What are the preferred aminoglycosides (e.g. tobramycin, gentamicin, amikacin) for treating Pseudomonas aeruginosa infections?

From the Guidelines

For treating Pseudomonas aeruginosa infections, amikacin is generally the preferred aminoglycoside due to its enhanced activity against this pathogen, as suggested by the most recent guidelines 1.

Key Points

• Amikacin is typically dosed at 15-20 mg/kg/day for adults, often as a single daily dose.
• Gentamicin and tobramycin are alternative options, but their use should be guided by susceptibility testing and clinical context.
• Aminoglycosides are rarely used as monotherapy for Pseudomonas infections and are instead combined with antipseudomonal beta-lactams like piperacillin-tazobactam, cefepime, or meropenem.
• Combination therapy provides synergistic activity and reduces the risk of resistance development, as recommended by recent guidelines 1.

Treatment Considerations

• Therapeutic drug monitoring is essential when using aminoglycosides to maintain peak concentrations for efficacy while avoiding toxicity.
• Target peak levels for amikacin are 15-20 μg/mL and trough levels below 2 μg/mL.
• Careful monitoring for nephrotoxicity and ototoxicity is necessary, especially in patients with renal impairment, the elderly, or those receiving other nephrotoxic medications.

Clinical Context

• The choice of aminoglycoside and combination therapy should be guided by the severity of the infection, the site of infection, and the susceptibility pattern of the isolate.
• Recent guidelines recommend considering the use of old antibiotics, chosen from among the in vitro active antibiotics on an individual basis and according to the source of infection, under the consideration of antibiotic stewardship 1.
• The use of new beta-lactam/beta-lactamase inhibitors (BLBLI) should be reserved for extensively resistant bacteria, and their use should be guided by susceptibility testing and clinical context 1.

From the FDA Drug Label

Gentamicin has been shown to be active against most of the following bacteria, both in vitro and in clinical infections... Gram-Negative Bacteria... Pseudomonas aeruginosa The combined effect of gentamicin and carbenicillin is synergistic for many strains of Pseudomonas aeruginosa Gentamicin injection has been used effectively in combination with carbenicillin for the treatment of life-threatening infections caused by Pseudomonas aeruginosa

Preferred aminoglycosides for treating Pseudomonas aeruginosa infections include:

• Gentamicin, which has been shown to be active against Pseudomonas aeruginosa both in vitro and in clinical infections 2
• The combination of gentamicin and carbenicillin has a synergistic effect against many strains of Pseudomonas aeruginosa 2
• Gentamicin injection has been used effectively in combination with carbenicillin for the treatment of life-threatening infections caused by Pseudomonas aeruginosa 2

From the Research

Aminoglycosides for Treating Pseudomonas aeruginosa Infections

• The preferred aminoglycosides for treating Pseudomonas aeruginosa infections include tobramycin, gentamicin, and amikacin 3, 4, 5, 6.
• Tobramycin has been shown to be more active than gentamicin against Pseudomonas aeruginosa in vitro 3, 4.
• Gentamicin and tobramycin have similar clinical effectiveness, with 45.1% of patients responding favorably to each drug 3.
• Amikacin is also effective against Pseudomonas aeruginosa, but its use is often reserved for strains that are resistant to gentamicin and tobramycin 6.

Comparison of Aminoglycosides

• Tobramycin and sisomycin have been shown to have the highest antibacterial activity against clinical strains of Pseudomonas aeruginosa, with tobramycin being 4-8 times more effective than gentamicin 5.
• The combination of mecillinam and tobramycin has been shown to have a synergistic effect against Pseudomonas aeruginosa, with 18 out of 50 strains showing a synergistic effect 5.
• The combination of ticarcillin and an aminoglycoside (gentamicin, tobramycin, or amikacin) has been shown to be highly variable, with some strains showing synergy and others showing no effect or antagonism 6.

Synergistic Combinations

• The combination of a beta-lactam (piperacillin/tazobactam or cefepime) and an aminoglycoside (gentamicin) has been shown to be synergistic against Pseudomonas aeruginosa, with 79% of combinations showing synergy 7.
• The combination of a beta-lactam and a fluoroquinolone (ciprofloxacin or levofloxacin) has also been shown to be synergistic, with 58-67% of combinations showing synergy 7.
• The degree of synergy between a beta-lactam plus aminoglycoside and a beta-lactam plus fluoroquinolone has been shown to be comparable, with no statistical difference in the frequency of synergy 7.