Pneumocystis Pneumonia Flashcards
What is Pneumocystis pneumonia (PCP) caused by?
Pneumocystis jirovecii
PCP is a clinical syndrome caused by the fungus Pneumocystis jirovecii, which was previously referred to as Pneumocystis carinii for the species infecting rats.
At what age do two-thirds of healthy children have antibodies to P. jirovecii?
By age 2 to 4 years
Initial infection with P. jirovecii usually occurs in early childhood.
How is Pneumocystis believed to spread?
Airborne route
Rodent studies and case clusters in immunosuppressed patients suggest airborne transmission.
What was the incidence of PCP among people with advanced HIV before prophylaxis and ART?
70% to 80%
The mortality rate in individuals despite anti-Pneumocystis therapy was 20% to 40%.
What percentage of PCP cases now occur in people with HIV who are unaware of their HIV status?
Most cases
Incidence has declined substantially with the use of PCP prophylaxis and ART.
What are the most common clinical manifestations of PCP in people with HIV?
Subacute onset of progressive dyspnea, fever, non-productive cough, chest discomfort
Symptoms worsen within days to weeks.
What is the most characteristic laboratory abnormality in PCP?
Hypoxemia
It can range from mild to severe based on arterial oxygen partial pressure.
What does a chest radiograph typically show in PCP patients?
Diffuse, bilateral, symmetrical ‘ground-glass’ interstitial infiltrates
A normal chest radiograph may occur in people with early disease.
What is required for a definitive diagnosis of PCP?
Histopathologic or cytopathologic demonstration of organisms
This can be done in tissue, bronchoalveolar lavage fluid, or induced sputum samples.
What method has replaced staining methods in many laboratories for diagnosing PCP?
Polymerase chain reaction (PCR)
PCR is highly sensitive and specific for detecting Pneumocystis.
What is 1,3 β-D-glucan and its relevance to PCP diagnosis?
A component of the cell wall of Pneumocystis cysts, often elevated in people with HIV who have PCP
The sensitivity of the β-glucan assay for diagnosis appears to be high.
What is the indication for initiating primary prophylaxis for PCP?
CD4 count 100–200 cells/mm3 with detectable plasma HIV RNA or CD4 count <100 cells/mm3
Patients on pyrimethamine-sulfadiazine for toxoplasmosis do not require additional prophylaxis.
What is the preferred therapy for primary prophylaxis against PCP?
TMP-SMX, 1 DS tablet PO daily or 1 SS tablet PO daily
TMP-SMX also provides protection against toxoplasmosis.
What should be done if a patient with HIV has a CD4 count increased to ≥200 cells/mm3 for ≥3 months?
Consider discontinuing primary prophylaxis
This is contingent on the response to ART.
What alternative prophylactic regimens can be used for patients who cannot tolerate TMP-SMX?
Dapsone, aerosolized pentamidine, intravenous pentamidine, atovaquone
These regimens are for those with intolerance or severe renal dysfunction.
What should be done for patients with life-threatening adverse reactions to TMP-SMX?
Permanently discontinue TMP-SMX
No rechallenge should occur in cases like Stevens-Johnson syndrome.
What is the recommendation for pregnant patients receiving PCP prophylaxis?
Continue chemoprophylaxis as for nonpregnant adults
TMP-SMX is the recommended agent, with consideration for supplemental folic acid.
True or False: Isolation is a standard practice to prevent PCP.
False
There is insufficient data to support isolation as standard practice.
What is a common non-specific laboratory finding in PCP patients?
Elevation of lactate dehydrogenase levels >500 mg/dL
This finding is common but not specific to PCP.
What should clinicians consider for patients with mild adverse reactions to TMP-SMX?
Continue TMP-SMX if clinically feasible
Reinstitution of therapy may be considered after resolution of the reaction.
What are the recommended alternatives for prophylaxis against PCP and toxoplasmosis for HIV patients who cannot tolerate TMP-SMX?
Dapsone plus pyrimethamine plus leucovorin or atovaquone
Dapsone alone and pentamidine have not shown activity against toxoplasmosis.
What should be checked prior to starting dapsone?
Glucose-6-phosphate dehydrogenase (G6PD) levels
G6PD deficiency poses risks of hemolysis and methemoglobinemia.
What is the utility of IV pentamidine as PCP prophylaxis primarily evaluated in?
Retrospective/observational studies in immunosuppressed patients without HIV
Experience in people with HIV is limited.
What is the recommendation for discontinuing primary prophylaxis for PCP in HIV patients?
