Opportunistic Infections Objectives: After reviewing this material and attending lecture, the student should be able to 1) Define an opportunistic infection (OI). 2) Recommend an appropriate treatment for the following OIs, given diagnosis and relevant patient information a. PCP b. Toxoplasmosis c. MAC disease d. Cryptococcal Meningitis e. Histoplasmosis f. Cryptosporidiosis g. Microsporidiosis h. Coccidioidomycosis 3) Recommend appropriate primary or secondary prophylaxis, if given relevant information for a patient. 4) Identify monitoring parameters to evaluate the patient’s treatment for a given OI. 1) Definition a) Opportunistic infection (OI) = “infection that occurs in persons with weak immune systems” b) Examples of persons at risk for OIs • HIV/AIDS • Cancer • Immunosuppressive drugs ◊ Long-term, high-dose corticosteroids ◊ Chemotherapy ◊ Immunosuppressive drugs used for stem cell and organ transplants c) Examples of OIs • Bacterial pneumonias • Pneumocystis jiroveci pneumonia • Histoplasmosis • Tuberculosis • Syphilis • Mucocutaneous candidiasis • Aspergillosis • Cryptosporidiosis • Mycobacterium avium complex disease • Cryptococcus • Cytomegalovirus (CMV) disease • Hepatitis B and C 2) Treatment versus prophylaxis a) Prophylaxis = trying to prevent disease for which the patient is at risk • Primary prophylaxis ◊ Patient has never had the disease before • Secondary prophylaxis ◊ Patient has had disease before but wish to prevent recurrence of disease b) Treatment = eradicate/control organism causing infection and eliminating signs and symptoms of disease 3) Pneumocystis jiroveci pneumonia (PCP) a) Cause • Pneumocystis jiroveci (fungal organism) • Previously called P. carinii b) Transmission • Usually occurs due to a latent infection that is reactivated • Airborne transmission (?)c) Signs/symptoms • 90% of cases in those with CD4< 200 cells/µL or CD4< 15% • Progressive over days to weeks ◊ Exertional dyspnea ◊ Fever ◊ Nonproductive cough • Labs ◊ PaO2 at room air ♦ PaO2 > 70 mm/Hg: mild-to-moderate PCP ♦ PaO2 < 70 mm/Hg: severe PCP ◊ LDH > 500 mg/dL ◊ Chest X-ray ♦ Early on, X-ray will appear normal ♦ Later in disease, will see diffuse, bilateral infiltrates; no cavitation or pleural effusion ◊ CT scan ♦ Ground-glass attenuation ♦ Usually will show abnormalities that are not seen on X-ray with mild to moderate cases d) Diagnosis • Culture of organisms ◊ Bronchoalveolar lavage fluid (BALF) ◊ Induced sputum • Sensitivity of culture depends on method used and technique ◊ Induced sputum: < 50% - >90% ◊ Bronchoscopy with BALF: 90 – 99% ◊ Transbronchial biopsy: 95 – 100% ◊ Open lung biopsy: 95 – 100% e) Treatment • Length of therapy (LOT): 21 days, regardless of antibiotic regimen chosen First-Line Therapies Alternative Therapies Trimethoprim-sulfamethoxazole (TMP-SMX) Dosing is based on trimethoprim component 15 – 20 mg/kg/day IV or PO ÷ 3- 4 doses (q6h – q8h dosing) PO dose usually works out to be TMP/SMX DS 2 tabs TID Pentamidine (severe cases) 4 mg/kg IV qday Corticosteroids Indicated only for severe cases of PCP Prednisone 40 mg BID x 5 days Prednisone 40 mg qday x 5 days Prednisone 20 mg qday x 11 days (IV methylprednisolone = 75% of PO prednisone dose) Primaquine and clindamycin (mild to moderate cases) P 15 – 30 mg base PO qday + C 300 – 450 mg PO qday ÷ 3 – 4 doses (If consider IV clindamycin, dose is 600 – 900 mg/day ÷ 3 – 4 doses) Dapsone and trimethoprim (mild to moderate cases) D 100 mg PO qday + T 15 mg/kg/day ÷ 3 doses (PO) Trimetrexate and leucovorin (mild to moderate cases) T 1.2 mg/kg (45 mg/m2) IV qday + L 0.5 mg/kg (20 mg/m2) IV or PO qday Leucovorin should be continued for 3 days after end of trimetrexate treatment Atovaquone (mild cases) 750 mg PO BID with foodf) Prophylaxis First-Line Therapies Alternative Therapies Trimethoprim-sulfamethoxazole (TMP-SMX) TMP-SMX DS 1 tab qday Dapsone 50 mg PO BID or 100 mg PO qday Trimethoprim-sulfamethoxazole (TMP-SMX) TMP-SMX SS 1 tab qday Atovaquone 1500 mg PO qday Trimethoprim-sulfamethoxazole (TMP-SMX) TMP-SMX DS 3x/ week Dapsone and Pyrimethamine and Leucovorin D 50 mg PO qday + P 50 mg PO qweek + L 25 mg PO qweek OR D 200 mg PO + P 75 mg PO + L 25 mg PO, all qweek (Consider if intolerant of TMP-SMX and want to cover toxoplasmosis as well) Pentamidine, aerosolized 300 mg q month (nebulized with Respirgard nebulizer) • When to start? ◊ Primary prophylaxis ♦ CD4< 200 cells/µL ♦ CD4% < 14% ♦ Diagnosis of oropharyngeal candidiasis ♦ History of AIDS-defining illness ◊ Secondary prophylaxis ♦ After completion of treatment therapy for PCP • When to stop? ◊ Primary prophylaxis ♦ CD4 > 200 cells/µL for > 3 months ◊ Secondary prophylaxis ♦ CD4 increase from < 200 cells/µL to > 200 cells/µL for > 3 months due to HAART ♦ Consider for life if PCP episode at CD4 > 200 cells/µL g) Monitoring • Disease ◊ Should see improvement in 4 – 8 days in ABGs, pulmonary function ♦ If lack of improvement, consider adding to a regimen or switching regimen ♦ If patient is not on corticosteroids, patient may worsen initially in 3 – 5 days due to inflammatory response (i) Should still wait up to 8 days to monitor progress ♦ If fail TMP-SMX for moderate-to-severe cases, consider using (i) Pentamidine (ii) Primaquine + clindamycin (iii) Trimetrexate + leucovorin + dapsone (iv) No data has evaluated which one of these options is the best to switch to after TMP-SMX failure ♦ If fail TMP-SMX for mild cases, consider using (i) Atovaquone • Drugs: See Table 1 at end of notes 4) Toxoplasmosis a) Cause • Toxoplasma gondii b) Transmission • Primary infection ◊ eating undercooked meat with tissue cysts ◊ exposure from cat feces • Disease usually result of reactivation of latent tissue cystsc) Signs/symptoms • Usually seen in patients with CD4 < 100, with greatest risk at CD4 < 50 • Primary infection may either be acute cerebral disease (encephalitis) or disseminated disease • Encephalitis (most common presentation) ◊ Headache ◊ Confusion ◊ Motor weakness ◊ Fever ◊ Without treatment, disease will progress to seizures, stupor, and coma ◊ Physical exam/ laboratory findings ♦ Focal neurological abnormalities ♦ CT