principles of antimicrobial use Flashcards
what are the impacts of inappropriate antimicrobial use
poor patient outcomes and excess costs
what are some poor patient outcomes as a result of inappropriate antimicrobial use
ADR, organ toxicity, superinfection, abx resistance due to selection pressure, increase mortality
what are some examples of excess costs as a result of inappropriate antimicrobial use
drug acquisition cost, management of complications, prolonged hospital stay, costs associated with abx resistance1
what are the impacts of abx resistance
infections are more difficult to treat, require use of more expensive and more toxic abx, increase length of hospital stay due to more complications, increase healthcare costs, increase mortality and morbidity
what is the cause of abx resistance
broad spectrum abx kills off many normal microbiota which then allows other bacteria to invade and cause another infection
what is an infection
an infection is when an organism invades the host tissues and elicit inflammatory host responses
what are the symptoms of an infection
erythema, fever, swelling
describe the spectrum of infection
mild - localised and self limiting, moderate - systemic and non life threatening, severe - life threatening, septic shock - profound hemodynamic (dysregulated HR and BP) and metabolic (acidosis) abnormalities
what is sepsis
sepsis is a life threatening organ dysfunction caused by a dysregulated host response to an infection
what is the approach to antimicrobial use
confirm presence of infection, identify pathogen, selection of antimicrobial and regimen, monitor response
what are the steps to confirming the presence of an infection
risk factors, subjective and objective evidence, what are the possible sites of infection
what are the risk factors of an infection
disruption of natural protective barriers (innate immunity), age, immunocompromised, alterations in normal flora leading to an overgrowth of microorganisms in the host
what are some conditions that promote alterations in host’s normal flora
use of abx and uncontrolled blood glucose
what groups of people may be immunocompromised
malnutrition, underlying disease, drugs (chemo, steroids, immunosuppressants)
what are subjective evidences
localised and systemic symptoms
what are some localised symptoms that may point towards an infection
N,V,D, abdominal distension, cough and purulent sputum, dysuria, frequency and urgency, pain and inflamm at site of infection, erythema, swelling and warmth, purulent discharge
what are some systemic symptoms that may point towards an infection
feverish, chill rigors, malaise, palpitations, shortness of breath, mental status changes, weakness
what are objective evidence
vital signs, lab tests and radiological imaging
what are some vital signs to look at to confirm presence of infection
fever, hypotension, tachypnea, tachycardia, mental status
what are some lab tests markers
elevated or depressed WBC, increased neutrophils, increased CRP, increased erythrocyte sedimentation rate, increased procalcitonin
what are some examples of radiological tests
x ray, CT scan, MRI, ultrasound
what are the values for fever, hypotension, tachypnea, tachycardia
fever >38degC, hypotension SBP<100mmHg, tachypnea RR>22bpm, tachycardia HR>90bpm
how to determine the possible site of infection
based on clinical presentation, risk factors of possible sites, subjective and objective evidence
what is the role of procalcitonin
supplements clinical assessment, only used if can help to determine presence of bacterial infection, reflects severity of bacterial infection, guides initiation and discontinuation of abx, monitor progression of infection or response to treatment
what are the guidelines for starting or stopping use of abx based on procalcitonin levels
starting: conc <0.25mcg/L strong discouraged, conc = 0.25 <0.5 discouraged, conc = 0.5 <1 encouraged, conc >1 strongly encouraged
stopping: conc <0.25 strong encouraged, conc decr by > equal 80% or conc 0.25 <0.5 encouraged, conc decr by < 80% or conc > equal 0.5 discouraged, increase in conc compared to peak and conc > equal 0.5 strongly encouraged to change abx
what are pathogens
pathogens are organisms that are capable of damaging and invading host tissues and eliciting a host response and signs and symptoms of an infection
where are pathogens derived from
may be acquired from environment or from normal flora
what are colonisers
colonisers indicate presence of normal flora or pathogenic organisms without eliciting a host response
what is the likely coloniser in urine culture
yeast
what is the likely coloniser on skin
coagulase negative staphylococcus
what are contaminants
