AU Edited: 05/06/15 Case Histories: HIV Related- Opportunistic Infections in 2015 Henry Masur, MD Clinical Professor of Medicine George Washington University School of Medicine Bethesda, Maryland Washington, DC: May 13, 2015 Slide 3 of 55 Learning Objectives After attending this presentation, participants will be able to: Develop strategies for managing asymptomatic cryptococcal antigenemia Describe issues related to PCR diagnosis of opportunistic infections Recognize changes in management of diarrhea Cryptococcosis Pneumocystosis Diarrhea Outline Slide 6 of 55 Washington, DC: May 13, 2015 1
Slide 7 of 55 Opportunistic Infections Are Still Common Reviews Demonstrate Dramatic Progress in Reducing Incidence of Opportunistic Infections but Absolute Number Still High Late diagnoses of HIV Failure to attain durable viral suppression Events during initial ART Expertise in OI Management is Waning Graying of experienced providers Expansion of HIV epidemic to small towns and central/south US 2015 NIH/CDC/IDSA Guideline Preventing Disease Because the incidence of cryptococcal disease is low among HIV-infected patients in the United States, routine testing of asymptomatic persons for serum cryptococcal polysaccharide antigen is not recommended for patients residing there. Slide 9 of 55 Slide 10 of 55 Washington, DC: May 13, 2015 2
Slide 11 of 55 March 10, 2015 Global Burden of Cryptococcal Meningitis-All Patients Cases 958,000 Deaths 625,000 Slide 12 of 55 Slide 13 of 55 US Burden of Cryptococcal Meningitis Attack Rate Among HIV Infected (2006) 2-7 cases per 1000 patient years Mortality Among HIV Infected 12% Cryptococcal antigen Detectable at 22 days median pre-disease Up to 100 days Washington, DC: May 13, 2015 3
Clinical Infectious Diseases Slide 14 of 55 April 2009 Volume 48, Number 7 Screening for Crypt Antigenemia in South Africa Slide 15 of 55 Antigenemia Is An Independent Predictor Mortality Crypt meningitis Titer >/= 1;8 was 100% sensitive and 96% specific during first year of ART 92% occurred at CD4 <100 cells/ul Unresolved Issues Were patients durably suppressed for HIV Would fluconazole therapy have changed outcome How many acute meningitis events were IRIS rather than acute fungal disease Slide 16 of 55 Washington, DC: May 13, 2015 4
Clinical Infectious Diseases Slide 17 of 55 August 2010 Volume 51, Number 4 WHO Recommendation 12/2011 Slide 18 of 55 All HIV positive patients with CD4<100 Screen for Crypt Ag Positive patients Treat with anticryptococcal therapy Fluconazole 800 mg qd x 2w and 400 mg qd x 8w (Expert Opinion) Clinical Infectious Diseases Slide 19 of 55 November 2014 Washington, DC: May 13, 2015 5
Slide 20 of 55 Asymptomatic Cryptococcal Antigenemia Stored Sera Random selection from MACS and WIHS 1872 sera CD4<100 Incidence All patients 2.9% Patients CD4 <50 cells 4.6% Implications Prior crypt meningitis was risk factor Survival shorter if crypt ag + (2.4 yrs) vs (3.8 yrs) Slide 21 of 55 Frequency Distribution of Positive Crypt Anitgen,1986 2012 10/55 = Prior Cryptococcal Disease McKenney J et al. Clin Infect Dis. 2014 Nov 24. Survival Analysis by Cryptococcal Antigen Test Result MACS and WIHS, 1986 2012 Mean Survival Crypt Ag + 2.8 years Crypt Ag - 3.8 years Slide 22 of 55 McKenney J et al. Clin Infect Dis. 2014 Nov 24. Washington, DC: May 13, 2015 6
Conclusions Prevalence of asymptomatic crypt antigenemia is substantial Specific therapy for cryptococcal disease in patients with crypt antigenemia is warranted Slide 23 of 55 Unanswered Questions Slide 24 of 55 Is crypt antigen a marker for immunosuppression Would ART prevent cryptococcal disease Would anticrypt rx change outcome If yes: what dose, duration 2015 OI Guidelines Slide 25 of 55 Routine testing of asymptomatic HIV-infected persons for serum cryptococcal polysaccharide antigen is.. A lumbar puncture for a CSF evaluation for meningitis.. Treatment of asymptomatic Cr Ag positive patients should be.. Washington, DC: May 13, 2015 7
