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Anti-Infectives Exam 2 > Lecture 3 - Cells of immune system & Glycopeptides/Lipoglycopeptides > Flashcards

Lecture 3 - Cells of immune system & Glycopeptides/Lipoglycopeptides Flashcards

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1
Q

Two distinct systems of immunity

A

Innate (non-specific)

Adaptive (specific)

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2
Q

Innate (non-specific) Immunity

A
  1. Physical barriers, phagocytes (Neutrophils + macrophages), proteins
  2. Strategically redeployed and prepositioned to prevent and/or quickly neutralize infection
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3
Q

Adaptive (Specific) Immunity

A
  1. Evolves and adapts against invading pathogens

2. Divided into humoral (B Lymphocytes) and cellular (T lymphocytes) mediated arms

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4
Q

Functional Divisions of Immune System: Innate

A

Exterior defenses: Skin, mucus, cilia, normal flora, etc

Specificity: Limited + fixed

Memory: none

Time to response: hours

Soluble factors: Lysozymes, complement, C-reactive protein, interferons

Cells: Neutrophils, monocytes, macrophages, NK cells, eosinophils

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5
Q

Functional Divisions of Immune System: Adaptive

A

Exterior defenses: none

Specificity: Extensive

Memory: yes

Time to response: days

Soluble factors: Antibodies, cytokines

Cells: B + T lymphocytes

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6
Q

Barriers of entry to microorganisms into the body

A 
Skin
Mucous Membranes
Respiratory Tract
GI tract
Genitourinary Tract
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7
Q

Skin info

A

Physical + immunologic barrier to invasion

Dryness, salinity, mild acidity, combined w/ normal skin flora help make inhospitable for invading pathogens

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8
Q

Mucous Membranes info

A

Most pathogens enter through mucosal surfaces of respiratory, GI and urogenital tracts

Mucus, formed by highly glycosylated proteins called mucins

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9
Q

Respiratory Tract info

A

Trachea, bronchi, and bronchioles are lined with a ciliated epithelia surface that propels mucus upward

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10
Q

GI Tract info

A

Acidic pH of stomach and antibacterial effect of pancreatic enzymes, bile, and intestinal secretions are effective, non-specific, antimicrobial defense factors

Small intestine = mucus limit number of bacteria that can reach epithelium + Peyer patches

Large intestine = inner mucus layer relatively free of bacteria, outer layer supports commensal flora

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11
Q

Genitourinary Tract info

A

Lactobacillus spp. lowers pH of vagina = restricts growth of invading organisms

Vaginal flora prevents bacterial vaginosis, yeast infections, UTI and HIV

Urine is bactericidal for some strains of bacteria

Uromodulin (glycoprotein) made by kidneys, protects against kidney stones and binds to E.coli preventing them from attaching to cellular lining of urinary tract

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12
Q

Eye info

A

constant bathing of eye by tears effective means of protection

Foreign substances are diluted and washed away via tear ducts into nasal cavity

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13
Q

What is an elevated WBC?

A

> 10,000

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14
Q

Blood work signs of infection?

A

High % of Poly PMNs

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15
Q

What is a Left shift?

A

Bands increased ~5% during acute infection and shift to the left

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16
Q

Gram positive Antibiotics

A

Glycopeptides & Lipoglycopeptides
Oxazolidinones
Misc

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17
Q

Glycopeptides & Lipoglycopeptides

A 
Vancomycin
Daptomycin
Telavancin
Dalbavancin
Oritavancin
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18
Q

Oxazolidinones

A

linezolid

Tedizolid

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19
Q

Miscellaneous Gram + antibiotics

A

Clindamycin

Lefamulin

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20
Q

Vancomycin MOA

A
  1. Inhibit late stage of cell wall synth
  2. Forms complex with carboxyl-terminal D-ala residues of peptidoglycan precursors
    * 1st line MRSA *
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21
Q

Vancomycin resistance is valued by….

A

D-Ala residue turning into D-Lac

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22
Q

Most common Vancomycin Resistance?

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A

Vancomycin A

thought to have picked it up from another bacteria

23
Q

Vancomycin has no activity in….