presence of microorganism typically acquired during collection or processing of host specimen without evidence of host response
what are likely contaminants in blood culture
staphylococcus epidermis, bacillus spp
why should you obtain a culture before administering antimicrobials
follow up cultures are less reliable than pretreatment cultures and may result in false negative and may not reflect the initial causative organisms
what are the types of microbiological tests that can identify pathogen
initial gram stain, antimicrobial susceptibility test (AST)
what are the considerations when identifying pathogen
is it usually on site, single growth or mixed growth, signs of invasion of tissues, isolated from multiple cultures or specimens, epidemiology and likelihood of pathogen in causing disease/ infection
what does single growth pathogen suggest
more likely to invade tissues
what does mixed growth pathogen suggest
other microbiota can help prevent disease
what are the types of antimicrobial regimens
empiric, definitive, prophylaxis
when is empirical therapy started
when microbiological results not available
based on clinical presentation, likely microorganism at that site of infection, likely susceptibility from antibiogram or from spectrum of activity
what is definitive therapy and when is it started
definitive therapy is culture directed therapy
based on patient specific microbiological results (culture and susceptibility)
what is antibiotic prophylaxis
abx given to prevent an infection
what are the principles of abx use
timely initiation of appropriate agents (most effective, least toxic and narrowest spectrum possible), administration of dosage individualised to patient and appropriate to microorganism and site of infection, timely and appropriate alteration in response to clinical responses and microbiological data (use for shortest time possible)
what are organism factors to consider
indentity of organism (fungal, bacteria, virus) - genus and species, susceptibility/ resistance of infecting organisms, consider combination therapy
what are host factors to consider
age, g6pd, history of allergy and ADR, pregnancy or lactation, renal or hepatic impairment, status of host immune function, severity of illness, recent abx use (past 6 months use), healthcare associated risk factors
what are the benefits of combination therapy
extended spectrum of activity, achieve synergistic bactericidal effect, prevent development of resistance
what are the disadvantages of combination therapy
increased risk of toxicity and allergic reactions, increased risk of DDI, increased cost, increased risk of superinfection, potential concern for antagonistic effect, selection of MDR bacteria
what is the concern about use of abx in g6pd deficiency
hemolysis of RBC (breakdown) due to increase oxidative stress which decreases O2
what are the drugs to avoid in g6pd deficiency
sulfonamides, nitrofurantoin, fluoroquinolones
what are the drugs to avoid in kids
fluoroquinalones, tetracyclines
what are the drugs that are safe and to avoid in pregnancy or lactation
safe: betalactam, macrolides
avoid: co-trimoxazole, fluoroquinolones, tetracyclines
what are drugs to avoid for hepatic impairment
pyrazinamide, amoxicillin-clavulanate
what are drugs to avoid for renal impairment
aminoglycosides, high dose vancomycin
what are the drug factors to consider
activity against suspected organism, ability to reach site of infection, bactericidal vs bacteriostatic, PK PD, route of administration, side effect profile, drug interaction, cost, duration of use
how to determine if an abx is bactericidal
MBC is within one 2-fold dilution of MIC
what are some bactericidal antibiotics
beta lactams, aminoglycosides, fluoroquinolones, glycoproteins, lipopeptides, polymixins
what are some bacteriostatic antibiotics
trimethoprim, sulfonamides, tetracyclines, macrolides
what is the preferred route for abx
PO
when is PO route not preferred
absorption problem, suitable abx not available in PO, high tissue conc essential, urgent treatment required, non compliant
what are abx with good F
linezolid, co-trimoxazole, fluoroquinolone, metronidazole
what is the PK PD target for beta lactams
fT > MIC for 40-70% of dosing interval
if critically ill or poor sites of penetration, fT > MIC for 50-100% of dosing interval
what is the PK PD target for vancomycin
AUC24h/MIC 400-600
what is the PK PD target for aminoglycosides
Cmax/MIC > 8-10x
what is the PK PD target for fluoroquinolones
for gram pos, AUC/MIC >30
for gram neg, AUC/MIC >125, Cmax/MIC 8-12x
what are the types of abx
conc dependent abx, time dependent abx (short half life), time dependent abx (long half life with PAE)
what are the characteristics and dosing strategies of conc dependent abx
