How do antibiotics act in the body?

Comprehensive Description of Antibiotics Actions in the Body

Antibiotics act in the body primarily by targeting essential bacterial structures or biosynthesis pathways, including bacterial cell wall, DNA, RNA, or proteins, thereby inhibiting bacterial growth by either killing bacteria or preventing them from reproducing and spreading. 1, 2

Mechanisms of Action

Antibiotics employ various mechanisms to combat bacterial infections:

Inhibition of Protein Synthesis

• Macrolides (like erythromycin, clarithromycin, and azithromycin) inhibit RNA-dependent protein synthesis by binding to the 50S ribosomal subunit in bacteria 3
• This binding prevents the formation of peptide bonds between amino acids, effectively halting bacterial protein production 3

Inhibition of DNA/RNA Synthesis

• Fluoroquinolones (like levofloxacin) inhibit bacterial topoisomerase IV and DNA gyrase (both type II topoisomerases), which are enzymes required for DNA replication, transcription, repair, and recombination 4
• By interfering with these essential enzymes, these antibiotics prevent bacterial DNA from unwinding and duplicating 4

Disruption of Cell Wall Synthesis

• Beta-lactam antibiotics (penicillins, cephalosporins) target the bacterial cell wall, which is essential for bacterial survival but absent in human cells 2
• This selective toxicity allows antibiotics to kill bacteria without necessarily damaging host cells 5

Other Mechanisms

• Some antibiotics may cause partial inhibition of growth below the Minimum Inhibitory Concentration (MIC), changes in bacterial morphology, alterations in adhesion to surfaces, or changes in toxin production 3

Pharmacokinetics and Pharmacodynamics

• Pharmacokinetics is the study of drug concentrations over time in different body compartments after administration 3
• Pharmacodynamics examines the relationship between pharmacokinetic parameters and the magnitude and time course of the pathogen's response 3
• These properties determine how antibiotics distribute throughout the body and reach their target sites 3

Post-Antibiotic Effects

• The post-antibiotic effect (PAE) is the continued suppression of bacterial growth after antibiotic exposure has ended 3
• This effect allows for dosing intervals that may exceed the time the drug concentration remains above the MIC 3
• The PAE index measures the time needed for bacterial counts to increase by a factor of 10 after antibiotic removal 3

Antibiotic Interactions

Antibiotics can interact with each other in several ways when used in combination:

• Synergism: The combined effect exceeds the sum of individual effects 3
• Antagonism: The combined effect is less than the effect of the most effective individual antibiotic 3
• Additive effects: The combined effect equals the sum of individual effects 3
• Indifference: The combined effect equals that of the most active component 3

Antibiotic Resistance

Bacteria can develop resistance to antibiotics through various mechanisms:

• Genetic mutations: Spontaneous mutations in bacterial DNA can confer resistance, though this occurs rarely (range: 10⁻⁹ to 10⁻¹⁰) 4
• Mobile genetic elements: Resistance genes can be located on plasmids or transposons, which can be inherited by bacterial progeny and transferred to other bacterial species 3
• Specific resistance mechanisms against macrolides include:
  • Reduced permeability of bacterial cell envelope (especially in Gram-negative bacteria) 3
  • Plasmid-mediated increased efflux (in Staphylococcus species) 3
  • Alteration of the 50S target site, reducing binding affinity 3
  • Enzymatic inactivation (such as by phosphotransferases) 3

Ecological Impact and Resistance Spread

• Antibiotic use can lead to "collateral damage" in the microbiome, with disappearance of commensal bacteria and replacement by resistant organisms 3
• This shift can include emergence of problematic pathogens like MRSA, C. difficile, and resistant Gram-negative bacteria 3
• Resistance mechanisms can spread between bacteria, even from non-pathogenic to pathogenic species 3

Antibiotic Classification and Stewardship

The World Health Organization (WHO) categorizes antibiotics into three groups to guide appropriate use:

• Access antibiotics: First or second-choice options for common infections that should be widely available 3
• Watch antibiotics: Have greater concerns about resistance development and should be targets for stewardship programs 3
• Reserve antibiotics: Last-resort options for multidrug-resistant infections that should be protected through careful use 3

Clinical Considerations

• Antibiotic efficacy can be affected by patient factors such as renal function, hepatic function, and gender 4
• Dosage adjustments may be necessary in patients with impaired renal function to avoid drug accumulation 4
• Monitoring antibiotic levels may be important to establish therapeutic levels, monitor antibiotics with narrow therapeutic/toxic ratios, and detect accumulation of metabolites 5

Pitfalls and Caveats

• Inappropriate antibiotic use contributes to resistance development, which threatens their future effectiveness 6
• The rise in antimicrobial resistance is of national and international concern 3
• Even when antibiotic exposure stops, resistant bacteria do not necessarily revert to being susceptible 3
• Antibiotics can affect non-target bacteria in the microbiome, potentially leading to secondary infections 3