Is Amikacin effective against gram-positive or gram-negative bacteria?

Amikacin Spectrum of Activity

Amikacin is primarily effective against gram-negative bacteria, though it also has activity against certain gram-positive organisms, particularly Staphylococcus species. 1

Primary Activity: Gram-Negative Coverage

Amikacin demonstrates excellent activity against gram-negative bacteria and is the aminoglycoside of choice for serious gram-negative infections, particularly those caused by gentamicin- or tobramycin-resistant strains. 2

Specific Gram-Negative Organisms Covered:

• Pseudomonas species 1
• Escherichia coli 1
• Proteus species (both indole-positive and indole-negative) 1
• Klebsiella species 1
• Enterobacter species 1
• Serratia species 1
• Acinetobacter species 1
• Citrobacter freundii 1

Clinical Evidence in Gram-Negative Infections:

• Amikacin achieved 77% favorable response rates in gram-negative bacteremia, with particular success in urinary tract infections (21 of 24 cases) and bacteremias (10 of 12 cases). 3
• In patients with gentamicin-resistant gram-negative organisms, amikacin achieved cure in 11 of 12 infections, demonstrating its critical role when other aminoglycosides fail. 4

Secondary Activity: Limited Gram-Positive Coverage

Amikacin has activity against Staphylococcus species but demonstrates low-order activity against other gram-positive organisms. 1

Important Limitations:

• Aminoglycosides in general, including amikacin, have limited effectiveness against most gram-positive organisms beyond staphylococci. 1
• Amikacin is known to be ineffective against Salmonella and Shigella species in patients, and susceptibility results should not be reported for these organisms. 1

Resistance Profile and Clinical Advantages

Amikacin resists degradation by aminoglycoside-inactivating enzymes that affect gentamicin, tobramycin, and kanamycin, making it particularly valuable for multidrug-resistant gram-negative infections. 1

Resistance Data from Clinical Settings:

• In low- and middle-income countries treating gram-negative neonatal sepsis, amikacin resistance rates were 26% for E. coli, 37% for Klebsiella species, 43% for Enterobacter species, 31% for Pseudomonas species, and 64% for Acinetobacter species—substantially lower than gentamicin resistance rates of 42-70% across these organisms. 5

Synergistic Combinations

Amikacin combined with beta-lactam antibiotics acts synergistically against many clinically significant gram-negative organisms, and it is the aminoglycoside least inactivated by semisynthetic penicillins. 1, 2

Recommended Combinations:

• For carbapenem-resistant Enterobacteriaceae (CRE) infections, aminoglycoside-containing combination therapy (particularly amikacin) reduced clinical treatment failures by 417 per 1000 patients compared to non-aminoglycoside regimens. 5
• For Pseudomonas endocarditis, high-dose antipseudomonal penicillins combined with aminoglycosides have shown salutary effects in right-sided infections. 5

Critical Clinical Pitfalls

• Amikacin should not be relied upon as monotherapy for gram-positive infections beyond staphylococcal species—combination therapy with appropriate gram-positive coverage is essential for mixed infections. 1
• Local antimicrobial susceptibility testing is critical, as CRE strains show highly variable susceptibility to different aminoglycosides; for example, Chinese CRE isolates showed significantly higher susceptibility to amikacin than gentamicin. 5
• Therapeutic drug monitoring should be performed during amikacin treatment, especially with high-dose regimens, to minimize nephrotoxicity and ototoxicity risks while maintaining efficacy. 5