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Exam 5 - Therapeutics > Prophylaxis of opportunistic infections > Flashcards

Prophylaxis of opportunistic infections Flashcards

1
Q

What are opportunistic infections?

A

Infections that are more frequent/severe because of HIV-mediated immunosuppression
-Get into CD4 cells and destroys them –> some CD4 counts never rebound & will need to maintain prophylaxis

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2
Q

Common historical infections

A

PJP
Toxoplasma encephalitis
CMV retinitis
Cryptococcal meningitis
TB
MAC disease
Histoplasmosis
Other pneumonias
Kaposi sarcoma
Lymphomas

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3
Q

3 key aspects of HIV

A

Decreased CD4 count
Inflammation
Immune cell activation

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4
Q

Normal CD4 counts in adults

A

800-1200 cells/mm3
**ALWAYS a delayed CD4 count drop
**Once pts get back up to this level, they are no longer considered immunocompromised

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5
Q

CD4 counts < _____ cells/mm3, and especially < ___ cells/mm3 are associated with the development of OI

A

500
200

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6
Q

Why is there still morbidity/mortality from OI

A

Some pts don’t know they have HIV
Some don’t want to take meds
Financial/psychosocial issues
DRUG INTERACTIONS

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7
Q

Get the ___ that the person you got it from has. Example:

A

Strain
If the person you got it from has a strain resistant to a med, you are resistant to that same med

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8
Q

Which infections can occur at any CD4 cell count

A

Mycobacterium TB
Pneumonias
Dermatomal Varicella zoster

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9
Q

CD4 count < 500 cells/mm3 infections

A

Candidiasis and leukoplakia (redish/raw lesion in mouth)

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10
Q

CD4 count < 200 cells/mm3 infections

A

PJP, CMV retinitis, toxoplasmosis, MAC, cryptococcus meningitis or diarrhea, lymphomas, and Kaposi’s sarcoma
** Incidence really starts going up here

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11
Q

TB and syphilis can ____ the viral load which ____ risk of viral transmission and progression

A

Increases
Increases

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12
Q

What are 2 main symptoms/clinical clues of low CD4 counts

A

Night sweats and weight loss

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13
Q

Primary prophylaxis

A

Administration of an anti-infective agent to prevent the FIRST episode of a particular OI in a patient living with HIV when they are at risk for developing that OI based on their CD4 count
**For pts already with HIV; do not give prophylaxis to everyone

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14
Q

Secondary prophylaxis

A

-Chronic maintenance/chronic suppressive therapy
-Administration of anti-infective therapy to prevent further recurrences of a particular OI in a patient living with HIV after they have been successfully treated for that OI and remain at risk for developing that OI based on their CD4 cell count
**Already had the OI

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15
Q

Initiation of ART during an acute OI is very useful in the management of OIs for which ______.

Examples of infections this is beneficial for

A

Effective therapy is not available

PML, cryptosporidiosis, Kaposi’s sarcoma
**No good drugs for these, so try to get viral load < 20 ASAP

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16
Q

Disadvantages to immediately starting ART for acute OI

A

IRIS
Overlapping or additive drug toxicities
Drug interactions between ART and OI tx

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17
Q

What is IRIS

A

Immune reconstitution inflammatory syndrome
-Fever, inflammation, and worsening clinical manifestations of OI
-More likely to occur in pts with low CD4 count (<50 cells/mm3) and high HIV RNA levels (>100,000 copies/ml)
-Most clinicians wait for a clinical response to OI tx, usually 2 weeks before starting ART

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18
Q

Exception to waiting 2 weeks between OI tx and ART

A

Start ART within 2 weeks of starting TB tx if CD4 count , 50 cells/mm3 or within 8 weeks if CD4 count is higher

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19
Q

If IRIS is going to happen, it is most common within the first ____ of ART

A

4-8 weeks

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20
Q

IRIS tx

A
  1. Treat the OI (bc sx may get worse)
  2. Mild disease: NSAID for fever/pain
    Inhaled corticosteroid for bronchospasms
  3. Severe disease: Prednisone 1-2 mg/kg daily x 1-2 weeks followed by a taper
    **Avoid steroids in cryptococcal meningitis or Kaposi’s sarcoma
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21
Q

Common infections in today’s era

A
  1. Infections from Candida spp
  2. Infections due to Cryptococcus neoformans
  3. Histoplasmosis
  4. Infections due to Mycobacterium avium complex (MAC)
  5. Pneumocystis jirovecii pneumonia (PJP)
  6. Infections due to Toxoplasma gondii
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22
Q

