Use of antibiotics Flashcards
what are the basic pharmacokinetic parameters?
what does AUC mean
Cmax
what is meant by pharmacodynamics?
this is the relationship between antibiotic concentration and antibacterial effect
this is different from pharmacokinetics (which is drug dosing and drug concentration at the site of action)
which antibiotics are associated with concentration dependent killing?
aminoglycosides
quinolones
aim for high peaks and large AUC
what are some non concentration-dependent antibiotics?
beta lactams
beyond a certain point, there is no benefit in increasing the concentration, and so the goal of dosing is to maximise the time of exposure to the drug (esp time above MIC)
which are the bacteriostatic antibiotics?
tetracyclines and erythromycon are both bacteriostatic antibiotics and they are best to avoid during serious, difficult-to-treat infections such as IE
what are some of the important gaps in the meropenem spectrum?
stenotrophomonas
enterobacter faecium
What are the ESCAPPM bugs?
what type of bug?
these are Gram negative rods
NOTE: THIS CLEARLY EXCLUDE ENTEROCOCCUS (GRAM POS COCCI)
Enterobacter
Serratia
Citrobacter
Aeromonas
Proteus
Providencia
Morganella
which of the beta lactams are most associated with hepatitis?
fluclox and diclox
augmentin also, but in that case it’s thought to be the clavulanic acid, rather than the methicillin addition to the beta lactam
what are the three aminoglycosides?
what is their mechanism of action?
what do they cover? (which bugs)
- gentamicin
- amikacin
- tobramycin
they inhibit protein synthesis at ribosomes
Gram negative aerobic cover ONLY
all of them have adverse kidney (reversible) and hearing/vestibular (irreversible) issues
what’s more important in aminoglycosides, high peak or large AUC?
Dr Munckhof did not elaborate, but the answer is large AUC, but only just
how do the quinolones work, and what are some of their names?>
ciprofloxacin
moxifloxacin
they work by inhibiting DNA gyrase
what is the spectrum of the newer quinolones?
what are the major ADR to quinolones?
is there any special info about when to give these meds/what not to give them WITH?
any drug interactions?
tremor, headaches (esp elderly)
QT prolongation
maybe abn cartilage in kids
N/V/rash
you should give them at least 2 hours apart from calcium/antacids/iron tablets
they interact with phenytoin and theophylline
what are the macrolides, and what is their mechanism of action?
are they bacteriocidal or static?
what is their main spectrum?
they are erythromycin, roxithromycin, azithromycin and clarithromycin
they inhibit protein synthesis at ribosomes
- they are bacteriostatic
- work against MSSA, strep (so, gram pos), works against aerobic gram negs, not really against anaerobes
their main spectrum is legionella, mycoplasma, chlamydia, diptheria pertussis
major indication: atypical pneumonias, pertussis, chlamydial genital infections, atypical mycobact infections
what are the lincosamides?
what is their use and mechanism of action?
they are clindamycin and lincomycin
useful against anaerobes and gram pos cocci (staph and strep BUT NOT ENTEROCOCCI)
they work by inhibiting bacterial ribosomal protein synthesis
they cover staph well, including MRSA
they have good bone and joint penetration
cause N/V
c diff is a big deal
what are the tetracyclines? what is their mechanism of action
what is their major indication?
doxycycline in the main one we use
they work by binding to the bacterial ribosome and stopping binding between tRNA and mRNA
they have good activity against mycoplasma, chlamydia, Q fever
What are the nitroimidazole?
what are their mechanism of action?
what do they cover best?
metronidazole, tinidazole
they cover ONLY anaerobes (and parasites like giardia)
they interact with bacterial nucleic acid and screw up DNA synth
what are the indications for bactrim? how do these drugs work?
ADRs?
they both work on the folate synthesis pathway
- the addition of the sulpha group rarely adds efficacy, as most of the anti-microbial activity seems to come from the trimethoprim component
the sulpha component causes rash and haematological abnormalities
there are some indications for both - PJP and stenotrophomonas, for example
What is the role of colisitin?
how does it work
what is its spectrum?
this is a gram negative agent
very difficult to dose and major toxicity is the nephrotoxicity
it works like a detergent. it is both hydrophilic and hydrophobic (in parts)
it gets in the gram neg bacteria plasma membrane, and displaces some of the proteins, like LPS, and leads to cells break down
what are the glycopeptides?
what is their mechanism of action?
major ADR?
vancomycin is the major drug of this class
needs to be monitored
Good Gram POS coverage, but no gram neg and no anaerobic cover
need to watch for red man syndrome
it works by blocking the cross linking bonds in the cell wall synthesis of bacteria
the other glycopeptide is teicoplanin
- this has similar coverage, but also can treat some VRE (the VanB subtype - most common in Australia)
what is the oral treatment of hospital acquired MRSA?
this is tricky
one needs to use dual agents, to prevent development of resistance
the best combination is rifampicin and fusidic acid, but this has a significant side effect profile, including nausea, hepatitis and the red urine/tears
rif also has lots of p450 interactions
what is the oral treatment for CA-MRSA?
usually these have a strange resistance profile
oral options usually include clindamycin and cotrimoxazole
the IV would be vancomycin
what are the glycylcyclines?
what is their benefit?
tigecycline
broad spectrum of action - gram neg and gram pos, but there are gaps in the coverage - no good against pseudomonas or proteus
they are a new class of modified tetracycline (which disturb bacterial DNA synthesis)
they manage to evade bacterial efflux and ribosomal resistance mechanisms (which was a problem for tetracyclines)
what are the oxazolidinones?
how do they work?
what do they work on?
