10.2 Antibiotics – Antibiotic Resistance
Key concepts
- Antibiotics act on specific bacterial structures or processes (cell‑wall synthesis, protein synthesis, DNA replication).
- Use of an antibiotic creates selection pressure: susceptible cells die, resistant cells survive and multiply.
- Resistance may be intrinsic (natural, e.g., Gram‑negative outer membrane, efflux pumps in Pseudomonas aeruginosa) or acquired (mutation or horizontal gene transfer).
- Horizontal gene transfer (plasmids, transposons, bacteriophages) spreads resistance genes between species.
- WHO (Global Antimicrobial Resistance Report 2022) estimates >10 million deaths per year worldwide by 2050 if current trends continue.
Mode of action of penicillin (AO1)
- Penicillins belong to the β‑lactam group; the β‑lactam ring is essential for activity.
- The β‑lactam ring binds irreversibly to bacterial penicillin‑binding proteins (PBPs), which are trans‑peptidases that catalyse the final cross‑linking of peptidoglycan strands.
- Key phrase for exam recall: inhibition of PBPs → failure of peptidoglycan cross‑linking → weakened cell wall → osmotic lysis during growth.
- Because the target is absent in human cells, penicillin is selectively toxic to bacteria.
Why antibiotics do not affect viruses (AO1)
- Viruses lack the cellular structures targeted by antibiotics (no cell wall, no ribosomes, no bacterial‑type DNA‑replication enzymes).
- Antibiotics act on processes that are simply not present in viruses, so there is no pharmacological target.
- Consequently, antibiotics are ineffective against viral infections such as the common cold, influenza, or COVID‑19.
Antibiotic resistance – definition
Antibiotic resistance occurs when bacteria acquire or express mechanisms that reduce or eliminate the efficacy of an antibiotic that would normally inhibit or kill them.
Intrinsic vs. acquired resistance
- Intrinsic resistance – natural features of a species:
- Gram‑negative outer membrane blocks many β‑lactams.
- Efflux pumps in Pseudomonas aeruginosa expel a wide range of antibiotics.
- Lack of the target enzyme (e.g., some bacteria lack dihydropteroate synthase, rendering sulfonamides ineffective).
- Acquired resistance – obtained after the organism is already susceptible:
- Mutation in chromosomal genes (e.g., rpoB mutations → rifampicin resistance).
- Horizontal gene transfer – acquisition of resistance genes on plasmids, transposons or bacteriophages.
Major antibiotic target groups (required for AO1)
| Target group | Representative drug class | Example drug |
|---|
| Cell‑wall synthesis | β‑lactams | Penicillin, amoxicillin |
| Protein synthesis | Tetracyclines | Tetracycline, doxycycline |
| DNA replication / transcription | Fluoro‑quinolones | Ciprofloxacin, levofloxacin |
Consequences of antibiotic resistance (AO2)
- Increased morbidity and mortality – infections become harder to treat, leading to longer hospital stays and higher death rates.
- Higher healthcare costs – need for expensive second‑line or combination therapies, prolonged intensive care, and additional diagnostic tests.
- Reduced safety of medical procedures – surgeries, organ transplants, chemotherapy and intensive care rely on effective prophylactic antibiotics.
- Spread of resistance genes – plasmid‑mediated transfer accelerates emergence of multi‑drug‑resistant (MDR) strains across species.
- Impact on agriculture and food security – use of antibiotics in livestock selects resistant bacteria that can reach humans via the food chain.
- Global public‑health threat – WHO projects up to 10 million deaths annually by 2050 if current trends continue (WHO 2022).
Key examples of resistant pathogens
| Pathogen | Common resistance mechanism | Clinical impact |
|---|
| Staphylococcus aureus (MRSA) | Altered PBP (PBP2a) – reduced β‑lactam binding | Skin, bloodstream and respiratory infections unresponsive to β‑lactams |
| Mycobacterium tuberculosis (MDR‑TB) | Mutations in rpoB (rifampicin) and katG (isoniazid) | Long‑term therapy with second‑line drugs; higher fatality |
| Escherichia coli (ESBL‑producing) | Extended‑spectrum β‑lactamases that hydrolyse cephalosporins | Urinary and gastrointestinal infections resistant to many β‑lactams |
| Neisseria gonorrhoeae | Efflux pumps & altered PBPs | Untreatable sexually transmitted infection |
Steps to reduce the impact of antibiotic resistance (AO2)
- Prudent prescribing (reducing selection pressure)
- Prescribe only when a bacterial infection is confirmed or highly suspected.