When do infections with Candida spp mainly occur

A

When CD4 count < 200 cells/mm3

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23
Q

Majority of Candida spp infections are caused by ____ which is usually susceptible to ______

A

Candida albicans
Fluconazole

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24
Q

Candida infections due to non-albicans spp and/or fluconazole-R organisms may develop in pts who have received _______________

A

Repeated or long-term exposure to fluconazole

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25
Diagnosis of oropharyngeal candidiasis (thrush)
Clinical exam: plaque-like lesions on buccal mucosa/tongue surface -Dry mouth/taste alteration -Can easily scrape off
26
Preferred tx for oropharyngeal candidiasis
Fluconazole 200 mg (loading dose), followed by 100-200 mg PO QD for 7-14 days
27
Alternative tx for oropharyngeal candidiasis
Topical agents for initial, mild to moderate episodes only *Advantages: reduces systemic drug exposure, diminishes risk of drug-drug interactions, and decreases risk of resistance
28
Topical agents used in oropharyngeal candidiasis
1. Nystatin suspension (100,000 units/ml): swish and swallow 5 ml QID x 7-14 days. Should be thoroughly rinsed in mouth and retained in mouth for as long as possible before swallowing. 2. Clotrimazole troches (10 mg lozenge): Use 1 lozenge 5 times daily for 7-14 days. Should be dissolved slowly in the mouth over 15-30 minutes.
29
If pt has oral thrush, what is the next question you should ask?
What does it feel like to swallow? **To check for esophageal candidiasis
30
What is esophageal candidiasis?
Fever, retrosternal burning pain or discomfort, dysphagia, odynophagia -Endoscopic examination reveals whitish plaques (similar to thrush) with superficial ulceration of the esophageal mucosa with white surface exudates
31
Preferred tx for esophageal candidiasis
Fluconazole 200 mg (up to 400 mg) IV or PO QD for 14-21 days
32
Which topical agents are used for esophageal candidiasis?
NONE! Topical therapy is not effective for esophageal candidiasis (if it hurts to swallow, no topical)
33
What is vulvovaginal candidiasis?
White, thick, vaginal discharge, vaginal itching, vaginal burning, and vulvar erythema Symptoms may be more severe/frequent with advanced immunosuppression **Yeast infection
34
Treatment for uncomplicated vulvovaginal candidiasis
Fluconazole 150 mg PO x 1 dose Topical azoles (clotrimazole, butoconazole, miconazole, tioconazole, or terconazole) x 3-7d Ibrexafungerp 300 mg PO BID x 1d
35
Treatment for severe vulvovaginal candidiasis
Fluconazole 100-200 mg PO QD or topical antifungals for >/= 7d
36
Treatment for azole-refractory C. glabrata vaginitis
Boric acid 600 mg vaginal suppository once daily x 14d
37
Prophylaxis in vulvovaginal candidiasis
Routine primary and secondary prophylaxis is NOT recommended **Daily prophylaxis should only be considered for patients with frequent or severe recurrences of esophagitis or vaginitis
38
What is cryptococcal meningitis?
Fever, malaise, HA, nausea, dizziness, lethargy, irritability, impaired memory, and behavioral changes
39
Classic sx of cryptococcal meningitis
Neck stiffness and photophobia (often missing)
40
Majority of Cryptococcus neoformans infections are observed among patients with ____ and CD4 counts < ___ cells/mm3
AIDS 100
41
Diagnosis of Cryptococcus neoformans
CSF analysis -Increased intracranial pressure -Mildly elevated protein and low-to-normal glucose -Few WBC with lymphocytic predominance -Increased cryptococcal antigen titer in CSF and serum -India ink stain positive for encapsulated yeast forms -Biofire PCR/CSF culture positive
42
Initiation of ART and OI tx in Cryptococcus neoformans
If pt not on ART, ART should be initiated 2 weeks (after induction) or 10-12 weeks (total induction / consolidation phases) to avoid IRIS
43
What are the 3 phases of Cryptococcus neoformans tx
Induction Consolidation Maintenance
44
Preferred tx for induction of Cryptococcus neoformans
Amphotericin B 3-4 mg/kg IV once daily + flucytosine 25 mg/kg PO QID x 2 weeks, followed by consolidation *Follow pts in hospital at least 7d *Check daily LPs if ICP elevated
45
