1. 2013 Infectious Diseases Update David H. Spach, MD Professor of Medicine Division of Infectious Diseases University of Washington, Seattle

2. Infectious Diseases: 2013 Update Central Nervous System Infections Respiratory Tract Infections Zoonotic Infections New Hepatitis C Testing Recommendations Skin and Soft Tissue Infections

3. Central Nervous System Infections

4. A 29-year-old male is bitten on the shoulder by a bat and the bat escaped. What percent of Rabies Immune Globulin should be given at the wound site? 1. 25% 2. 50% 3. 75% 4. 100% Case History: Question Silver-Haired Bat

5.  “If anatomically feasible, the full dose of HRIG is infiltrated around and into any wound(s). Any remaining volume is injected intramuscularly at a site distant from vaccine administration.” CDC and Prevention. MMWR 2010;59 (RR-02):1-9. Rabies Postexposure Prophylaxis Human Rabies Immune Globulin

6. Rabies: Post-Exposure Prophylaxis  Wound cleansing  * Rabies Immune Globulin  + Rabies Vaccine: day 0,3,7,14 Not Previously Vaccinated *Administer vaccine as IM in deltoid + Administer full dose of RIG around wound if possible; remaining volume give at site distant from vaccine site *Note: Number of recommended doses of rabies vaccine changed from 5 to 4 (ACIP June 24, 2009) Source: CDC and Prevention. MMWR 2010;59 (RR-02):1-9.

7. Case History: Meningitis A 63-year-old woman with CLL is admitted to the hospital with fever. She is started on Ceftriaxone and Vancomycin, but 2 days later has no improvement. LP now shows 2,600 WBCs (65% polys) and gram-positive rods.

8. Case History: Meningitis What would you recommend at this point: 1. Add Ampicillin 2. Change Ceftriaxone to Imipenem 3. Add Clindamycin 4. Add Levofloxacin

9. Listeria Meningoencephalitis Risk Factors & CSF Findings  Risk Factors - Pregnancy - Neonates - Neoplastic disease - Corticosteroid therapy - Organ transplantation  CSF Findings - Range 100% polys to 100% monos - Greater than 25% monos suggests Listeria - Low sensitivity of Gram’s stain (0-40%) - Gram’s stain often misleading

10. Therapy for Bacterial Meningitis in Adults Ceftriaxone # + Vancomycin^ + Dexamethasone Age 18-50Age > 50 Ampicillin + Ceftriaxone # + Vancomycin + Dexamethasone # Cefotaxime can be substituted for Ceftriaxone ^ Vancomycin trough should be maintained at 15-20 ug/ml

11. Ceftriaxone Neisseria meningitidis Haemophilus influenzae Streptococcus pneumoniae Drug-Resistant Streptococcus pneumoniae Listeria monocytogenes Vancomcycin Ampicillin Therapy for Bacterial Meningitis in Adults

12. Dexamethasone in Adults with Bacterial Meningitis  Methods - N = 301 adults - Acute bacterial meningitis - Randomized, double-blind  Regimens - Dexamethasone* - Placebo Study DesignOutcome From: de Gans J et al. N Engl J Med 2002; 347:1549-56. *10 mg 15-20 minutes before (or with) first dose of antibiotics, then q 6h x 4 days P = 0.03 P = 0.04

13. Respiratory Tract Infections

14. Case History: Pharyngitis  A 26-year old is diagnosed with group A streptococcal pharyngitis. What is the likelihood that this organism is resistant to penicillin? 1. 0-5%? 2. 5-10? 3. 20-30% 4. 40-50%

15. “Penicillin resistant group A streptococcus has never been documented.” Shulman ST, et al. Clin Infect Dis 2012;55:1279-82.

16. Group A Streptococcal Pharyngitis IDSA Treatment Guidelines for Adults  Oral: Penicillin V - 250 mg qid x 10d - 500 mg bid x 10d  Amoxicillin - 50 mg/kg (max = 1000 mg) once daily x 10d - 25 mg/kg (max = 500 mg) twice daily x 10d  Parenteral: Benzathine Penicillin G - Weight ≥ 27 kg: 1,200,000 units IM x 1 - Weight < 27 kg: 600,000 units IM x 1 Source: Shulman ST, et al. Clin Infect Dis 2012;55:1279-82.

17. Case History: CAP  A healthy 38-year-old man is diagnosed with community-acquired pneumonia. He is stable and you plan to treat him as an out-patient. He has no allergies.

