Amikacin dosing

The amikacin dosing regimen is best determined using therapeutic drug monitoring. The suggested peak concentration of amikacin (1 h after administration) is 25 xg/ml and the trough concentration should be <5 xg/ml. 

Monitoring plasma drug levels is important when aminoglycosides are used. In this case the patient seems to be improving, so a decrease of the amikacin dose in proportion to decreased creatinine clearance is most appropriate. Since creatinine clearance is only one-third of the starting value, a dose reduction should be made to one-third of that given initially. The answer is (B). 

Because they are hepatically cleared, isoniazid and rifampin do not require dose modification in renal failure.31,36,39 Pyrazinamide and ethambutol typically are reduced to three times weekly to avoid accumulation of the parent drug (ethambutol) or metabolites (pyrazinamide).28,31 Renally cleared TB drugs include the aminoglycosides (e.g., amikacin, kanamycin, and streptomycin), capreomycin, ethambutol, cycloserine, and lev-ofloxacin.28,31,33,39 Dosing intervals need to be extended for... 

Amikacin/ kanamycin Adults See footnote8 Children 15-30 mg/kg per day intravenous or intramuscular as a single daily dose Ototoxicity, nephrotoxicity Baseline audiogram, vestibular testing, Romber testing and SCr Monthly assessments of renal function and auditory or vestibular symptoms... 

Amikacin Yes 12-15 mj kg per dose two to three times per week (not daily)... 

The steady-state maximum plasma concentration, Cmaxss, of gentamycin and tobramycin are 6 to 10 mcg/mL. The Cmax ss of amikacin is 25 to 30 mcg/mL. The Cmin ss of both gentamycin and tobramycin is 0.5 to 1.5 mcg/mL, while that of amikacin is 5 to 8 mcg/mL. In order for these drugs to be effective, it is important to closely monitor their therapeutic concentrations. An important observation of these antibiotics is that with prolonged therapy, the Cminsl, values increase. This increase is due to the renal impairment. In the case where Cmin ss is less than the desired Cmin ss, the dose may be insufficient. 

The steady-state maximum concentration (Cmaxss) after the administration of amikacin was 38 mcg/mL, and the steady-state minimum serum concentration was 10 mcg/mL. If the dosing regimen has to be changed, how should it be done ... 

Dialysis Approximately half the normal mg/kg dose can be given after hemodialysis in peritoneal dialysis, a parenteral dose of 7.5 mg/kg is given, and then amikacin is instilled in peritoneal dialysate at a concentration desired in serum. 

Like all aminoglycosides, amikacin is nephrotoxic and ototoxic (particularly for the auditory portion of the eighth nerve). Serum concentrations should be monitored. Target peak serum concentrations for an every-12-hours dosing regimen are... 

Amikacin Intravenous resistant to many enzymes that inactivate gentamicin and tobramycin higher doses and target peaks and troughs than gentamicin and tobramycin... 

It is important to monitor peak and trough plasma levels (see p. 20) of gentamicin, tobramycin, netilmicin, and amikacin to avoid concentrations that cause dose-related toxicities (Figure 31.7). [Note Peak levels are defined as those obtained 1/2 to 1 hour after infusion. Trough levels are obtained immediately before the next dose.] Patient factors, such as old age, previous exposure to aminoglycosides, gender, and liver disease, tend to predispose patients to adverse reactions. The elderly are particularly susceptible to nephrotoxicity and ototoxicity. 

The aminoglycoside, amikacin. The aminoglycosides can inhibit Ca++ uptake which is required for the release of acetylcholine at the neuromuscular junction, and can cause neuromuscular blockade. This is rare at usual doses of the drug, but patients with myasthenia gravis are particularly susceptible. 

INDOMETACIN AMINOGLYCOSIDES T amikacin, gentamicin, and vancomycin levels in neonates Uncertain indometacin possibly 1 renal clearance of these aminoglycosides Halve the dose of antibiotic. Uncertain whether this applies to adults but suggest check levels. Otherwise use an alternative NSAID... 

Dose. The equivalent of 15 mg of amikacin/kg daily, given parenterally maximum of 1.5 g daily. The total dose should not exceed 15 g. 

After administration of the recommended doses of amikacin for 10 days, renal damage probably occurs in less than 10% of cases. Limited data support the view that amikacin is less nephrotoxic than other aminoglycosides, possibly because of lower binding affinity to proximal tubular cells or reduced potential to cause phospholipidosis (SEDA-20,236). In several prospective randomized studies the liability of amikacin to cause nephrotoxicity was no greater than that of gentamicin or tobramycin (6-8). In a prospective study there was significantly lower nephrotoxicity with amikacin 15 mg/kg/day (4% toxicity) compared with netilmicin 7 mg/kg/day (12%) (9). As with other aminoglycosides, renal toxicity is reversible in most cases (10). 

In a retrospective study in 81 men and 29 women, hearing loss of 15 decibels at two or more frequencies, or at least 20 decibels at at least one frequency, was found in 18% of patients treated with aminoglycosides (amikacin, kanamycin, and/or streptomycin) (24). In those treated with kanamycin the rate was 16%. Age, sex, treatment duration, total aminoglycoside dose, and first serum creatinine concentration were not associated with hearing loss. 

Once-daily amikacin was as effective and safe as twice-daily dosing in a prospective randomized study in 142 adults with systemic infections (160). 

Hottendorf GH, Gordon LL. Comparative low-dose nephrotoxicities of gentamicin, tobramycin, and amikacin. Antimicrob Agents Chemother 1980 18(1) 176-81. 

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