Intro to Infectious Disease Flashcards
Establishing presence of infection: fever
fever –> hallmark of infection
>38 degrees celsius (100.4)
Non-infectious causes (false-positives) of a fever
drug-induced fevers: fever coincides temporally with administration of the offending agent and disappears promptly with withdrawal of offending agent
malignancies
blood transfusions
auto-immune disorders
False-negatives of a fever (absence of fever in patients with signs/symptoms consistent with infection)
antipyretics (acetaminophen, NSAIDs, aspirin): can mask poor therapeutic response –> use discouraged during treatment
corticosteroids
overwhelming infection (may be hypothermic, <36 or 96.8)
Establishing presence of infection: systemic signs
systemic signs:
vital signs: blood pressure - hypotension (SBP < 90 or MAP < 70); heart rate - tachycardia (>90 BPM); respiratory rate - tachypnea (>20 RPM); fever (>38 or <36); increased/decreased WBC count - >12,000 or <4,000 or >10% immature forms
4 criteria for systemic inflammatory response syndrome (SIRS)
tachycardia, tachypnea, fever, and increased/decreased WBC count
at least 2 criteria needed
Establishing presence of infection: systemic symptoms
chills, rigors, malaise, mental status changes
Establishing presence of infection: local signs and symptoms
symptoms referable to specific body system, pain and inflammation, inflammation in deep-seated infections (pneumonia, meningitis, UTIs)
may be absent in neutropenic patients
Establishing presence of infection: lab test (WBC)
defend the body against invading organisms
normal: 4,500-11,000 cells/mm^3 - represents total # of WBC, includes neutrophils, lymphocytes, monocytes, eosinophils, and basophils
elevated in response to infectious and non-infectious causes: non-infectious - steroids, leukemia, stress, RA, pregnancy
Mature neutrophils
most common WBC
fight infections
Immature neutrophils (bands)
increase during infection
Eosinophils
involved in allergic reactions and immune response to parasites
Basophils
associated with hypersensitivity reactions
Lymphocytes
humoral (B-cell) and cell-mediated (T-cell) immunity
Monocytes
mature into macrophages
serve as scavengers for foreign substances
Establishing presence of infection: lab test - leukocytosis
increased neutrophils +/- bands –> associated with bacterial infections
presence of bands indicates increased bone marrow response to infection
may be elevated due to non-infectious diseases (leukemia, stress) or drugs (steroids)
leukopenia (abnormally low WBC) may be sign of overwhelming infection, poor prognostic sign
Establishing presence of infection: lab test - lymphocytosis
associated with viral, fungal, or tuberculosis infections
B-lymphocyte: proliferate into plasma cells –> produce antibodies and memory B-cells
T-lymphocytes: T-helper and T-suppressor
T-helper (CD4)
regulation of the immune system; help with antibody production and secrete lymphokines to help protect against bacterial/viral infections and tumors; depleted in HIV infection
T-suppressor (CD8)
bind to and directly kill tumor cells; help with regulation of humoral and cell-mediated immunity
Establishing presence of infection: lab test - absolute neutrophil count (ANC)
total # of circulating segs and bands
Establishing presence of infection: lab test - neutropenia
ANC < 500 cells/mm^3
ANC expected to decrease to <500 cells/mm^3 in the next 48hrs
ANC <100 cells/mm^3 is termed profound neutropenia
risk of infection dramatically increases as ANC decreases: start to worry when ANC < 1000 cells/mm^3
Establishing presence of infection: lab test - acute phase reactants (ESR and CRP)
ESR (erythrocyte sedimentation rate) and C-reactive protein (CRP) are elevated in the presence of an inflammatory process –> does NOT confirm infection
normal levels: ESR = 0-15 mm/hr (males), 0-20 mm/hr (females); CRP = 0-0.5 mg/dL
often elevated in presence of infection
Establishing presence of infection: lab test - acute phase reactants (procalcitonin)
procalcitonin (PCT): precursor to calcitonin –> more specific for bacterial infections than ESR and CRP; normal level: <0.05 mcg/L; increase 3-12hrs after stimulation, decline over 24-72hrs
<0.25 mcg/L –> low risk of infection
>0.5 mcg/L –> antibiotics should be continued
serial measurements every 1-2 days useful to assess response to therapy and when to d/c antibiotics
Establishing presence of infection: radiographic tests
x-rays, computed tomography (CT), magnetic resonance imaging (MRI), nuclear imaging (bone scans, WBC-labled scans), echocardiograghy (transthoracic echocardiogram (TTE) or transesophageal echocardiogram (TEE)
Identification of the pathogen: microbiological studies
infected body material must be sampled, if possible or practical: before initiation of anti-infective therapy: gram stain might reveal causative pathogen, premature use of anti-infectives can suppress growth of pathogens –> leads to false-negatives or alterations of infected fluid
For microbiological studies you must avoid _____
contamination: introduction of an organism into the clinical specimen during sample collection or process
Identification of the pathogen: microbiological studies - type of culture collected
type of culture collected depends on site (or presumed site) of infection
