Recomendados
Más contenido relacionado
La actualidad más candente
La actualidad más candente (19)
Similar a Lieu noon conference - PJP
Similar a Lieu noon conference - PJP (20)
Más de Virginia Mason Internal Medicine Residency
Más de Virginia Mason Internal Medicine Residency (20)
Último
Último (20)
Lieu noon conference - PJP
- 2. © 2016 Virginia Mason Medical Center 2 Objectives Pneumocystis pneumonia • Discuss risk factors • Discuss clinical presentation • Discuss diagnostic tests • Discuss treatment and prophylaxis • Review illness script
- 3. © 2016 Virginia Mason Medical Center Risk factors • HIV infection • Glucocorticoid use • Other immunosuppressive medications • Cancer • Hematopoietic cell or solid organ transplant • Primary immunodeficiencies 3
- 4. © 2016 Virginia Mason Medical Center Clinical presentation Respiratory failure Fever Dry cough 4
- 5. © 2016 Virginia Mason Medical Center Diagnostic tests • Elevated LDH • Elevated serum beta-D-glucan assay • Chest x-ray: diffuse, bilateral, interstitial infiltrates • Less commonly: lobar infiltrates, nodules, cysts, pneumothorax, pleural effusions • Microscopy with staining • Induced sputum or BAL fluid • Decreased organism burden in HIV-uninfected patients • PCR 5
- 6. © 2016 Virginia Mason Medical Center 6
- 7. © 2016 Virginia Mason Medical Center 7 Treatment TMP-SMX 15-20 mg/kg, IV or orally daily, in 3 or 4 divided doses • IV until clinically stable (PaO2 >60, RR <25) • Duration: 21 days • Monitor K Adjunctive steroids • If PaO2 <70, A-a gradient >35, or hypoxemia on pulse ox
- 8. © 2016 Virginia Mason Medical Center Treatment Alternatives • Atovaquone • Clindamycin + primaquine • TMP + dapsone • IV pentamidine • Toxicity: hypotension, hypoglycemia, nephrotoxicity, pancreatitis 8
- 9. © 2016 Virginia Mason Medical Center Question A 28-year-old man with newly diagnosed HIV infection is hospitalized with Pneumocystis pneumonia. Despite treatment with TMP-SMX, he rapidly deteriorates and requires intubation and mechanical ventilation. On physical examination, temperature is 39.6 C (103.3 F) and respiration rate is 28/min. Arterial blood gas studies show a PO2 of 82 mmHg on 60% oxygen and positive end-expiratory pressure of 7.5 mmHg. Which of the following is the most appropriate treatment at this time? a. Add azithromycin b. Add pentamidine c. Add prednisone d. Switch to pentamidine 9
- 10. © 2016 Virginia Mason Medical Center Question 33M with AML s/p allogeneic bone marrow transplant 17 days ago is admitted to ICU because while within hours of evidence of his bone barrow recovering he became increasingly dyspneic and hypoxemic, and a chest radiograph showed diffuse bilateral infiltrates. On arrival to ICU temp is 37.8, BP 133/94, pulse 122, RR 36. O2 say on non- rebreather @ 100% oxygen is 88%. Neck veins flat, no peripheral edema, using accessory muscles to breath, lungs with bilateral scattered crackles, heart w/o MRG. Hct stable @ 26%, plts 26, hasn’t produced sputum. Broad spectrum abx started. Which of the following is most appropriate next step in patient’s management? a. Intravenous corticosteroids. b. Continuous positive airway pressure (CPAP) c. Bronchoscopy with bronchoalveolar lavage. d. Noninvasive positive-pressure ventilation (NPPV) e. Intubation 10
- 11. © 2016 Virginia Mason Medical Center Prophylaxis Indications • Steroid use >20 mg of prednisone daily for >1 month • Treatment with alemtuzumab, temozolomide, fludarabine, idelalisib • Hematopoietic stem cell transplant • Solid organ transplant • Acute lymphocytic leukemia • SCID, other primary immunodeficiencies 11
- 12. © 2016 Virginia Mason Medical Center Prophylaxis TMP-SMX • 1 DS tablet daily or 3 times per week • 1 SS tablet daily Dapsone Atovaquone 12
- 13. © 2016 Virginia Mason Medical Center Illness Scripts 13 Pneumocystis pneumonia Community-acquired pneumonia Pathophysiology Pneumocystis jirovecii S. pneumoniae, respiratory viruses Epidemiology HIV infection, glucocorticoid use, other immunosuppressive medications, cancer, hematopoietic cell or solid organ transplant, primary immunodeficiencies Older age, COPD, other chronic lung diseases, CHF, viral respiratory tract infections, smoking Time course Subacute Subacute Clinical presentation Respiratory failure, fever, dry cough Dyspnea, fever, cough, pleuritic chest pain Diagnostics Labs: LDH, beta-D-glucan assay CXR: diffuse, bilateral, interstitial infiltrates Microscopy with staining of sputum or BAL fluid, PCR Labs: WBC, procalcitonin CXR: lobar consolidations, interstitial infiltrates, cavitations Sputum culture, blood cultures, S. pneumoniae urine antigen, Legionella PCR, respiratory viral PCR Therapeutics TMP-SMX, steroids, 21 days Prophylaxis: TMP-SMX Empiric antibiotics, 5-7 days
Notas del editor
- HIV-infected patients with low CD4 count are at highest risk of PCP Most significant risk factors in HIV-uninfected patients: glucocorticoid use and defects in cell mediated immunity Glucocoritcoid use with a second form of immunosuppression (steroid use in asthma isn’t sufficient to cause risk of PCP) Other immunosuppressive meds Especially glucocorticoids in combination with cytotoxic agents (e.g. cyclophosphamide) And those receiving multiple chemotherapeutic agents Cancer Especially hematologic malignancies: leukemia or lymphoma Hematopoietic cell or solid organ transplant Due to immunosuppression Primary immunodeficiencies SCID
