Establishing Presence of Infection systemic signs - BP (hypotension SBP ___ BPM) - RR (tachypnea > ___ RPM) - fever ( > ___ or ___ or ___ % immature forms (bands)) systemic symptoms - chills - rigors - malaise - mental status changes

- 90 - 90 - 20 - 38, 36 - 12,000, 4,000, 10

ID 1 Rybakov Flashcards by Reagan Smith

Establishing Presence of Infection

___ : hallmark of infection
- > ___ C or ___ F

non-infectious causes (false positives)
- ___ induced fevers
- malignancies
- blood transfusions
- autoimmune disorders

no fever with s/s (false negatives)
- ___ ( ___ , ___ , and ___.)
- corticosteroids
- overwhelming infection may be hypothermic

fever
- 38, 100.4
- drug
- antipyretics (acetaminophen, NSAIDs, aspirin)

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Establishing Presence of Infection

systemic signs
- BP (hypotension SBP < ___ mmHg)
- HR (tachycardia > ___ BPM)
- RR (tachypnea > ___ RPM)
- fever ( > ___ or < ___ C)
- increased/decreased WBC (> ___ or < ___ or > ___ % immature forms (bands))

systemic symptoms
- chills
- rigors
- malaise
- mental status changes

90
90
20
38, 36
12,000, 4,000, 10

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Establishing Presence of Infection

4 criterias for systemic inflammatory response syndrome (SIRS)
at least 2 criteria needed

HR
RR
fever
WBC

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Establishing Presence of Infection: Local Signs and Symptoms

___ and ___
- may be absent in ___ patients

pain, inflammation
- neutropenic

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Establishing Presence of Infection: Lab Tests (WBC)

normal: ___ - ___ cells/mm3
- neutrophils, lymphocytes, monocytes, eosinophils, and basophils
- dependent on age, gender, and comorbidity status

elevated in response to infectious and non-infectious causes
- non-infectious: ___ , ___ , stress, rheumatoid arthritis, pregnancy

4,500-11,000
steroids, leukemia

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Establishing Presence of Infection: Lab Test (WBC)

mature neutrophils (PMNs, polys, ___ )
- most common WBC
- fight infections

immature neutrophils ( ___ )
- increase during infections = ___ shift

___ : involved in allergic reactions and immune response to parasites

___ : associated with hypersensitivity reactions
___ : __ cell (humoral) and __ cell (cell mediated) immunity

___ : mature into macrophages, serve as scavengers for foreign substances

segs
bands
eosinophils
basophils
lymphhocytes, B, T
monocytes

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Establishing Presence of Infection: Lab Test (WBC)

Leukocytosis
- increased neutrophils w/wo ___ = assocaited with ___ infections
- bands present = increased ____ response ( ___ shift)
- may be elevated due to non-infectious disease ( ___ or ___ ) or drugs ( ___ )
- ___ (abnormally low WBC) may be a sign of overwhelming infection; poor prognosis

bands, bacterial
bone marrow, left
leukemia, stress, steroids
leukopenia

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Establishing Presence of Infection: Lab Test (WBC)

Lymphocytosis
- associated with ___ , ___ , or ___ infections
- ___ cells and ___ cells

fungal, viral, TB
B, T

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Establishing Presence of Infection: Lab Test (WBC)

Absolute Neutrophil Count (ANC)
- total number of circulating ___ and ___

Neutropenia
- ANC < ___ cells/mm3
- ANC expected to decrease to < ___ cells/mm3 in the next ___ hrs
- ANC < ___ cells/mm3 is termed profound neutropenia

Risk of infection dramatically ___ as ANC ___
- ANC < 500 = substantial risk of infection
- start to worry when ANC is < ___ cells/mm3

segs, bands
500
500, 48
100
increases, decreases
500
1000

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Establishing Presence of Infection: Acute Phase Reactants (ESR and CRP)

erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
- elevated in the presence of an ___ process: does NOT confirm ___

Normal levels
- ESR: ___ - __ mm/hr (males); __ - ___ mm/hr (females)
- CRP: __ - __ mg/dL

Often elevated in presence of infection
- ___ measurements useful to determine response to treatment

inflammatory, infection
0-15, 0-20
0-0.5
serial

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Establishing Presence of Infection: Acute Phase Reactants: Procalcitonin

Procalcitonin (PCT)
- precursor to ___ = more ___ for bacterial infections than ESR and CRP
- normal level: ___ mcg/L
- increase 3-12 hours after stimulation; decline over 24-72

Magnitude of elevation provides useful diagnostic information
- < ___ mcg/L = low risk of infection
- > ___ mcg/L = antibiotics should be continued

