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3151 finals > CDAD, STI, HIV > Flashcards

CDAD, STI, HIV Flashcards

1
Q

Clostridioides difficile

A
  • Gram positive, spore-forming anaerobic bacillus
    • Toxigenic strains
      ○ Produce toxin A, B
      § Irritate mucosa, inflammation
      ○ Non toxin producing strains
    • Non-toxigenic strains
      ○ Asymptomatic
      § Mostly in children
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2
Q

CDAD hosp transmission

A
  • Nosocomial diarrhea
    • Incr duration of hosp
    • Incr healthcare cost
  • Spores transmitted via FECAL-ORAL ROUTE (need infection control)
    • Room of pt with CDI
    • Hands oh HCW
      *Medical instruments
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3
Q

pathogenesis of CDAD

A

1) Fecal-oral route, colonisation of intestinal tract with C.difficile

2) Lead to inflammation and diarrhea
1. Pseudomembranous colitis
a. Yellowish plaque over damaged epithelium

3) Antibodies to toxins (MABs) can be used (adjunct for fulminant)
- Asymptomatic carrier develop Ab > than pt who develop clinical disease

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4
Q

3 factors for colonisation of Cdiff in intestinal tract

A
  1. Facilitated by Abx use
    a. Disrupt barrier function of normal colonic flora, allow C.difficile to multiply and produce toxins
    b. All Abx but high risk for
    i. Clindamycin, cephalosporins (3,4th), amipicillin, amoxicillin, FQ
  2. C.difficile contains endospore
    a. Survive acidity of stomach, to reach large intestine
    b. Grow and multiply
  3. Toxigenic C.difficile
    a. Release toxin A and B
    b. Toxin B: clinically more impt toxin, 10-40x more potent
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5
Q

risk factors for CDAD

A
  • Advanced age > 65yr
  • Multiple/ severe comorbidities
  • Immunosuppression
  • History of CDI
  • GI usrgey
    • Alteration, affect ecology og GIT
  • Tube feeding
    • Biofilm
  • Prior hosp (last 1 yr)
  • Duration of hosp
  • Residence in nursing homes/ LTC facilities

Use of Abx
Use of gastric acid suppressive therapy (PPI)

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6
Q

use of ABx

  • incr dose (DDD)
  • incr duration of exposure
  • incr n.o. of Abx used
A
  • All Abx incr propensity for development of CDI
  • Incr risk for those that cover gram -ve, anaerobes (gut bact), broad spectrum
    ○ Clindamycin
    ○ 3rd/ 4th cephalosporins
    ○ FQ
  • Risk highest (receive Abx > 12 wks later)
  • Some Abx may be protective, switch to them
    ○ Doxycycline/ tigecycline
    ○ Active against C.difficile growth, inhibit toxins production
    ○ Minimal effect on GIT flora
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7
Q

greatest risk Abx

A

○ Clindamycin
○ 3rd/ 4th cephalosporins
○ FQ

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8
Q

Use of gastric acid suppressive therapy (PPI)

A
  • Acid suppression
    ○ Stop unnecessary PPI
    ○ Reduce prescription for unindicated use of PPI
    § Insuff evidence for discontinuation of PPI as measure for preventing CDI
  • Use of probiotics
    ○ Prevent, treat CDI not routinely recommended
    ○ Unknown strain, dose, duration
    ** ensure formulation no interact with Abx to treat CDI/ other drugs
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9
Q

CDI infection control & prevention

Reduce CDI, other modalities

A

1) Isolation
1. Pt in private room, attached toilet to decr transmission to other pt
2. If limited private single room
a. Prioritize pt with stool incontinence
b. Cohorted in same room
i. Esp when outbreak/ not enough single room
ii. Spores transmit easily through formites

2) Hand hygiene
1. Wear gloves, gowns
2. Handwash soap + water > alcohol
a. Remove spores

3) Environmental cleaning
1. Sporicidal agents (aldehydes, chlorine compounds, QAC? )

4) Antimicrobial stewardship
1. Minimise freq, duration of high risk therapy
2. Number of Abx agents prescribed

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10
Q

Clinical presentation

Asymptomatic carriage —> fulminant disease

A

WATERY diarrhea
○ >3 loose stool in 24hrs
○ Not explained by other factors/ cause

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11
Q

MILD CDI

A

Diarrhea, abdominal cramps

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12
Q

moderate CDI

A

Fever, diarrhea, N, malaise
Abdominal cramps and distension
Leukocytosis (WBC incr)
Hypovolemia (diarrhea, dehydration)

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13
Q

severe CDI

A

Fever, diarrhea, diffused abdominal cramps and distension

WBC > 15 x10*9/L
OR

SCr > 133 umol/L (1.5mg/dL)

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14
Q

fulminant CDI

A

Hypotension/ shock
ileus (gut not move)
megacolon (inflam, swell)

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15
Q

diagnosis of CDAD

A
  1. Presence of diarrhea
    = 3 unformed stools in 24hrs
  2. OR: radiographic evidence of ileus/ toxic megacolon
               AND
  3. positive stool test result for C.difficile/ toxins
    OR Colonoscopic/ histopathologic evidence of pseudomembranous colitis (yellow plaque)
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16
Q

when is CDI testing done

A

CDI testing only in sx pt.