Preferred tx for consolidation of Cryptococcus neoformans
Fluconazole 800 mg PO QD (400 mg PO QD in stable pts with sterile CSF [shows negative cryptococcus] and on ART) x at least 8 weeks, followed by maintenance
46
Preferred tx for maintenance (secondary prophylaxis) of Cryptococcus neoformans
Fluconazole 200 mg PO QD x at least 1y
47
Primary prophylaxis in Cryptococcus neoformans
NOT recommended
48
Secondary prophylaxis in Cryptococcus neoformans
Required after induction/consolidation tx. Continue oral fluconazole for at least 1 year.
49
Criteria to D/C secondary prophylaxis in Cryptococcus neoformans
*May be D/C if pt has completed 1 year, is asymptomatic, and CD4 count >/= 100 cell/mm3 for 3 months on ART with a suppressed viral load [MUST MEET ALL 4 CRITERIA]
50
When would prophylaxis need to be restarted in a patient with Cryptococcus neoformans?
CD4 count < 100 cells/mm3
51
How do patients present with Mycobacterium avium Complex (MAC)?
Fever, NIGHT SWEATS, weight loss, diarrhea, abdominal pain, and malaise/fatigue *In pts with HIV with advanced immunosuppression who are not on ART, MAC generally presents as a disseminated multi-organ infection
52
Which patients are at highest risk for MAC?
Patients with a CD4 count < 50 cells/mm3, viral replication despite ART, and previous or concurrent OIs are at higher risk
53
Diagnosis of MAC
-Physical exam/radiographic exam may reveal hepatomegaly, splenomegaly, or lymphadenopathy -Lab tests may reveal anemia and elevated liver alkaline phosphatase -Confirmed dx based on clinical s/sx + isolation of MAC from acid-fast bacilli cultures of blood, lymph fluid, bone marrow, or other tissue/body fluids
54
When should ART and OI be initiated in a patient with MAC?
Start ART ASAP; may start at same time as OI tx
55
Tx of MAC should include at least _____ drugs as initial tx to prevent/delay emergence of resistance
2
56
Preferred tx for MAC
1. Clarithromycin 500 mg PO BID + ethambutol 15 mg/kg PO QD 2. Azithromycin 500-600 mg PO QD + ethambutol 15 mg/kg PO QD (if clarithromycin cannot be used)
57
In more severe cases of MAC, which agent should be added?
Rifabutin 300 mg PO QD *** CONCERN FOR DRUG INTERACTIONS ***
58
When should a 4th drug be considered?
1. More severe disease present 2. High mortality risk 3. Drug resistance is likely 4. CD4 count < 50 5. High mycobacterial load in blood 6. Ineffective ART
59
Drugs that should be considered if a fourth drug is needed for MAC
1. Levofloxacin or Moxifloxacin 2. Amikacin or Streptomycin 3. Linezolid, Tedizolid, or omadacycline
60
Treatment for disseminated MAC should be administered for at least ____________
12 months
61
Use of primary prophylaxis for MAC
Not recommended for those who immediately initiate ART after HIV diagnosis
62
Reasons for primary prophylaxis of MAC
1. CD4 count < 50 AND not receiving ART or remains viremic on ART or no other options for fully suppressive ART regimen 2. Ensure no active MAC before starting primary prophylaxis 3. D/C primary prophylaxis if pt is continuing on fully suppressive ART regimen 4. Restart primary prophylaxis if CD4 falls < 50 cells/mm3 and not on fully suppressive ART
63
Preferred regimen for primary prophylaxis of MAC
Azithromycin 1200 mg PO QW
64
Secondary prophylaxis of MAC considerations
1. Tx duration should be at least 12 months (shorter duration may be considered, but CD4 count should be >100 cells/mm3 for at least 6 months in response to ART) 2. Restart secondary prophylaxis if CD4 count < 100 cells/mm3 and a fully suppressive ART regimen is not possible
65
Reasons secondary prophylaxis can be stopped for MAC
MUST MEET ALL CRITERIA 1. Completed at least 12 months of therapy 2. No s/sx of MAC disease 3. Have sustained (>6 mos) CD4 count > 100 cells/mm3 in response to ART
66
Secondary tx for MAC
Clarithromycin 500 mg PO BID + ethambutol 15 mg/kg PO QD +/- Rifabutin 300 mg PO QD
67
Clinical presentation of PJP
Subacute onset of progressive dyspnea, fever, non-productive cough, and chest discomfort that worsens over days-weeks HYPOEXMIA is the most characteristic lab abnormality
68
Dx of PJP
-pO2 might be hypoxemic (<70 mmHg) -Elevated LDH (> 500 mg/dL) -CXR: interstitial infiltrates in butterfly pattern -Lab culture positive (BAL fluid) -PCR