- Choose the narrow‑spectrum agent that matches the identified pathogen.
- Follow the correct dose, route and duration to minimise surviving bacteria.
- Infection prevention and control (IPC) (reducing transmission)
- Hand hygiene, sterilisation of instruments and isolation of infected patients.
- Vaccination programmes to lower the incidence of bacterial disease.
- Antibiotic stewardship programmes (monitoring use)
- Multidisciplinary teams review prescriptions and give feedback.
- Electronic alerts and audit tools flag inappropriate choices.
- Public education and awareness (behavioural change)
- Explain the importance of completing the full course.
- Discourage self‑medication and the use of leftover antibiotics.
- Surveillance and monitoring (data‑driven action)
- National databases record resistance patterns and antibiotic consumption.
- Rapid diagnostic tests identify pathogens and resistance genes, allowing targeted therapy.
- Research and development (new tools)
- Incentives for novel antibiotics, bacteriophage therapy, antimicrobial peptides and vaccines.
- Studies on resistance mechanisms to design drugs that bypass them (e.g., β‑lactamase inhibitors).
- Regulation of antibiotic use in agriculture (reducing selection pressure in animals)
- Ban non‑therapeutic use of antibiotics as growth promoters.
- Implement veterinary stewardship comparable to human healthcare.
Case study – MRSA outbreak in a hospital ward (AO2 & AO3)
Background: In 2023 a surgical ward reported 18 cases of MRSA infection over 3 months. The infection rate rose from 2 cases / 1 000 patient‑days to 12 cases / 1 000 patient‑days.
Intervention (6 weeks):
- Enhanced hand‑hygiene audit – compliance ↑ from 62 % to 95 %.
- Stewardship protocol – all empirical antibiotics reviewed within 48 h.
- Environmental cleaning with sporicidal agents.
Result: Post‑intervention infection rate fell to 3 cases / 1 000 patient‑days (≈75 % reduction).
Assessment links:
- AO2 – students discuss how reducing selection pressure (targeted therapy) and breaking transmission routes (IPC) lowered resistant infections.
- AO3 – students can plot pre‑ and post‑intervention rates, calculate the percentage reduction and evaluate which mitigation step was most effective.
Suggested practical investigation (AO3)
Title: Effect of sub‑inhibitory concentrations of penicillin on the growth of Escherichia coli and calculation of mutation frequency.
| Step | Procedure |
|---|
| 1. Preparation | Inoculate a starter culture of E. coli in nutrient broth; incubate overnight at 37 °C. |
| 2. Dilution series | Prepare broth tubes containing 0 µg mL⁻¹ (control), 0.5× MIC, 0.25× MIC and 0.1× MIC of penicillin. |
| 3. Inoculation | Add a fixed inoculum (≈10⁴ CFU mL⁻¹) to each tube; incubate 24 h, measuring optical density (OD₆₀₀) every 2 h. |
| 4. Plating for mutants | After 24 h, plate 100 µL from each tube onto agar containing 4× MIC penicillin. Incubate 48 h. |
| 5. Data collection | Count colonies on selective plates (resistant mutants) and on non‑selective plates (total viable cells). |
| 6. Calculation | Mutation frequency = (resistant colonies) / (total viable cells). |
| 7. Replication | Perform three independent replicates for each concentration to ensure statistical reliability. |
| 8. Evaluation | Discuss sources of error (pipetting, contamination, incubation conditions) and how sub‑inhibitory antibiotic levels can increase the chance of selecting resistant mutants. |
Summary
Antibiotic resistance threatens the treatment of bacterial infections, inflates mortality and healthcare costs, and endangers modern medical procedures. Understanding the biochemical basis of antibiotic action (e.g., penicillin’s inhibition of PBPs), why antibiotics do not affect viruses, and the mechanisms behind resistance (selection pressure, intrinsic vs. acquired, horizontal gene transfer) equips students to discuss the serious consequences and to evaluate mitigation strategies. The case‑study and practical investigation provide concrete AO2 and AO3 tasks, reinforcing both conceptual knowledge and experimental skills required by the Cambridge 9700 syllabus.
Reference: World Health Organization, *Global Antimicrobial Resistance Report 2022*, WHO, 2022.