Inpatient Viral Infections: Which Ones Should We Think About, Test - PDF document

10/26/2015 Inpatient Viral Infections: Which Ones Should We Think About, Test For, and Treat Management of the Hospitalized Patient October 2015 Jennifer Babik, MD, PhD Assistant Clinical Professor Division of Infectious Diseases, UCSF Disclosures  I have no disclosures. 1

10/26/2015 Learning Objectives 1. To recognize the key clinical features of the most common viral infections encountered in hospitalized patients. 2. To develop a framework for diagnosis and management of common inpatient viral infections. Viruses Covered  Herpesviruses  CMV  HSV  VZV  Respiratory viruses  Influenza  Other respiratory viruses 2

10/26/2015 Case #1 47 year old M with no PMH is admitted with fever and respiratory distress. CT shows prominent GGO. HIV Ab test is positive and CD4 is 56. BAL is performed and is positive for PCP. BAL is also positive for CMV culture. Plasma CMV PCR is positive at 970 IU/mL. What Antibiotics Should You Start? 1. TMP ‐ SMX alone 2. TMP ‐ SMX plus ganciclovir 3. TMP ‐ SMX plus acyclovir 4. TMP ‐ SMX plus IVIG 3

10/26/2015 Approach to CMV Infections: Define the Host Immunocompetent Immunocompromised  Primary infection  Primary or reactivation  Clinical  Clinical Asymptomatic viremia • Usually asymptomatic • CMV syndrome • • Heterophile ( ‐ ) mononucleosis End ‐ organ disease • • Case reports of severe disease  Diagnosis  Diagnosis Serology not helpful •  Serology > PCR Tissue biopsy >> culture •  Usually self ‐ limiting, no Rx Blood PCR •  Usually requires treatment Navalpotro et al, J Clin Virol 2006; 35:193. Wreghitt et al, Clin Infect Dis 2003; 37:1603. CMV Infection in Immunocompromised Patients CMV Infection Asymptomatic CMV Syndrome End ‐ Organ Disease Viremia Asymptomatic Fever plus bone • Neuro: Encephalitis, marrow suppression Retinitis, Polyradiculopathy (leukopenia and/or • Pneumonitis thrombocytopenia) • GI: Colitis>Esophagitis • Others: hepatitis, nephritis, myocarditis, pancreatitis Plasma CMV PCR (+) Plasma CMV PCR (+) Plasma CMV PCR (+) Decision to treat (except GI disease can be depends on viral load compartmentalized) and host; may just Treat all patients Treat all patients follow levels 4

10/26/2015 CMV in HIV vs Transplant HIV Transplant  Host:  Host:  SOT and HSCT  End ‐ organ disease in CD4<50  Also patients taking high levels of immunosuppressives or  Most common presentations: steroids (e.g. rheum patients)  Asymptomatic viremia common (15 ‐ 35% pts w/CD4<200)  Most common presentations:  Retinitis  Asymptomatic viremia  GI (colitis > esophagitis)  CMV syndrome  Pneumonitis is rare: BAL+ for  Pneumonitis CMV in ~50% of patients with  Colitis other respiratory OIs Durier et al, Clin Infect Dis 2013;57:147. Deayton et al, Lancet 2004; 363: 2116. Hayner et al, Chest 1995;107;735. Miles et al, Chest 1990;97;1072. CDC/NIH/HIVMA Guidelines for the prevention and treatment of OIs in HIV ‐ infected adults, 2015. CMV End ‐ Organ Disease CMV Colitis Fever, diarrhea (+/ ‐ bloody), abd pain • Dx by colonoscopy with path, IHC • Blood PCR can be negative • CMV Pneumonitis Fever, mild to severe resp failure • CT shows diffuse bilateral GGO • Dx by BAL: culture, path • Blood PCR usually positive • 5

10/26/2015 CMV Treatment  IV vs PO?  IV ganciclovir for severe EOD, high VL, concerns re: oral absorption  PO valganciclovir okay for mild ‐ moderate disease (VICTOR trial)  IVIG?  Case ‐ by ‐ case basis for severe disease (pneumonitis)  How long to treat?  2 ‐ 3 weeks and until PCR negative  Consider secondary ppx in selected patients  PCR monitoring?  Check 2 wks after starting rx (VL may stay the same or  in 1 st wk)  Then check qweek until negative Razonable et al, Am J Transplant 2013; 13:93. Asberg et al (VICTOR study group), Am J Transplant 2007; 7:2106. Case #1 Continued The patient was treated for PCP and started on ARVs. He was not treated for CMV. 3 weeks later he represents with fever but no other localizing signs or symptoms. Labs:  WBC 1.0, platelets 81 (both previously normal)  CMV viral load in the plasma is now 226,091 IU/mL. 6

10/26/2015 Review question: What is the diagnosis? 1. Asymptomatic CMV viremia 2. CMV syndrome 3. CMV end ‐ organ disease CMV: Take ‐ Home Points  Define your host: immunocompetent or immunocompromised (HIV vs transplant/other)  Determine which type of CMV infection your patient has:  Asymptomatic viremia  CMV syndrome  End ‐ organ disease  HIV+ patients are a special category:  Commonly have asymptomatic viremia  Can have severe end ‐ organ disease (retinitis, GI most common)  Rarely have pneumonitis despite frequent +BAL for CMV 7

10/26/2015 Case #1 Continued The patient now tells you he has been having severe mouth pain. Oral exam shows significant ulcerations on his tongue and angular cheilitis. You are concerned about CMV vs HSV. The most sensitive test for HSV is this situation is: 1. Ulcer swab for HSV DFA 2. Ulcer swab for HSV culture 8

