Immunology - Antibiotics Flashcards
Mechanism of penicillin?
- Inhibit penicillin-binding proteins such as the enzyme DD-transpeptidase (this catalyses the cross-linking of peptidoglycans in bacterial cell walls)
- Inhibition of this process weakens the cell walls, allowing an influx of water into the cell
- This leads to cell swelling and then cell lysis.
What are 4 example Penicillin drugs?
- Penicillin V
- Amoxicillin/Co-Amoxiclav
- Flucloxacillin
- Tazocin
What is Penicillin V used to treat?
- Streptococcal infections e.g. tonsillitis, pneumonia, endocarditis and skin infections
- Clostridial infections e.g. tetanus
- Meningococcal infections e.g. meningitis
What is Amoxicillin/Co-Amoxiclav used to treat?
Gram-positive or Gram-negative pneumonia
E. coli UTI
Intra-abdominal sepsis
H. pylori eradication
What is Flucloxacillin used to treat?
Streptococcal infections including skin and soft tissue, osteomyelitis and septic arthritis
What is Tazocin used to treat?
Used for only very severe infections, especially where there is a broad spectrum of potential causative organisms, including Pseudomonas.
It is used to treat sepsis of almost all causes, in particular respiratory, urinary, skin, soft-tissue and intra-abdominal infections.
What are common side effects of penicillins?
GI upset, including antibiotic-associated C. difficile infection.
How common is a penicillin allergy?
A degree of allergy to penicillin is very common, affecting up to 10% of the population
Why are Cephalosporins and Carbapenems grouped together?
Due to their similar structural properties and mechanisms of action.
Mechanism of Cephalosporins and Carbapenems?
Like penicillins, these antibiotics get their antimicrobial effect from the presence of a ß-lactam ring in their structure; they inhibit the cross-linking of peptidoglycans in bacterial cell walls.
What are 3 examples of Cephalosporins?
- Cefotaxime
- Cetriaxone
- Cefuroxime.
What is major example of Carbapenems?
Meropenem
What are Cephalosporins and Carbapenems used to treat?
Broad-spectrum, but as they have evolved, cephalosporins have become more suited for use against Gram-negative bacteria.
As both these types of antibiotic have a high chance of leading to bacterial resistance, they are usually reserved for very serious infections.
Common side effects of Cephalosporins and Carbapenems?
Simple GI upset
Antibiotic-associated colitis
Hypersensitivity reactions.
Why must extra care be taken giving Cephalosporins and Carbapenems in penicillin-allergic patients?
As their structure and mechanism is similar to penicillin, there may be cross-reactivity in penicillin-allergic patients, thus extreme caution must be taken.
Cautions/contraindications of Cephalosporins and Carbapenems?
Use with extreme caution in those with penicillin allergy
Use with caution in those at high risk of C. difficile
Use with caution in renal impairment
Mechanism of glycopeptides?
Glycopeptides prevent the formation of cross links in the peptidoglycan cell wall.
How do glycopeptides differ from penicillins?
While penicillins irreversibly and competitively inhibit DD-transpeptidase, glycopeptides bind to the proteins in the cell wall themselves to prevent DD-transpeptidase from binding.
2 examples of glycopeptides?
- Vancomycin
2. Teicoplanin
What is Vanomycin used for?
- Orally for severe C. difficile infections
- Intravenously for severe soft tissue/bone/joint infections as gram-positive cover.
What is Teicoplanin used for?
- IV for gram-positive cover, either as treatment
- Commonly used as surgical prophylaxis in penicillin allergic patients.
Cautions of Vancomycin?
Vancomycin accumulates in renal disease, and so dosing is done according to the patient’s weight and creatinine clearance (not eGFR).
Mechanism of aminoglycosides?
Inhibit bacterial protein synthesis by binding to the 30S subunit of the ribosome.
Most commonly used aminoglycoside?
Gentamicin
What are aminoglycosides used for?
Aminoglycosides tend to be used for severe infections, especially those caused by Pseudomonas.
They are also often combined with penicillins or metronidazole where the causative organism of severe infection is unknown.
Common side effects of aminoglycosides?
- Nephrotoxicity, especially if combined with other nephrotoxic drugs
- Ototoxicity – usually only if used long-term. Symptoms can include tinnitus, hearing loss or vertigo, and these may be irreversible.
Interactions of aminoglycosides?
Loop diuretics such as Furosemide – high risk of otoxocity
Vancomycin – risk of nephrotoxicity and ototoxicity
Mechanism of Macrolides?