(some ASx, just colonised, dont require tx)

lab test cannot distinguish b. colonisation vs infection

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17
Q

4 diagnostic test for Cdiff and toxins

A

○ Nucleic acid amplification test NAAT

○ Polymerase chain reaction PCR

○ Enzyme immunoassay (EIA) toxins A & B

○ Glutamate dehydrogenase (GDH) immunoassay

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18
Q

NAAT & PCR

A

Nucleic acid amplification test NAAT
§ identify genes that produce toxin A, B

Polymerase chain reaction PCR
§ Faster, identify genes that produce toxin A, B

§ Not differentiate genes activated/ toxins produced actively

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19
Q

EIA & GDH immunoassay

A

Enzyme immunoassay (EIA) toxins A & B
§ can tell if toxin A or B but not picked up well

Glutamate dehydrogenase (GDH) immunoassay
§ Identify all C.difficile

§ Not differentiate toxigenic strains vs non-toxigenic (coloniser?)

if pt sx, just PCR find out genes = Cdiff +ve

GDH (toxins?) –> PCR (genes present?)
you have cdiff but maybe not infection

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20
Q

Stool test for C.difficile & toxins

A
  • Not test on Asx pt
  • Limited to pt with diarrhea (>3 loose stools/ day)
  • Confirm pt Not received laxative within 48hr of test
  • Not repeat test <7 days
    § Test positive even when clinical response improve
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21
Q

Treatment principle for CDAD

A
  • Do not treat Asx pt with positive C.difficile
    • Waste resources, single pt room etc
    • Confirm Sx consistent with CDI exist prior to prescribing therapy
  • Discontinue any Abx therapy not specifically treating CDI
  • If additional Abx therapy necessary
    • Select narrowest agent
    • Avoid agent with strong association with CDI
      ○ Clindamycin, 3/4th
    • Switch to protective Abx
      ○ Tetracycline, tigecycline
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22
Q

non-severe CDI tx
WBC < 15x10*9 L & SCr <133umol/L

A

1st:
* PO fidaxomicin 200mg BD (only in US)
○ Preferred due to lower recurrence rate
* PO vancomycin 125mg QDS
○ If pt high morbidity, more affected by CDI

Alternative:
* PO metronidazole 400mg TDS

For less severe, based on comorbidities, presentation

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23
Q

severe CDI tx

WBC > 15x10*9 L & SCr > 133umol/L

A

PO fidaxomicin 200mg BD (only in US)
PO vancomycin 125mg QDS

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24
Q

fulminant CDI tx
(hypotension/ ileus/ megacolon)

A
  • IV metronidazole 500mg Q8H
    ○ Enterohepatic recirculation, conc in GIT
  • (+) PO vancomycin 500mg QDS
  • (+/-) PR vancomycin 500mg QDS
    ○ Per rectal, enema
    ○ No IV: as poor accumulation in GIT
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25
Q

duration for 1st CDAD

A

Duration: 10-14days (if sx not completely resolved)

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26
Q

RECURRENT CDI

A

Resolution of CDI Sx –> subsequent reappearance fo Sx after Tx discontinued
~30% pt exp recurrent CDI within 30d of Tx

Risk factors for recurrence:
* Admin of other Abx during/ after initial Tx of CDI
* Defective humoral immune response against C.difficile toxins
* Decr immunity (Advanced age, severe underlying disease)
* Continue use of PPI

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27
Q

First recurrence CDI tx
If used fidaxomicin/ vancomycin for initial episode

A
  • PO fidaxomicin 200mg BD 10d
  • PO fidaxomicin 200mg BD 5d
    ○ 5mg EOD x 20d
  • PO vancomycin tapered/ pulsed
    ○ 125QDS 10-14d
    ○ 125 mg BD 7d
    ○ 125mg daily 7d
    ○125mg every 2-3days x2-8wks
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28
Q

First recurrence CDI tx
If used metronidazole for initial episode

A

PO vancomycin 125mg QDS 10d

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29
Q

Second/ subsequent recurrence (FYI)

A
  • PO fidaxomicin 200mg BD 5d
    ○ Then 5mg EOD x 20d
  • PO vancomycin tapered/ pulsed
    ○ 125QDS 10-14d
    ○ 125 mg BD 7d
    ○ 125mg daily 7d
    ○ 125mg every 2-3days x2-8wks
  • PO vancomycin 125mg QDS 10d
    ○ Then rifaximin 400mg TDS, 20d

Fecal microbiota transplant

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30
Q

monitor for CDI

A
  • Sx resolve in 10d
    • Otherwise extend by 4d
  • Additional diagnostics/ escalation of pharm tx if poor response
  • Do not continue C.difficile tx
    • Just because pt is still on other Abx, does not have protective/ prophylaxis effect
    • Only used 10-14d
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31
Q

STI bact

A
  • Syphilis
    • Treponema pallidum
  • Gonorrhoea
    • Neisseria gonorrhoeae
  • Non-gonococcal urethritis
    • Chlamydia trachomatis
    • Ureaplasma urealyticum
    • Mycoplasma genitalium
  • Chancroid
    • Haemophilus ducreyi
  • Lymphogranuloma venereum
    • Chlamydia trachomatis
  • Granuloma inguinale
    *Calymmatobacteria granulomatis
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32
Q