major ADRs?
these are a new class of drugs
linezolid is within this class
they have a unique mechanism of action, working on the ribosome preventing bacterial protein synthesis
they are good against GRAM POS, but because of cost, we only really use it for bad VRE, VISA or VRSA
they have no useful activity against gram neg or anaerobes
major ADR is myelosuppression
there is also stories of peripheral neuropathy
what are the glycolipopeptide class?
what do they work against?
what are we allowed to use them for?
any blood tests you need to do regularly (while patients are on it?)
this class includes daptomycin
they are bacterial cell membrane destabilisers
this has an excellent activity against most Gram pos, but nothing good against Gram neg or anaerobes
because of cost, we use them for VISA/VRE
side effect is myositis
also small incidence of eosinophilic pneumonia
if giving this to people you need to monitor serum cK
what is amphotericin?
what are the major preparations, and what are the major risks of this drug?
what is the spectrum?
how does it work?
pretty broad spectrum - includes moulds (aspergillus) and yeasts (candida and cryptococcus)
renal toxicity is a major issue
liposomal preparation has less renal toxicity, but is 15 times more costly!
it works by binding to ergosterol and disrupts the fungal cell membrane and creates a cross-membrane channel
what is fluconazole?
what is its spectrum?
what is its mech of action?
fluconazole is the main drug.
the spectrum is mostly YEASTS - cryptococcus and candida particularly (not mouldy ol’ aspergillus)
they work by binding to the fungal cyto P450 and preventing creation of ergosterol which is essential for cell wall sythesis
it is more common to have resistance if patient has been on fluconazole in the past
major ADRs are related to p450 interactions
aside from fluconzaole there are some newer azole drugs.
what are they, what are their spectrum and interactions?
do you have to do any special therapeutic monitoring with these drugs?
voriconazole and posaconazole are the two main ones
they are more expensive
they have a broadened spectrum and also cover some moulds, incl aspergillus
they still have p450 interactions which are a big deal
it is important to monitor the levels of voriconazole
what are the echinocandins?
how do they work
what is their spectrum?
caspofungin is the main one in Australia
given IV
the spectrum is reasonably narrow - candida (a yeast) and aspergillus (a mould)
but no activity against other moulds
its benefit is that it is rarely toxic
works by inhibiting beta-glucan-sythase, leading to loss of cell wall integrity
what is the most important parameter for prescribing of beta lactams?
a. peak concentration/MIC ratio
b. AUC
c. AUC/MIC ratio
d. time above MIC
e. both AUC/mic ratio and peak concentration/MIC ratio
the answer with beta lactams is really just about time above the MIC
the most important thing is to keep the blood levels above MIC. There is a plateau around 3x MIC, above which treatment does not provide benefit
see image
diabetic foot infections are usually mixed infections, including staph aureus, strep pyogenes, some gram negs, some anaerobes
the main thing with diabetic foot ulcers is to make sure that your antibiotics have some anaerobic coverage
(recall that bugs can be defined as: gram pos aerobes, gram neg aerobes, anaerobes and atypicals)
the best answer is B, which will cover anaerobes well
see image
this is important because there has been a historical thinking that group a strep isn’t covered by fluclox, which is wrong.
another option would be cephazolin (but not asked here because that would create redundancy)
the answer is D
however, in the future there is a real possibility that first line will switch to vancomycin, once resistances get worse
see image
this is about a 12 year old that progresses on oral amoxy
there are right basal CXR changes
in this setting (progression on orals), we should look at IV treatment.
The best option would be Iv penicillin and oral roxi/doxy
however, that isn’t an option, so instead IV penicillin
(IV cefotaxime is too broad)
if you had a neutropenic patient with sepsis, normal regimen is pip/taz
is there any rationale for the addition of gentamicin?
the PAH ID/haem team argues that gentamicin should be given to cover for ESCAPPM, as up to 30% of hosp acquired infections are related to these
and the thinking is that neutropenics are in and out of hospital all the time
this is also the reason for the changing to ceftazadime in many haem units
the importance of gram neg coverage in neutropenic sepsis = must cover pseudomonas! (can kill overnight)
see image
what is the treatment post surgically?
we need to cover pneumococci, haemophilis and meningococci
in this day and age, if we see something that represents pneumococci or recent sinus/neuro surgery, you MUST add vancomycin to ceftriaxone
there is also a strong argument for steroids before antibiotics (based on eTG)
what is the prophylaxis for meningococcus meningitis?
what about pregnancy etc?
if non preggo:
- rifampicin
- ciprofloxacin
- ceftriaxone
if preggo:
- ceftriaxone (IM is fine)
see image
ct is a likely brain abscess
- need to cover anaerobes, gram pos mouth flora
aciclovir isn’t necessary - not HSV
rifampicin not a strong treatment agent
vanco and rif don’t have anaerobe coverage
the real question is B vs D
the reason for B (the answer) is that the penicillin gives coverage of millerei. Vancomycin might be useful in the future, once CA-MRSA becomes an even bigger problem
see image
all except CTX have decent anaerobe cover
cipro also has poor anaerobic coverage
chloramphenicol isn’t used much, but had very good anaerobe cover
see image
the key to this question is recognising the anaerobic nature of bacteroides fragilis
the next step is to identify which of the antibiotic options has anaerobic coverage
the answer is b - clindamycin
which of moxifloxacin or ciprofloxacin has better pseudomonas coverage?
cipro has best pseudo cover
moxi loses some pseudo coverage to gain gram pos cover
pseudomonas coverage is an important concept to understand
CTX has no pseudomonas coverage
this is VITAL to know
