principles of antimicrobial use Flashcards
4 steps in systematic approach
- confirm presence of infection
- identification of pathogens
^ both for confirming indication of antibiotic - selection of antimicrobial and regimen
^ choice, route, dose, duration - monitoring response
how to confirm is presence of infection
- look at risk factors
- subjective evidence
- objective evidence
- whats the possible site of infection
what are possible risk factors for infection
1.disruption of natural barriers
eg break in skin or mucous membrane eg ulcer
or damaged cilia or resp tract
ANY disruption to host immune system innate or adaptive
- age , very old or very young
- immunosuppression
eg malnutrition, acquired or hereditary ( hiv/aids)
drugs eg chemo or immunosuppresants , steroids - alterations in normal flora
eg use of ab - clear susceptible bacteria but stronger bact grows
or uncontrolled blood sugar - nutrients for bact to grow
what are localised subjective evidence of infection
think location wise
git - diarrhea, nausea, vomitting, abdominal distension
resp tract - cough , sputum
uti - frequency , urgency, dysuria
purulent discharge - in wound, urethal or vaginal
pain and inflamation @ site , eythema, swelling , warmth
why is pus a sign of infection
pus > wbc > there to rescue during infection
what are systemic subjective evidence of infection
fever , chills, rigors malaise - general tiredness palpitations sob mental status changes weakness
vital signs indicating infection IMPT
objective evidence
- fever > 38 deg
- may be masked by use of antipyretics,
panadol, nsaids, ibuprofen or aspirin - hypotension SBP < 100MMhG
- tachypnea resp rate > 22bpm
- heart rate > 90bpm
- mental status esp in elderly, drop is glasglow coma scale
non infectious causes of fever (5)
cancer autoimmne disease intracranial hemrrhage drug fever - could be hypersensitivity but reduces when drug removed hyperthyroidism
which drugs often cause drug fever
blactams, antiepileptic or anticonvulsants, allopurinol
lab tests indicating infection
acute phase reactants - conc inc during inflammation
1. elevated or depressed Total white
normal 4-10 x 10^9 /L
- inc neutrophils normal 45-75%
- inc CRP c reactive protein , normal < 10, infection> 40
- inc ESR , erythrocyte sedimentation rate ESR ( more useful for bone and joint infection not rlly for general infection
- inc procalcitonin
whats an impt consideration for objective infection
compare against baseline values
procalcitonin guide for starting ab
conc 1 or more microgram/L - AB stronly encouraged
0.5 to < 1 - ab encouraged
0.25 to < 0.5 AB discouraged
<0.25 AB strongly discouraged
what to consider for renally impaired patients and their procalcitonin levels
procalcitonin excreted renally so there could be continued inc in the levels, so compare with baseline levels
if blood sample taken for calculation of procalcitonin concentration at early stage of episode , when to take the second reading
obtain a second procalcitonin concentration 6-12 hr later
procalcitonin guidelines for stopping AB
- inc from peak conc & 0.5 or more - change ab
- dec < 80% from peak conc & 0.5 or more - cont AB
- dec 80% or more from peak conc & 0.25 to 0.5 - stop AB
- conc < 0.25 - stop AB strongly encouraged
objective evidence from radiological imaging
tissue changes ,
collections,
abscess, - pus collection
obstructions - disruption = higher chance of growth
which are the common sites of infection
uti, rti , ssti and intra abdominal
why is it impt to send pretreatment cultures and not follow up culture
could result in false negatives bc empiric therapy could have killed the pathogen
- could leave behind other pathogens that are not the causative ones
likely contaminant from blood culture
staphylococcus epidermis , bacillus spp.
likely coloniser from urine culture
yeast
what to consider when choosing the antimicrobial regimen
purpose - empiric, definitive or prophylaxis
which route, dose, dosing and duration
consider host and drug factors too
differentiate between prophylaxis, empiric and definitive
empiric:
- microbio results not out yet
- use ab based on clinical presentation of likely infection site, likely organism at the site and likely susceptibility from antibiogram
definitive
- when microbio test results avail
- culture-directed therapy
prophylaxis
- ab given to prevent infection
eg of prophylaxis situations
surgical prophylaxis
or post exposure prophylaxis eg for hiv or std to remove microorganism and prevent infection
what happens if overtreat
ab associated toxicity
c difficile - diarrhea
resistance = inc cost
guidelines for which to choose
narrowest spectrum
dose individualised
shortest duration
t/f active antimicrobials shld be administered as soon as possible for severly ill patients
true
3 diff outcomes of combination therapy
indifference - combo of A and B slightly better
synergy - combo is much more effective
antagonism - combo gives a worse effect
which combination for hospital acquired pneumonia
piperacillin-tazobactam + vancomycin
which combination for ventilator associated pneumonia
piperacillin-tazobactam + ciprofloxacin to cover pseudomonas aeruginosa
which combi for entercoccus endocarditis
ampicillin + gentamicin/ ceftriaxone
whats another ab combination that has synergistic bactericidal effect
trimethoprim + sulfamethoxazole
why use combi treatment
for empiric treatment
following antibiogram combine to get as close to 100% coverage as possible
disadvantages of combination therapy
