This document provides information about different classes of antibiotics, including their mechanisms of action, examples within each class, and how bacteria can develop resistance. It discusses six classes: penicillins and cephalosporins which act on the bacterial cell wall; macrolides, aminoglycosides, tetracyclines, and others which inhibit bacterial protein synthesis; metronidazole and fluoroquinolones which act on bacterial DNA; and trimethoprim/sulfamethoxazole which inhibit bacterial folic acid synthesis. It also outlines several mechanisms by which bacteria develop resistance, such as genetic mutations, acquisition of resistance genes from other bacteria, and destruction or inactivation of antibiotics.

1. Antibiotics
Online Module
LEARNING OBJECTIVES
Know the names of different classes of antibiotics and how they act on bacterial cells.
Know the names of the antibiotics within each class used in Tayside.
Know which antibiotics are excreted in urine and which via the biliary system.
Understand how bacteria acquire resistance to antibiotics.
Know mechanisms of resistance.
IMPORTANT CONCEPTS
Antibiotics must be selectively toxic, i.e. kill bacteria without damaging the host.
- Bactericidal kill bacteria
Bacteriostatic inhibit bacterial growth
- Narrow spectrum act on a limited range of bacteria
Broad spectrum act on a wide range of Gram negative + positive bacteria
When given orally, antibiotics are absorbed from the small intestine and spread to all parts of the body.
- However, significant amounts are excreted unchanged in faeces into the environment.
Antibiotics work by 3 mechanisms:
Act on bacterial cell wall
o Mammalian cells do not have a cell wall.
Act on bacterial ribosome
o Mammalian ribosomes are structurally different from bacterial ribosomes.
Act on bacterial DNA directly
o Bacterial DNA is structurally different from mammalian DNA.
 Bacterial DNA has single, circular chromosomes.

2. ACTION ON CELL WALLS
PENICILLINS inhibit cell wall synthesis (bactericidal). Any antibiotic ‘cillin’ = penicillin group.
- Safe, notably in pregnancy; very few side effects.
- Range from narrow to broad spectrum.
- Excreted rapidly via kidneys.
Drawbacks include hypersensitivity (allergy) and frequent dosing (4-6 daily) required.
Penicillin is available in 3 forms:
- Benzylpenicillin contains penicillin G; administer intravenously
gram positive organisms
- Phenoxymethyl penicillin contains penicillin V; administer orally
gram negative organisms
- Long-acting penicillin administer intramuscularly
It is mainly used for Clostridium, Streptococcus and Neisseira infections.
Flucloxacillin is a very narrow spectrum antibiotic.
- Useful for Staphylococci and Streptococci infections only; commonly prescribed since Staph and
Strep skin infections are common.
o Skin, soft tissue and wound infections.
o Cellulitis (infection of soft tissues under the skin).
o Drug of choice for Staph. aureus infection.
- Given orally or intravenously.
Amoxicillin is a safe, well-tolerated antibiotic but has become less effective over the years due to
organisms producing β-lactamase, an enzyme that destroys the antibiotic.
- Well absorbed when given orally.
- Used for Strep, Enterococcus, Clostridium, H. influenzae and Neisseira infections.
- Given orally or intravenously.
Co-amoxiclav is a combination of amoxicillin + clavulanic acid (β-lactamase inhibitor).
- Combination extends the range of bacteria that can be treated.
o Extends to Bacteroides, Staph. aureus and E. coli infections.
- Given orally or intravenously.
Piperacillin-Tazobactam combination (antibiotic + β-lactamase inhibitor) is a broad spectrum penicillin
with an extended range of action.
- Will treat most Gram negative bacterial infection, including Pseudomonas infection.
o Will not treat MRSA or ESBL-producing organisms (very resistant coliforms).

