Pneumocystis jirovecii: Difference between revisions

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Pneumocystis jirovecii
m (Text replacement - "Clinical Presentation" to "Clinical Manifestations")
m (→)
Line 1: Line 1:
−
* Opportunistic fungal infection of the lower respiratory infection
 +
*Opportunistic fungal infection of the lower respiratory infection
   
−
== Background ==
 +
==Background==
−
=== Microbiology ===
 +
===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
  
   
  +
*Yeast-like fungus in the Ascomycota phylum
−
=== History ===
  
  +
*Has not been able to be grown in culture, and species within the genus have tropism for their specific host
−
* ''P. jirovecii'' was previously thought to be ''P. carinii'', but it was later realized that they were two species within the same genus
  
  +
*It's cell wall lacks ergosterol, so has inherent resistance to many antifungals
−
** ''P. carinii'' and ''P. wakefieldiae'' infect rats, ''P. murina'' infects mice and ''P. jiroveci'' infects humans
  
  +
*β-1,3 glucan, however, is an important cell wall component
−
* Also previously thought to be a protozoan, but reclassified as fungus based on phylogenetic analysis, most closely related to ''Schizosaccharomyces pombe''
  
  +
*The major immunogenic protein is major surface glycoprotein (Msg), or gpA
   
−
=== Epidemiology ===
 +
===History===
−
* 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
  
   
  +
*''P. jirovecii'' was previously thought to be ''P. carinii'', but it was later realized that they were two species within the same genus
−
=== Pathophysiology ===
  
  +
**''P. carinii'' and ''P. wakefieldiae'' infect rats, ''P. murina'' infects mice and ''P. jiroveci'' infects humans
−
* After inhalation of cyst, trophic forms are released and adhere to type I pneumocytes in the alveolar epithelium
  
  +
*Also previously thought to be a protozoan, but reclassified as fungus based on phylogenetic analysis, most closely related to ''Schizosaccharomyces pombe''
−
* 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
  
   
  +
===Epidemiology===
−
== 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
  
   
  +
*Worldwide distribution
−
=== Adults ===
  
  +
**May be environmental, associated with outdoor activities and spaces (but not clear)
−
* Worsening exertional dyspnea, fever, and non-productive cough
  
  +
**Human-to-human transmission is possible
−
** Symptoms usually more insidious in severe HIV
  
  +
*Only circulates within humans, with reservoirs including children and immunocompromised patients
−
** Symptoms may develop after tapering immunosupressive drugs like steroids
  
  +
**Primary infection occurs in infants, who are likely the natural host; most have been exposed by 2-3 years of age
−
* Tachypnea and tachycardia with exertional hypoxemia
  
  +
**Includes asymptomatic carriage by patients with HIV, malignancy, and long-term steroid use, and in pregnant women
−
* CXR may initially be normal, then progresses to whiteout
  
  +
*Colonization is common, associated with the following:
−
** Can also show unilateral consolidation, nodules, cysts, pneumatoceles, mediastinal lymphadenopathy, and pleural effusions
  
  +
**Immunosuppressive conditions (HIV, low CD4 cell count, cancer, autoimmune diseases, organ transplantation)
−
* High LDH from lung damage
  
  +
**Immunosuppressive drugs (corticosteroids, TNF-α inhibitors)
−
* In advanced HIV, can disseminate to lymph nodes, spleen, liver, bone marrow, GI tract, eyes, thyroid, adrenal glands, and kidneys
  
  +
**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===
−
== 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
  
−
* CBC often normal
  
   
  +
*After inhalation of cyst, trophic forms are released and adhere to type I pneumocytes in the alveolar epithelium
−
== Diagnosis ==
  
  +
*The immune response involves a combination of humoral and cell-mediated immunity
−
* Cannot be cultured
  
  +
**Alveolar macrophages are the first response, but require CD4 cells to respond fully
−
* Specimens include sputum (best), BAL, or biopsy
  
  +
**IgM antibodies recognize common fungal carbohydrate antigens
−
* Microscopy
  
  +
**CD4 cells are important for the memory response
−
** The gold standard
  
  +
*The alveolus fills with ''Pneumocystis''
−
** Direct fluorescent antibody (DFA) staining from induced sputum or BAL
  
  +
*The inflammatory response may damage the lung
−
** Can also use Gomori Methenamine-Silver or Diff-Quik staining
  