18. Case History: CAP  What antibiotic would be appropriate? 1. Azithromycin 2. Amoxicillin 3. Amoxicillin-clavulanic acid 4. Trimthoprim-sulfamethoxazole

19. Community-Acquired Pneumonia Most Common Pathogens Streptococcus pneumoniae Mycoplasma pneumoniae Chlamydia pneumoniae Haemophilus influenzae

20. 2007 IDSA CAP Guidelines Out-Patient Management Out-Patient Presence of Comorbidities Macrolide Azithromycin Clarithromycin Erythromycin Strong Recommendation From: Mandell LA et al. Clin Infect Dis 2007;44:S27-42. Out-Patient Previously Healthy & No Risk Factors for DRSP Doxycycline Weak Recommendation Fluoroquinolon e Moxifloxacin Gemifloxacin Levofloxacin Strong Recommendation Macrolide plus Beta-Lactam Strong Recommendation

21. 2007 IDSA CAP Guidelines Hospitalized Hospitalized ICU Macrolide plus Beta-Lactam From: Mandell LA et al. Clin Infect Dis 2007;44:S27-42. Hospitalized Non-ICU Treatment Fluoroquinolo ne Moxifloxacin Gemifloxacin Levofloxacin Beta-Lactam plus Fluoroquinolone or Macrolide

22. Case History  A previously healthy 49-year-old man is airlifted to HMC with respiratory distress. Illness began 1 week prior with cough and flu-like symptoms. No recent travel; no animal or pet exposure. Married. Mechanic. No HIV risk factors. Takes no meds. Had negative angiogram for PE prior to transfer.  Exam - P = 128; SBP=80; RR 24/26; T = 39°C - Intubated (thick red-tinged secretions)  Labs - WBC 1.06 (ANC = 506); Hct = 35; Plt = 105K - ABG: 7.25/47/54/20 (100% FIO2)  Antibiotics on Transfer - Levofloxacin, Imipenem

23. Case History Chest Radiograph Chest CT

24. Case History  What antimicrobial would you add: 1. Nafcillin 2. Vancomycin 3. Fluconazole 4. Doxycycline

25. Case History: Hantavirus Pulmonary Syndrome A 49-year-old woman is admitted to the hospital with dyspnea, deep muscle aches, and a suspected diagnosis of hantavirus pulmonary syndrome. Which of the following would be LEAST characteristic of the clinical presentation of hantavirus pulmonary syndrome? 1. CSF pleocytosis 2. Increased hematocrit 3. Increased white blood cell count with immature forms 4. Thrombocytopenia

26. Hantavirus Pulmonary Syndrome: Reservoir Source: CDC and Prevention Peromyscus maniculatus Deer Mouse

27. Hantavirus Pulmonary Syndrome: Chest Radiograph CDC Early Stage Later Stage Severe Interstitial Source: CDC and Prevention

28. Hantavirus Pulmonary Syndrome Therapy  Careful volume replacement (PAP=12-15 mm)  Vasopressors -Dopamine -Dobutamine  Good ICU care  Some experts recommend extracorporeal membrane oxygenation (ECMO) in severe cases

29. Case History  A healthy 28-year-old man presents with flu-like symptoms, followed one day later by fever, hypotension, diaphoresis, chest pain, confusion, & leukocytosis. He has not traveled recently and has no outdoor exposure.

30. Gram’s Stain  The patient worsens and becomes obtunded. Gram’s stain on lung biopsy and CSF both show similar findings.  What do you think is the most likely diagnosis? 1. Nocardiosis 2. Anthrax 3. Drug-Resistant Pneumococcus 4. Leptospirosis

31. Zoonotic Infections

32. West Nile Virus Which of the following is True regarding West Nile Virus infection in the United States? 1. Most human cases involve direct transmission from birds 2. More than 50% of infections are asymptomatic 3. Poliomyelitis is the most common neurologic manifestation 4. In the past 10 years, the number of cases have steadily increased

33. West Nile Virus: Organism Single stranded RNA Virus Genus Flavirus 40-60 nm in size

34. West-Nile-Like Virus: Transmission Picture Birds (Reservoir) Humans Mosquitoes (Vector)

35. Source: CDC and Prevention. West Nile Virus Activity in US, 2012 (through November 27)

36. Source: CDC and Prevention. West Nile Virus Activity in US, 2012 (through November 27) Total Human Cases reported = 5,245 Neuroinvasive Disease = 2,663 Deaths = 236

