antibiotic concepts Flashcards
how are bacterial infections treated?
with antibiotics to inhibit bacterial growth
how do we test how susceptible an antibiotic is to a bacteria?
we determine the minimum amount of antibiotic that stops the bacteria from growing - minimum inhibitory concentration
what is the MIC?
it is the minimum concentration of antibiotic that inhibits bacterial growth in a standard culture media and standard bacteria inoculum
what is the only variable in MIC tests?
the concentration of AB
how are ABs dosed?
to ensure that all patients get blood concentrations of ABs that are associated with increased survival - pharmacodynamic target
what happens if the AB exceeds the PD target?
there is no additional efficacy benefit
what characteristics does the MIC have?
measurable, important and variable
what needs to be considered with AB doses?
the intraspecies variation in MIC values - the bacterial population and its variations and the serum concentrations of ABs
what three factors are important for AB cure?
human populations and the variation within it, the MIC and the antibiotic pharmacokinetics
where is there variation in the antibiotic concentration profiles?
in how it is distributed around the body and cleared from the body
what are simulations?
they are statistical analyses that predict the optimal antibiotic dose. They determine the probability that if a patient was to be treated with a certain AB for a certain infection, that they would attain the desired pharmacodynamic target - know as the probability of pharmacodynamic target attainment - determine what dose of AB will achieve a high PTA
when can the target dose be used to treat?
if it has an acceptable toxicity profile - patients must get just enough
why are some drugs only available IV?
They are not absorbed well orally and they may be required to quickly and reliable achieve the targeted serum AB concentration
in what infections are oral and IV ABs comparable?
joint and bone infections, pyelonephritis, empyema, febrile neutropenia
what are the benefits of PO?
no IV access is required, therefore no side effects from this access, there is self administration and is cheaper - also once it has reached systemic circulation it is considered as equal efficacy to IV
what are the disadvantages of PO?
slower absorption, absorption may vary, antibiotic associated diarrhoea, required the small bowel for absorption
what are the benefits of IV?
it is faster or instantaneous absorption, and the staff can vary the absorption rate. No small bowel is required for absorption and it reached the targeted serum concentration quicker and reliably
what are the disadvantages of IV?
antibiotic associated diarrhoea, no benefit over PO once in systemic circulation, IV access required and there are side effects with this such as thrombophlebitis, thrombosis and infection, medical staff are required for administration and is more expensive
what are AB durations?
short or long course for all depending on clinical response and it is biomarker driven
what does the choice of course depend on?
the evidence, social and clinical factors, costs and resources available
what needs to be balanced in AB duration?
maximising the cure whilst minimising adverse events - there is a positive correlation between duration and number of adverse events and a negative correlation between failure rates and duration
when should antibiotics be started?
when the benefits of giving them outweigh the disadvantages - always in a patient with sepsis - start early and stop early
what are two methods of administering antibiotics?
start narrow and look to broaden asap
start broad and look forward to when to narrow
what affects when ABs are given?
patient factors, plan for other treatments and overall management plans, delayed with plan when to, when there is no sign of infection such as in autoimmune inflammation
what are the benefits of early AB therapy?
prevent infection metastases, if clinically stable can give broad, oral AB and assess response, reduce morbidity and mortality
what are disadvantages of early AB therapy?
may increase the chance of giving the wrong antibiotic or not enough, reduce time to do investigations and therefore overtreat, may reduce time to do cultures and therefore not know pathogen, not know diagnosis and not give targeted therapy, not enough time to check allergies
what are vancomycin, teicoplanin and gentamicin sometimes used for?
surgical antibiotic prophylaxis
what is done when using gentamicin, teicoplanin or vancomycin?
therapeutic drug monitoring - these drugs target glycosides (V and T) and aminoglycosides (g) and are both ototoxic and nephrotoxic but if are used sub therapeutic levels then efficacy is reduced
what is an antimicrobial stewardship programme?
it is a coherent set of guidelines which promote the use of antimicrobials responsibly
what is the 30% rule for?
it is a rule that is used for antimicrobial prescribing facts:
30% of inpatients will be receiving antimicrobials
over 30% in community are inappropriate
up to 30% used as surgical prophylaxis are inappropriate
up to 30% of hospital pharmacy costs are due to antimicrobial use
up to 30% of pharmacy costs could be saved by antimicrobial stewardship programmes
what does antimicrobial stewardship involve?
timely and optimal selection, dose and duration
best clinical outcome for prevention or treatment
minimal toxicity
minimal impact on resistance and ecological events
how do penicillins interact?
they have limited interactions but reduce the excretion of methotrexate
what type of drug alters phenytoin concentrations?
quinolones
what are the interactions of macrolides?
they increase plasma phenytoin and digoxin concentrations and enhance the anticoagulation effect
what are the interactions between trimethoprim and a) ACE inhibitors and b) cyclosporin?
a) hyperkalaemia
b) nephrotoxicity
what are the interactions of glycopeptides ABs?
nephrotoxicity with aminoglycosides and loop diuretic interactions
what drugs interact with frusemide to result in ototoxicity?
aminoglycosides
what are the complications of linezolid?
seretonin syndrome
what are beta lactams?
they are a class of AB that have a beta lactam ring as part of their chemical structure - there are three classes - carbapenems, cephalosporins and penicillins
what is the prevalence of penicillin allergy?
10% report - may also cross over to other types
what are the reactions from penicillin and amoxivillin-clavulanic acid?
penicillin gives the standard allergic reaction and amoxicillin clavulanic acid gives cholestatic jaundice
what antibiotic adverse effects result in a) diarrhoea and b) erythema multiforme?
a) macrolides
b) trimethoprim
what will an adverse reaction to quinolones result in?
tendonitis and a prolonged QT interval
what can result in oto, nephrotoxicity and red man syndrome?
glycopeptide ABs
what does an adverse reaction to linezolid result in?
optic neuropathy and blood disorders
what does an adverse reaction to aminoglycoside ABs result in?
oto and nephrotoxicity
what is an adverse reaction to metronidazole?
disulfiram reaction with alcohol
what can all types of ABs result in?
antibiotic associated diarrhoea and C difficle infection
what ABs should be avoided in pregnancy and why?
quinolones - arthropathy
trimethoprim - folate antagonist therefore teratogenic in 1st trimester
nitrofurantoin - at term neonatal haemolysis
aminoglycosides - ototoxic
what are limitations of AB use?
may require surgical intervention as well
does not treat non-infectious or contaminated cases
all will damage the microbiome
what is the relevance of T>MIC?
the efficacy of antibiotics can be predicted by knowing the time in hours that the blood concentration of antibiotic is above the MIC value
what is the bacteria above and below a certain MIC?
above - resistant
below - susceptible