69
When to initiate ART and OI tx for PJP
If not already started, ART should be initiated in pts within 2 weeks of PCP dx (do not start at the same time)
70
Preferred tx for moderate-severe PJP
Trimethoprim-Sulfamethoxazole (TMP-SMX) 15-20 mg/kg/d of the TMP component IV divided Q6-8H x 21d (may switch to PO after clinical improvement)
71
Alternative tx for PJP if severe sulfa allergy
Primaquine + Clindamycin Pentamidine
72
When would adjunctive CCS be used for moderate to severe PJP? Which med is used?
pO2 < 70 mmHg on room air Start within 72 hours of PJP tx Prednisone 40 mg PO BID x 5d, then 40 mg PO QD x 5d, then 20 mg PO QD x 11 days (IV methylprednisolone if needed)
73
Preferred tx for mild-moderate PJP
TMP-SMX 15-20 mg/kg/day PO in 3 divided doses x 21d TMP-SMX: 2 DS tablets PO TID x 21d
74
Alternative tx for mild-mod PJP disease What lab value must be checked prior to initiation?
Dapsone or Primaquine **Check G6PD levels -- if deficiency, these agents cannot be used
75
Primary prophylaxis for PJP
-Recommended to prevent the first episode of PJP in all HIV-infected pts with 1. CD4 100-200 cells/mm3, if HIV RNA level above detection limit (viral load present) 2. CD4 < 100 cells/mm3, regardless of HIV RNA level
76
Secondary prophylaxis for PJP
Must be given after completion of tx for an acute episode of PJP in ALL patients
77
Considerations for PJP secondary prophylaxis discontinuation
-Can D/C when CD4 count >/= 200 cells/mm3 for > 3 months in response to ART -Can consider when CD4 count is 100-200 cells/mm3 if HIV RNA remains below the limit of detection for at least 3-6 months -Restart prophylaxis when CD4 < 100 cells/mm3 regardless of HIV RNA level
78
Prophylaxis tx for PJP
Bactrim DS or single strength QD Bactrim DS M, W, F
79
Clinical disease of toxoplasma gondii exclusively occurs because of _______________ *Greatest risk of developing disease is among pts with CD4 cell count ______________
Reactivation of latent tissue cysts < 50 cells/mm3
80
Clinical presentation of toxoplasma gondii
-Most common is FOCAL ENCEPHALITIS: HA, focal neurologic deficits (Hemiparesis), and fever -Progression of infection may result in seizure, stupor, and coma
81
Dx toxoplasma gondii
-Seropositive IgG antibodies -CT/MRI reveals ring-enhancing lesions in gray matter of the cortex or basal ganglia
82
Treatment duration for toxoplasma gondii
Clinical response usually seen within 14 days of tx. Tx for acute infection should be continued for at least 6 weeks.
83
When should adjunctive CCS be given to a pt with toxoplasma gondii?
If there is mass effect associated with focal lesions or associated edema and discontinued ASAP
84
When should anticonvulsants be given to a pt with toxoplasma gondii?
Pts with a hx of seizures at least through the period of acute tx, but should NOT be administered prophylactically in all patients
85
When should ART and OI tx be started in toxoplasma gondii?
ART should be started within 2-3 weeks of diagnosis/tx of PJP
86
Preferred regimens for acute infection of toxoplasma gondii
1. Pyrimethamine 200 mg PO x 1 followed by weight-based dosing 2. TMP/SMX 5 mg/kg based on TMP component (IV or PO) BID x at least 6 weeks
87
Primary prophylaxis tx for toxoplasma gondii Which patients should receive this?
TMP-SMX DS 1 tab PO QD -Pts whop are toxoplasma IgG positive with CD4 count < 100 cells/mm3
88
When to D/C & restart prophylaxis in toxoplasma gondii
D/C: CD4 > 200 for > 3mos in response to ART -OR- CD4 100-200 cells/mm3 and HIV RNA below limits of detection x 3-6 mos Restart primary prophylaxis if CD4 count falls <100 -OR- CD4 100-200 and HIV RNA above detection limits
89
Secondary prophylaxis considerations for toxoplasma gondii
Given to ALL patients after completion of tx for an acute episode -TMP/SMX DS 1t PO BID -Pyrimethamine
90
D/C & restart secondary prophylaxis for toxoplasma gondii
D/C: CD4 > 200 cells/mm3 for > 6 mos in response to ART & pt had successful completion with initial tx & pt is asx (MUST MEET ALL CRITERIA) Restart: CD4 <200 regardless of HIV RNA level

Exam 5 - Therapeutics (11 decks)

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