Pneumocystis jirovecii: Difference between revisions
From IDWiki
Pneumocystis jirovecii
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== Treatment == |
== Treatment == |
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| + | * First-line: [[TMP-SMX]] 15-20 mg/kg IV or PO divided q6-8h |
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| − | * Septra 5-6mg/kg po BID for 3 weeks |
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| + | ** If mild-moderate, can give [[TMP-SMX]] DS 2 tabs PO tid |
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| − | * If pO2 <70mmHg or A-a gradient ≥35: prednisone |
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| + | * Alternatives: |
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| − | * Alternative: clindamycin-primaquine or IV pentamidine |
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| + | ** [[Clindamycin]] 600-900 mg IV q6-8h with [[primaquine]] 15 to 30 mg PO daily |
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| + | ** [[Pentamidine]] 4 mg/kg IV daily |
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| + | ** Trimethoprim 15 mg/kg PO divided q8h with [[dapsone]] 100 mg PO daily |
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| + | ** [[Atovaquone]] 750 mg PO bid (for mild-moderate only) |
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| + | * Adjunctive: [[Prednisone]] 40 mg PO bid for 5 days, followed by 40 mg PO daily for 5 days, followed by 20 mg po daily for 11 days |
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| + | ** Can use methylprednisolone at 75% of predisone dose |
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| + | ** Typically indicated if PaO<sub>2</sub> ≤70 mmHg or A-a O<sub>2</sub> gradient >35 mmHg |
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* Duration is 21 days (3 weeks) |
* Duration is 21 days (3 weeks) |
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=== Prophylaxis === |
=== Prophylaxis === |
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| + | * Indications |
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| + | ** Medications: prenisolone ≥20 mg daily for >4 weeks; TNF-α inhibitors; steroids plus a steroid-sparing agent |
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| + | ** Cancer treatment: steroids and cyclophosphamide; alemtuzumab for at least 2 months after treatment and until CD4 >200; temozolomide and radiation therapy, until CD4 >200; fludarabine and T-cell depletion, until CD4 >200; any antileukemic therapy |
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| + | ** HIV: prior ''Pneumocystis'' pneumonia; CD4 <200; oropharyngeal ''Candida'' regardless of CD4 |
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| + | ** Rheumatology treatment: GPA receiving cyclophosphamide, especially with steroids |
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| + | ** Transplantation: [[allogeneic stem cell transplantation]] for at least 180 days; [[autologous stem cell transplantation]] for at least 3 to 6 months |
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| + | ** Primary immunodeficiency: [[SCID]]; idiopathic CD4 lymphocytopenia; [[hyper-IgM syndrome]] |
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| + | * First-line: [[TMP-SMX]] DS or SS 1 tab PO daily |
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| + | * Alternatives: |
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| + | ** [[TMP-SMX]] DS 1 tab po tiw |
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| + | ** [[Dapsone]] 100 mg po daily, or 50 mg po bid |
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| + | ** [[Dapsone]] 50 mg po daily with [[pyrimethamine]] 50 mg po weekly and leucovorin 25 mg po weekly |
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| + | ** [[Pentamidine]] 300 mg inhaled monthly |
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| + | ** [[Atovaquone]] 750 mg po bid or 1500 mg po daily |
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| + | ** [[Atovaquone]] as above with [[pyrimethamine]] 25 mg po daily and leucovorin 10 mg po daily |
||
* Usually instituted if the risk of PJP is greater than 3.5% per year |
* Usually instituted if the risk of PJP is greater than 3.5% per year |
||
Revision as of 21:17, 25 September 2019
- Opportunistic fungal infection of the lower respiratory infection
Microbiology
- Yeast-like fungus in the Ascomycota phylum
- Has not been able to be grown in culture, and species within the genus have tropism for their specific host
- It's cell wall lacks ergosterol, so has inherent resistance to many antifungals
- β-1,3 glucan, however, is an important cell wall component
- The major immunogenic protein is major surface glycoprotein (Msg), or gpA
History
- P. jirovecii was previously thought to be P. carinii, but it was later realized that they were two species within the same genus
