obtained 5
hours after the first dose and equaled 19 μg/mL. Compute a revised tobramycin dose for this patient to provide steadystate peak concentrations of
greater than 25 μg/mL and steadystate trough concentrations of less than 1 μg/mL.
18. DT is a 3dayold, 2050g female with suspected neonatal sepsis. Her serum creatinine has not been measured, but it is assumed that it is typical for
her age and weight. Compute an initial tobramycin dose for this patient.
19. Patient DT (see problem 18) was prescribed tobramycin 5 mg every 12 hours. Steadystate tobramycin concentrations were obtained, and the peak
concentration (obtained ½ hour after a ½hour infusion of tobramycin) was 4.5 μg/mL while the trough concentration (obtained within ½ hour
before dosage administration) was 0.9 μg/mL. Compute a revised tobramycin dose for this patient to provide a steadystate peak concentration of 6
μg/mL and a steadystate trough concentration of 1.5 μg/mL, using conventional dosing.
20. UL is a 7yearold, 24kg, 3ft 11in male with gramnegative sepsis. His serum creatinine is 0.5 mg/dL, and it has been stable for the last 2 days.
Compute an initial gentamicin dose for this patient.
21. Patient UL (see problem 20) was prescribed gentamicin 60 mg every 8 hours and was expected to achieve steadystate peak and trough
concentrations equal to 8 μg/mL and less than 2 μg/mL, respectively. Steadystate concentrations were measured and were 4.5 μg/mL 1 hour after
the end of a 1hour infusion and 1.5 μg/mL 4 hours after the end of infusion. Calculate a new gentamicin dose that would provide a steadystate
peak of 9 μg/mL and a trough 1 μg/mL.
22. RD is a 59yearold, 79kg (height = 5 ft 11 in) male with a gramnegative pneumonia. His current serum creatinine is 1.5 mg/dL, and it has been
stable over the last 3 days. A gentamicin dose of 450 mg every 24 hours was prescribed and expected to achieve steadystate peak and trough
concentrations equal to 30 μg/mL and less than 1 μg/mL, respectively. After the second dose, steadystate concentrations were measured and were
16.1 μg/mL 2 hours after the end of a 1hour infusion and 2.5 μg/mL 16 hours after the end of infusion. Calculate a new gentamicin dose that would
provide a steadystate peak of 30 μg/mL and a trough less than 1 μg/mL.
23. DH is a 56yearold, 69kg (height = 5 ft 7 in) female with gramnegative sepsis. Her current serum creatinine is 1.2 mg/dL, and it has been stable over
the last 5 days since admission. A tobramycin dose of 500 mg every 24 hours was prescribed. After the third dose, steadystate peak and trough
concentrations were measured and were 19 μg/mL and 1.9 μg/mL, respectively. Calculate a new tobramycin dose that would provide a steadystate
peak of 25 μg/mL and a trough 1 μg/mL.
24. NM is a 55yearold, 135kg (height = 5 ft 8 in) male with an intraabdominal infection secondary to a knife wound. His current serum creatinine is 1.3
mg/dL, and it has been stable since admission. He was prescribed gentamicin 500 mg every 24 hours infused over 1 hour. Steadystate gentamicin
concentrations were obtained after the third dose, and the concentration 2 hours after the infusion ended was 10.2 μg/mL while the concentration
10 hours after the infusion ended was 1.1 μg/mL. Compute a revised gentamicin dose for this patient to provide a steadystate peak concentration
of 25 μg/mL and a steadystate trough concentration of less than 1 μg/mL using extendedinterval dosing.
25. MI is a 27yearold, 68kg (height = 5 ft 4 in) female with salpingitis. Her current serum creatinine is 1.4 mg/dL, and it has been stable over the last 3
days. Compute a tobramycin dose for this patient to provide a steadystate peak concentration of 25 μg/mL and a steadystate trough of less than 1
μg/mL using extendedinterval dosing.
26. Patient MI (see problem 25) was prescribed tobramycin 475 mg every 24 hours. After the third dose, steadystate concentrations were measured
and equaled 17.0 μg/mL 1 hour after the end of a 1hour infusion and 9.8 μg/mL 6 hours after the end of infusion. Calculate a new tobramycin dose
that would provide a steadystate peak concentration of 25 μg/mL and a steadystate trough of 1 μg/mL.
27. EK is a 23yearold, 67kg (height = 5 ft 8 in) male with peritonitis. His current serum creatinine is 0.8 mg/dL, and it has been stable over the last 3
days. A tobramycin dose of 350 mg every 24 hours was prescribed and expected to achieve steadystate peak and trough concentrations equal to 25
μg/mL and less than 1 μg/mL, respectively. After the seconddose, steadystate concentrations were measured and equaled 9.6 μg/mL 2 hours after
the end of a 1hour infusion and 2.6 μg/mL 6 hours after the end of infusion. Calculate a new tobramycin dose that would provide a steadystate
AUC of 81 (mg • h)/L.
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