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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

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?

A

Vancomycin A

thought to have picked it up from another bacteria

23
Q

Vancomycin has no activity in….

A

Gram -
Gram - anaerobes
Atypical

24
Q

Vancomycin Spectrum of Activity Gram +

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
Q

Vancomycin + ceftriaxone combo used for…

A

S. Pneumoniae meningitis

26
Q

Vancomycin Gram + Anaerobes Spectrum of activity

A

Txm of choice for Clostridioides difficile (Oral)**

also covers Peptostreptococci + P.acnes

27
Q

Oral vs IV Vancomycin

A

Cant use IV Vanco for C.dif

Cant use oral vancomycin for systemic infection

28
Q

Vancomycin absorption

A

Can be given bunch of ways, but IM not recommended

Poor systemic absorption when given PO

29
Q

Vancomycin Elim

A

Excreted primarily unchanged via kidney

1/2life = 4-6hrs w/ normal renal fxn

non renal clearance ~ 5-10% loss per day

30
Q

Vancomycin efficacy is associated with….

A

AUC / MIC ratio

Target goal is 400 - 600

31
Q

Vancomycin ADR

A
  1. Nephrotoxicity
  2. Infusion-related reaction
  3. Hematologic effects
  4. Delayed hypersensitivity reactions
32
Q

Risk factors for Vancomycin associated nephrotoxicity

A 
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
Q

Infusion-related reaction vancomycin

A

Most common SE

Rapid onset of rash, itchy skin, etc

Premeditate w/ Benadryl + slow infusion rate = will be fine

34
Q

Hematologic effects Vancomycin

A

Leukocytoclastic Vasculitis (rare)
Thrombocytopenia
Pancytopenia
Neutropenia 1-2%

35
Q

Daptomycin MOA

A

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
Q

Daptomycin Spectrum of Activity Gram +

A

** Txm of choice for Vancomycin-resistant Enterococci VRE ***

Covers MSSA/MRSA

Covers most Streptococci species, gaps in S.anginosus + Viridians Streptococci

37
Q

Daptomycin + Vancomycin MRSA Cross Resistance

A
  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
Q

Daptomycin and Enterococci

A

Treatment for E.faecium (VRE) is dose dependent.

Have to give a certain dose or no point in using to treat

39
Q

Daptomycin Spectrum of Activity Gram + anaerobes

A

Covers Peptostreptococci and P. acnes

40
Q

What does Daptomycin not have activity for?

A

Gram -
Gram - anaerobes
Atypical

41
Q

Daptomycin Distribution

A

** Cannot be used for pneumonia, becomes inactivated by surfactant **

1/2life = 7.3-9.6hrs

little pen across uninflamed meninges

42
Q

Daptomycin Elimination

A

unchanged via kidney

1/2life = 8-9hrs

43
Q

Risk factors for CPK elevations in Daptomycin

A

Concomitant statin use, obesity, critically ill pt, higher doses, and severe renal impairment

44
Q

Daptomycin ADR

A

CPK elevations ( Do baseline + wkly lvls)
Eosinophilic pneumonia = rare
Hepatic
GI

45
Q

Lipoglycopeptides MOA

A
  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
Q

Where do Lipoglycopeptides not have activity?

A

Gram -
Gram - anaerobes
Atypical

47
Q

Lipoglycopeptide drugs

A

Dalbavancin
Oritavancin
Telavancin

48
Q

Lipoglycopeptides Spectrum of activity Gram +

A

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
Q

Which Lipoglycopeptides lack S.pneumoniae coverage?

A

Oritavancin

Dalbavancin

50
Q

Lipoglycopeptides Spectrum of activity Gram + anaerobes

A

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
Q

Lipoglycopeptides Elim & 1/2 lives

A 
Tela = 7-10hrs
Dalbavancin = 346hrs**
Oritavancin = 245hrs**

** useful for bone infections…req way fewer doses due to 1/2 life **

52
Q

Lipoglycopeptides ADR

A 
CNS
Hematologc
GI
Injection site reaction
Nephrotoxicity (Telavancin)
53
Q

Renal monitoring Telavancin

A

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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