Discontinue if CD4 counts increase from <200 to ≥200 cells/mm3 for ≥3 months
Most participants had a CD4 count >300 cells/mm3 at discontinuation.
What is the preferred therapy for moderate-to-severe PCP?
TMP-SMX: TMP 15–20 mg/kg/day and SMX 75–100 mg/kg/day IV
May switch to oral formulation after clinical improvement.
What adjunctive treatment is recommended for moderate-to-severe PCP based on specific criteria?
Corticosteroids
Criteria include PaO2 <70 mmHg or A-a gradient ≥35 mmHg.
What is the dosing schedule for prednisone in treating moderate-to-severe PCP?
Days 1–5: 40 mg PO twice daily; Days 6–10: 40 mg PO daily; Days 11–21: 20 mg PO daily
IV methylprednisolone can be given as 80% of prednisone dose.
What are the alternative therapies for mild-to-moderate PCP?
Dapsone plus TMP, primaquine plus clindamycin, atovaquone
Dapsone and primaquine should be used cautiously in G6PD deficiency.
What should be monitored in pregnant persons receiving corticosteroids for PCP?
Maternal glucose levels and blood pressure, fetal growth
Corticosteroids can improve treatment outcomes.
What should be done if TMP-SMX is discontinued due to mild adverse reactions?
Consider reinstitution of therapy after the reaction has resolved
Can gradually increase dose or reduce frequency.
What is the recommended duration of therapy for PCP?
21 days
Shorter durations may be effective but have not been systematically studied.
What is the treatment of choice for PCP?
TMP-SMX
Standard doses must be adjusted for abnormal renal function.
True or False: Aerosolized pentamidine is recommended for treating PCP.
False
It has limited efficacy and is associated with more frequent relapse.
What should be considered when initiating ART in patients with PCP?
Initiate within 2 weeks of diagnosis if possible
Early ART initiation is associated with lower incidence of AIDS progression or death.
What is the preferred therapy for pregnant persons with moderate-to-severe PCP?
TMP-SMX
Risks associated with first-trimester exposure are outweighed by benefits.
Fill in the blank: Patients with documented or suspected PCP and moderate-to-severe disease should receive ________ as soon as possible.
adjunctive corticosteroids
What is a potential risk associated with primaquine use in pregnancy?
Hemolytic anemia in G6PD deficient fetuses
G6PD deficiency cannot be diagnosed antenatally.
What should be done if a patient’s CD4 count decreases after stopping prophylaxis?
Reintroduce prophylaxis if CD4 count drops to 100 to 200 cells/mm3
Prophylaxis should always be reintroduced if CD4 drops below 100 cells/mm3.
What should be monitored in people with HIV who have non-life-threatening adverse reactions to TMP-SMX?
Continue TMP-SMX if clinically feasible
Consider desensitization or reduced dosing if necessary.
What was the median time to ART initiation for participants who delayed ART?
45 days
This was compared to a median of 12 days for those who initiated ART early.
What is Paradoxical immune reconstitution inflammatory syndrome (IRIS)?
A rare condition following an episode of PCP characterized by fever and exacerbation of pulmonary symptoms
Most cases occur within weeks of the PCP episode.
What are common adverse effects of TMP-SMX in people with HIV?
- Rash (30% to 55%)
- Fever (30% to 40%)
- Leukopenia (30% to 40%)
- Thrombocytopenia (15%)
- Hepatitis (20%)
- Azotemia (1% to 5%)
Severe reactions can include Stevens-Johnson syndrome and toxic epidermal necrolysis.
What is the recommended management for clinical failure in PCP treatment?
Wait 4 to 8 days before switching therapy
This allows for the exclusion of other causes of clinical failure.
What is the preferred therapy for secondary prophylaxis against PCP?
TMP-SMX, 1 DS tablet PO daily
This regimen also provides protection against toxoplasmosis.
When should secondary prophylaxis for PCP be discontinued?
- CD4 count increased from <200 to ≥200 cells/mm3 for ≥3 months due to ART
- Consider if CD4 count is 100–200 cells/mm3 and HIV RNA is undetectable for 3 to 6 months
Discontinuation is supported by observational studies.
What should be done if an episode of PCP occurs at a CD4 count >200 cells/mm3?
Consider continuing PCP prophylaxis for life
This is especially true if plasma HIV RNA is below the level of detection.
What are alternative therapies for secondary prophylaxis if TMP-SMX is intolerable?
- Dapsone
- Atovaquone
- Aerosolized or IV pentamidine
Dapsone can be combined with pyrimethamine and leucovorin.