STI virus

A
  • Ano-genital herpes
    • Herpes simplex virus (HSV type 1 & 2)
  • Ano-genital warts
    • Human papillomavirus (HPV)
  • Viral hepatitis
    • Hepatitis A,B,C virus
    • Transmitted via other routes too
  • AIDS/ HIV infection
    • Human immunodeficiency virus (HIV) type 1 & 2
  • Molluscum contagiosum
    • Molluscum contagiosum virus
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33
Q

STI fungi

A
  • Vaginal candidiasis
    • Candida albicans
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34
Q

protozoa STI

A
  • Scabies
    • Sarcoptes scabiei
  • Pediculosis pubis
    *Phthirus pubis
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35
Q

STI Mode of transmission

A
  • Sexual contact with infected person
    □ Direct contact of broken skin <— open sores, blood, genital discharge
  • Receive contaminated blood
  • Infected mother to CHILD
    □ Preg, childbirth, breastfeed
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36
Q

preg, childbirth, breastfeed

A

□ Preg: syphilis, HIV
- In-utero, cross placenta

□ Childbirth: chlamydia, gonorrhea, HSV
- Mother’s blood contact

□ Breastfeeding: HIV

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37
Q

Epidemiology

A

○ Chlamydia, gonorrhoea > syphilis > genital warts > genital herpes
§ Asx/ mild Sx more likely to be transmitted

○ 20-29 > 30-39
§ Sexually active age grp

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38
Q

Risk factors STI

A

○ Unprotected sexual intercourse
§ No barrier/ condom
§ Doesn’t matter if have hormonal contraceptives

○ Number of sexual partners
§ Multiple sexual partners more likely to acquire, transmit STI
§ Sexual contact with people who have multiple sexual partners

○ Men who have sex with men
○ Prostitution, commercial sex worker
○ Illicit drug use
§ Contaminated needle sharing
§ Risky behaviour, less protection use

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39
Q

Individual prevention methods for STI

A

○ Abstinence and reduction of number of sexual partners
§ Long term, mutually monogamous rs with uninfected partner

○ Barrier contraceptive methods
§ Male latex condoms when used consistently and correctly

○ Avoid drug use and sharing needles

○ Pre-exposure vaccination
§ HPV, hep B
□ But not 100% efficacy

○ Pre- and post-exposure prophylaxis
§ HIV
§ Esp for HCW exposed to pt
§ Partner has HIV

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40
Q

Why need manage and prevent STI

A

○ Reduce morbidity, progression to complicated disease
○ Prevent HIV transmission
§ Incr risk of HIV transmission or acquisition in pt with
□ genital herpes, gonococcal and syphilis infections

○ Prevent serious complications in women
§ Preventable cause of infertility
□ Gonococcal, chlamydia –> perm damage to fallopian tubes
□ Prevention of HPV decr risk of women with cervical cancer

○ Protect babies
§ Untreated STI associated with congenital and perinatal infections in neonates
§ Premature deliveries
§ Neonatal death
§ Stillbirth

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41
Q

gonorrhoea caused by

A
  • Neisseria gonorrhoeae
    • Intracellular gram neg diplococci
  • Transmission
    • Sexual contact
    • Mother-to-child during childbirth
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42
Q

gonorrhoea diagnosis

A
  • Gram stain of genital discharge
  • Culture
    • Get AST for resistance strains
  • NAAT
    Nucleic acid amplification test (PCR)
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43
Q

presentation of gonorrhea

A

Infect various sites
* Urethritis, cervicitis, proctitis, pharyngitis, conjunctivitis, disseminated (systemic infection)

MAYBE ASYMPTOMATIC
sx – uncomplicated/ complicated

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44
Q

Uncomplicated sx of gonorrhea

complicated sx

A

M: Purulent urethral discharge, dysuria, urinary freq
F: mucopurulent vag discharge, dysuria, urinary freq

Complicated
○ M: epididymitis, prostatitis, urethreal stricture, dissem
○ F: pelvic inflamm disease, ectopic preg, infertility, dissem

○ Disseminated
Skin lesions, tenosynovitis, monoarticular arthritis

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45
Q

Pharm management of gonorrhea

A
  1. Ceftriaxone 500mg IM
    a. Single dose for <150kg
    b. >150kg, use 1g
  2. Gentamicin 240mg IM + azi 2g PO
  3. Cefixime 800mg PO
  • Accompanied with anti-chlamydia therapy
    Doxycycline 100mg PO BD 7d
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46
Q

considerations of gonorrhea tx

A
  • FQ not recommended, incr resistance (esp ciprofloxacin)
    *anti-chlamydia therapy
    • Treat concurrent infection, unless chlamydia excluded
  • Single dose, low dose as good susceptibility

SG: need test of cure (after 14days)

