1 / 52

Opportunistic Infections

Opportunistic Infections. ID Fellows course 2010 Christian B. Ramers , MD, MPH. Learning Objectives. Develop systematic approach to diagnosis of OI’s in immunocompromised patients Describe preferred initial therapy of select OI’s Review CD4 cell count thresholds/risk of OI’s

luisa
Télécharger la présentation

Opportunistic Infections

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Opportunistic Infections ID Fellows course 2010 Christian B. Ramers, MD, MPH

  2. Learning Objectives • Develop systematic approach to diagnosis of OI’s in immunocompromised patients • Describe preferred initial therapy of select OI’s • Review CD4 cell count thresholds/risk of OI’s • Discuss timing of HAART in setting of acute OI

  3. Case #1: HPI • 54 yo Latino male with fever, diarrhea, cough • Presented to Pioneer Square clinic 5/09 with 1 month of fever and diarrhea, 2 months dry cough • HIV Ab and Western Blot positive in clinic • 20 lbs involuntary weight loss • 10+ watery stools/day • Cough mostly dry, some scant whitish mucus • What are you worried about?

  4. Case #1: Additional History • Risk Factor: MSM exclusively, 3 lifetime partners • No prior illnesses/hospitalizations • Rare social EtOH, Denies tobacco, IVDU • Born & raised in Cuernavaca, Mexico • 1986 emigrated to Phoenix, AZ • 1998 moved to Minneapolis, MN • 5/2009 moved to Seattle • Worked odd jobs in AZ, MN, now homeless

  5. Case #1: PEX • Vitals: 38.9, 99, 18, 113/72, SaO2 98% on RA • Gen: thin Latino man, mild distress • Chest: inspiratory crackles B bases • CV: RRR no murmurs • Abd: scaphoid, tympanetic, liver edge palpable at R costal margin, no splenomegaly • Extr: No edema • Skin: No lesions, no rash

  6. Initial Work-up?

  7. CXR 6/1/09

  8. Case #1: Initial Labs • Initial CBC: WBC 4.46, Hct 32, Plt 102 • LFT’s: AST/ALT 97/52; Alb 2.4, LDH 248 • CD4: 21 (3%), HIV VL 580,000; genotype pending What else do you want? AFB sputum smears x 3: NEGATIVE

  9. CT 6/2/09

  10. CT 6/2/09

  11. CT 6/2/09

  12. CT 6/2/09

  13. CT 6/2/09

  14. How would you approach this patient?

  15. Case #1: DDx – undifferentiated fever • TB • MAC • CMV • Bartonella • Lymphoma • Histoplasmosis • Cryptococcus • Leishmania • (Malaria, Penicilliumspp, Amebic liver abscess)

  16. Case #1: DDx – Chronic Watery Diarrhea • Giardia • CMV • MAC • Cryptosporidium • Microsporidium • Cyclospora • Isospora • ‘HIV enteropathy’ • Salmonella • Shigella • Campylobacter • E. coli (EAEC) • C. difficile • E.histolytica

  17. Case #1: DDx – dry cough w/ nodules • TB • KS • Lymphoma • Histoplasmosis • Coccidiomycosis • Legionella • Rhodococcus • Cryptococcus (vargrubii, vargattii) • Nocardia • Toxoplasma • MAC • M. kansasii • Pneumocystis • CMV

  18. Case #1: Follow-up Labs • Stool Studies: • C. difficileA&B toxin NEGATIVE • 6/1 O&P (concentrated/trichrome): NEGATIVE • 6/2 O&P (concentrated/trichrome): NEGATIVE • 6/2 Giardia Ag: NEGATIVE • 6/3 Modified Acid-fast: POSITIVE source: www.hivwebstudy.org

  19. Cryptosporidiosis source: www.hivwebstudy.org

  20. Cryptosporidiosis • Etiology: Cryptosporidium parvum • Presentation: • Self-limited diarrhea in normal hosts • Worse in CD4 < 150: range from foul-smelling bulky to watery ‘cholera-like’. Can also cause biliary, respiratory disease • Pathophysiology: inflammation & villous atrophy  malabsorption, increased permeability, solute flux into the gut lumen; rarely invasive • Diagnosis: Usually missed by traditional ‘O&P’ exam (4-6 mm, similar to yeast); fluorescent or modified Acid-fast stain MMWR April 10,2009; 58 (RR4): 1-206

  21. Cryptosporidiosis - Treatment • Specific therapy usually not necessary • Some data for nitazoxanide for special cases MMWR 2009; 58 (RR4): 1-132