- risk of toxicity and allergic reactions
- ddi risk
- inc cost
- selection pressure
- inc risk of superinfections
( 2nd infection superimposed on the orignal infection cause by another microroganism resistant to the initial treatment used ) - antagonistic effect use
eg of antagonistic combination
in treatment of aspergillus, combination of amphotericin and itraconazole
which ab avoided in children generally
tetracyclines ( discolouration )
fluoroquinolones - cause joint athropathy in animals
why g6pd deficiency is concern for ab
concern about hemolysis of rbc
which ab to avoid if g6pd deficiency present
sulfonamides
nitrofurantoin
fluoroquinolones ( inconsistent data )
what causes cross reactivity between penicillins, cephalosporins and carbapenems
similar side chain not class effect
drugs safe for pregnancy
blactams and macrolides
avoid in pregnancy
aminoglycosides
co-trimoxazole
fluoroquinolones
tetracyclines
causes nephrotoxicity
aminoglycosides, high dose vancomycin
causes hepatoxicity
pyrazinamide
amoxicillin-clav ( augmentin )
if immunocompromised use what and give examples
bactericidal growth - kills bact
eg blactams, guinolones, aminoglycosides, vanco
t/f if immunocompromised give broader spectrum coverage
true
covers esbl producing enterobacterales
5th gen cephalosporins
covers amp-c producing enterobacterales
4th gen cephalosporins onwards
impt consideration for amp c producing
may appear sensitive because inherently able to product amp c upon exposure to 3rd gen so must be careful
bc could be induced to produce amp c and become resistant during treatment
- for sick patients use carbapenams to treat
unable to reach adaqueate csf conc
gen 1 and 2 cephalo
aminoglycosides
macrolides
clindamycin
used for csf
meropenam peniciilins ceftriaxone cefepime ceftazidime vancomycin ( option for mrsa, give intrathecal)
why is daptomycin not for pneumonia
inactivated by lung surfectant
why aminoglycosides not for abscesses
acidic environmetn
which drugs for prostatitis and why
ciprofloxacin and
co-trimoxazole
bc distribute well into prostate
concentration dependant pkpd meaning and examples of drug like this
rate and extent of killing is related to the ab conc
= higher conc = more rapid and extensive killing
grps : aminoglycosides and fluoroquinolones
what is the dosing strategy for conc dependant pkpd
optimise peak - MIC ratio
peak is 8-10x above mic
high auc/mic ratio or cmax /mic
- larger doses at extended intervals eg once daily aminoglycoside dosing
for conc dependant killing would u choose 250mg q12h or 500mg q24h
to achieve high peak, give less frequency
for better bacterial kill based on pkpd, choose 500mg q24h
higher cmax/mic ratio
what is pae and what does this mean
post antibiotic effect
dosent matter if trough is below mic
why is once daily dosing given instead of multiple daily dose for aminoglycoside
- conc dependant killing
- pAE
- prevents adaptive resistance
= prevents selection of more resistant mutants - less nephrotoxicity
- save cost
describe time dependant bacteria killing with no persistent effect aka short half life
rate and extent of killing to do with amt of time ab conc is above the mic
time dependant killing for which classes
pencillins , cephalosporins and carbapenems
dosing strategy for time dependant killing
optimise %T>MIC
40-70% of dosing interval shld be above mic
- more frequent administration
- iv infusion or intermittent infusion
what is used to block excretion of drugs
probenacid
describe time dependant bact killing with persistent effect aka long half life or PAE
rate and extent of killing related to overall drug exposure AUC vs MIC
classes that experience the time dependant killing w persistent half life
vanco
dosing strategy for time dependant killing with persistent half life
optimise AUC : MIC ratio
auc : dose/clearance
eg vanco target for 400-600 for MRSA
give 500mg q12 or 1g q24 for vanco
1g q24hr bc
auc = dose/cl and
for same patient both have same total dose so reducing adm freq = save cost
when to give iv
hospitalised, severe inf
when need high blood conc
when to avoid oral
gi pathology
suitable oral antibiotic not avail ( eg aminogly)
high tissue conc needed eg endocarditis or meningitis , bone or joint
urgent treatment
non compliance
antimicrobes with good oral bio
fluoroquinolones
metronidazole
linezolid
co-trimoxazole
im examples
im ceftriaxone
IM streptomycin
Im benzathine penicillin
topical eg
clotrimazole pessaries for vaginal candidiasis
aerosolised or nebulised drug eg
nebulised colistin for mdr pseudomonas aeruginosa pneumonia
drug that could cause collateral damgage
fluoroquinolones
- can select for resistant bacteria or other resistance patient wasnt even exposed to
what cannot be use d with carbapenams
valproate
- bc wanna keep high conc but ddi reduces the conc
which class cant be used with cyp450 inhibitbors
azole antifungals and macrolides
which class cant be used with cyp450 inducers
rifampicin
adr for aminoglycoside to monitor for
serum creatinine , urine output
adr for vancomycin
flushing , hypotension, itch , red man syndrome
slow infusion start 500mg over 1 hr and monitor
what to consider when modifying therapy
if can narrow, do that
if can use oral do that
stop if completed duration
what could cause unsatisfactory response
- inappropriate diagnosis
- resistance
- non compliance
- renal function
- ddi
- collections or abscess- needing surgery or drainage
- immune response
- superinfection
- toxicity
how long to given empiric treatment for
48 to 72 hrs to work