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47
Q

sexual partner of gonorrhea

A
  • Sex partners of last 60d evaluated and treated
  • Partner > 60d, treat most recent partner
  • Minimise disease transmission
    • Abstain from sexual activity for 7d after tx
    • after resolution of sx
  • Minimise risk for reinfection
    • Abstain from sexual intercourse until ALL sex partners have been treated
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48
Q

chlamydia caused

A
  • Chlamydia trachomatis
  • Transmission
    • Sexual contact
    • Mother-to-child during childbirth
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49
Q

chlamydia diagnosis

A

NAAT

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50
Q

chlamydia tx

A
  • Doxycycline 100mg PO BD 7d
  • Azithromycin 1g PO
    • Long intracell half-life 68-70h in WBC
    • 1st line if adherence is problem
  • Levofloxacin 500mg PO OD 7d
    (Only FQ effective)
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51
Q

chlamydia considerations

A
  • Treatment highly effective
    • Low chlamydia resistance
  • No need test of cure
    • Unless specific concerns
      ○ Preg, non-adherence
      ○ Sx persists

partners, sx, presentation similar to gonorrhea but milder

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52
Q

chlamydia management of sex partners

A
  • sex partners in last 60d should be evaluated and tx. if last sexual exposure > 60d, most recent partner evaluated
  • minimise disease transmission
    abstain from sexual intercourse for 7d after (single dose - azithro therapy)
    OR complete 7 day regimen, resolved sx (if any)
  • minimise reinfection
    abstain intercourse until all sex partners treated
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53
Q

Syphilis caused by

A
  • Treponema pallidum
  • Transmission
    • Sexual contact
    • Mother-to-child
      Preg due to transplacental
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54
Q

syphilis diagnosis

A
  • Darkfield microscopy
    • Exudates from lesions
      ○ Spot protozoa org
  • 2 serological test
    • Treponemal (confirmatory)
    • non-treponemal (quantitative + monitor)
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55
Q

Treponemal

A

Use treponemal antigen to detect treponemal Ab
- (TPHA) T.pallidum Hemagglutination test
- (TPPA) T.pallidum passive particle agglutination assay

○ More sensitive and specific than nontreponemal tests
○ CONFIRMATORY TEST

○ Reactive for life
Not to monitor response to tx

56
Q

Non-treponemal

A

Use non treponemal antigen (cardiolipin) to detect treponemal Ab
-(VDRL) venereal disease research lab slide test
-(RPR) rapid plasma reagin card test

○ +ve = presence at any stage of syphilis
- Less specific, Used to screen, Need trep for confirmation

○ QUANTITATIVE TEST
- Higher dilute serum conc w/ +ve reaction = higher viral load ( 1:16 vs 1:32)

○ MONITOR response to tx
- Ab titre correlate to disease activity
- Use same test for monitoring
□ VDRL/ RPR
□Test titres usually declines after tx, non-reactive with time

57
Q

clinical presentation of syphilis 1*

A

localised
○ Occurs 2-6wk following infections
○ Heals spontaneously in 1-8wk

○ Site:
-External genitalia, perianal region, mouth, throat
○ Signs and sx
- Single painless ulcer/ chancre at site of infection
-Can be multiple, atypical
- Painful lesions

58
Q

clinical presentation of syphilis 2*

A

systemic
○ Occurs 2-6mnths after 1*
○ Disappears in 4-10 wks if untx

○ Site:
- Multisystem involvement due to hematogenous
-Lymphatic spread

○ Signs and sx
- Skin rash
-Mucocutaneous legions
- Patchy alopecia
-Lymphadenopathy

59
Q

clinical presentation of syphilis Latent = Asx, depends on pt recall

A

Early <1 yr
Late >1 yr
-Develops wk after 2* in utx/ inadequate tx

○ Site:
- Multisystem involvement

○ Signs and sx
- Asx, picked up by serology testing
- Internal organ continue to be affected by infection

60
Q

Neurosyphilis (at any stage of syphilis)

A
  • CNS involvement
  • Signs and sx
    ○ Cognitive dysfunction
    ○ Motor. Sensory deficit
    ○ Ophthalmic. Auditory sx
  • Signs and sx of meningitis, stroke
61
Q

1, 2, early latent <1yr syphilis tx

A

IM benzathine pen G 2.4 million units x 1 dose
○ Prolonged release over 1wk

PO doxycycline 100mg BD 14d
○ GIT, oseophagitis
§ Full glass of water, upright 30min
§ 2hr apart milk, Ca, fe
§ photosensitivity

62
Q

Late latent >1 yr/ unknown duration, 3* syphilis tx

A

IM benzathine pen G 2.4 million units once wk x 3dose

PO doxycycline 100mg BD 28d

63
Q

Neurosyphilis tx

A

IV crystalline pen G (norm) continuous infusion x 10-14d
○ 3-4 million units Q4H
○ 18-24 MU/d

IM procaine pen G 2.4MU daily
○ + PO probenecid 500mg QDS 10-14d
§ Inhibit renal tubular excretion

IV/IM ceftriaxone 2g daily x10-14d
○ No similar R1 side chain
○ Desensitise if penicillin allergy