  22. Case #1: Follow-up Labs • Sputum for AFB negative x 3 • TB AMPLIFIED DIRECT TEST - Sputum POST BRONCH AFB POS SMEAR • Last Update: 06/11/09 12:14 Collected: 06/05/09 15:30 • MTB Complex rRNA: POSITIVE • AFB CULTURE W/STAIN - Sputum, Induced mucoid in cup • Last Update: 06/23/09 11:01 Collected: 06/02/09 13:00 • AFB Stain: No acid fast bacilli seen (concentrated smear) by Auramine stain • Culture: Presumptive Mycobacterium tuberculosis complex isolated from broth only : • AFB CULTURE W/STAIN - Sputum POST BRONCH in cup • Last Update: 07/07/09 10:13 Collected: 06/05/09 15:30 • AFB Stain: Rare Acid Fast Bacilli by Auramine stain • Culture: 2+ Mycobacterium tuberculosis : Identification by DNA probe and phenotypic analyses • 2+ MYCOBACTERIUM TUBERCULOSIS - AFB MGIT • Ethambutol (5 mcg/mL) S • Isoniazid (0.1 mcg/mL) S • Rifampin (1 mcg/mL) S • Streptomycin (1 mcg/mL) S

  23. Case #1: Clinical course • Intensive IV fluid, nutrition, electrolytes • Started on RIPE • Developed pancytopenia, transaminitis • Many drug changes • Continuous fever • Who wants to start HAART?

  24. ACTG 5164 – HAART in setting of Acute OI Early ART: within 14 dof OI diagnosis(n = 141) • Entry OI’s: PJP (63%), Crypto (12%), Bacterial Infection (12%), Toxo (5%), Histo (4%), CMV (2%), MAC (2%), [Multiple 33%] Deferred ART: after OItreatment completed(n = 141) 1x Zolopa A, et al PLoS One 2009; 4(5): 5575

  25. ACTG 5164 – HAART in setting of Acute OI • HR 0.53 (95%CI 0.3-0.92) favoring early ART Zolopa A, et al PLoS One 2009; 4(5): 5575

  26. Case #1: Clinical course • Patient had remained relatively stable on RIPE • Discharged with Madison Clinic f/u • HAART deferred due to transaminitis, ongoing fevers, diagnostic uncertainty • Presented to Madison Clinic for initial visit: febrile to 39.0, AST/ALT 150’s • Now what?

  27. Case #1: Follow-up Labs • Serum Histoplasma Ag (6/6/09): POSITIVE 36.0 • AFB CULTURE, BLD CULT BOTTLES - Blood Arm, Right Aerobic and anaerobic bottles • Last Update: 06/29/09 15:36 Collected: 06/03/09 13:23 • Culture: No acid fast bacilli isolated in 26 days. Histoplasmacapsulatum isolated from mycobacterial broth : identification by sequence analysis . • LOWER RESP FUNGAL W/DIR. EXAM - BronchoalveolarLavage No. 2 Lung, Right Middle Lobe Cloudy • Last Update: 07/06/09 11:12 Collected: 06/05/09 14:15 • Stain for Fungus: No fungi seen • Culture: 2+ Presumptive HistoplasmacapsulatumSEE BLOOD CULTURE 6/3/09 FOR CONFIRMATION • AFB CULTURE, BLD CULT BOTTLES - Blood Arm, Left Yellow top tube • Last Update: 08/11/09 11:34 Collected: 06/06/09 07:45 • Culture: Mycobacterium tuberculosis complex isolated from broth only Presumptive identification by colonial morphology. : see sputum of 6/5/09 for susceptibilities Presumptive Histoplasmacapsulatumisolated from mycobacterial broth

  28. Histoplasmosis • Etiology: Histoplasmacapsulatum • Presentation: • Acute: febrile pulmonary infection • Reactivation: fever, chills, wt loss, bone marrow failure, anemia, high LFT’s, may have evidence of old disease on CXR • Pathophysiology: Initially latent disease, with reactivation upon immunosuppresion • Diagnosis: Direct visualization of fungus, culture, Serum or Urine Antigen test • Mortality: low in immune competent; high in immunosuppressed. • Risk Factors: dyspnea, plt < 100K, high LDH

  29. Histoplasma Distribution Edwards LB; Am Rev Repir Dis. 1969; 99(4):Suppl: 1-132

  30. Histoplasma Distribution Mochi A and Edwards PQ; Bull WHO, 1952(5): 252-291

  31. Histoplasmosis - Treatment MMWR 2009; 58 (RR4): 1-132

  32. Case #1: Resolution • Later dx’d with CMV gastritis, Late latent syphilis, H.pylorigastritis (received PCN, Gancyclovir/Val-G, Amox/Clarithro/PPI) • Complicated by ARF, LFT’s, pancytopenia • Started HAART 9/09 (FTC/TDF+ATZ/r) • Developed 3 new liver masses, AST/ALT 200/175 • Liver biopsy: granulomas, no growth (TB/Histo IRIS) • Now doing well on HAART, INH/Ethambutol, Itraconazole, pentamidine (CD4 88, VL < 40)

