Transcript Slide 1
Guidelines for Prevention and Treatment of
Opportunistic Infections in HIV-Infected
Adults and Adolescents
Pneumocystis jiroveci Pneumonia Slide Set
Prepared by the AETC National Resource Center
based on recommendations from the CDC,
National Institutes of Health, and HIV Medicine
Association/Infectious Diseases Society of America
About This Presentation
These slides were developed using recommendations
published in May 2013. The intended audience is
clinicians involved in the care of patients with HIV.
Users are cautioned that, owing to the rapidly
changing field of HIV care, this information could
become out of date quickly. Finally, it is intended that
these slides be used as prepared, without changes in
either content or attribution. Users are asked to honor
this intent.
-AETC National Resource Center
http://www.aidsetc.org
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Pneumocystis jiroveci Pneumonia:
Epidemiology
Caused by P jiroveci (formerly P carinii)
Ubiquitous in the environment
Initial infection usually occurs in early
childhood
PCP may result from reactivation or
new exposure
In immunosuppressed patients,
possible airborne spread
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PCP: Epidemiology (2)
Before widespread use of PCP prophylaxis and
effective ART, PCP seen in 70-80% of AIDS
patients in the United States
In advanced immunosuppression, treated PCP
associated with 20-40% mortality
Substantial decline in incidence in United
States and Western Europe, owing to
prophylaxis and ART
Most cases occur in patients unaware of their
HIV infection, in those who are not in care, and
in those with advanced AIDS (CD4 count <100
cells/µL)
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PCP: Epidemiology (3)
Risk factors:
CD4 count <200
cells/µL
Recurrent bacterial
pneumonia
CD4 percentage
<14%
Unintentional
weight loss
Prior PCP
High HIV RNA
Oral thrush
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PCP: Clinical Manifestations
Progressive exertional dyspnea, fever,
nonproductive cough, chest discomfort
Subacute onset, worsens over days-weeks
(fulminant pneumonia is uncommon)
Chest exam may be normal, or diffuse dry
rales, tachypnea, tachycardia (especially with
exertion)
Extrapulmonary disease seen rarely; occurs
in any organ, associated with aerosolized
pentamidine prophylaxis
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PCP: Diagnosis
Clinical presentation, blood tests, radiographs
suggestive but not diagnostic
Organism cannot be cultured
Definitive diagnosis should be sought
Hypoxemia: characteristic, may be mild or
severe (PO2 <70 mmHg or A-a gradient >35
mmHg)
LDH >500 mg/dL is common but nonspecific
1,3β-D-glycan may be elevated; uncertain
sensitivity and specificity
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PCP: Diagnosis (2)
CXR: various presentations
May be normal in early disease
Typical: diffuse bilateral, symmetrical
interstitial infiltrates
May see atypical presentations, including
nodules, asymmetric disease, blebs, cysts,
pneumothorax
Cavitation, intrathoracic adenopathy, and
pleural effusion are uncommon (unless
caused by a second concurrent process)
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PCP: Diagnosis (3)
Chest CT, thin-section
Patchy ground-glass attenuation
May be normal
Gallium scan
Pulmonary uptake
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PCP: Diagnosis (Imaging)
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Chest X ray: PCP with bilateral, diffuse
granular opacities
Chest X ray: PCP with bilateral perihilar
opacities, interstitial prominence, hyperlucent
cystic lesions
Credit: L. Huang, MD; HIV InSite
Credit: HIV Web Study, www.hivwebstudy.
org, © 2006 University of Washington
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PCP: Diagnosis (Imaging) (2)
High-resolution computed tomograph (HRCT) scan of the chest showing
PCP. Bilateral patchy areas of ground-glass opacity are suggestive of PCP.