64
Q

Therapeutic response in syphilis tx

A
  • Jarisch-Herxheimer reaction
    ○ Acute febrile reaction, headache, myalgia, other sx
    ○ Occur iwthin first 24hr after therapy for syphilis
  • Antipyretics help, but not prevent
65
Q

monitor in syphilis

A
  • 1/2/latent syphilis
    ○ Quantitative VDRL/ RPR at 2,6,12,18,24 mnths
    ○Tx success when decr in VDRL, RPR titre by >4x
    ○ 1:64 –> 1:16
  • Neurosyphilis
    ○CSF examination every 6mnths until CSF normal
66
Q

must monitor VDRL/ RPR on

A

6, 12, 24 mnths

2,6,12,18,24

67
Q

Treatment failure of sypilis

A

at 6mnths
* Sign and sx of disease
* Failure to decr VDRL/ RPR titre 4x or there is incr
* Retreat, re-evaluate for unrecognised neurosyphilis
1dose –> 3 dose –> neuro

68
Q

partner of syphilis

A
  • All at risk sexual partners should be evaluated for STIs and treated if tested +ve
    • All other STIs
  • Receiving syphilis tx must abstain from sexual contact with new partners
    • Until syphilis lesions completely healed
    • Careful assessment
      ○ Response to tx
      ○ Fully treated
      ○ Or ASx
69
Q

Genital herpes caused by

A
  • Herpes simplex virus (HSV1 & 2)
    • HSV2: most genital herpes
    • HV1: oral herpes
  • Transmission
    • Transfer of body fluids
    • Skin-to-skin contact
  • Intermittent viral shedding from epithelial cells
    • Can be Asx when shedding , transmission occurs

CHRONIC, LFIE-LONG VIRAL INFECTION

70
Q

pathogenesis of herpes

A

1) Primary mucocutaneous infection
2) Infection of nerve ganglia
3) Latency in spinal ganglion
4) Reactivation
a. Triggers, stress, fever, trauma, sun, mensus, immune

5) Recurrent outbreaks/ flair
a. Vesicles develop over 7-10d
b. Heal in 2-4wks
c Viral shedding

71
Q

diagnosis of genital herpes

A
  • Patient history
    • Previous lesion
    • Sexual contact with similar lesions
  • Virologic tests
    • Viral cell culture
    • NAAT (PCR) for HSV DNA from genital lesions
  • Type-specific (HSV1/ HSV2) serologic tests
72
Q
  • Type-specific (HSV1/ HSV2) serologic tests
A

Antibodies to HSV develop during 1st several wks after infection, persists indefinitely
* Serology not useful for 1st episode infection as takes
○ 6-8 wks for serological detection from 1st episode
○ IgG build up
*Presence of HSV2 = anogenital infection

73
Q

classic sx of genital herpes

A
  • Painful multiple vesicular (fluid filled)
    ○ Burst = ulcerative lesions
  • Local itching, pain, tender inguinal lymphadenopathy
  • Flu-like Sx
    ○ Fever, headache, malaise during 1st few days after appearance of lesions
74
Q

Prodromal sx

A
  • Mild burning, itch, tingling
    Seen in 50% of pt prior to recurrent lesion
75
Q

recurrent herpes

A
  • Less severe Sx
    ○ Less lesions, heal faster, milder Sx
  • Build up of Antibodies’ after initial infection
76
Q

goal for herpes

A

GOAL:
* Relieve sx, shorten clinical course, prevent complications & recurrences, decr transmission

SUPPORTIVE CARE:
* Warm saline bath relieves discomfort
* Sx management
○ Analgesia
○ Anti-itch
* Good genital hygiene
○ Prevent superinfection
* Counselling regarding natural history
○ Life-long

77
Q

ANTI-VIRAL TX effectiveness

A
  • PO acyclovir, valacyclovir
    • Reduce viral shedding by 7d
    • Reduce duration of Sx by 2d
    • Reduce time to heal of 1st ep by 4d
  • MOA: inhibit viral DNA pol
    • Inhibit DNA synthesis, replication
  • Comparable efficacy and tolerability, choice dependent on pt compliance and cost
  • When drug discontinued:
    • Does not prevent latency
    • or affect freq and severity of recurrent diseases after drug discontinued
  • Max benefit when initiated at earliest stage of disease (within 72hrs)
78
Q

X TOPICAL ANTIVIRAL

A

Minimal clinical benefit, cause local irritation, discourage use

79
Q

1st episode: tx

A

Acyclovir PO 400mg TDS 7-10d
* IV 5-10mg/kg Q8H 2-7d
○ Complete with PO for 10d
** severe disease, complications require hosp

Valacyclovir PO 1g BD 7-10d

80
Q

Acyclovir considerations

A

F=10-20%, poor bioavail, t1/2 ~ 3hr

Counselling:
○ Take w/o regard to food
○ Take after food if GI upset
○ Malaise, headache, NV, diarr
§ Hydration! Prevent crystallisation in renal tubules = AKI

81
Q

Valacyclovir incrt t1/2

A

L-valine ester of acyclovir

F=10-20%, poor bioavail, t1/2 ~ 3hr
Give less freq, preferred

82
Q

Recurrent genital herpes occurs how often? 2 ways to tx

A
  • 4 recurrences the year after 1st sx ep
    • Use therapy based on pt preference

episodic therapy/ Chronic suppressive therapy

83
Q

CHRONIC SUPPRESSIVE THERAPY pros and cons

A

○ Less freq recurrence (70-80%) in pt who have freq recurrence >6/ yr
○ Asx outbreaks
○ Improve QOL
○ LT safety, efficacy
○ Decr risk of transmission
+ condom use, abstinence during recurrences

