HMA - Antibiotics

Natural

antibiotics purified from microbial productions, including fungi and bacteria in soil.

Semi-synthetic

antibiotics made from chemical modification of natural antibiotics to improve spectrum, stability, or resistance.

Synthetic

antibiotics entirely manufactured through chemical synthesis rather than being derived from a natural product.

Selective toxicity

antibiotics target structures and metabolism unique to bacteria, minimising toxicity to human cells.

Narrow spectrum

active against a limited range of bacteria, can be used when causative bacterium is known; less likely to disrupt normal microbiota or select for resistant bacteria.

Broad spectrum

active against a wider range of bacteria, can be used for empirical treatment when causative bacterium is not yet known.

Bacteriostatic

antibiotics that inhibit bacterial growth.

Bactericidal

antibiotics that kill bacteria.

Minimum inhibitory concentration (MIC)

lowest concentration of an antibiotic preventing visible growth of a microorganism under defined laboratory conditions, typically within 18-24 hours in incubation.

Minimum bactericidal concentration

lowest concentration of an antibiotic that kills atleast 99.9% of the original bacterial population under defined laboratory conditions.

Cell wall, membrane, DNA/RNA synthesis, protein synthesis, folic acid synthesis

What are the 5 main antibiotic targets?

Bacterial cell wall

antibiotics inhibit peptidoglycan synthesis or cross-linking, weakening the cell wall and causing bacterial lysis, e.g. β-lactams.

Bacterial cytoplasmic membrane

antibiotics disrupt membrane structure or permeability, causing leakage of ions and cellular contents and ultimately cell death, particularly for gram+ bacteria.

Bacterial DNA or RNA synthesis

antibiotics interfere with DNA replication or RNA transcription, preventing bacteria from reproducing or producing essential proteins, e.g. fluoroquinolones, rifampicin.

Bacterial protein synthesis

antibiotics interfere with protein synthesis by targeting the 30s or 50s bacterial ribosomal subunits (vs 40s and 60s in humans), e.g. tetracyclines, macrolides.

Bacterial folic acid synthesis

antibiotics block bacterial folate production, which bacteria require to synthesise nucleotides and DNA (humans obtain folate from diet), e.g. sulfonamides, trimethoprim.

Penicillin

major β-lactam class that inhibits bacterial cell-wall synthesis, commonly used against Gram+ and some Gram- bacteria, depending on the specific drug.

Penicillin binding proteins

enzyme binding to terminal D-Ala-D-Ala to cross link newly synthesised peptidoglycans.

Penicillin G

natural penicillin usually given intramuscularly or by IV, active against gram+ bacteria and a limited range of other organisms; choice treatment for syphillis caused by Treponema pallidum.

Penicillin V

natural penicillin taken orally as improved acid-stability, used to treat streptococcal throat infections and mild oral/skin infections.

Amoxicillin

aminopenicillin that can be taken orally and has broader Gram- activity than natural penicillins. Commonly used for respiratory, ear, urinary and dental infections.

Ampicillin

aminopenicillin with broader Gram- activity than natural penicillins. Commonly used for enterococcal, Listeria and some respiratory/urinary infections.

R group

What is synthetically modified on natural penicillins to allows them to pass through some gram- outer-membrane porins to inhibit penicillin binding proteins in the periplasm?

Amoxicillin

aminopenicillin that can be taken orally and has broader Gram- activity than natural penicillins. Commonly used for respiratory, ear, urinary and dental infections.

Ampicillin

aminopenicillin with broader Gram- activity than natural penicillins given IV. Commonly used for enterococcal, Listeria and some respiratory/urinary infections.

Flucloxacillin & dicloxacillin

antistaphylococcal penicillins designed to resist staphylococcal β-lactamase. Mainly used for methicillin-susceptible Staphylococcus aureus (MSSA) skin and soft-tissue infections; usually oral.

Piperacillin

antipseudomonal penicillin with broader gram- activity including Pseudomonas aeruginosa. Usually given IV, often combined with tazobactam (β-lactamase inhibitor).

GIT upset

nausea, vomiting, and diarrhoea, often due to penicillin disruption of normal microbiota.

Maculopapular rash

flat and raised skin rash of macules and papules commonly a delayed, non-IgE-mediated reaction to penicillins forming antigen complexes with host proteins.

Candidiasis

overgrowth of Candida fungi (e.g. oral or vaginal thrush) due to disruption of normal bacterial microbiota by penicillin.

Urticaria

raised, itchy, transient red or pale welts caused by histamine release within minutes-hours after exposure associated with IgE-mediated allergy to penicillin

Angioedema

swelling of deeper tissues, commonly affecting the lips, tongue, face or throat within minutes-hours after exposure associated with IgE-mediated allergy to penicillin.