3. CEPHALOSPORINS inhibit cell wall synthesis (bactericidal) by preventing cross-linking of peptidoglycan
in the same way as penicillins. Any antibiotic ‘ceph’/‘cef’ = cephalosporin.
- Safe, notably in pregnancy.
- A few side effects.
- Excreted via kidneys and urine.
They are broad-spectrum antibiotics, which significantly affects the normal bowel flora.
- Kill of normal gut bacteria + allow overgrowth of C. difficile, causing gastroenteritis. Use in Tayside is
restricted due to this.
1st
generation Cephalosporins Cefalexin urinary tract infections oral
2nd
generation Cephalosporins Cefuroxime used rarely oral, IV
3rd
generation Cephalosporins Cefixime gonorrhoea oral
Ceftriaxone meningitis IV
Ceftazidime pseudomonas IV
GLYCOPEPTIDES are cell-wall active antibiotics (bactericidal) that work differently from penicillins and
cephalosporins.
- Bind to end of growing pentapeptide chain during peptidoglycan synthesis, preventing cross-linking
and weakening the bacterial cell wall.
- Must be administered intravenously (not absorbed orally).
- Excreted via the kidneys and urine.
o Toxic levels can build up in patients who have kidney failure, causing damage.
- Only active against Gram positive bacteria cell walls.
Vancomycin is not absorbed from the gut but can be given orally to treat C. difficile infection, where it
acts topically on the gut lumen.
- Used for Clostridium, Strep, Enterococcus, Staph. aureus and MRSA infections.

4. ACTION ON BACTERIAL RIBOSOME (inhibit protin synthesis)
Inhibit protein synthesis by attaching to bacterial ribosomes – these are structurally different to
mammalian ribosomes.
Protein synthesis can resume when the antibiotic is removed, so most antibiotics are bacteriostatic.
- Inhibit growth but does not kill the bacteria; the bacteria are killed by WBCs.
MACROLIDES are excreted via the liver, biliary tract and the gut (not excreted in urine).
They are lipophilic and pass through cell membranes easily and are useful in treating infections where
bacteria get into host cells in order to avoid immune system attack.
Erythromycin, clarythromicin and azithromycin.
- Erythromycin is safe in pregnancy; others have not been trialled.
- Indicated for:
o Treating infections caused by intracellular organisms (e.g. Legionella).
o Treating infections caused by organisms that do not have a proper bacterial cell wall (e.g.
Mycoplasma, Chlamydia).
o Alternative for some, but not all, infections in penicllin-hypersensitive patients.
- Used for Clostridium, Strep, Staph aureus, Neisseria and H. influenzae infections.
AMINOGLYCIDES (Gentamicin) are not absorbed from the gut and must be given intravenously,
sometimes intramuscularly.
They bind to ribosomes to inhibit protein synthesis but are bactericidal.
- Active mainly against Gram negative aerobic organisms (coliforms, Pseudomonas) and is used in
hospital for treating life-threatening Gram negative infection.
- Excreted in the urine.
- Used for Staph aureus, MRSA, Pseudomonas, E. coli and Neisseria infections.
There is a very narrow margin between giving enough antibiotic to treat the infection and overdosing
the patient, so blood levels of these antibiotics must be regularly monitored.
- Can cause damage to the kidneys and the 8th
cranial nerve -> renal failure+deafness.
TETRACYCLINES attach to ribosomes and are bacteriostatic. They are excreted via the liver and biliary
system into the gut.
Doxycycline is used for treating infections caused by bacteria that do not have a proper cell wall, and
some chest/skin infections for those who are penicillin-allergic.
OTHERS also inhibit protein synthesis.
Clindamycin is a 2nd
line treatment for Staph and Strep infections, especially in penicillin-allergic patients.
They are also active against the “true” anaerobes.
Chloramphenicol is mainly used as a topical treatment for eye infections (eye drops).

5. ACTION ON BACTERIAL DNA
METRONIDAZOLE acts by causing strand-breakage of bacterial DNA.
It issued for infection caused by true anaerobes and some protozoa (single-celled parasites).
- Used for Clostridium and Bacteriodes infections.
TRIMETHOPRIM/SULPHAMETHOXAZOLE inhibit bacterial folic acid synthesis.
- Trimethoprim can be given on its own (orally) or in combination with sulphamethoxacole as co-
trimoxacole (Septrin).
- Excreted in urine.
- Safe in pregnancy from 4th
month onwards.
- Used for some Gram negative and some Gram positive bacteria.
FLUOROQUINOLONES act by interacting with topoisomerases – enzymes responsible for supercoiling
and uncoiling of bacterial DNA. This results in the bacteria being unable to replicate.
- Can cause Clostridium difficile gut infection, especially in elderly patients.
- Only antibiotics that can be given orally to treat Pseudomonas infection.
- Excreted in urine.
Ciprofloxacin (IV, oral) is used for complicated urinary tract infection.
Levofloxacin (IV only) is only used for severe community-acquired pneumonia in penicillin-allergic
patients.