Inhibit bacterial protein synthesis by binding to the 50S subunit of the ribosome, preventing ribosomal translocation and therefore protein elongation.
Examples of macrolides?
- Clarithromycin
- Erythromycin
- Azithromycin
What are macrolides used to treat?
- Usually used for respiratory, skin and soft tissue infections in those with a penicillin allergy.
- Used in H. pylori eradication (along with a PPI + amoxicillin or metronidazole – this is known as “triple therapy”)
Side effects of macrolides?
- GI irritation/upset common if given orally – macrolides are pro-kinetic and can be used therapeutically in gastroparesis.
- Prolonged QT interval.
- Ototoxicity.
Interactions of macrolides?
Macrolides are CYP450 inhibitors (except Azithromycin) so increase the concentration of drugs metabolised by CYP450 enzymes – this increases the bleeding risk with warfarin, for example. CYP450 inhibitors in turn decrease the efficacy of macrolides.
Macrolides should also not be given with other drugs that prolong the QT interval.
What is effect of CYP450 inhibitors on macrolides?
CYP450 inhibitors in turn decrease the efficacy of macrolides.
Cautions of macrolides?
Use with caution in severe renal or hepatic impairment
Mechanism of Quinolones?
Inhibit bacterial DNA duplication through inhibition of topoisomerases, which interfere with DNA unwinding and therefore transcription and translation.
Most commonly used quinolone?
Ciprofloxacin
What are quinolones used to treat?
- Gram-negative infections. They should be reserved for 2nd or 3rd-line treatment only as there is increasing resistance to these antibiotics, and they also commonly cause C. difficile.
- Ciprofloxacin is the only antibiotic available in oral form which is active against Pseudomonas aeruginosa
Side effects of quinolones?
GI upset
Prolonged QT interval
High risk of C. difficile
Interactions of quinolones?
Should not be used with other drugs that prolong the QT interval
Mechanism of Metronidazole?
Once in its reduced form, Metronidazole inhibits bacterial DNA synthesis. As metronidazole is only reduced in this way in anaerobic bacteria, it is a specific antibiotic for anaerobic infections.
What are metronidazoles used to treat?
Used against anaerobic bacteria including C. difficile, oral infections and intra-abdominal or pelvic infections.
However, it is also active against protozoal infections e.g. giardiasis, dysentery and trichomonas vaginalis.
Side effects of metronidazoles?
GI upset
Hypersensitivity reactions
Peripheral and optic neuropathy (high dose/long term use only)
Seizures and encephalopathy (high dose/long term use only)
Interactions of metronidazoles?
Inhibits CYP450 so increases the effect of drugs metabolised by these enzymes, and in turn these drugs will decrease the efficacy of metronidazole
Lithium – metronidazole increases the risk of lithium toxicity
Cautions/Contraindications of metronidazoles?
Alcohol must not be drunk while on metronidazole and for ~48 hours after the end of the course. Metronidazole interferes with alcohol metabolism and gives severe side effects as a result.
Use with caution in severe liver disease
Mechanism of Nitrofurantoin?
Damages bacterial DNA causing cell death.
What are nitrofurantoins used to treat?
Used to treat UTIs caused by both Gram-positive and Gram-negative bacteria.
Side effects of nitrofurantoins?
GI upset
Hypersensitivity reactions
Cautions/Contraindications of nitrofurantoins?
Contraindicated in pregnant women towards term and babies in the first 3 months of life
Contraindicated in renal impairment
Caution if using as long-term prevention as higher risk of side effects
Mechanism of Trimethoprim?
Inhibits bacterial folate synthesis through inhibition of dihydrofolate reductase.
What are trimethoprims used to treat?
Used to treat UTIs caused by both Gram-positive and Gram-negative bacteria, although resistance is increasing and therefore it is less commonly used now as the first-line treatment for UTI.
Also used as treatment or prophyalxis for Pneumocystis pneumonia as Co-Trimoxazole (Trimethoprim combined with Sulfamethoxazole, a sulfonamide antibiotic)
Side effects of trimethoprims?
Commonly causes a skin rash
GI upset
Hypersensitivity is common and can be severe
Hyperkalaemia
Interactions of trimethoprims?
Drugs which also cause hyperkalaemia e.g. ACE inhibitors, spironolactone, angiotensin II receptor blockers
Folate antagonists or drugs that increase folate metabolism e.g. methotrexate and phenytoin
Enhances effect of Warfarin due to gut flora death
Cautions and Contraindications of trimethoprims?
Contraindicated in 1st trimester of pregnancy
Caution in folate deficiency and renal impairment