Diarrhea Slide 26 of 55 Multidrug-resistant Shigellosis Spreading in the United States Press Release Thursday, April 2, 2015 Slide 31 of 55 Imported Drug-Resistant Stomach Bug Spreading in US By THE ASSOCIATED PRESS APRIL 2, 2015, 2:45 P.M. E.D.T. Mutant, drug-resistant stomach bug is spreading in the U.S., CDC warns By Abby Ohlheiser April 3 2015 Drug-Resistant Stomach Bug Spreading Across the U.S. By Kimberly Leonard April 2, 2015 Shigella: What to Know About America's New Drug-Resistant Bug Apr 3, 2015, 12:38 PM ET By SYDNEY LUPKIN via World News Slide 32 of 55 Washington, DC: May 13, 2015 8
Shigellosis in United States Cases per Year 500,000 Transmission Low Inoculum: 10-100 organisms since they are relatively resistant to stomach acid Person to person (sex), food, water Secondary cases are common Slide 33 of 55 Shigellosis in Patients with HIV When to Treat Severe Bloody stool, >6/day, high fever High risk for transmission Slide 34 of 55 What s New About Shigella Slide 35 of 55 Increasing antimicrobial resistance Quinolone resistance domestic and international Most resistant isolates = Shigella sonnei Treatment of Choice for Empiric Therapy Quinolone x 7-10 days Alternatives: azithromycin or TMP-SMX Washington, DC: May 13, 2015 9
Campylobacter Increasing quinolone resistance Not as transmissible person to person Slide 36 of 55 What Are the Most Common Causes of Diarrhea Slide 37 of 55 in Patients with HIV Infection in US? Clostridium difficile 54% Health care facilities Antibiotics Campylobacter 14% Shigella 14% Flexneri > Sonnei Salmonella 7% Staph aureus 4% Mycobacteria 4% Others 4% Aeromonas, Yersinia ASD, Sanchez, CID, 2007 Slide 38 of 55 Clostridium Difficile in Patients with HIV Infection Clinical Manifestations HIV no different from non HIV Low CD4 may predispose to disease Diagnosis PCR of one stool preferred Therapy Metronidazole alone is NOT preferred by some experts New IDSA Guidelines 2016 Washington, DC: May 13, 2015 10
Slide 39 of 55 Clinical Success by Clostridium Difficile Infection (CDI) Severity in the Combined Studies Johnson S. Clin Infect Dis 2014;59(3):345 54. Recurrence of Clostridium Difficile Slide 40 of 55 Johnson S. Clin Infect Dis 2014;59(3):345 54. Slide 41 of 55 Treatment of Clostridium Difficile for Patients with HIV Infection Oral Vancomycin probably preferred over oral metronidazole for all patients with HIV, or perhaps those with CD4<200 Combination therapy with metronidazole plus oral vancomycin is preferred for severe disease Fidaxomycin does not have a clear role Fecal transplant..another lecture! Washington, DC: May 13, 2015 11
Case 3 46 year old MSM with chronic alcoholism Non adherent with ARVs and OI prophylaxis CD4 count = 16 (2%), VL = 295,648 Prior History esophageal candidiasis (azole R) Disseminated MAC (2007) PCP (2011) Presents with several months of cough which has become worse in past 3 days with higher fever and new onset shaking chills Sputum was scant for weeks, now is purulent and more copious He also has mild dysphagia Slide 42 of 55 Exam and Lab Physical Exam T 38.5 C; BP 120/80; P=120 Oral candidiasis Diffuse rales Consolidated right lower lung field Laboratory O 2 Sat on room air: 92% Sputum: purulent, gram stain shows mixed flora Slide 43 of 55 HIV Associated PCP May 23 June 13 Slide 44 of 55 Washington, DC: May 13, 2015 12
Segmental Consolidation Plus Diffuse Interstitial Infiltrate Slide 45 of 55 More Results Bronchoalveolar Lavage Gram stain and wet mount Negative Pneumocystis PCR-positive (qualitative test) Direct Fluorescent antibody test---send out Slide 48 of 55 Slide 49 of 55 How to Establish Diagnosis of PCP Washington, DC: May 13, 2015 13
Serum PCR Not sensitive Serologic Tests for PCP LDH Sensitivity depends on lung severity Non-specific Beta Glucan Not sensitive or specific Follow efficacy of therapy if positive? Slide 50 of 55 Plasma Beta-Glucan for Pneumocystis Pneumonia in AIDS Patients With Respiratory Symptoms (n=139) Slide 51 of 55 3 Sax, AIDS, March 2013. Slide 52 of 55 Role of PCR for Diagnosis of Disease High negative predictive value Disappointing positive predictive value Washington, DC: May 13, 2015 14
Final Diagnosis Pneumocystis Pneumonia Subacute Bacterial Pneumonia Acute, probably aspiration Slide 53 of 55 Washington, DC: May 13, 2015 15