Cost & compliance

84
Q

CST regimen

A

Acyclovir 400mg PO BD

Valacyclovir 500mg -1g OD
500mg not if freq recurrence >10/yr

Famciclovir 250mg BD

85
Q

Duration for CST

A

pt, disease course dependent

○ Discuss w/ pt annually because genital HSV2 recurrence decr over time <– Antibodies

○ Indefinites supp for
- Complicated disease course
- Disseminated disease (encephalitis, meningitis, keratitis) in immunocomp host

86
Q

EPISODIC THERAPY pros and cons

A

Pros:
○ Shorten duration and severity of Sx
○ Less costly than CST
○ Pt more likely to be compliant

Cons
○ require initiation of therapy in 1d of lesion onset
○ Initiate when prodrome, before outbreak
○ Does not reduce risk of transmission

87
Q

EPISODIC THERAPY regimen

A

Acyclovir 800mg PO BD 5d
800mg TDS 2d

Valacyclovir 500mg BD 3d
1g OD 5d

Famciclovir 1g BD (one day)
500mg OD then 250mg BD for 2days
125mg BD 5d

88
Q

pt herpes counselling

A
  • Educate on natural hist of disease (X cure)
  • Encourage informing current & future sex partners
  • Sexual transmission during Asx
  • Remain abstinent with uninfected partners when
    ○ Lesions, prodromal Sx
  • Risk HSV sexual transmission decr by CST
  • Latex condoms to reduce risk for genital herpes transmission
  • Risk for neonatal HSV infection
  • Incr risk for HIV
    ○Test and screen periodically
89
Q

sexual partner of herpes

A
  • Sx sex partners evaluated and tx with same manner as those with genital lesions
  • Asx sex partners
    • Qn about hist of genital lesions
    • Encourage lesions examination themselves
      ○ Seek medical attention early if lesions occur
      ○ Type specific serologic testing for HSV2
90
Q

HIV —> AIDS

A
  • HIV – belongs to lentivirus grp of retrovirus family
  • HIV attacks and destroys infection-fighting CD4 T cells of immune system
  • Loss of CD4 T cells make it difficult for immune system to fight infection
    ——> Lead to Acquired Immunodeficiency Syndrome (AIDS)
91
Q

Mode of transmission HIV

A
  • Transmitted through specific body fluids
    (Blood, serum, genital fluids, breast milk)

1) Unprotected sexual intercourse with infected person
2) Share infected syringes and needles
3) Mother-to-child transmission
○ Preg, at birth, breast feeding
4) Transfusion with contaminated blood, blood pdts

92
Q

at risk grp

A
  • IV drug users
  • Person who have unprotected sex with multiple partners
  • Man who have sex with man
  • CSW
  • Persons treated with STDs
    • Will be screened for HIV
  • Recipient of multiple blood transfusion
  • Persons who have been sexually assaulted
  • Preg women
    - Mandatory testing in SG
93
Q

diagnosis of HIV

A
  • Serum Ab detection
    • HIV enzyme immunoassay Ab test
      ○ HIV EIA tests
    • Western blot
  • HIV RNA detection/ quantification (viral load)
    • Nucleic acid amplification (PCR)
94
Q

HIV Presentation
Based on stages

A

1) ACUTE (primary) HIV infection
a) After contracting HIV
b) Flu-like illness, swollen lymph nodes, fever, malaise, rash
c) Lasting about 2-3 wks

2) Asymptomatic stage
a) No signs and sx
b) Persists for many years

3) Persistent generalised lymphadenopathy
a) Persistent unexplained lymph node enlargement in neck, underarms, groin
b) More than 3mnths

4) AIDS & related conditions Advanced stage of disease

95
Q

AIDS

A

AIDS = CD4 < 200/mm3
Presence of AIDS-defining diseases
i) Pt succumb to infections by unusual org, opportunistic infections
§ Pneumocystis carinii pneumonia
§ TB, candida, herpes
ii) Involve organs: lung, eye, GIT, CNS, skin
iii) Systemic sx: fever, unexplained weight loss, diarrhea
iv) Rare cancers: lymphoma, kaposi sarcoma

96
Q

Goals for antiviral therapy (HIV)

A
  • Reduce HIV associated morbidity and mortality
    • Good CD4 cell count, no progression to AIDS
  • Prolong duration and quality of survival
    • Less complications, better QOL
  • Restore and preserve immunologic function
  • Maximally and durably SUPPRESS plasma HIV viral load
  • Prevent HIV transmission
    - Undetectable viral load, less transmission
97
Q