Anaphylaxis

rapid, life-threatening systemic IgE mediated allergic reaction to penicillin.

(1) Cefalothin/cephazolin

cephalosporins with strong gram+ activity commonly used for skin/soft-tissue infections and surgical prophylaxis.

(3) Ceftriaxone/cefotaxime

cephalosporins with increased gram- activity compared with earlier generations and penetrated the CNS, so used for serious systemic infections and meningitis.

(5) Ceftaroline

advanced cephalosporins with activity against MRSA in addition to various Gram-positive and Gram-negative bacteria.

Stewardship principle

antibiotics should only be used when bacterial infection is suspected or confirmed, and when treatment is clinically indicated.

Vancomycin (a glycopeptide)

antibiotic that inhibits bacterial-cell wall cross bridge synthesis mainly in gram+ bacteria. Used to treat serious and resistant gram+ bacterial infections.

Clostrifioides difficile

infection that can be treated by orally administered Vancomycin as it is poorly absorbed.

D-ala residues, no cross-bridge formation

Where does Vancomycin bind and what action does this cause?

Red man syndrome

fast infusion of vancomycin triggers mast cells to release histamine causing a red, itchy rash; prevented with 1-2 hour infusion period or pretreatment with antihistamines.

Nephrotoxicity

damage to kidneys associated with glycopeptide and aminoglycoside usage.

Gentamicin (an aminoglycoside)

antibiotic that inhibits bacterial protein synthesis by binding to 30s subunit given only by IV or IM to treat serious aerobic gram- infections.

30s ribosomal subunit, misreading mRNA

Where does gentamicin bind, and what action does this cause?

Ototoxicity

damage to the ear associated with glycopeptide and especially aminoglycoside usage.

Ciprofloxacin (a fluoroquinolone)

a broad-spectrum antibiotic inhibiting DNA gyrase and topoisomerase for DNA replication, preventing growth and survival of many gram- and gram+ bacteria.

Salmonella Typhi

bacterium causing seriously infect the GIT and can enter the bloodstream causing systemic infection that is treated with ciprofloxacin.

DNA gyrase

bacterial enzyme that removes positive super helical twists in DNA, allowing DNA replication to continue.

Topoisomerase IV

bacterial enzyme allowing separation of newly synthesised chromosomes into different daughter cells.

DNA gyrase, topoisomerase, no DNA replication

Where does ciprofloxacin bind and what action does this cause?

Children under 14 years, pregnant, or breastfeeding women

Contraindications for fluroquinolones due to damage to joints shown in immature animals.

Doxycycline (a tetracycline)

broad-spectrum antibiotics that inhibit bacterial protein synthesis by distorting 30s subunit in gram+/- bacteria, obligate intracellular pathogens like chlamydia, and the cell wall deficient mycoplasma.

30s ribosomal subunit, prevents peptide bond forming

Where does doxycycline bind and what action does this cause?

Azithromycin (a macrolide)

antibiotic that inhibits protein synthesis by binding to 50s subunit in gram+ bacteria and some atypical respiratory pathogens.

50s ribosomal subunit, prevents peptide bond forming

Where does azithromycin bind and what action does this cause.

Macrolides

antibiotics accumulating in leucocytes, enhancing drug delivery to site of infection.

Metronidazole & Tinidazole (Nitroimidazoles)

antibiotic that are activated inside susceptible anaerobic bacteria or protozoan, generating radicals that damage DNA.

Toxic nitro radicals

metabolites produced by the reduction of nitroimidazoles in anaerobes that damage DNA.

Glycopeptides

What class of antibiotic is used to treat MRSA and serious Gram+ infections?

Glycopeptides

What class of antibiotic inhibits cell wall synthesis by binding to D-Ala-D-Ala, to prevent crossbridge formation?

Glycopeptides

What class of antibiotic can cause nephrotoxicity, ototoxicity, or red-man syndrome?

Aminoglycosides

What class of antibiotic is used to treat severe aerobic Gram- infections, including sepsis?

Aminoglycosides

Aminoglycosides

What class of antibiotic binds to 30s subunit, causing misreading of mRNA and the production of faulty proteins?

Aminoglycosides

What class of antibiotic causes nephrotoxicity and irreversible ototoxicity, and sometimes a rash.

Fluoroquinolones

What class of antibiotic is broad spectrum, and can be used to treat Typhoid fever?

Fluoroquinolones

What class of antibiotic inhibits DNA gyrase and topoisomerase to disrupt DNA synthesis?

