Recommendations for Aminoglycoside Use in Serious Bacterial Infections
Aminoglycosides should be used as concentration-dependent antibiotics with once-daily dosing (5-7 mg/kg daily gentamicin equivalent) in patients with preserved renal function to optimize peak drug plasma concentrations, which provides comparable clinical efficacy with potentially decreased renal toxicity compared to multiple daily dosing regimens. 1
Indications for Aminoglycoside Use
Aminoglycosides (gentamicin, tobramycin, amikacin) are indicated for the treatment of serious bacterial infections caused by susceptible organisms, including septicemia, lower respiratory tract infections, CNS infections, intra-abdominal infections, skin/bone/skin structure infections, and complicated UTIs 2, 3
Aminoglycosides are particularly effective against aerobic gram-negative bacteria including Pseudomonas aeruginosa, Enterobacterales (E. coli, Klebsiella, Enterobacter, Serratia), and certain Staphylococcus species 2, 3
Aminoglycosides are recommended as part of combination therapy for initial treatment of patients with severe pneumonic or septicemic plague 1
Aminoglycosides have shown superior outcomes compared to tigecycline-containing regimens for carbapenem-resistant Enterobacterales (CRE) infections, particularly for complicated urinary tract infections 1
Dosing Recommendations
For serious infections in adults: 3 mg/kg/day divided into 3 equal doses (1 mg/kg every 8 hours) 2
For life-threatening infections in adults: Up to 5 mg/kg/day divided into 3 or 4 equal doses 2
Once-daily dosing (5-7 mg/kg daily gentamicin equivalent) is recommended for patients with preserved renal function to optimize peak drug plasma concentrations 1
For gentamicin in adults: 5 mg/kg every 24 hours IV or IM 1
For tobramycin in adults: 5-7 mg/kg every 24 hours IV or IM 1
For amikacin in adults: 15-20 mg/kg every 24 hours IV or IM 1
For children ≥1 month to ≤17 years: Gentamicin 4.5-7.5 mg/kg every 24 hours IV or IM 1
Monitoring and Safety Considerations
Therapeutic drug monitoring is essential to minimize toxicity - primarily to ensure trough concentrations are sufficiently low to minimize renal toxicity 1
Monitor renal function and serum aminoglycoside concentrations in all patients receiving these agents 2
Reduce the dose or discontinue aminoglycoside if renal impairment occurs 2
Monitor for symptoms of ototoxicity (auditory and vestibular toxicity can be irreversible) 2
Be aware of potential neuromuscular blockade, particularly in high-risk patients 2
Aminoglycosides can cause fetal harm when administered to pregnant women 2
Combination Therapy Considerations
In sepsis and septic shock, aminoglycosides should be initiated with a full, high-end loading dose to rapidly achieve therapeutic levels due to increased volume of distribution in these patients 1
Aminoglycosides are often recommended as part of combination therapy for empiric treatment of suspected or proven pseudomonas sepsis 1
Aminoglycosides have been used effectively in combination with carbenicillin for life-threatening Pseudomonas aeruginosa infections 3
Aminoglycosides have shown efficacy when used in conjunction with a penicillin-type drug for treatment of endocarditis caused by group D streptococci 3
For neonatal sepsis, aminoglycosides (usually gentamicin) combined with ampicillin or benzylpenicillin are recommended as first-line empiric treatment 1
Special Considerations
Patients with chronically mildly impaired renal function should still receive a once-daily-equivalent dose but with an extended period (up to 3 days) before the next dose 1
Once-daily dosing regimen should not be used in patients with severe renal dysfunction in whom the aminoglycoside is not expected to clear within several days 1
Aminoglycosides are not recommended for routine use in gastrointestinal infections due to toxicity concerns 4
Aminoglycosides are not indicated in uncomplicated initial episodes of urinary tract infections unless the causative organisms are susceptible to these antibiotics and not susceptible to antibiotics having less potential for toxicity 3
Potential Adverse Effects
Major toxicities include nephrotoxicity and ototoxicity (auditory and vestibular) 2, 5
Risk factors for toxicity include prolonged use, volume depletion, and concomitant administration of other potentially nephrotoxic agents 6
Allergic reactions including anaphylaxis, exfoliative dermatitis, toxic epidermal necrolysis, erythema multiforme, and Stevens-Johnson Syndrome have been reported 2
Neuromuscular blockade can occur at high doses or with concurrent use of neuromuscular blocking agents 2
By following these evidence-based recommendations, clinicians can optimize the efficacy of aminoglycosides while minimizing their potential toxicities in the treatment of serious bacterial infections.