Surrogate markers in HIV

A

1) CD4
2) VIRAL LOAD (plasma HIV RNA)
- undetectable

98
Q

CD4 marker

A

a) Healthy: 500-1200 cells/mm3
a. Adaptive immunity (activate cytotoxic T cells, Ab production)
b) Indicates immune function in HIV infected pt
c) Predicts subsequent disease progression and survival
d) Determine urgency of antiretroviral therapy
e) Assess response to antiretroviral therapy
a. Assessed at baseline. Every 3-6mnths after tx initiation
i. Every 12mnths after adequate resp
b. Adequate CD4 response = incr in CDC4 count
(50-150 cells/mm3) during 1st yr of therapy

f) Use to assess need for initiating/ discontinue prophylaxis for opportunity infections
a. Pneumocystis pneumonia when CD4 cells <200 cells/mm3

99
Q

Adequate CD4 response

A

= incr in CDC4 count
(50-150 cells/mm3) during 1st yr of therapy

100
Q

VIRAL LOAD (plasma HIV RNA) marker

A

a) Amt of virus in plasma
b) Indicate response to antiretroviral therapy
c) Predicts clinical progression
d) Viral load measured
a. Before initiation of therapy
b. Within 2-4 wks (<8wk) after tx initiate/ modification
c. Every 4-8wks until viral load suppressed
i. Achieved viral supp 8-24wks
1) Undetectable HIV RNA lvl

		ii. Stable regimen, supp viral load
			1)  Monitor every 3-6-12 mnths
101
Q

When to initiate therapy

A

ASAP
* Antiretroviral therapy (ART) recommended for all HIV-infected individuals —– Regardless of CD4 cell count
* Reduce morbidity and mortality associated with HIV infection
* Prevent transmission of HIV

  • Before initiate:
    1) Educate pt regarding benefits and considerations regarding ART
    2) Address strategies to optimise adherence
    ○ (95% adherence needed)
  • Defer initiation
    • Clinical/ psychosocial factors
      ○ Non-adherent –> leads to viral resistance to ART
102
Q

Start ASAP (BENEFITS)

A
  • Maintain higher CD4 count, prevent irreversible damage to immune system
  • Decr risk of HIV associated complications
    ○ That occurs when CD4 counts> 350 cells/mm3
    § TB, non-Hodgkin lymphoma, Kaposi’s sarcoma, peripheral neuropathy, HIV-associated cognitive impairment
  • Decr risk of non-opportunistic conditions
    ○ CVS, renal disease, liver disease, non-AIDS associated malignancies and infections
  • Decr risk of HIV transmissions to others
    ○ Positive public health implications
103
Q

CONs of earlier tx

A
  • Develop tx-related SE, toxicities
  • Develop drug resistance
    ○ Incomplete viral suppression
    ○ Loss of future tx options
  • Transmission of drug-resistant virus in pts who do not maintain full virologic suppression
    ○ Non-adherent + sexually active
  • Less time for pt to learn about HIV and tx
    ○ Less time prep for need of adherence
  • Incr total time on medication, tx fatigue
  • Incr cost ($500/mnth, more ex than other chronic diseases)
104
Q

Factors to consider when selecting initial regimen for HIV

A

Individualised, based on factors:
* Pt understanding of HIV
* Cost, availability
* Adherence issues, convenience
○ Pill burden, dosing freq, food and fluid considerations (DDI)
§ 3 in 1 pill
* Virologic efficacy
* Potential ADR
○ Comorbidities, DDI
* Childbearing potential
○ Tx is teratogenic
* Genotypic drug resistance testing
○ Hard to grow virus, cannot do phenotypic
○ So look at the genes in HIV that infected the pt
§ Any resistant genes

105
Q

Recommended TRIPLE combinations for pt 1st ART

A

2NRTI + 1 INSTI
□ Tenofovir + emtricitabine + bictegravir
□ Tenofovir + emtricitabine + dolutegravir
□ Abacavir + lamivudine + dolutegravir

□ 3in1
□ Less pill burden, incr compliance
□Less toxicity, DDI
106
Q

Dual therapy

A

1 NRTI + 1 INSTI
□ emtricitabine + dolutegravir

NOT FOR:
□ HIV load high (>500,000 copies/mL)
□ HBV coinfection
- Requires 2 antivirals to cover (tenofovir, emtricitabine / lamivudine)
- If use dual therapy, only 1 covers = risk of resistance
□ Need HIV genotypic resistance test + HBV test

107
Q

Nucleoside reverse transcriptase inhibitors (NRTIs) eg + ADR

A

Tenofovir – BMD, renal
Emtricitabine – hyperpig
Abacavir – no hep adj, hypersensitive, MI
Lamivudine – minimal
Zidovudine – myopathy, bone marrow supp

108
Q

NRTI ADV

A
  • Established dual backbone of combi ART
    • 2NRTI
  • Renal elimination, less DDI concerns
109
Q

NRTI DISADV

A
  • ADR related to mitochondrial toxicity (Z>T>A> L)
    • Rare but serious
    • Lactic acidosis
    • Hepatic steatosis
      ○ (fatty infiltrate)
    • Lipoatrophy
      ○ Loss of fat
  • Require dose adjustment in renal impaired pt
    • Except abacavir
110
Q

Tenofovir

A
  • NVD
  • Renal impairment
    ○ TAF < TDF
  • Decr BMD
    ○ TAF < TDF
111
Q

Emtricitabine

A

Minimal toxicity
Hyperpigmentation
ND

112
Q

Abacavir

A

NVD

Hypersensitivity reaction
○ In pt with HLAB*5701
§ Rash, fever, malaise, fatigue, LOA, cough, SOB
○ Discontinue, do not rechallenge
○ Test for absence before initiate