osteomyelitis –> bone biopsy
meningitis –> CSF
endocarditis –> blood cultures, heart valve tissues
Identification of the pathogen: microbiological studies - blood cultures
should be performed in acutely ill febrile patients
obtained from 2 different peripheral sites as 2 sets
1 set = 1 aerobic and 1 anaerobic bottle
1 hour apart optimal
Identification of the pathogen: microbiological studies - colonization
a potentially pathogenic organism is present at the body site but is not invading host tissue or eliciting a host immune system
Identification of the pathogen: microbiological studies - infection
a pathogenic organism is present at the body site and is damaging host tissue and eliciting host responses and symptoms consistent with an infection
Identification of the pathogen: cultures
minutes to hours: retrieve cultures from body and send to micro lab
24-48+ hours: plate the organism, await growth, gram-stain growing organisms
48-72+ hours: identification and susceptibility testing
Identification of the pathogen: rapid diagnostic tests - MRSA PCR nasal test
nasal swab used to identify presence/absence of MRSA in the nares
Identification of the pathogen: rapid diagnostic tests - biofire filmarray panels
respiratory, blood culture, gastrointestinal, meningitis/encephalitis, pneumonia, joint infections
PCR test to detect variety of pre-determined pathogens commonly associated with the infection
Identification of the pathogen: rapid diagnostic tests - verigene panels
respiratory, blood culture, gastrointestinal
PCR test to detect variety of pre-determined pathogens commonly associated with the infection
Identification of the pathogen: susceptibility testing definitions - minimum bactericidal concentration (MBC)
Lowest concentration of drug that kills ≥99.9% of initial inoculum
Identification of the pathogen: susceptibility testing definitions - minimum inhibitory concentration (MIC)
Lowest antimicrobial concentration that prevents visible growth
Identification of the pathogen: susceptibility testing definitions - MIC50
Antibiotic concentration that inhibits 50% of the bacteria tested
Identification of the pathogen: susceptibility testing definitions - MIC90
Antibiotic concentration that inhibits 90% of the bacteria tested
Identification of the pathogen: susceptibility testing definitions - inoculum effect
Increase in MIC when a higher than standard inoculum of bacteria is used in susceptibility testing
Identification of the pathogen: susceptibility testing definitions - tolerance
MBC ≥ 32xMIC ( antibiotic susceptible microorganism’s ability to survive extended periods of exposure to bactericidal antibiotics)
Identification of the pathogen: susceptibility testing definitions - breakpoint
MIC or zone diameter value used to categorize an organism as susceptible, susceptible-dose dependent, intermediate, resistant, or non-susceptible
Identification of the pathogen: susceptibility testing definitions - susceptible (S)
Isolates with an MIC at or below or a 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
bacteria unable to grow at a stanfard dosage of an antibiotic
Identification of the pathogen: susceptibility testing definitions - susceptible dose dependent (S-DD)
Implies susceptibility is dependent on the dosing regimen used
Identification of the pathogen: susceptibility testing definitions - intermediate (I)
Isolates with MICs approach achievable blood or tissue concentrations and response rates may be lower than for susceptible isolates
a microorganism falls within a range where the antibiotic may not be fully effective at standard dosages, suggesting that a higher dose might be needed or that the drug may only be effective in certain body compartments depending on the infection site
Identification of the pathogen: susceptibility testing definitions - resistant (R)
Isolates not inhibited by usually achievable concentrations of agent with normal dosage schedules; clinical efficacy has not been reliably demonstrated
Identification of the pathogen: susceptibility testing definitions - non-susceptible (NS)
Used for isolates for which only susceptible breakpoint is designed; if MIC is above or zone diameter is below the susceptible breakpoint, isolate is categorized as NS
Identification of the pathogen: MIC testing (broth dilution)
broth dilution (microdilution, macrodilution): gold standard
standardized bacterial inoculum added to each tube of doubling serial dilutions of antimicrobials
dilutions incubated for 16-24hrs and then examined for visible bacterial growth (MIC = concentration with lowest visible growth)
semi-quantitative –> no ability to determine exact inhibitory concentration
Identification of the pathogen: susceptibility testing (disk diffusion assay)
disk diffusion reduces labor for tube dilution testing
up to 12 antibiotic impregnated disks placed on agar streaked with suspension of bacteria
drugs in disk diffuse in a concentration gradient out into the agar: visual bacterial growth only in areas where drug concentrations below those required for growth; zone diameters measured and compared with standard zone size ranges
only results are susceptible, intermediate, or resistant - CANNOT derive a MIC from the zone of inhibition
Identification of the pathogen: susceptibility testing (gradient strip tests)