What is the definition of clinical failure in PCP treatment?
Lack of improvement or worsening of respiratory function documented by arterial blood gases after 4 to 8 days of treatment
This occurs in approximately 10% of people with HIV with mild-to-moderate PCP.
What should be monitored during PCP therapy?
Treatment response and detection of toxicity
Follow-up includes assessment for early relapse.
What are the indications for restarting secondary prophylaxis?
- CD4 count <100 cells/mm3 regardless of HIV RNA
- CD4 count 100–200 cells/mm3 with HIV RNA above detection limit
Restarting is crucial for those at risk of PCP recurrence.
What considerations should be made for pregnant individuals regarding PCP prophylaxis?
- Discuss deferring pregnancy until prophylaxis can be safely discontinued
- Consider increasing folic acid to 4 mg/day if not deferring
TMP-SMX is recommended for prophylaxis, but alternatives are suggested during the first trimester.
What are the most common adverse effects of alternative therapies for PCP?
- Methemoglobinemia and hemolysis with dapsone
- Rash and fever with dapsone
- Azotemia and pancreatitis with pentamidine
Adverse effects vary by medication choice.
What should be done if TMP-SMX is discontinued due to a mild adverse reaction?
Consider reinstituting therapy after resolution of the reaction
Gradual dose increase can facilitate desensitization.
What is the risk associated with PCP during pregnancy?
Increased risk of PCP-associated mortality and all-cause pneumonia complications
Close monitoring for preterm labor is advised for those affected.
What are alternative prophylactic regimens for first-trimester TMP-SMX exposure?
Aerosolized pentamidine or oral atovaquone
Dapsone should only be used if other alternatives are not available or tolerated due to concerns about hemolytic anemia.
What is the classification of trimethoprim?
Folic acid antagonist
It acts as a dihydrofolate reductase inhibitor.
What congenital anomalies are associated with first-trimester exposure to TMP-SMX?
- Neural tube defects
- Cardiovascular anomalies
- Oral clefts
- Urinary tract anomalies
- Multiple anomalies
What was the pooled prevalence of congenital anomalies found in a systematic review of TMP-SMX use in pregnancy?
3.5% (95% CI, 1.8% to 5.1%)
What is the adjusted odds ratio (aOR) for spontaneous abortion associated with first-trimester TMP-SMX exposure?
2.94 (95% CI, 1.89–4.57)
What is the recommended daily dosage of folic acid supplementation for women of reproductive potential?
0.4 mg/day
This is to reduce the risk of neural tube defects.
What is the effect of higher doses of folic acid supplementation (4-6 mg/day)?
- Less frequent neural tube defects
- Fewer oral clefts
- Reduced recurrent preeclampsia
True or False: Higher doses of folic acid (4 mg/day) have been shown to reduce the risk of congenital malformations.
False
A clinical trial did not show an advantage of higher doses on congenital malformations.
What is the effect of leucovorin when used with TMP-SMX?
Increased risk of therapeutic failure and death
What is the preferred initial therapy for PCP during pregnancy?
TMP-SMX (AI)
What should clinicians consider for pregnant patients on TMP-SMX?
Supplemental folic acid 4 mg/day
This should be given as soon as possible in the first trimester.
What are the risks associated with long-term corticosteroid use in pregnancy?
- Maternal hypertension
- Preeclampsia
- Hyperglycemia
- Premature rupture of membranes
- Intrauterine growth restriction
- Infection
What is the safety profile of clindamycin during pregnancy?
Considered safe for use throughout pregnancy (BIII)
What should be monitored closely when corticosteroids are used during pregnancy?
- Maternal glucose levels
- Blood pressure
- Fetal growth
What is the recommendation regarding primaquine use in pregnant women?
Not to be administered due to the risk of hemolytic anemia in a G6PD-deficient fetus.
What is the potential risk associated with dapsone use in the first trimester?
Hemolytic anemia in pregnant persons or exposed fetuses
What is the association between TMP-SMX exposure and low birth weight?
Adjusted odds ratio of 1.61 (95% CI, 1.16–2.23)
What is the pooled odds ratio for neural tube defects associated with first-trimester TMP-SMX exposure?
2.5 (95% CI, 1.4–4.3)
Fill in the blank: The quality of evidence regarding pregnancy outcomes after TMP-SMX exposure was considered _______.
very low
What is the recommended follow-up for fetal anatomy in pregnant individuals exposed to TMP-SMX?
Ultrasound at 18 weeks to 20 weeks
True or False: There have been cases of kernicterus reported in neonates after maternal ingestion of sulfonamides.
False
