Antibiotics Flashcards
Penicillins MOA
Binds to penicillin binding proteins on bacterial cell walls, inhibiting cell wall biosynthesis (disrupt the synthesis of the peptidoglycan layer). Bactericidal. Demonstrates time-dependent killing.
Amoxicillin Coverage
Streptococci; Enterococcus faecalis; Listeria; N. meningitidis
Some Staph coverage
Excellent bioavailability.
Ampicillin Coverage
Streptococci; Enterococcus faecalis; Listeria; N. meningitidis. [Same spectrum as amoxicillin.]
Good CSF penetration. Useful in severe listeria infections due to availability of an IV formulation
Flucloxacillin Coverage
MSSA (and sometimes some MRSAs) some Streptococci (other penicillins covers more Streptococci species)
Pencillin V
Streptococci; oral anaerobes (e.g. Actinomyces, Clostridium perfringens, Peptostreptococci,
Propionibacterium). Still no resistance with Group A Streptococcus (aka Streptococcus pyogenes)
Rheumatic fever prophylaxis
Cephalosporins MOA
Binds to penicillin binding proteins on bacterial cell walls, inhibiting cell wall biosynthesis (disrupt the synthesis of the peptidoglycan layer). Bactericidal. Demonstrates time-dependent killing. Gram-negative coverage increases as generation increases.
All cephalosporins lack coverage of Listeria, atypicals, MRSA, & Enterococci (LAME).
Cephalexin coverage
Streptococci; MSSA; ?Proteus; E. coli; Klebsiella Ceftriaxone
Cefuroxime (2nd gen cephalosporin) coverage
Streptococci; MSSA; Moraxella; Haemophilus influenzae; Proteus; E. coli; Klebsiella.
Oral bioavailability greatly increased with food
Ceftriaxone (3rd gen cephalosporin) coverage
excellent gram-negative coverage (e.g. Citrobacter, E. coli, Klebsiella,
Morganella, Proteus, Serratia)
1 off IM for Gonorrhoea
Macrolides MOA
Macrolides are protein synthesis inhibitors.
This is by preventing peptidyltransferase from adding the growing peptide attached to tRNA to the next amino acid and inhibiting ribosomal translocation.
Macrolide antibiotics do so by binding reversibly to the P site on the 50S subunit of the bacterial ribosome.
Bacteriostatic.
Macrolides are actively concentrated within leukocytes, and thus are transported into the site of infection.
Which Macrolide doesn’t interact with CYP3A4 ?
Azithromycin
Benefit of Macrolides prophylaxis - specifically in chronic bronchiectasis?
Macrolides inhibit biofilm formation, inhibits production of immunostimulatory cytokines (from neutorphils) in response to pseudomonas and other chronic colonised infections.
Azithromycin also increases gut motility
Azithromycin coverage
Streptococci; N. gonorrhoeae; Moraxella; Haemophilus influenzae; Legionella; many atypicals.
When using in pneumonia - the additional coverage compared with doxy is predominantly legionella cover (an Aaron ward question)
Clarithromycin coverage
Erythromycin Coverage
CLINDA:
Streptococci; Moraxella; Haemophilus influenzae; Legionella; many atypicals.
(SAME AS AZITHRO BUT NO N.GONORRHOEA COVER)
ERYTHRO
As above but NO H. INFLUENZAE COVER - so only of use in young patients (<12) for pneumonia empirical therapy
Key Drug interactions of Macrolides
Clarithromycin and erythromycin CYP3A4 & p-glycoprotein inhibitors (clarithromycin > erythromycin)
Tetracycline Antibiotics MOA
Protein synthesis inhibitors. Bacteriostatic. They inhibit the initiation of translation in variety of ways by binding to the 30S ribosomal subunit, which is made up of 16S rRNA and 21 proteins.
Condition to be wary of in Macrolide and Aminoglycoside antibiotics
Caution in myasthenia gravis
Doxycycline coverage
Staphylococci (& often MRSA); Strep pneumoniae; Moraxella;
Haemophilus influenzae; many atypicals; many anaerobes including spirochetes
Aaron ward question: Why do we give doxy with amoxy in CAP? H.Influenzae coverage but as we can see above - also atypical and anaerobes
Take on empty stomach
Fluroquinolones MOA
Inhibits DNA-gyrase, causing breakdown of bacterial DNA. Bactericidal. Concentration dependent killing (aim for high peak concentrations)
Classical Adverse events on fluroquinolones
QT prolongation; confusion/psychosis, seizure, tendinopathy/tendon rupture, retinal detachment
Drug interactions of fluroquinolones
CYP1A2 inhibition ↑levels of clozapine, duloxetine, methotrexate
increased INR with warfarin.
