IC7 Flashcards
definition of infection
pathogen invade -> host inflammatory response
definition of sepsis
life threatening organ dysfunction in response to dysregulated host response to infection
progression of infection - 5 stages
1) mild
- localised, self-limiting, transient
2) moderate
- systemic, non-life threatening
3) sepsis
- life threatening
4) septic shock
- profound haemodynamic & metabolic abnormalities
5) Death
broad 4 step approach to antimicrobial use
1) confirm presence of infection
2) identification of pathogen
3) regimen
4) monitor response & plan
what do you look out for to confirm presence of infection (4x)
risk factors, object evidence, subjective evidence, possible site of infection
what are some risk factors for infection
1) disruption of innate immunity (protective barrier)
- break in skin/mucous membrane
- damaged cilia of respiratory tract
- protective enzymes
2) age
- young: immature immune system
- old: impaired immune system
3) immunosuppression
- malnutrition, underlying disease, drugs
4) alteration in normal flora of host w conditions that promotes microorganism overgrowth
- antibiotic use
- uncontrolled blood sugar
subjective evidence for infection - localised symptoms
- D/N/V, abdominal distension
- cough, purulent sputum
- dysuria, increase frequency, urgency
- pain & inflammation at site of infection (Red, swell, warm)
- purulent discharge
subjective evidence for infection - systemic symptom
- X pinpoint exact location
- fever, chill, rigor, malaise
- palpitation, SOB, mental status change, weakness
objective evidence for infection - vital signs
- fever ≥ 38.5 (might be masked by use of anti-pyretic and maybe not caused by infection)
- hypotension
- tachypnoea
- HR > 90 bpm
- deterioration of mental status
objective evidence for infection - lab tests (Everything but procalcitonin)
- non-specific biomarkers
- acute-phase reactant (increase conc during inflammation)
- change in WBC count
- increased neutrophil, CRP, erythrocyte sedimentation rate
objective evidence for infection - lab test - procalcitonin
- take 1 blood sample to determine start/stop Abx (take after 6-12 hr if early stage)
1) when to start
- < 0.25 microg/L : strongly discourage
- 0.25 ≤ conc < 0.5 : discourage
- 0.5 ≤ conc < 1 : encouraged
- conc ≥ 1 : strongly encouraged
2) when to stop
- conc < 0.25 : strongly discourage
- conc decrease by ≥ 80% or 0.25 ≤ conc < 0.5 : discourage
- decrease by 80% AND conc ≥ 0.5 : encourage
- conc < peak conc AND conc ≥ 0.5 : strongly encourage
objective evidence for infection - radiological imaging
tissue change, collection, abscess, obstruction, x-ray, ultrasound, CT scan, MRI
possible sites of infection
urinary tract, respi tract, skin, soft tissue, intra-abdominal
identification of pathogen - why is follow up culture less reliable than pretreatment culture?
- false negative
- won’t reflect initial causative organism
AST report results
1) true pathogen
- capable of damaging host tissue & eliciting host response
- S&S of infection
- acquired from env/part of normal flora
2) colonisers
- normal flora/pathogenic organism wo eliciting host response
3) contaminant
- presence of microorganism acquired during collection/processing of host specimen wo evidence of host response
considerations of AST reports
- isit usually found at site
- single (huge inoculum) or mixed growth
- isolated from multiple cultures/specimen
- signs of tissue invasion
- signs & symptoms of infection
- epidemiology & likelihood of causing disease
regimen - classifications of antimicrobial therapy
1) empiric
- X microbiological results
- Abx based on clinical presentation of likely site of infection/organism/susceptibility
2) definitive
- culture-directed therapy
- Abx choice based on pt specific microbiological results
3) prophylaxis
- Abx given to prevent infection
regimen - benefits of combination therapy
1) extend spectrum of activity
- empiric to cover all resistant strain of same organism
- empiric/definitive therapy for polymicrobial infection
2) synergistic bactericidal effect
3) prevent development of resistance
regimen - disadvantages of combination therapy
1) increased risk of toxicity, allergic reaction, DDI
2) $$$$
3) selection of multi-drug resistant bacteria
4) increased risk of superinfections (infection cuz of current infection)
5) possible antagonistic effect
regimen - host factors that affect what Abx to use
1) age: Abx avoided in children
2) G6PD deficiency: concern of RBC haemolysis
3) allergy/ADR history
4) pregnancy/lactation: affect fetus safety, PK different in pregnancy
5) renal/hepatic impairment: affect PK (dose adjustment), avoid those that cause nephrotoxicity
6) host immune function
7) illness severity
8) recent antimicrobial use (Risk of resistance)
9) healthcare-associated factors
PDPK drug factors that affect regimen - time dependent antimicrobials
1) with NO persistent effect (short t1/2)
- optimise % T > MIC
- more frequent administration
- continuous IV infusion or prolonged intermittent
- block excretion w probenecid
2) with persistent effect (long t1/2 or post-Abx effect)
- optimise AUC : MIC ratio
- dependent on total daily dose
PDPK drug factors that affect regimen - concentration dependent strategies
1) optimise peak : MIC ratio
2) larger dose at extended intervals
PDPK drug factors that affect regimen - concentration dependent strategies rationale
1) concentration dependent bacterial killing
2) post-Abx effect (PAE)
3) prevent adaptive resistance = prevent selection of more resistant mutants
4) less nephrotoxicity
5) cheaper
which Abx are concentration dependent
aminoglycoside, daptomycin, quinolones, metronidazole
which Abx are time dependent
beta lactams
what Abx are exposure-dependent
clindamycin, macrolide, linezolid, tetracycline, vancomycin
target for beta lactams
- fT > MIC for 40-70% dose interval
target for vancomycin
AUC 400-600
target for aminoglycoside
Cmax/MIC > 8-10
when do you not give oral Abx
1) absorption problem
2) X suitable oral Abx
3) high tissue concentration required
4) urgent treatment
5) patient non-compliant
treatment outcomes
1) undertreatment
- ineffective, mortality, LOS, $$$
2) pathogen directed therapy
- :)
3) overtreatment
- Abx toxicities
- resistance
- cost
- C. difficle
