From the Guidelines
Antibiotics cannot always eradicate an organism due to the unique characteristics of infected tissues, such as high bacterial density, slow rate of bacterial growth within biofilms, and low microorganism metabolic activity, as well as host characteristics like impaired immunity. The primary goal of antibiotic treatment is to eradicate infection, but this can be challenging due to several factors, including:
- Focal infection with high bacterial density, which can lead to the formation of biofilms that shield bacteria from antibiotics 1
- Slow rate of bacterial growth within biofilms, making it difficult for antibiotics to target and kill the bacteria 1
- Low microorganism metabolic activity, which can reduce the effectiveness of antibiotics that target actively growing bacteria 1
- Impaired immunity in the host, which can make it harder for the body to fight off the infection, even with antibiotic treatment 1
- Increased binding of the drug to serum proteins, perturbations of antibiotic penetration into the vegetation, and unique antibiotic pharmacokinetic/pharmacodynamic (PK/PD) features, which can all impact the effectiveness of antibiotic treatment 1
- Development of resistance due to conventional mechanisms, such as genetic mutations or acquiring resistance genes, which can reduce the effectiveness of antibiotics 1
- Formation of protective biofilms that shield bacteria from antibiotics, making it difficult to eradicate the infection 1
- Ability of some bacteria to enter a dormant state called persistence, where they temporarily stop growing, making them less susceptible to drugs that target active cellular processes 1
- Inability of antibiotics to penetrate effectively into certain body sites, such as abscesses, the central nervous system, or bone tissue, which can make it difficult to eradicate the infection 1
- Patient factors like immune system status, underlying diseases, and medication interactions, which can all impact treatment success 1
From the FDA Drug Label
Amikacin, an aminoglycoside, binds to the prokaryotic ribosome, inhibiting protein synthesis in susceptible bacteria. Aminoglycosides are known to be ineffective against Salmonella and Shigella species in patients Amikacin resists degradation by certain aminoglycoside inactivating enzymes known to affect gentamicin, tobramycin, and kanamycin.
Antibiotics, such as Amikacin, cannot always eradicate an organism due to several reasons, including:
- Mechanism of Resistance: Bacteria can develop resistance to antibiotics, making them ineffective.
- Intrinsic Resistance: Certain bacteria, like Salmonella and Shigella species, are inherently resistant to aminoglycosides.
- Enzymatic Degradation: Some bacteria can produce enzymes that inactivate antibiotics, although Amikacin is resistant to some of these enzymes 2.
From the Research
Reasons for Ineffective Antibiotic Treatment
- Biofilms can lead to antibiotic resistance, making it challenging to eradicate organisms using antibiotics alone 3, 4, 5, 6
- The complex structure of biofilms, including the exopolysaccharide matrix, hinders the penetration of antibiotics and prevents the accumulation of bactericidal concentrations throughout the entire biofilm 5, 6
- Gradients of nutrients and oxygen within the biofilm generate different metabolic states of individual cells, favoring the development of antibiotic tolerance and bacterial persistence 5, 6
- Biofilms can develop antibiotic resistance through various mechanisms, including the expression of efflux pumps, mutation frequency, and horizontal gene transfer 4, 5, 6
Specific Examples of Antibiotic Resistance
- Multiple drug-resistant tuberculosis (MDR-TB) infections, where antibiotic resistance is an emerging problem 7
- Staphylococcal infections related to foreign bodies, which persist due to biofilm formation 5
- Chronic Pseudomonas aeruginosa lung infection in cystic fibrosis patients, caused by biofilm-growing mucoid strains 5