characteristics: rate and extend of killing as a function of abx conc, higher conc results in more rapid and more extensive bacterial killing
dosing strategy: optimise peak:MIC ratio 8-10, usually larger doses at extended intervals
what are examples of conc dependent abx
aminoglycosides which has OD dosing as it has conc dependent bacterial killing and post abx effect (PAE), fluoroquinolone, daptomycin, metronidazole
what are the benefits of OD dosing of aminoglycosides
less cost, less nephrotoxicity as allow drug to reach much lower conc until non detectable, prevents adaptive resistance
when does adaptive resistance occur
occurs when always exposed to drug, prevents selection of more resistant mutants/ strains in body
what are the characteristics and dosing strategies of time dependent abx with short half life
characteristics: rate and extent of bacterial killing are related to the amount of time the abx conc is above MIC of organism
dosing strategy: %T>MIC 40-70, more frequent administration either continuous IV or prolonged intermittent
what is the role of probenecid
to block excretion of abx, useful for time dependent abx with short half life
what are examples of time dependent abx with short half life
penicillin, cephalosporins, carbapenems, monobactams
what is the characteristics and dosing strategy for time dependent abx with long half life/ PAE
characteristics: rate and extent of bacterial killing are related to overall drug exposure (AUC) vs MIC
dosing: optimise AUC: MIC ratio, dependent on total daily dose
what are examples of time dependent abx with long half life/ PAE
vancomycin, clindamycin, macrolides, tetracyclines
what are the PK drug interactions that may occur
- impaired absorption - fluoroquinolone chelates into divalent, antiacids can incr GI pH which decreases conc of abx that requires acidic pH, erythromycin has prokinetic effects which reduces oral absorption
- effects on hepatic metabolism - cyp inhibitors, inducers, substrates (3a4, 2c9, 1a2, 2c19)
- reduced excretion - probenecid competes for renal tubular excretion
what are examples of cyp3a4 substrates
macrolides
what are some examples of cyp3a4 inhibitors which can cause toxicity
azole, macrolides, anti HIV
what are some examples of cyp3a4 inducers which can cause treatment failure
rifamycins
what are the PD drug interactions that may occur
- additive/ aggravate toxicity potential through QT prolongation, nephrotoxicity, myelosuppression, photosensitivity, serotonergic syndrome
- alter intestinal flora (alter enterohepatic circulation of contraceptives, reduce production of vitamin K)
what are the drugs that can cause QT prolongation
erythromycin, clarithromycin, fluoroquinolones, azoles
what are the drugs that can cause nephrotoxicity
aminoglycosides, vancomycin, amphotericin B
what are the drugs that can cause myelosuppression
co-trimoxazole, linezolid
what are the drugs that can cause photosensitivity
sulfonamides, tetracyclines, quinolones
what are the drugs that can cause serotonergic syndrome
linezolid
what are the drugs that can alter intestinal flora
pencillin, tetracyclines, rifampicin
what are the components when monitoring response
treatment goals, therapeutic response, adr, therapy modifications
what are the treatment goals when monitoring response
achieve therapeutic response, minimal adr
how do you monitor for therapeutic response
resolution/ reduction in signs and symptoms (objective and subjective), microbiological clearance, absence of complications or progressions
when is therapy modifications necessary
when AST available (escalate or de escalate), satisfactory response (convert IV to PO or stop if completed adequate duration and patient is well), unsatisfactory response (reevaluate for possible causes)
what are the causes of unsatisfactory response
inappropriate diagnosis (non infectious causes, non bacterial infection), inappropriate choice of agent, subtherapeutic concentration due to non compliance, impaired renal function, drug interactions, collections or abscess which requires surgery or drainage, impaired host defence, superinfection, toxicity of drug
what is the general patient counselling points
this is an abx to treat xx infection, take xx capsules xx times a day about xx hours apart. take xx food, do not take together with xx, space xx hours apart. side effects may include xx. complete whole xx day course unless signs of allergy like rash, itch or swollen eyes, or if serious side effects occur. if allergy or any intolerable side effects occur, stop taking and see doctor immediately. you should feel better in 2-3 days if not please see your doctor. do remember to finish the course even if you feel better to ensure that infection is adequately treated