  33. Case #1: Summary • Cryptosporidium is a common cause of watery diarrhea in immunocompromised. Best diagnosed with Modified Acid-Fast Stain • Immunocompromised patients often have multiple OI’s (sometimes 5!!) • Evidence appears to support early initiation of HAART in the setting of select OI’s (ACTG 5164) but still handled case-by-case • Beware of IRIS

  34. Ockam’s razor Pluralitas non estponenda sine neccesitate • “Plurality is not to be posited without necessity” Frustra fit per plura quod potestfieri per pauciora • “It is futile to do with more things that which can be done with fewer”

  35. Case #2: HPI • 46 yo Caucasian Male 50 lbs wt loss, GI issues • Odynophagia for solids, diarrhea (5-10 loose, foul-smelling BM’s/day) • Out of care x 3 years, previously seen in FL • On Atripla but resistant to ‘two of the three’ • Stopped ARV’s because he felt well • Prescribed Raltegravir + Darunavir/Ritonavir + Etravirine but never picked up

  36. Case #2: Additional History • HIV dx’d 2002, risk: MSM • Previous Nadir CD4 76 • HIV-related hx: thoracic zoster, KS posterior neck, PJP, Oral/Esophageal Candidiasis, HIV wasting, esophageal ulcers, chronic diarrhea • Worked as a flight attendant but lost job • Reports > 30 lifetime partners • Recently moved back to Whidbey Island w/mom

  37. Case #2: PEX • Vitals: 36.5, 76, 20, 110/78, SaO2 98% on RA, 66 kg (6’1”) • Gen: anxious cachectic Caucasian man, no distress • HEENT: temporal wasting, thrush on buccal mucosa, OHL on lateral tongue, angular chelitis • Chest/CV: CTAB, RRR • Abd: scaphoid, no HSM, hyperactive BS • Extr: thin, with atrophy • Skin: scaly erythematous plaques on face concentrated around eyebrows & ears

  38. What can you do on the 1st visit?

  39. Case #2: • Records pending, FL doc gave some via phone • CD4 27 (4%), VL 538,500 • CBC: WBC 2.3, Hct 35, Plt 159 • LFT’s normal, Cr 0.7 • Stool studies: • 6/2/10 O&P (concentrated/trichrome): NEGATIVE • 6/3/10 O&P (concentrated/trichrome): NEGATIVE • 6/2/10 Modified Acid Fast stain: NEGATIVE • 6/2 Giardia Ag: POSITIVE • 6/9/10 O&P (concentrated/trichrome): POSITIVE for G. lamblia cysts and trophozoites

  40. Case #2: Stool Studies Photo courtesy of Carolyn Wallis (HMC Microbiology)

  41. Case #2: Initial Management • TMP/SMX DS – PJP prophylaxis • AzithromycinQweek – MAC prophylaxis • Ketoconazole topical – for Seborrheicderm • (Metronidazole 250 TID x 5 d) • Fluconazole 100 mg PO QD x 3 wks (planned) • Sent Trofile assay, HIV genotype

  42. Candidiasis - Treatment MMWR 2009; 58 (RR4): 1-132

  43. Case #2: • Returns 2 weeks later with improved diarrhea, but worsening odynophagia • EGD scheduled urgently • What’s your pre-EGD Differential Dx?

  44. Case #2: Ddx – Odynophagia • Esophageal Candidiasis • HSV • VZV • CMV • Aphthous ulcers • Gastric/Esophageal KS • Lymphoma • Severe H. pylori gastritis

  45. Case #2: EGD Ulceration – mid-esophagus

  46. Case #2: EGD Patchy erythema – mid-Antrum

  47. Case #2: Esophageal Biopsy Granulation tissue, inflammation, rare inclusions

  48. Case #2: Esophageal Biopsy CMV Inclusions

  49. Cytomegalovirus • Etiology: CMV – β-herpesvirus • Clinical Manifestations: • Seroprevalence 60-70% in US, ~100% in Africa • Mono-like ‘CMV syndrome’, esophagitis, colitis, interstitial pneumonitis, hepatitis, retinitis, meningoencephalitis, myocarditis • Pathophysiology: After acute infection, cycles of latent/reactivated disease • Diagnosis: Serology, Shell vial, serum PCR suggestive, but must demonstrate CMV in tissue to call disease • Mortality: MAJOR cause of mortality in iatrogenicallyimmunosupressed, most common congenital infection

  50. CMV Disease - Treatment MMWR 2009; 58 (RR4): 1-132

More Related