Credit: L. Huang, MD; HIV InSite
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PCP: Diagnosis
Definitive diagnosis requires demonstrating
organism:
Induced sputum (sensitivity <50% to >90%)
Spontaneously expectorated sputum: low sensitivity
Bronchoscopy with bronchoalveolar lavage
(sensitivity 90-99%)
Transbronchial biopsy (sensitivity 95-100%)
Open-lung biopsy (sensitivity 95-100%)
PCR: high sensitivity for BAL sample; may not
distinguish disease from colonization
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PCP: Diagnosis (Histopathology)
Lung biopsy using silver stain to
demonstrate P jiroveci organisms in
tissue
Credit: A. Ammann, MD; UCSF Center for HIV Information
Image Library
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PCP: Diagnosis
Treatment may be initiated before
definitive diagnosis is established
Organism persists for days/weeks after
start of treatment
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PCP: Preventing Exposure
Insufficient data to support isolation as a
standard practice, but data suggest highrisk patients may benefit from isolation
from persons with known PCP
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PCP: Primary Prophylaxis
Initiate:
CD4 <200 cells/µL or history of oropharyngeal
candidiasis
Consider for:
CD4% <14% or history of AIDS-defining illness
CD4 200-250 cells/µL if Q 3-month CD4 monitoring
is not possible
Discontinue:
On ART with CD4 >200 cells/µL for >3 months
Reinitiate:
CD4 decreases to <200 cells/µL
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PCP: Primary Prophylaxis (2)
Preferred:
Trimethoprim-sulfamethoxazole (TMP-SMX)
DS 1 tablet PO QD*
TMP-SMX SS 1 tablet PO QD
For patients who experience non lifethreatening adverse events, consider
desensitization or dosage reduction
* Effective as toxoplasmosis prophylaxis (for CD4 count <100 cells/µL +
positive serology)
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PCP: Primary Prophylaxis (3)
Alternative:
TMP-SMX DS 1 tablet PO 3 times Q week
Dapsone 100 mg PO QD or 50 mg BID
Dapsone 50 mg QD + pyrimethamine 50 mg Q week +
leucovorin 25 mg Q week*
Dapsone 200 mg + pyrimethamine 75 mg + leucovorin 25
mg, all Q week*
Aerosolized pentamidine 300 mg Q month via Respirgard
II nebulizer (other devices not recommended)
Atovaquone 1,500 mg PO QD*
* Effective as toxoplasmosis prophylaxis (for CD4 count <100
cells/µL + positive serology)
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PCP: Treatment
Duration: 21 days for all treatment
regimens
Preferred: TMP-SMX is treatment of
choice
Moderate-severe PCP
TMP-SMX: 15-20 mg/kg/day TMP and 75-100 mg/kg/day
SMX IV or PO in divided doses Q6-8H
Mild-moderate PCP
As above, or TMP-SMX DS 2 tablets TID
Adjust dosage for renal insufficiency
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PCP: Treatment (2)
Alternatives
Moderate-severe PCP
Pentamidine 4 mg/kg IV QD
Recommended for patients who cannot tolerate TMPSMX or experience clinical failure with TMP-SMX; do
not combine use
Primaquine 30 mg (base) PO QD + clindamycin
600 mg IV Q6H or 900 mg IV Q8H or 300 mg PO
Q6H or 450 mg PO Q8H
More effective than pentamidine, less toxicity
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PCP: Treatment (3)
Alternatives
Mild-moderate PCP
Dapsone 100 mg PO QD + TMP 15 mg/kg/day PO
in divided doses TID
Similar efficacy, fewer side effects than TMP-SMX, but
more pills
Primaquine 30 mg (base) PO QD + clindamycin 300
mg PO Q6H or 450 mg PO Q8H
Atovaquone 750 mg PO BID
Less effective than TMP-SMX, but fewer side effects
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PCP: Treatment (4)
Adjunctive:
Corticosteroids
For moderate-to-severe disease (room air PO2
<70 mmHg or A-a gradient >35 mmHg)
Give as early as possible (within 72 hours)
Prednisone 40 mg BID days 1-5, 40 mg QD
days 6-10, 20 mg QD days 11-21, or
methylprednisolone at 75% of respective
prednisone dosage
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PCP: ART Initiation
For patients not on ART, start ART within
2 weeks of PCP diagnosis, if possible
In one study, lower rates of AIDS
progression or death with early ART initiation
(no data on patients with respiratory failure
requiring intubation)
IRIS has been reported; follow for
recurrence of symptoms
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PCP: Monitoring and Adverse Events