Fluoroquinolones

What class of antibiotic is associated with nausea, upper GI discomfort, rashes, dizziness, photosensitivity, and tendon damage?

Tetracyclines

What class of antibiotic is very broad spectrum and can treat Chlamydia, Rickettsia, and Mycoplasma species?

Tetracyclines

What class of antibiotic binds to 30s subunit, distorting the ribosome and preventing aminoacyl-tRNA attachment?

Tetracyclines

What class of antibiotic causes GI upset, photosensitivity, and tooth staining?

Macrolides

What class of antibiotic binds to 50s subunit, inhibiting peptide elongation?

Macrolides

What class of antibiotic is used to treat respiratory infections including atypical pneumonia, and also H. pylori infections?

Nitroimidazoles

What class of antibiotic requires anaerobic activation to produce DNA-damaging metabolites?

Nitroimidazoles

What class of antibiotic is used to treat anaerobic bacteria, protozoans, and H. pylori?

Antibiotic resistance

ability of bacteria to survive or grow despite exposure to an antibiotic.

Acquired resistance

resistance developed through new genetic changes, such as chromosomal mutations or via horizontal gene transfer.

Intrinsic resistance

naturally occurring resistance due to a bacterial species’ inherent characteristics.

Chromosomal mutations

random, spontaneous changes in bacterial DNA that can alter antibiotic targets or other resistance-related traits becoming dominant in a population by selection pressures.

Horizontal gene transfer

transfer of genetic material between bacteria, potentially spreading antibiotic resistance.

Transformation

uptake and incorporation of free DNA from the environment by a bacterial cell, often originating from lysed bacteria.

Transduction

bacterial DNA is packaged and delivered to a recipient bacterium by bacteriophages.

Conjugation

direct transfer of plasmids or transposons between bacteria via a mating bridge, typically with conjugative pili.

Target modification

alteration of the antibiotic’s target, reducing antibiotic binding and effectiveness.

Decrease uptake/permeability

reduced antibiotic entry into bacteria due to changes or loss of membrane porins.

Antibiotic inactivation

chemical modification or destruction of an antibiotic by bacterial enzymes.

Active efflux

efflux pumps actively remove antibiotics from bacterial cells, reducing intracellular concentrations.

Methicillin-susceptible S. aureus (MSSA)

carries blaZ gene encodes for β-lactamase that inactivates regular penicillin by hydrolysing the β-lactam ring. Gene acquired from plasmids or other mobile elements.

Methicillin-resistant S. aureus (MRSA)

carries mecA gene encoding for altered penicillin binding protein (PBP2a) which has low affinity for methicillin and other β-lactam antibiotics, inhibiting their action.

blaZ gene

gene in methicillin-susceptible staphylococcus aureus encoding for β-lactamase that inactivates regular penicillin by hydrolysing the β-lactam ring.

mecA gene

gene in methicillin-resistant staphylococcus aureus for altered penicillin binding protein (PBP2a) which has low affinity for methicillin and other β-lactam antibiotics, inhibiting their action.

PBP2a

enzyme coded for by mecA in methicillin-resistant staphylococcus aureus which has low affinity for methicillin and other β-lactam antibiotics, inhibiting their action.

Vancomycin-resistant S. aureus (VRSA)

carries vanA operon allowing synthesis of cell wall precursor ending in D-Ala-D-lactate, greatly reducing vancomycin binding. Operon acquired from an Enterococcus spp.

Vancomycin-resistant enterococci (VRE)

GIT microbiota carrying gene synthesising cell wall precursor ending in D-Ala-D-lactate or D-Ala-D-Serine, greatly reducing vancomycin binding.

D-Ala-D-Ala

normal peptidoglycan terminating sequence to which vancomycin binds to inhibit cell wall synthesis.

D-Ala-D-lactate or serine

peptidoglycan terminating sequence in vancomycin-resistant staphylococcus aureus and enterococci that greatly reduces vancomycin binding.

vanA operon

cluster of genes coding for cell wall precursor ending in D-Ala-D-lactate in vancomycin-resistant staphylococcus aureus that greatly reduces vancomycin binding.

Flucloxacillin, dicloxacillin

narrow-spectrum β-lactam antibiotics with bulky side chains protecting the β-lactam ring from hydrolysis by penicillinase, so are active against penicillinase-producing MSSA, but NOT MRSA.

Beta-lactamase inhibitors

restore or extend activity of partner β-lactam antibiotics against enzymatic inactivation, but have little antibacterial activity when used alone, e.g. piperacillin is always paired with tazobactam.

Piperacillin-tazobactam

β-lactam and β-lactamase inhibitor with activity against pseudomonas aeruginosa.