It is not appreciably absorbed orally and is renally excreted unchanged. In renal impairment the half-life is prolonged. Most side-effects are related to sustained high trough concentrations. Efficacy, on the other hand, is related to peak concentrations that are well in excess of the minimum inhibitory concentration of the infecting organism. Plasma concentration monitoring is essential.
High-dose single daily dosing of aminoglycosides has become more popular recently. It ensures that target peak concentrations are achieved in all patients and may also be less nephrotoxic. It also makes monitoring of gentamicin levels easier.
Uses
Sepsis of unknown origin (with a penicillin and/or metronidazole)
Intra-abdominal infections (with a penicillin and metronidazole)
Acute pyelonephritis (with ampicillin)
Infective endocarditis (beta lactam)
Hospital-acquired pneumonia (with a third-generation cephalosporin)
Severe infections due to P. aeruginosa (with ceftazidime or piperacillin/ tazobactam)
Enterococcal infections (with amoxicillin)
Febrile neutropenia (with ceftazidime or piperacillin/tazobactam)
Contraindications
Pregnancy
Myasthenia gravis
Administration
• Rapid IV bolus: 1–1.5 mg/kg IV 8 hourly
In renal impairment:
CC (ml/min)
|
Dose (mg/kg)
|
Interval (h)
|
20–50
|
1.5
|
12–24
|
10–20
|
1.0–1.5
|
12–24
|
<10
|
1.0
|
24–48
|
• High dose single daily dosing protocol
Avoid this regimen in renal replacement therapy or if the CC <20 ml/min.
IV infusion: 7 mg/kg in 50 ml glucose 5% or sodium chloride 0.9% given over 1 hour. For obese patients lean body weight should be used. The interval is then decided after referring to the Hartford nomogram (developed and validated by DP Nicolau et al, Division of Infectious Diseases,Hartford Hospital,Hartford,Connecticut, USA). A blood level is taken after the first dose to determine subsequent
dosing interval. Alternative nomograms have also been developed for 5 mg/kg dosing. Do not use this nomogram for any other
single dosing protocol.
Monitoring: Take a single blood sample at any time 6–14 hours after the start of an IV infusion. It is essential that the exact time is recorded accurately.
 |
| Time between start of infusion and blood sampling |
Evaluate the nomogram. If the level lies in the area designated Q24, Q36 or Q48, the interval should be every 24, 36 or 48 hourly respectively. Frequency of repeat levels depends on underlying renal function.
If the point is on the line, choose the longer interval. If the dosing interval is greater than 48 hours, an alternative antibiotic should be
used. Single daily dosing should not be used for children, pregnant women, burns patients, infective endocarditis and patients with significant pre-existing renal impairment. It should be used with caution in very septic patients with incipient renal failure.
How not to use gentamicin
Do not mix in a syringe with penicillins and cephalosporins (aminoglycosides inactivated)
Adverse effects
Nephrotoxicity – ↑ risk with amphotericin, bumetanide, furosemide, vancomycin and lithium
Ototoxicity – ↑ risk with pre-existing renal insufficiency, elderly, bumetanide and furosemide
Prolonged neuromuscular blockade – may be clinically significant in patients being weaned from mechanical ventilation
Cautions
Renal impairment (reduce dose)
Concurrent use of:
• amphotericin – ↑ nephrotoxicity
• bumetanide, furosemide – ↑ ototoxicity
• neuromuscular blockers – prolonged muscle weakness
Organ failure
Renal: increased plasma concentration – ↑ ototoxicity and nephrotoxicity
Renal replacement therapy
CVVH dialysed, loading dose 2 mg/kg then 1 mg/kg 12hourly; alternatively some units dose 3–5 mg/kg daily and monitor levels. Levels must be monitored, and dose and interval adjusted accordingly. HD/PD dialysed, dose as in CC 5–10 ml/min, i.e. 2 mg/kg every 48–72 hours; for HD, dose post-dialysis. One hour peak levels should not exceed 10 mg/ml and pre-dose trough should be <2 mg/l.
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