___ measurements every 1-2 days useful to assess response to therapy and when to d/c antibiotics

calcitonin, specific
0.05
0.25
0.5
serial

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Establishing Presence of Infection: Radiographic Tests

X-rays
CT
MRI
Nuclear imaging
echocardiography

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Identification of the Pathogen: Microbiological Studies

infected body materials must be sampled, if possible or practical

Before initiation of anti-infective therapy
1) ___ might reveal causative pathogen
2) ___ use of anti-infectives can suppress growth of pathogens: leads to false negatives or alterations of infected fluid

Must avoids contaminations
- example: isolation of ___ negative staphylococcus from 1 of 2 blood cultures where blood was collected by peripheral stick

gram stain
premature
coagulase

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Identification of the Pathogen: Microbiological Studies

type of culture collected depends on ___ of infection
- Osteomyelitis: ___ biopsy
- Meningitis: ___
- Endocarditis: ___ cultures, heart valve tissues

Blood cultures
- shoud be performed in acutely ill ___ patients
- obtained from 2 different ___ sites as ___ sets: 1 set = 1 ___ and 1 ____ bottle (1 hr apart optimal)

site
bone
CSF
blood
febrile
peripheral, 2, aerobic, anerobic

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Identification of the Pathogen: Microbiological Studies

Colonization:
- A potentially ___ organism is present at the body site but is not invading host tissue or eliciting a host immune ___
- no symptoms, there but not doing anything

Infection:
- A pathogenic organism is present at the body site and is ___ host tissue and eliciting host ___ and symptoms consistent with an infection
- symptoms

pathogenic
response
damaging, response

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Identification: Rapid Diagnostics for Bloodstream Infections

Which 2 tests cannot detect resistance genes?
A) PhenoTest BC Kit
B) BioFire BCID2
C) ePlex BCID
D) T2 Bacteria
E) Verigene

A) PhenoTest BC Kit
D) T2 Bacteria

Identification of the Pathogen: Other Rapid Diagnostic Tests

MRSA PCR Nasal Test
◦ Negative predictive value to rule out MRSA respiratory infections is ~ ___ %

Biofire FilmArray Panels
◦ Respiratory, blood culture, GI, meningitis/encephalitis, pneumonia, joint infections
◦ ___ test to detect a variety of pre-determined pathogens commonly associated with the infection

Verigene Panels
◦ Respiratory, blood culture, GI
◦ ___ test to detect variety of pre-determined pathogens commonly associated with the infection

Definitions

Minimum Inhibitory Concentration (MIC)

lowest antimicrobial concentration that prevents visible growth

Definitions

Breakpoint

MIC or zone diameter value used to categorize an organism as S, S-DD, I, R, or NS

Definitions

Susceptible (S)

Isolates with an MIC or zone diameter at or below the (S) breakpoint are inhibited by the usually achievable concentrations of antimicrobial agent when normal dosing regimens are used, resulting in
likely clinical efficacy

Definitions

Susceptible-dose dependent

implies susceptibility is dependent on the dosing regimen used

Definition

Intermediate (I)
Resistant (R)
Non-susceptible (NS)

do not choose antibiotics with these markers

Identification of the Pathogen: MIC Testing (Broth Dilution)

Broth dilution
- gold standard
- MIC = concentration with lowest visible growth
- “ ___ “ = no ability to determine exact inhibitory concentration

what would the MIC of this picture be?

semi-quantitative
2

Identification of the Pathogen: Susceptibility Testing (Disk Diffusion)

Disk Diffusion (Kirby-Bauer method)
- zone diameters measured and compared with standard zone size ranges

only results are ___ , ___ , or ___
- cannot derive a ___ from the zone of inhibition

S, I, R
MIC

# Identification of the Pathogen: Susceptibility (Gradient Strip Tests) - also called ___ test - plastic strip with known antibiotic concentration gradient placed on agar plate streaked with known bacteria - MIC = concentration on strip where inhibition zone intersects the scale on the strip - more ___ than standard methods

- Epsilometer, E-test - precise

# MIC Testing via Automated Systems ___ System - Uses small reagent “cards” that test predetermined bug/drug combos - Growth curves calculated for all wells compared to growth control curve - Algorithm-derived MIC ___ WalkAway - Uses fluorogenic substrate hydrolysis as an indicator of bacterial growth - Uses standard microdilution trays - Algorithm-derived MIC __ ___ ___ ___ System - Utilizes an oxidation-reduction detector and turbidometric growth detection system to determine susceptibility - Uses microdilution trays - Algorithm-derived MIC