plastic strip impregnated with known prefixed antibiotic concentration gradient placed on agar streaked with known bacteria: MIC = concentration on strip where inhibition ellipse intersects the scale of the strip
more precise than standard methods
Identification of the pathogen: MIC testing via automated systems - vitek-2 system
Uses small reagent “cards” that test predetermined bug/drug combinations
Growth curves calculated for all wells compared to growth control curve
Algorithm-derived MIC produced
Identification of the pathogen: MIC testing via automated systems - microscan walkaway
Uses fluorogenic substrate hydrolysis as an indicator of bacterial growth
Uses standard microdilution trays
Algorithm-derived MIC
Identification of the pathogen: MIC testing via automated systems - BD phoenix automated microbiology system
Utilizes an oxidation-reduction detector and turbidometric growth detection system to determine susceptibility
Uses microdilution trays
Algorithm-derived MIC
Factors to consider in antibiotic selection: empiric therapy
initiation of anti-infective therapy before identification and susceptibility results are known
anti-infective selected should cover most common pathogens
usually very broad coverage; may require 2-3 anti-infectives depending on site
Factors to consider in antibiotic selection: directed (targeted) therapy
therapy selected after organism identification and/or susceptibility is known
Factors to consider in antibiotic selection: de-escalation
selecting an anti-infective with the narrowest spectrum of activity
can be stepwise or all at once
Factors to consider in antibiotic selection: spectrum of activity
what anti-microbials does the drug cover
Factors to consider in antibiotic selection
pneumonia: empiric, cefepime
preliminary cultures growing e.coli: de-escalation, ceftriaxone
pan-susceptible e.coli: de-escalation, amoxicillin
Factors to consider in antibiotic selection: antibiogram
annual summary of institution-specific anti-infective susceptibility: contain # of nonduplicate isolates from common species and % susceptible to anti-infectives tested; can be narrowed to unit-specific; can be general or very detailed
how susceptible a microorganism is to various antimicrobial drugs
Factors to consider in antibiotic selection - patient related
patient history
allergy to meds
age/weight
pregnancy
metabolic/genetic variation
organ dysfunction
concomitant drugs/disease states
drug factors
Factors to consider in antibiotic selection: monitoring therapeutic response
culture and sensitivity reports
WBC, temp, physical complaints (radiological improvements lags behind clinical improvement)
therapeutic drug monitoring
IV to PO switch
antimicorbial failure: drug selection, host factors, mircoorganism
Antimicrobial resistance
occurs when germs (bacteria, fungi, viruses, or parasites) develop the ability to defeat the drugs designed to kill them
How AR spreads
germs are everywhere –> antibiotics kills germs that cause infections, but antibiotic-resistant germs find ways to survive –> antibiotic germs can multiply, some resistant germs can also give their resistance directly to other germs –> antibiotics also kills helpful germs that protect us, w/o helpful germs, resistant germs have an even bigger advantage –> once AR emerges it can spread into new settings
How germs fight against antibiotics
germs develop new cells processes that avoid using the antibiotic target –> germs change or destroy the antibiotcs with enzymes (proteins that break down the drug) –> germs restrict access by changing the entryways or limiting the # of entryways –> germs get rid of antibiotics using pumps –> germs change the antibiotics target to the drug can no longer fit and do its job
How can we combat antimicrobial resistance?
antimicrobial stewardship
Antimicrobial stewardship
coordinated interventions designed to improve and measure the appropriate use of antibiotic agents by promoting the selection of optimal drug regimen including dosing, duration of therapy, and rout of administration
Primary goal of AMS
optimize clinical outcomes while minimizing unintended consequences - toxicity, selection of pathogenic organism such as C. diff, emergence of resistant pathogens
Secondary goal of AMS
reduce healthcare cost without adversely impacting quality of care
CDC core elements of AMS
leadership commitment, accountability, pharmacy expertise, action, tracking, reporting, education
Examples of AMS strategies - antibiotic de-escalation
Switching to narrower-spectrum antibiotic that targets causative pathogen(s) identified on culture or those thought to be causing the infection
Examples of AMS strategies - prospective audit and feedback
external review of antibiotic therapy with suggestions to optimize use after the agent has been prescribed
Examples of AMS strategies - pre-authorization
requiring approval from ID pharmacy/ID physician prior to use of certain antibiotics
Examples of AMS strategies - antibiotic timeout
reassessment of the continuing need and choice of antibiotic, usually after 48-72 hours of therapy
Examples of AMS strategies - misc.
Development of policies and protocols aimed at optimizing antimicrobial use
Creation of order sets aimed at optimal antibiotic selection for difference disease states
