Pneumocystis jirovecii
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Pneumocystis jirovecii / (Redirected from Pneumocystis jirovecii pneumonia)
- Opportunistic fungal infection of the lower respiratory infection
Background
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
- May be environmental, associated with outdoor activities and spaces (but not clear)
- Human-to-human transmission is possible
- Only circulates within humans, with reservoirs including children and immunocompromised patients
- Primary infection occurs in infants, who are likely the natural host; most have been exposed by 2-3 years of age
- Includes asymptomatic carriage by patients with HIV, malignancy, and long-term steroid use, and in pregnant women
- Colonization is common, associated with the following:
- Immunosuppressive conditions (HIV, low CD4 cell count, cancer, autoimmune diseases, organ transplantation)
- Immunosuppressive drugs (corticosteroids, TNF-α inhibitors)
- COPD and other chronic lung disorders
- Other conditions (pregnancy, cigarette smoking)
- Lack of surfactant
- But also 20% of healthy people
- Infection is mostly associated with HIV
- Much higher risk with HIV/AIDS with low CD4 count <200
- More common in Asian and South/Central America
- Infection is still possible in immunocompetent hosts
- TNF-alpha inhibitors, B-cell inhibitors, and corticosteroid use
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 Manifestations
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
- In advanced HIV, can disseminate to lymph nodes, spleen, liver, bone marrow, GI tract, eyes, thyroid, adrenal glands, and kidneys
Investigations
- CXR
- Typical: bilateral diffuse patchy disease
- Atypical:
- Normal (15%)
- Localized
- Pneumothorax
- Upper lobe, if on pentamidine
- 6min walk test: will desaturate, even if well-oxygenated at rest
- LDH increased, though it has an LR+ of 1.5 and LR– of 0.61, so neither sensitive nor specific
- CBC often normal
Diagnosis
- Cannot be cultured
- Specimens include sputum (best), BAL, or biopsy
- Test characteristics of non-invasive (i.e. non-BAL) samples are summarized in 1
- Microscopy
- The gold standard
- Direct fluorescent antibody (DFA) staining from induced sputum or BAL (about 75% sensitive from sputum)
- Can also use Gomori Methenamine-Silver or Diff-Quik staining
- Molecular
- PCR from induced sputum or BAL (about 99% sensitive)
- Nasopharyngeal aspirate is about 90% sensitive
- Whole serum is about 80% sensitivty and specific
- Can detect lower burden of PJP, especially in immunocompetent hosts where it is likely not causing disease but is instead helping to circulate it among the population
- Serology
- Not sensitive or specific
- 1,3-β-D glucan levels may be elevated (Sn 95%, Sp 86%)
- diagnostic accuracy was not different between HIV positive and HIV negative patients
- Can be used as a screening tool
- False positives with other IFIs, Candida, IV amoxicillin-clavulanic acid, treatment of patients with immunological preparations (albumins or globulins), use of cellulose membranes and filters made from cellulose in hemodialysis, and use of cotton gauze swabs/packs/pads and sponges during surgery
Management
- 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)
- Possibly anidulafungin2
- 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)
Prevention
Prophylaxis
- Indicated in population with risk of PJP >3.5% per year
- HIV: prior Pneumocystis pneumonia; CD4 <200; oropharyngeal Candida regardless of CD4
- Medications: prednisolone ≥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
- 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 1500 mg po daily (or 750 mg po bid)
- Atovaquone as above with pyrimethamine 25 mg po daily and leucovorin 10 mg po daily
- No consensus on when to stop prophylaxis
- Although there are no clear data guiding when to stop prophylaxis, it is probably reasonable to stop once the dose prednisone drops below 15-20 mg daily or equivalent
- In patients with HIV, stopping once CD4 count is above 200 for 3 months
- In patients receiving chemotherapy, at least one guideline recommends continuing for 6 weeks after the steroid-tapering period3
- For renal transplantation, AST guidelines recommend 6-12 months after transplantation and European guidelines recommend 4 months after transplantation4
Further Reading
- Pneumocystis Colonization Is Highly Prevalent in the Autopsied Lungs of the General Population. Clin Infect Dis. 2010;50:347. doi: 10.1086/649868
- Near-Universal Prevalence of Pneumocystis and Associated Increase in Mucus in the Lungs of Infants With Sudden Unexpected Death. Clin Infect Dis. 2013;56:171. doi: 10.1093/cid/cis870
References
- ^ Julien Senécal, Elizabeth Smyth, Olivier Del Corpo, Jimmy M. Hsu, Alexandre Amar-Zifkin, Amy Bergeron, Matthew P. Cheng, Guillaume Butler-Laporte, Emily G. McDonald, Todd C. Lee. Non-invasive diagnosis of Pneumocystis jirovecii pneumonia: a systematic review and meta-analysis. Clinical Microbiology and Infection. 2022;28(1):23-30. doi:10.1016/j.cmi.2021.08.017.
- ^ 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.