QT prolongation (watch for other QT-prolonging agents)
Ciprofloxacin coverage
Primarily gram-negative coverage: Pseudomonas; Enterobacteriaceae; ?Neisseria; Haemophilus;
Moraxella; Pasteurella; many atypicals. Essentially no anaerobic coverage.
Moxifloxacin
Strep pneumoniae; MSSA; Enterobacteriaceae; Neisseria; Haemophilus; Moraxella; Pasteurella;
many atypicals; some anaerobes
Does not penetrate urine
Norfloxacin
Strep pneumoniae; MSSA; Enterobacteriaceae
Antifolates MOA
Prevent bacterial folate synthesis. Sulfamethoxazole & trimethoprim inhibit successive steps in folic acid pathway, & thus are synergistic in combination. Combination bactericidal; concentration-dependent killing.
Antifolates: contraindicated cohorts
History of drug induced-immune thrombocytopenia from sulfonamides or trimethoprim; megaloblastic anemia from folate deficiency; severe liver disease; previous SJS from sulfonamides.
Caution: patients with G6PD deficiency (risk of hemolysis)
And caution with those on K+ sparing diuretics: impairs urinary K excretion
Sulfamethuxozole / Trimethoprim
Staphylococci (& often MRSA); Streptococcus pneumoniae; S. maltophilia; Moraxella;
Haemophilus influenzae; Enterobacteriaceae; Shigella; ?Listeria; Burkholderia; Brucella; Pneumocystis.
Timethoprim alone
Same as bactrim but no moraxella
Staph, Strep, haemophilus, enterobacteriaceae
Clindamycin MOA, adverse effects and coverage
Protein synthesis inhibition through binding of 50S ribosomal subunit (similar to macrolides). Lincomycin group of antibiotics
Staphylococci;
Streptococci; many oral anaerobes. Unreliable MRSA
Deranged LFTs. Rare: leukopenia, thrombocytopenia. Higher risk of Clostridium
difficile than other agents.
Metronidazole MOA, adverse effects and coverage
Disrupts DNA of bacterial cells. Bactericidal. Coverage: most anaerobes, including anaerobic protozoa.
neuropathy if long-term use (e.g. > 6 wks)
Reaction with alcohol - nausea vomiting rash
Nitrofurantoin MOA, adverse effects and coverage
Damages bacterial DNA/proteins (bacteria convert nitrofurantoin into reactive forms).
Coverage: Staphylococci; E. coli; Enterococcus faecalis; Citrobacter; Klebsiella.
Concentrated in the urine and turns urine a brownish colour.
Fosfomycin MOA and coverage
Inhibits cell-wall formation by inactivating the enzyme UDP-N-acetylglucosamine-3-enolpyruvyltransferase, also known as MurA. Bactericidal. Coverage: ?Staphylococci; Enterococci; Enterobacteriaceae
Linezolid MOA and coverage
Inhibits bacterial protein synthesis through disruption of mRNA. Usually bacteriostatic, but bactericidal against Streptococci. Its also a weak, non-selective, reversible monoamine oxidase inhibitor
Streptococci; Enterococci (including VRE); Staphylococci (including MRSA)
First line in Enterococcus faecium (VRE)
Probenicid use and mechanism of action
Prolongs penicillin levels by competitively inhibiting their excretion. Give 30-45min prior to IV penicillin dose
Also increases uric acid excretion by interacting with the organic anion transporter.
Vancomycin MOA and coverage
Inhibits cell-wall formation by binding to the D-Ala-D-Ala terminal of the growing peptide chain during cell wall synthesis
Coverage: The only oral use is for treatment of Clostridium difficile colitis (drug of
choice if severe infection, or if second recurrence of C. diff infection
Also coverage of MRSA (and MSSA), strep,and enterococcus.
Carbapenums Coverage
Gram-positives: Generally very good, but does miss MRSA and Enterococcus faecium.
Gram-negative coverage:
Overall excellent (including pseudomonas, ESBL and Amp-C multi-drug resistant species).
Some carbapenem resistance is starting to emerge among enterobacteriaceae (especially among Klebsiella pneumoniae);
Anaerobic coverage: Excellent (but doesn’t cover Clostridium difficile)
Ertopenum vs. Meropenum coverage
Main differences compared to meropenem:
1) Lacks coverage of pseudomonas and acinetobacter.
2) Limited ertopenum activity against enterococci.
May be superior for non-pseudomonal gram-negatives
Carbapenum MOA
Bactericidal beta-lactam antibiotics that bind to penicillin-binding proteins (PBPs). By binding and inactivating these proteins, carbapenems inhibit the synthesis of the bacterial cell wall. Much the same as other beta-lactams.
Steven-Johnson Syndrome causative agents
Allopurinol > Antiepileptics > Sulfonoamides > NSAIDs