6. SIDE EFFECTSOF ANTIBIOTICS
GENERAL side effects include:
- nausea and diarrhoea failure of oral contraception
overgrowth of toxic C. difficile -> severe diarrhoea
- resistance sub-optimal doses, prolonged periods encourages resistance
SPECIFIC side effects:
Aminoglycosides
o Gentamicin damages kidneys and causes deafness/dizziness
Glycopeptides
o Vancomycin damages kidneys, occasionally “red man syndrome”
Tetracyclines
o Doxycycline permanent staining of teeth/bones in children < 12 years
Quinolones
o Ciprofloxacin weakens tendons, joint damage in children, seizures
The main ALLERGIC effect is penicillin hypersensitivity (type 1 hypersensitivity).
- Itchy rash, difficulty breathing, swelling of the mouth/tongue/larynx.
- Low blood pressure.
- Swelling at the injection site.
PREGNANCY warnings include trimethoprim and metronidazole (first 3 months at least) and gentamicin,
tetracycline and fluoroquinolones altogether.

7. ANTIMICROBIAL RESISTANCE
Exposure of bacteria to antibiotics in the environment encourages resistance.
- Small “resistant mutants” will survive, while susceptible organisms die off.
=> Antibiotics are becoming less and less effective, and must be used with caution.
There are a few MECHANISMS by which bacteria acquire resistance.
Their ability is the result of a change in their bacterial DNA.
Genetic mutations
Bacteria can reproduce rapidly, doubling in population ever 20 mins in ideal conditions. As a result,
there is a wide scope for “misreading” their genetic code.
- Resistance can accidentally be developed!
Transfer of DNA that codes for antibiotic resistance from one bacterium to another.
Transformation
o When bacteria die + their cells break apart, “free-floating” DNA is released into the
surrounding environment.
o This can be scavenged by other bacteria and incorporated into their DNA.
o This DNA may contain genes that code for antibiotic resistance and benefit the recipient
cell.
Conjugation
o Bacteria often contain extra bits of circular DNA called plasmids. These can carry genes
that confer resistance to antibiotics.
o When two bacteria are in close proximity, a bridge-like structure forms between the two
cells, known as a pilus.
o The plasmid replicates and one copy is transferred via the pilus to the other bacterium.
o This enables a previously susceptible bacterium to acquire resistance.
Transduction
o Bacterial DNA is transferred from one bacterium to another via a virus that infects bacteria
– bacteriophages/phages.
o When a phage infects a bacterium, it takes over the bacteria’s genetic processes to
produce more phage.
o Bacterial DNA, which may code for resistance, may accidentally be incorporated into the
new phage DNA.
o When the host cell dies and the phage is released, they will contain DNA from the host
bacterium that can be transferred to other bacterial cells.

8. Altered antibiotic target binding site
A change in bacterial DNA can change the gene product that is the target of the antibiotic.
E.g. penicillins have to bind to PBP on the bacterial cell wall in order to act.
- A mutation in Staph. Aureus results in the production of abnormal PBP which no longer binds to
penicillins such as flucloxacillin, resulting in the strain becoming resistant – these are known as MRSA
strains.
Destruction/inactivation of antibiotic
Many bacteria code for enzymes that chemically degrade/inactivate the antibiotic, rendering them
ineffective.
E.g. β-lactamases and cephalosporinases target and disrupt the β-lactam ring on the antibiotics.
Increased efflux
Antibiotics enter bacterial cells through channels in the cell wall called porins.
Efflux pumps are channels that actively export antibiotics out of the bacterial cell wall.
Genetic change may increase the rate of efflux.
- Antibiotic pumped straight back out before it has time to act.