- Vitek-2 - MicroScan WalkAway - BD Phoenix Automated Microbiology

T or F: you can directly compare MIC values to determine the "best" option

FALSE | look at susceptibility to determine (and if broad coverage is needed)

# Factors to Consider In Antibiotic Selection: Definitions Empiric Therapy - Initiation of anti-infective therapy ___ identification and susceptibility results are known - Anti-infective selected should cover most common pathogens - Usually very ___ coverage; may require 2-3 anti-infectives depending on site Directed (targeted) Therapy - Therapy selected ___ organism identification and/or susceptibility is known De-escalation - Selecting an anti-infective with the ___ spectrum of activity - Can be stepwise or all at once Spectrum of activity - What ___ does the ___ cover

- before - broad - after - narrowest - bacteria, drug

# Factors to Consider In Antibiotic Selection pt has pneumonia - ___ : cefepime preliminary cultures growing E. coli - ___ : ceftriaxone pan-susceptible E. coli - ___ (targeted): amoxicillin

- empiric - de-escalation - de-escalation

# Factors to Consider in Antibiotic Selection: Antibiogram Annual summary of ___ -specific anti-infective susceptibility - Contain number of nonduplicate isolates from common species and ___ susceptible to anti-infectives tested - Can be narrowed to ___ -specific (ex. ICU vs. ED vs. Med/Surg) - Can be general or very detailed

- institution - % - unit

factors to consider in antibiotic selection

- patient Hx - allergy - age/weight - pregnancy - metabolic/genetic variation - organ dysfunction - concomitant drugs - concomitant disease states - drug factors (PK/PD, toxicity, cost, tissue penetration)

# Monitoring Therapeutic Response Culture and ___ reports WBC, temperature, physical complaints (should ___ ) - ___ improvement lags behind clinical improvement Therapeutic Drug Monitoring (TDM) __ to __ switch (if possible) Antimicrobial failure - Drug selection - Host Factors - Microorganism

- sensitivity - diminish - IV, PO

# Factors to Consider in Antibiotic Selection: Putting It All Together 1. ___ (s/s, imaging) 2. ___ (patho) 3. (Causative) ___ (empiric = probable, definitive = isolated) 4. ___ of Activity (bug/drug mismatch) 5. ___ Patterns (antibiogram considerations) 6. ___ Parameters (host factors, dose, target site penetration, bioavailability, etc.) 7. ___ Parameters (AE< allergies, DIs, TDM, etc.) 8. ___ of Therapy

1) Indication 2) Source 3) Pathogens 4) Spectrum 5) Resistance 6) PK/PD 7) Monitoring 8) Duration

# Factors to Consider in Antibiotic Selection: Putting It All Together "**I**nfections **S**care **P**eople **S**o **R**eally **P**ractice **M**emorizing **D**rugs"

1) Indication 2) Source 3) Pathogens 4) Spectrum of activity 5) Resistance patterns 6) PK/PD parameters 7) Monitoring parameters 8) Duration of therapy

# How Germs Fight Against Antibiotics - develop new cell processes that avoid using the antibiotic's target - change or destroy the antibiotics with enzymes - restrict access by changing the entryways (or limiting the number of entryways) - change the antibiotic's target so the drug can no longer fit and do its job - get rid of antibiotics using pumps

# Definition of Antimicrobial Stewardship (AMS) "Coordinated interventions designed to improve and measure the appropriate use of antibiotic agents by promoting the selection of ___ drug regimen including ___ , ___ of therapy, and ___ of administration”

- optimal - dosing, duration, route

# Goals of AMS Primary Goal: - Optimize clinical outcomes while minimizing unintended consequences Unintended consequences: - Toxicity - Selection of pathogenic organism such as ___ - Emergence of ___ pathogens Secondary Goal: - Reduce healthcare ___ without adversely impacting quality of care

- C. difficile - resistant - cost

# Examples of AMS Strategies Antibiotic de-escalation - switching to ___ -spectrum antibiotic that targets causative pathogen(s) identified on culture or those thought to be causing the infection Prospective ___ and feedback - external review of antibiotic therapy with suggestions to optimize use after the agent has been prescribed ____ - Requiring approval from ID Pharmacy/ID Physician prior to use of certain antibiotics Antibiotic ___ - Reassessment of the continuing need and choice of antibiotic, usually after 48-72 hours of therapy Development of policies and protocols aimed at optimizing antimicrobial use Creation of ___ aimed at optimal antibiotic selection for difference disease states

- narrower - audit - pre-authorization - timeout - order sets

B) Require ID pharmacist approval before ordering broad spectrum antibiotic