−
* Molecular
  
−
** PCR from induced sputum or BAL
  
−
** 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 species]], 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
  
   
  +
==Clinical Manifestations==
−
== Management ==
  
  +
===Infants===
−
* First-line: [[Is treated by::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:
  
−
** [[Is treated by::Clindamycin]] 600-900 mg IV q6-8h with [[Is treated by::primaquine]] 15 to 30 mg PO daily
  
−
** [[Is treated by::Pentamidine]] 4 mg/kg IV daily
  
−
** Trimethoprim 15 mg/kg PO divided q8h with [[dapsone]] 100 mg PO daily
  
−
** [[Is treated by::Atovaquone]] 750 mg PO bid (for mild-moderate only)
  
−
** Possibly [[Is treated by::anidulafungin]][[CiteRef::chen2019an]]
  
−
* 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 PaO<sub>2</sub> ≤70 mmHg or A-a O<sub>2</sub> gradient &gt;35 mmHg
  
−
* Duration is 21 days (3 weeks)
  
   
  +
*Interstitial plasma cell pneumonia between 6 weeks and 4 months
−
=== Prophylaxis ===
  
  +
*Typically in orphanages under crowded conditions
  +
*Insidious onset with poor feeding, progressing to cyanosis
   
  +
===Adults===
−
* 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
  
   
  +
*Worsening exertional dyspnea, fever, and non-productive cough
−
== Further Reading ==
  
  +
**Symptoms usually more insidious in severe HIV
−
* ''Pneumocystis'' Colonization Is Highly Prevalent in the Autopsied Lungs of the General Population. ''Clin Infect Dis''. 2010;50:347. doi: [https://doi.org/10.1086/649868 10.1086/649868]
  
  +
**Symptoms may develop after tapering immunosupressive drugs like steroids
−
* 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: [https://doi.org/10.1093/cid/cis870 10.1093/cid/cis870]
  
  +
*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
  +
*CBC often normal
  +
  +
==Diagnosis==
  +
  +
*Cannot be cultured
  +
*Specimens include sputum (best), BAL, or biopsy
  +
*Microscopy
  +
**The gold standard
  +
**Direct fluorescent antibody (DFA) staining from induced sputum or BAL
  +
**Can also use Gomori Methenamine-Silver or Diff-Quik staining
  +
*Molecular
  +
**PCR from induced sputum or BAL
  +
**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 species]], 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: [[Is treated by::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:
  +
**[[Is treated by::Clindamycin]] 600-900 mg IV q6-8h with [[Is treated by::primaquine]] 15 to 30 mg PO daily
  +
**[[Is treated by::Pentamidine]] 4 mg/kg IV daily
  +
**[[Is treated by::Trimethoprim]] 15 mg/kg PO divided q8h with [[Is treated by::dapsone]] 100 mg PO daily
  +
**[[Is treated by::Atovaquone]] 750 mg PO bid (for mild-moderate only)
  +
**Possibly [[anidulafungin]][[CiteRef::chen2019an]]
  +
*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 PaO<sub>2</sub> ≤70 mmHg or A-a O<sub>2</sub> gradient &gt;35 mmHg
  +
*Duration is 21 days (3 weeks)
  +
  +
== Prevention ==
  +
  +
===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
  +
  +
==Further Reading==
  +
  +
*''Pneumocystis'' Colonization Is Highly Prevalent in the Autopsied Lungs of the General Population. ''Clin Infect Dis''. 2010;50:347. doi: [https://doi.org/10.1086/649868 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: [https://doi.org/10.1093/cid/cis870 10.1093/cid/cis870]
   
 
{{DISPLAYTITLE:''Pneumocystis jirovecii''}}
  
{{DISPLAYTITLE:''Pneumocystis jirovecii''}}

Revision as of 11:41, 15 August 2020

  • 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
  • CBC often normal

Diagnosis

  • Cannot be cultured
  • Specimens include sputum (best), BAL, or biopsy
  • Microscopy
    • The gold standard
    • Direct fluorescent antibody (DFA) staining from induced sputum or BAL
    • Can also use Gomori Methenamine-Silver or Diff-Quik staining
  • Molecular
    • PCR from induced sputum or BAL
    • 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 species, 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:
  • 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

  • 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:
  • Usually instituted if the risk of PJP is greater than 3.5% per year

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

  1. ^  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.

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