Monitor closely for response to
treatment, and for adverse effects of
treatment
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PCP: Monitoring and Adverse Events (2)
TMP-SMX: rash, Stevens-Johnson syndrome, fever,
leukopenia, thrombocytopenia, azotemia, hepatitis,
hyperkalemia
Atovaquone: headache, nausea, diarrhea, rash, fever,
transaminase elevations
Dapsone: methemoglobinemia and hemolysis, rash,
fever
Pentamidine: pancreatitis, hypo- or hyperglycemia,
leukopenia, fever, electrolyte abnormalities, cardiac
dysrhythmia
Primaquine and clindamycin: methemoglobinemia and
hemolysis, anemia, rash, fever, diarrhea
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PCP: Treatment Failure
Lack of clinical improvement or worsening of
respiratory function after at least 4-8 days of
treatment
If patient not on corticosteroid therapy, early
deterioration (day 3-5) may be caused by
inflammatory response to lysis of P jiroveci
organisms
Rule out concomitant infection
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PCP: Treatment Failure (2)
Treatment failure resulting from drug toxicities
in up to 1/3 of patients
Treat adverse reactions or switch regimen
Treatment failure caused by lack of drug
efficacy in 10% of patients
No data to guide treatment decisions
For TMP-SMX failure in moderate-to-severe PCP,
consider IV pentamidine or primaquine + IV
clindamycin
For mild disease, may consider atovaquone
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PCP: Preventing Recurrence
Secondary prophylaxis (chronic maintenance therapy)
for life unless immune reconstitution on ART
Preferred: TMP-SMX 1 DS PO QD, or 1 SS PO QD
Alternatives:
TMP-SMX DS 1 tablet PO 3 times Q week
Dapsone 100 mg PO QD or 50 mg BID
Dapsone 50 mg QD + pyrimethamine 50 mg Q week
+ leucovorin 25 mg Q week
Dapsone 200 mg + pyrimethamine 75 mg + leucovorin 25
mg, all Q week*
Aerosolized pentamidine 300 mg Q month via Respirgard II
nebulizer (other devices not recommended)
Atovaquone 1,500 mg PO QD
Atovaquone 1,500 mg PO QD + pyrimethamine
25 mg QD + leucovorin 10 mg PO QD
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PCP: Preventing Recurrence (2)
Discontinue secondary prophylaxis for patients
on ART with sustained increase in CD4 count
from <200 cells/µL to >200 cells/µL for ≥3
months
If PCP occurred at CD4 count >200 cells/µL,
prudent to continue prophylaxis for life (regardless
of CD4 count)
Restart maintenance therapy if CD4 count
decreases to <200 cells/µL or if PCP recurs at
CD4 count >200 cells/µL
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PCP: Considerations in Pregnancy
Diagnosis and indications for treatment:
as in nonpregnant women
Preferred treatment: TMP-SMX
Limited data suggest small increased risk
of birth defects after 1st trimester TMP
exposure, but pregnant women with PCP
should be treated with TMP-SMX
Consider increased doses of folic acid (>0.4
mg/day) in 1st trimester: may decrease risk of
congenital anomaly but may increase risk of
therapeutic failure
Pentamidine embryotoxic in animals
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PCP: Considerations in Pregnancy (2)
Dapsone: risk of mild maternal hemolysis with
long-term therapy; risk of hemolytic anemia in
fetuses with G6PD deficiency
Pentamidine embryotoxic in animals
Primaquine: not generally used in pregnancy,
risk of hemolysis; risk of hemolytic anemia in
fetuses with G6PD deficiency
Clindamycin, atovaquone: appear safe in
pregnancy
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PCP: Considerations in Pregnancy (3)
Corticosteroid indications as in nonpregnant
women; monitor for hyperglycemia
Increased risk of preterm labor and delivery;
monitor if pneumonia occurs after 20 weeks of
gestation
Prophylaxis as in nonpregnant adults
Consider aerosolized pentamidine or atovaquone
during 1st trimester, if risk of teratogenicity caused
by systemic agents is a concern
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Websites to Access the Guidelines
http://www.aidsetc.org
http://aidsinfo.nih.gov
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About This Slide Set
This presentation was prepared by Susa
Coffey, MD, for the AETC National
Resource Center in May 2013
See the AETC NRC website for the most
current version of this presentation:
http://www.aidsetc.org
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