- P. carinii and P. wakefieldiae infect rats, P. murina infects mice and P. jiroveci infects humans
- Also previously thought to be a protozoan, but reclassified as fungus based on phylogenetic analysis, most closely related to Schizosaccharomyces pombe
Epidemiology
- Worldwide distribution
- Only circulates within humans
- Most children have been exposed by age 2 or 3
- Children and immunocompromised patients being the reservoir
- Includes asymptomatic carriage by patients with HIV, malignancy, and long-term steroid use, and in pregnant women
- Risk factors for infection:
- HIV
- Immune-suppression, e.g. from steroids
Pathophysiology
- After inhalation of cyst, trophic forms are released and adhere to type I pneumocytes in the alveolar epithelium
- The immune response involves a combination of humoral and cell-mediated immunity
- Alveolar macrophages are the first response, but require CD4 cells to respond fully
- IgM antibodies recognize common fungal carbohydrate antigens
- CD4 cells are important for the memory response
- The alveolus fills with Pneumocystis
- The inflammatory response may damage the lung
Clinical Presentation
Infants
- Interstitial plasma cell pneumonia between 6 weeks and 4 months
- Typically in orphanages under crowded conditions
- Insidious onset with poor feeding, progressing to cyanosis
Adults
- Worsening exertional dyspnea, fever, and non-productive cough
- Symptoms usually more insidious in severe HIV
- Symptoms may develop after tapering immunosupressive drugs like steroids
- Tachypnea and tachycardia with exertional hypoxemia
- CXR may initially be normal, then progresses to whiteout
- Can also show unilateral consolidation, nodules, cysts, pneumatoceles, mediastinal lymphadenopathy, and pleural effusions
- High LDH from lung damage
Investigations
- CXR
- Typical: bilateral diffuse patchy disease
- Atypical:
- Normal (15%)
- Localized
- Pneumothorax
- Upper lobe, if on pentamidine
- LDH increased
- CBC often normal
Diagnosis
- Induced sputum or brochoalveolar lavage (normal sputum not sensitive enough)
- 6min walk test: will desaturate, even if well-oxygenated at rest
Treatment
- First-line: TMP-SMX 15-20 mg/kg IV or PO divided q6-8h
- If mild-moderate, can give TMP-SMX DS 2 tabs PO tid
- Alternatives:
- Clindamycin 600-900 mg IV q6-8h with primaquine 15 to 30 mg PO daily
- Pentamidine 4 mg/kg IV daily
- Trimethoprim 15 mg/kg PO divided q8h with dapsone 100 mg PO daily
- Atovaquone 750 mg PO bid (for mild-moderate only)
- Adjunctive: Prednisone 40 mg PO bid for 5 days, followed by 40 mg PO daily for 5 days, followed by 20 mg po daily for 11 days
- Can use methylprednisolone at 75% of predisone dose
- Typically indicated if PaO2 ≤70 mmHg or A-a O2 gradient >35 mmHg
- Duration is 21 days (3 weeks)
Prophylaxis
- Indications
- Medications: prenisolone ≥20 mg daily for >4 weeks; TNF-α inhibitors; steroids plus a steroid-sparing agent
- Cancer treatment: steroids and cyclophosphamide; alemtuzumab for at least 2 months after treatment and until CD4 >200; temozolomide and radiation therapy, until CD4 >200; fludarabine and T-cell depletion, until CD4 >200; any antileukemic therapy
- HIV: prior Pneumocystis pneumonia; CD4 <200; oropharyngeal Candida regardless of CD4
- Rheumatology treatment: GPA receiving cyclophosphamide, especially with steroids
- Transplantation: allogeneic stem cell transplantation for at least 180 days; autologous stem cell transplantation for at least 3 to 6 months
- Primary immunodeficiency: SCID; idiopathic CD4 lymphocytopenia; hyper-IgM syndrome
- First-line: TMP-SMX DS or SS 1 tab PO daily
- Alternatives:
- TMP-SMX DS 1 tab po tiw
- Dapsone 100 mg po daily, or 50 mg po bid
- Dapsone 50 mg po daily with pyrimethamine 50 mg po weekly and leucovorin 25 mg po weekly
- Pentamidine 300 mg inhaled monthly
- Atovaquone 750 mg po bid or 1500 mg po daily
- Atovaquone as above with pyrimethamine 25 mg po daily and leucovorin 10 mg po daily
- Usually instituted if the risk of PJP is greater than 3.5% per year
References
- ^ Po-Yi Chen, Chong-Jen Yu, Jung-Yien Chien, Po-Ren Hsueh. Anidulafungin as an alternative treatment for Pneumocystis jirovecii pneumonia in patients who could not tolerate Trimethoprim/sulfamethoxazole. International Journal of Antimicrobial Agents. 2019. doi:10.1016/j.ijantimicag.2019.10.001.
- ^ L. Cooley, C. Dendle, J. Wolf, B. W. Teh, S. C. Chen, C. Boutlis, K. A. Thursky. Consensus guidelines for diagnosis, prophylaxis and management ofPneumocystis jiroveciipneumonia in patients with haematological and solid malignancies, 2014. Internal Medicine Journal. 2014;44(12b):1350-1363. doi:10.1111/imj.12599.
- ^ N. Goto, S. Oka. Pneumocystis jirovecii pneumonia in kidney transplantation. Transplant Infectious Disease. 2011;13(6):551-558. doi:10.1111/j.1399-3062.2011.00691.x.