Concern for MI
○Not for high CVS risk pt

113
Q

Lamivudine

A

Minimal toxicity
NVD

114
Q

Zidovudine

A

NVD
Myopathy
Bone marrow supp
○ Full blood count
Risk anemia, neutropenia

115
Q

Integrase strand transfer inhibitor (INSTI) eg

A

Bictegravir – SCr
Dolutegravir – Scr
Raltegravir – CK (rhabdo)
Elvitegravir

116
Q

INSTI benefits

A
  • Bictegravir & Dolutegravir
    • Good virologic effectiveness
  • High genetic barrier to resistance
    ○ B/D > R/E
  • Well tolerated
117
Q

INSTI DISADV

A
  • ADR
  • DDI
    • Bioavailability lowered by concurrent ad of polyvalent cations (Ca, Fe)
    • B,D,E are CYP3A4 substrates
118
Q

ADR INSTI

A
  • Weight gain, ND, headache
  • depression, suicidality
    ○ Rarely reported with INSTI use
  • Primarily in pt with preexisting psychiatric conditions
  • Bictegravir, Dolutegravir
    • Incr in serum creatinine
  • Raltegravir
    • Pyrexia (fever)
    • creatine kinase elevation
      ○ Rhabdomyolysis

**inhibit tubular secretion of creatinine, no impact on glomerular function

119
Q

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) eg

A

Efavirenz – hyperLDL
Rilpivirine – depression

120
Q

NNRTI ADV

A
  • Long half life (daily dosing)
  • Less metabolic toxicity
    • Hyperlipidaemia
    • Insulin resistance
      ○ Than with PI

Used to be 2NRTI+1NNRTI+1P1
INSTI then become first choice

121
Q

NNRTI DISADV

A
  • Low genetic barrier to resistance
  • Cross resistance among approved NNRTIs
  • Skin rash, SJS,
    • E>R
  • Potential for CYP450 drug interactions
    • Inducers/ inhibitors
  • QTc prolongation
122
Q

Efavirenz SE

A
  • Rash
  • Hepatotoxicity
  • hyperlipidaemia
    ○ Incr LDLc, TG
  • Neuropsychiatric SE
    ○Dizzy, depression, insomnia, abnormal dream, hallucination
123
Q

Rilpivirine SE

A

Depression, headache

124
Q

NNRTI DDI

A

Mixed CYP inducer/ inhibitor
* E: CYP3A4 sub
○ CYP2B6, 2C19 inducer
* R: CYP3A4 sub
○ PO ab reduced when incr pH (no PPI)

125
Q

Protease inhibitors (PI) eg

A

Ritonavir
Lopinavir
Atazanavir
Darunavir
Fosamprenavir (ritonavir/ cobicistat)

126
Q

PI ADV

A
  • High genetic barrier to resistance
    • Esp those with high viral load, risk mutation
  • PI resistance is less common
127
Q

PI DISADV

A
  • Liver toxicity (if hep B,C)
  • DDI: CYP3A4 inhibitors, substrates
  • Metabolic complications
    • Dyslipidemia, insulin resistance
  • GIT — NVD
  • Morphologic complications
    • Lipohypertrophy, fat maldistribution
  • Incr risk of osteopenia/ osteoporosis
128
Q

Ritonavir SE

A

potent CYP3A4, 2D6inhibitor

Freq combined with other PI, boost lvl (Lopinavir/ ritonavir)

  • SE: paresthesia (numb in extremities), taste perversion
129
Q

Darunavir

A

GI tolerability
Less lipid effects
SE: skin rash, SJS (sulphonamide)

130
Q

Atazanavir

A

GI tolerability
Less lipid effects

Absorption depend on LOW pH
○ CI: PPI

SE: hyperbilirubinemia, prolong QT interval, skin rash

131
Q

Fusion inhibitors eg

A

Enfuvirtide

Sc inj 2x/day

132
Q

PROS AND CONS OF FI

A

pros: no DDI

cons:
* Inj site reaction
* Erythema/ induration
* Nodules/ cyst
* Pruritis
* Ecchymosis
* Rare hypersensitivity reaction
* Fever, chill, decr BP
* Incr bacterial pneumonia

133
Q

CCR5 antagonist eg

A

Maraviroc (selzentry)

134
Q

PROS AND CONS OF CCR5

A

pros:
* Used only in people whose strain of HIV uses CCR5 receptor to enter CD4 T cells
* Need co-receptor tropism assay before initiate
* CCR5 predominant
- Not for CXCR4/ dual-mixed tropism

cons: CYP3A4 substrate DDI

135
Q

ADR of CCR5

A
  • Abdominal pain
  • Cough
  • Dizziness
  • Musculoskeletal sx
  • Pyrexia
  • Rash
  • Upper resp tract infections
  • Hepatotoxicity
    Orthostatic hypotension
136
Q

HIV tx failure

A

Adherence >95%
Drug toxicity
Dosing schedule & requirements
DDI
Viral resistance
Regimen potency
Provider experience

3151 finals (9 decks)

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