10/26/2015 Diagnosis of Mucocutaneous HSV Lesion swab HSV Culture Vesicle 70 ‐ 90% Ulcer 30 ‐ 40% Crusted 20 ‐ 30% More sensitive than DFA DFA Vesicle 70 ‐ 90% Ulcer 30% Crusted 10% More rapid than culture PCR Overall 90% Best test if available Case #2 Continued  Oral ulcer swab:  HSV DFA QNS  HSV culture +HSV ‐ 1  Due to concurrent CMV, he was treated with IV ganciclovir then oral valganciclovir to complete 4 weeks.  After 1 week, CBC normalized and oral ulcers completely resolved. 9

10/26/2015 Antivirals Against Herpesviruses Antiviral HSV VZV CMV EBV Acyclovir ++ ++ + + Valacyclovir Famciclovir Ganciclovir ++ ++ ++ ++ Valganciclovir Case #2 55 year old man is brought in by his neighbor for bizarre behavior for 12 hours. He is found to be febrile and has a witnessed seizure in the ED. MRI is shown. He is started on vancomycin, ceftriaxone, and acyclovir and is tapped 24 h later. Lumbar puncture:  50 WBC (89% lymphs), 50 RBC, protein 80, glucose 78.  CSF culture is NGTD  PCR is negative for HSV and VZV. 10

10/26/2015 Your Next Management Step Would Be: 1. D/C acyclovir 2. Continue acyclovir 3. Add ampicillin 4. Add ganciclovir You Think The HSV PCR May Be Negative B/C: 1. He got 24 hours of acyclovir 2. It’s not a sensitive test 3. It’s early in the disease course 11

10/26/2015 HSV Encephalitis  Epidemiology:  Bimodal: 1/3 of cases <20 years old, 1/3 cases >50 years old  Accounts for 10 ‐ 20% of encephalitis  Microbiology:  >90% due to HSV ‐ 1, most are due to reactivation  HSV ‐ 2 rare, more common in immunocompromised patients  Clinical:  Frontal and temporal lobes affected  Fever, personality changes, aphasia, seizures, focal weakness HSV Encephalitis: CSF Profile  Classic profile:  WBCs: lymphocytic pleocytosis (median 130 cells/mm 3 )  RBCs: elevated (usually <500)  Protein: elevated (median 80 mg/dl)  Glucose: normal  CSF does not always have RBCs or WBCs:  RBCs normal in 15%  WBC normal in 4 ‐ 15% Whitley et al, JAMA 1982, 247:312. Whitley et al, JAMA 1989, 262:234. Tang et al, Clin Infect Dis 1999, 29:803. Domingues et al, Clin Infect Dis 1997, 25:86. 12

10/26/2015 HSV Encephalitis: Diagnosis and Rx  CSF PCR:  96% sensitive, 99% specific  May have false ( ‐ ) in the first 3d  if suspicion is high re ‐ tap  ACV has little effect on PCR (+) within the first 5 days of therapy  MRI: temporal lobe abnormalities in 90%  Treatment:  ACV 10mg/kg IV q8h x 14 ‐ 21 days  Consider checking an HSV PCR at day 14 to define duration DeBiasi and Tyler, Clin Microbiol Rev 2004, 17:903. Tyler, Herpes 2004, 11 Suppl 2: 57A HSV Aseptic Meningitis  1 st episode in 1 ˚ genital HSV ‐ 2 (women>men)  Recurrent aseptic meningitis:  20 ‐ 30% of patients will have at least 1 recurrence  Mollaret’s meningitis = repeated self ‐ limiting episodes, with or without recurrent skin lesions  Treatment:  Role of antivirals not clearly defined: can consider ACV 10 mg/kg q8h or valacyclovir 1gm PO tid x 7 ‐ 14d  May be of benefit in immunocompromised patients  Suppressive rx not effective to prevent recurrences Tyler, Herpes 2004, 11 Suppl 2: 57A. Aurelius et al, Clin Infect Dis 2012, 54: 1304. Berger and Houff, Arch Neurol 2008, 65:596. Sendi and Graber, CMAJ 2006, 174:1710. Noska et al, Clin Infect Dis 2015;60:237. 13

10/26/2015 HSV Neuro Complications: Take ‐ Home  HSV encephalitis is usually caused by HSV ‐ 1 and affects the frontal/temporal lobes  CSF HSV PCR is very sensitive for HSV encephalitis:  There can be false ( ‐ ) within the first 3 days of symptoms  ACV has little effect on sensitivity within the first 5 days  HSV meningitis is a complication of primary genital herpes from HSV ‐ 2 and can be recurrent Case #3 64 year old man presents with a blistering painful rash on his left leg in the L4 and L5 dermatomes. He is started on acyclovir but still has new lesions on his shin after 24 hours. 14

10/26/2015 The Most Likely Diagnosis Is: 1. Disseminated zoster 2. Resistant zoster 3. Uncomplicated herpes zoster Zoster: Key Clinical Features  80% have prodrome preceding lesions by 2 ‐ 3 days  New vesicles appear for 2 ‐ 4 days (antivirals  new lesion formation by 1 ‐ 2 days)  Overlap into adjacent dermatomes in 20% (normal variation in innervation)  PHN: pain lasting >3 months after zoster episode, occurs in 10 ‐ 20% Dworkin et al, Clin Infect Dis 2007; 44 (Suppl1): S1. 15