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A

Gram -
Gram - anaerobes
Atypical

24
Q

Vancomycin Spectrum of Activity Gram +

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A
  1. Broad gram + activity
  2. Txm of choice for MSSA + coagulase negative Staphylococci.
  3. Worse outcome compared to beta-lactams in MSSA (oxacillin/nafcillin or cefazolin)
  4. Covers all Streptococci species, used if resistant or beta-lactam intolerant/allergic
25
Vancomycin + ceftriaxone combo used for...
S. Pneumoniae meningitis
26
Vancomycin Gram + Anaerobes Spectrum of activity
Txm of choice for Clostridioides difficile (Oral)**** also covers Peptostreptococci + P.acnes
27
Oral vs IV Vancomycin
Cant use IV Vanco for C.dif Cant use oral vancomycin for systemic infection
28
Vancomycin absorption
Can be given bunch of ways, but IM not recommended Poor systemic absorption when given PO
29
Vancomycin Elim
Excreted primarily unchanged via kidney 1/2life = 4-6hrs w/ normal renal fxn non renal clearance ~ 5-10% loss per day
30
Vancomycin efficacy is associated with....
AUC / MIC ratio Target goal is 400 - 600
31
Vancomycin ADR
1. Nephrotoxicity 2. Infusion-related reaction 3. Hematologic effects 4. Delayed hypersensitivity reactions
32
Risk factors for Vancomycin associated nephrotoxicity
``` AUC > 650-1300 or trough > 14mc/ml Dose > 4g/day Duration > 7 days Wt > 101.4 kg Renal impairment > 65yrs old Critically ill using other nephrotoxic agents same time ```
33
Infusion-related reaction vancomycin
Most common SE Rapid onset of rash, itchy skin, etc Premeditate w/ Benadryl + slow infusion rate = will be fine
34
Hematologic effects Vancomycin
Leukocytoclastic Vasculitis (rare) Thrombocytopenia Pancytopenia Neutropenia 1-2%
35
Daptomycin MOA
A Lipopeptide Ca-dependent insertion of lipophilic tail into cytoplasmic membrane....causes Oligomerization and disruption of cell membrane....release of intracellular ions and cell death
36
Daptomycin Spectrum of Activity Gram +
** Txm of choice for Vancomycin-resistant Enterococci VRE *** Covers MSSA/MRSA Covers most Streptococci species, gaps in S.anginosus + Viridians Streptococci
37
Daptomycin + Vancomycin MRSA Cross Resistance
1. Exposure of vancomycin causes MRSA to inc the cell wall 2. MICs to vancomycin and daptomycin increase simultaneously 3. Oxacillin MICs decrease = improved oxacillin susceptibility
38
Daptomycin and Enterococci
Treatment for E.faecium (VRE) is dose dependent. Have to give a certain dose or no point in using to treat
39
Daptomycin Spectrum of Activity Gram + anaerobes
Covers Peptostreptococci and P. acnes
40
What does Daptomycin not have activity for?
Gram - Gram - anaerobes Atypical
41
Daptomycin Distribution
** Cannot be used for pneumonia, becomes inactivated by surfactant ** 1/2life = 7.3-9.6hrs little pen across uninflamed meninges
42
Daptomycin Elimination
unchanged via kidney 1/2life = 8-9hrs
43
Risk factors for CPK elevations in Daptomycin
Concomitant statin use, obesity, critically ill pt, higher doses, and severe renal impairment
44
Daptomycin ADR
CPK elevations ( Do baseline + wkly lvls) Eosinophilic pneumonia = rare Hepatic GI
45
Lipoglycopeptides MOA
1. Differ from vancomycin by presence of lipophilic side chain 2. Bind to d-ala-d-ala portion of cell wall, blocking cross-linking of peptidoglycans 3. Side chains enhance MOA by 2 mechanisms Long 1/2 life
46
Where do Lipoglycopeptides not have activity?
Gram - Gram - anaerobes Atypical
47
Lipoglycopeptide drugs
Dalbavancin Oritavancin Telavancin
48
Lipoglycopeptides Spectrum of activity Gram +
All provide coverage against E.faecalis, MSSA, MRSA Cover Streptococci species Oritavancin coverage against VRE Dalba + Telavancin active against Van-B/Van-c resistant enterococci strains but not Van-A
49
Which Lipoglycopeptides lack S.pneumoniae coverage?
Oritavancin | Dalbavancin
50
Lipoglycopeptides Spectrum of activity Gram + anaerobes
Very good gram + anaerobic activity Not active against Actinomyces spp. Covers Peptostreptococci, P.acne *used in setting of polymicrobial infections or beta-lactam intolerance*
51
Lipoglycopeptides Elim & 1/2 lives
``` Tela = 7-10hrs Dalbavancin = 346hrs** Oritavancin = 245hrs** ``` ** useful for bone infections...req way fewer doses due to 1/2 life **
52
Lipoglycopeptides ADR
``` CNS Hematologc GI Injection site reaction Nephrotoxicity (Telavancin) ```
53
Renal monitoring Telavancin
Monitor renal function prior to, during (atleast every 48/72hrs, more if needed) and following therapy in all patients

Anti-Infectives Exam 2 (8 decks)

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