Microbio - antimicrobials Flashcards
Most common systems affected in adverse reactions to ABx
GI upset Rash Renal dysfunction Anaphylaxis!! Hepatitis
Name 2 Abx commonly causing renal dysfunction
Gent + Vanc
4 things to consider when choosing an abx for an individual
- Host characteristics (age? disease?)
- Antimicrobial susceptibilities
- Organism
- Site of infection
Methods of identifying infecting organism?
Gram stain: from CSF, pus, joint aspirate
Immunofluorescence or PCR to identify an antigen rapidly
What clinical features of a patient would make you consider using an Abx?
systemic response: fever, neutrophilia (neutropenia in severe infection), raised CRP
When to switch from IV to po?
After 48 hours if pt has stabilised
3 patterns of Abx activity
- Concentration dependent killing (max concentration of drug)
- Time dependent killing (time that drug conc’n is above MIC)
- Both
Concentration-dependent Abx?
Aminoglycosides
Time-dependent abx?
penicillins
Recommended time of abx course for simple cystitis? gp a strep throat?
3 days - cystitis
10 days - strep throat
N. meningitidis meningitis - length of abx course?
7 days
Length of abx course for bacterial endocarditis? for acute osteomyelitis?
IE: 4-6 weeks
osteomyelitis - 6 weeks
Typical Abx for cellulitis/
flucloxacillin unless allergic or MRSA. MRSA –> vancomycin
Typical Abx for pharyngitis? how long for?
Benzylpenicillin for 10 days
Typical Abx for CAP - mild and severe?
mild = amoxicillin severe = coamoxiclav + clarithromycin
Typical Abx for HAP?
amoxicillin + gentamicin or tazocin
typical antibiotic for bacterial meningitis?
What is the exception?
Ceftriaxone
Or amoxicillin if young/old/immunocomp due to risk of listeria
typical Abx for UTI - community? hospital?
community = trimethoprim Nosocomial = co-amoxiclav/cephalexin
Typical Abx for Sepsis - severe?
Ceftriaxone/tazocin, metronidazole +/- Gentamicin
Typical Abx for Neutropenic sepsis?
Tazocin + gentamycin
Typical Abx Mx for C-difficile colitis
- STOP the cephalosporins!!!
- Start with metronidazole PO.
- If ineffective, use vancomycin
3 types of beta lactams
pencillins
cephalosporins
carbapenems
Name 4 penicillins and state what they vs
1) penicillin
2) amoxicillin - also cover enterococci + E. Coli!!!!
3) flucloxacillin - resistant to b-lactamases
4) piperacillin - also against pseudomonas + non-GI gram -ves
2 useful things to use with Abx?
clavulanic acid and tazobactam
How do the cephalosporins change from 1st –> 3rd gen?
Increased Gram -ve activity
Which cephalosporin is 2nd gen?
Cefuroxime
Which cephalosporin is assoc. with C. Difficile?
Ceftriaxone
Name the cephalosporin which covers Pseudomonas? which bacteria does it not cover?
Ceftazidime! Doesn’t cover any Gram +ve
Why were carbapenems developed?
bacteria developed extended spectrum beta lactamases, therefore resistant to cephalosporins
Name some carbapenems? Which things are resistant to them now?
Merapenem, Ertapenem
- MDR klebsiella, MDR acinetobacter
Advantages of using b-lactams?
Short half life
Relatively non-toxic
Doesn’t cross the BBB
Which cell wall synthesis inhibitors cannot be used against Gram-ves?
Glycopeptides - can’t penetrate the gram -ve cell wall
Name 2 glycopeptides
vancomycin, teicoplanin
What are glycopeptides particularly useful vs?
MRSA, C. Difficile, enterococci
What type of Abx is gentamicin?
MOA?
Amino glycosides!
Binds to 30S ribosomal subunit - inhibits elongation of pp chain + causes misreading of codons from mRNA.
Conc’n dependent
What are aminoglycosides particularly useful vs?
Neutropenic gram -ve sepsis, Pseudomonas
Doxycycline - which Abx class is it in? What is it useful against?
Tetracyclines
Intracellular organisms - chlamydiae, rickettsiae, mycoplasmas
Special considerations with tetracyclines?
Don’t give to children + pregnant women
- Causes a light sensitive rash
Name 3 macrolides.
Erythro/clarithro/azithromycin
MOA of macrolides
Bind to 50S ribosomal subunit
Interfere with translocation
Usefulness of macrolides vs?
Against strep/staph if penicillin allergic
Campylobacter, Legionella (CAP)
S. Typhi (w azithromycin)
Chloramphenicol - why isn’t it used much?
How is it used now - give 2 uses?
MOA?
- Risk of aplastic anaemia + grey baby syndrome
- Bacterial conjunctivitis + meningitis if pen-allergic
- Binds to 50S ribosomal subunit - inhibits translation
Linezolid - MOA?
- Prevents formation of 70S initiation complex
-
Linezolid - USE?
GRAM +VES ONLY
esp MRSA + VRE
Quinolone - eg? MOA?
Ciprofloxacin, levofloxacin
Binds to alpha subunit of DNA gyrase
Quinolones - 2 bacteria it is used against?
pseudomonas + chlamydia
Eg of nitroimidazoles?
metronidazole
2 useful groups which metronidazole is used against? give eg of each?
Protozoa and Anaerobes
Giardia + C Diff.
Name an RNA synthesis inhibitor?
RIfampicin
What does rifampicin bind to? what precautions must be taken - name 4
Binds to DNA dependent RNA polymerase
- MONITOR LFTs
- single a.a. change –> resistance therefore NEVER use alone
- Turns secretions orange
- DDIs - eg COC
name 2 cell membrane toxins
Daptomycin + Colistin.
When is colistin used? SE?
Last line for MDR- bacteria. eg klebsiella, acinetobacter, pseudomonas
- last line as it is nephrotoxic!
Name some useful folate metabolism inhibitors and what they’re used against
Co-trimoxazole - PCP
Trimethoprim - community UTI
4 mechanisms of Abx resistance
BEAT Bypassing Abx-sensitive step of pathway Enzyme mediated inactivation of Abx Accumulation impairment (efflux of abx from cell) Target alteration
2 main modes of resistance against beta lactams?
Enzyme mediated inactivation - beta lactamases
Target alteration - mecA gene by MRSA and PBP mutation in pneumococcus
Give e.g.s of 2 bacteria which have altered their target to become resistant to beta-lactams?
MRSA - mecA gene = encodes a novel PBP 2a
Pneumococcus - multiple PBP gene mutations
Macrolides - how have bacteria become resistant to them?
Erm gene encode for target alteration –> reduced binding of macrolides
Good prophylactic Abx for splenectomy patients against S. pneumonia?
Amoxicillin
2 major side effects of amoxicillin
Anaphylaxis
Steven Johnsons
Trimethoprim: MOA?
Folate antagonist
3 side effects of trimethoprim
- Megaloblastic anaemia
- Low platelets
- Hyperkalemia (by inhibiting DCT Na channels)
Abx against N. meningitidis
Cefotaxime
MOA of vancomycin
Glycopeptide which inhibits cell wall synthesis
What precautions are taken when giving vancomycin and why?
Vancomycin serum levels need to be monitored when given due to extensive side effects:
- Kidney failure
- Ototoxicity
- Anaphylaxis
- Blood disorders
- Rash