- Nearly all patients will have hypoxemia or increased A-a gradient
- Elevated LDH: may be elevated from underlying hematologic malignancy or other causes of acute lung injury Elevated serum beta-D-glucan assay: in cell wall of Pneumocystis, also in cell wall of fungi Nonspecific High negative predictive value Can be useful while awaiting microscopy results Definitive diagnosis: microscopy with staining of induced sputum or BAL fluid Pneumocystis can’t be cultured Direct fluorescent antibody staining Diagnostic yield is lower in HIV uninfected patients due to decreased organism burden PCR: increases diagnostic yield, especially helpful for HIV-uninfected patients Test induced sputum, BAL fluid, blood, or nasopharyngeal aspirates
- Diffuse, bilateral, interstitial infiltrates
- Bactrim: 15-20 mg/kg, IV or orally, daily, in 3 or 4 divided doses IV until clinically stable: PaO2 >60, RR <25 Duration: not adequately studied in HIV-uninfected patients 21 days based on recommended duration for patients with HIV infection: greater risk of relapse with 14 days of treatment vs. 21 Monitor K: before and periodically after institution of therapy due to risk of hyperkalemia with Bactrim Adjunctive glucocorticoids: if PaO2 <70, A-a gradient >35, or hypoxemia on pulse ox Regimen: 40 mg orally BID x5 days 40 mg orally QD x5 days 20 mg orally QD x11 days
- Alternatives: If patient is allergic, desensitization Atovaquone: for mild disease Clindamycin + primaquine: for moderate disease IV clindamycin + oral primaquine: for severe disease IV pentamidine: not often used due to toxicity
- Treatment failure: no improvement after 4-8 days of therapy May be due to severity of disease or concurrent infection not previously identified May switch from oral to IV TMP-SMX If failing IV TMP-SMX, initiate clindamycin-primaquine Investigate for concurrent infection Initiate adjunctive corticosteroids if a patient’s respiratory status worsens and they require supplemental O2 Increased A-a gradient due to inflammation in the lungs as organisms are killed
- The outcomes of decreased ICU mortality [92], a decreased intubation rate [92,93], and improved oxygenation [94] were also reported in separate randomized trials that enrolled patients with community-acquired pneumonia or immunosuppressed patients with pulmonary infiltrates and fever. However, NIV may be less effective in pneumonia patients with respiratory failure older than 65, where a mortality benefit was not observed in over the use of invasive mechanical ventilation in a large database analysis [95]. The patient has developed acute hypoxemic respiratory failure after bone marrow transplantation, and the differential diagnosis is large. Infectious causes such as nosocomial bacteria and such opportunistic organisms as cytomegalovirus, fungi, and Pneumocystis jirovecii must be considered. Cardiogenic and noncardiogenic forms of pulmonary edema, fluid overload, and reactions to drugs are also possible. Recurrence of leukemia with a leukoagglutination reaction is unlikely in view of the blood smear findings. A real possibility is diffuse alveolar hemorrhage, a reaction of unknown cause that occurs most often soon after bone marrow transplantation in concert with indications of incipient bone marrow recovery. Fluid balance should be optimized, although the patient is not manifesting evidence of fluid overload. Corticosteroids are sometimes used to treat presumed alveolar hemorrhage, although their benefit in this setting has not been established. Bronchoscopy might reveal evidence of hemosiderin-laden macrophages to suggest the diagnosis of alveolar hemorrhage, but the finding is nonspecific. Bronchoscopy might help identify infectious or malignant causes, but most clinicians would prefer to intubate such a patient before contemplating bronchoscopy. Intubation is potentially very hazardous in a patient at such high risk of bleeding or developing superinfections. The best early strategy is to initiate noninvasive positive-pressure ventilation, which, while still yielding a high mortality rate, reduced mortality compared to conventional oxygen therapy and intubation (if indicated) in a randomized controlled trial on a similar group of patients. Bronchoscopy can be performed during noninvasive ventilation if needed.
- Indications Steroid use >20 mg of prednisone daily for >1 month also with other cause of immunocompromise Treatment with alemtuzumab, temozolomide, fludarabine, idelalisib Hematopoietic stem cell transplant Solid organ transplant: 6-12 months following transplant and during periods of high doses of immunosuppression Lung transplant: typically lifelong prophylaxis There are more specific and detailed guidelines Acute lymphocytic leukemia SCID, other primary immunodeficiencies
- Continue prophylaxis until risk factor is no longer present
- Empiric treatment depends on local S. pneumoniae resistance rates