37. West Nile Virus: Clinical Manifestations Asymptomatic Infection (> 70% of infections) West Nile Fever Severe Disease - Meningitis - Encephalitis - Poliomyelitis

38. West Nile Virus: CNS Disease CSF Findings - Increased WBC (<3,000 & mainly lymphocytes) - Increased protein - Normal glucose Brain Imaging - CT: normal - MRI: normal (some with leptomenigeal enhancement)

39. West Nile Virus: Diagnosis Preliminary Diagnosis - Based on Clinical Features Laboratory Diagnosis - IgM ELISA on Serum or CSF - 4 FDA-approved WNV ELISA Kits - ELISA may cross react with other Flaviviruses

40. West Nile Virus: Prevention Mosquito Repellant Remove Standing Water Aware of Peak Mosquito Hours

41. Case History  What is the most likely diagnosis? 1. Malaria 2. Rocky Mountain Spotted Fever 3. Babesiosis 4. Anaplasmosis

42. Babesiosis: Transmission  Ticks - Ixodes scapularis - Ixodes pacificus  Transfusion- Associated - RBCs - Platelets

43.  First Line - Clindamycin plus Quinine or - Azithromycin plus Atovaquone Babesiosis: Treatment

44. Case History  A 28-year-old man presented to clinic with a 16 cm erythematous, annular skin lesion on his right flank and flu-like symptoms. He spent the past 30 days hiking in the mountains.

45. Case History  The most appropriate course of action is: 1. Give PO Doxycycline for 14-21 days 2. Reassure and don’t give antibiotics 3. Draw serology and treat if positive 4. Give IV Ceftriaxone for 14-21 days

46. Erythema Migrans Rash From: Steere AC. N Engl J Med. 2001;345:115-25.

47. National Lyme Disease Risk From: CDC Lyme Disease Home Page. www.cdc.gov/ncidod/dvbid/lyme/

48.  A 33-year-old woman living in Washington State is bitten on her hand by her cat while trying to break up a fight between her cat and dog. One day later her wound is red and painful and she comes to the ER for evaluation. Case History: Animal Bite

49.  Which of the following is TRUE? 1. Her risk of getting rabies from this cat bite is about 2% 2. Cat bites become infected more often than dog bites 3. Bartonella is the most likely cause of the infection 4. Pseudomonas is the most likely cause of the infection Case History: Animal Bite

50. Microbiology of Infected Cat Bites From: Talan DA, et al. NEJM 1999;340:85-92.

51. Case History: Question A 29-year-old is bitten by a dog on his hand while trying to break up a dog fight between 2 pets. This took place in Seattle.

52. Case History: Question Which of the following is TRUE regarding dog bites and infection? 1. His risk of getting rabies from this dog bite is about 5% 2. Pseudomonas cani is the most common pathogen 3. Optimal prophylaxis is Amoxicillin 4. Pasturella is one of the most common organisms isolated

53. Microbiology of Infected Dog Bites From: Talan DA, et al. NEJM 1999;340:85-92.

54. Dog & Cat Bites Wound Infections Therapy  Therapy (Oral) - Amoxicillin-CA x 7-14 days  Therapy (Intravenous - Ampicillin-sulbactam - Ertapenem  Therapy (Penicillin-Allergic) - Clindamycin plus Fluoroquinolone

55. New Hepatitis C Testing Recommendations

56. Hepatitis C: Testing Which of the following best describes the new 2012 CDC hepatitis C testing recommendations? A. Test all persons 40 to 55 years of age B. Test all persons 50 to 65 years of age C. Test all persons born from 1945 to 1965 D. Test all persons born from 1955 to 1975

57. Source: CDC and Prevention. MMWR. 2012;RR61:1-32.

58. 2012 CDC Birth Cohort HCV Testing Recommendations In addition to testing adults of all ages at risk for hepatitis C virus:  Adults born during 1945 to 1965 should receive 1-time testing for HCV without prior ascertainment of HCV risk.

59. Sources: Armstrong GL, et al. Ann Intern Med. 2006;144:705-14. Chak E, et al. Liver Int. 2011;31:1090-101. Estimated Prevalence of Chronic Active Hepatitis C in U.S. 3.2 - 4.1 Million Persons Living with Chronic HCV

60. Source: Armstrong GL, et al. Ann Intern Med. 2006;144:705-14. NHANES Survey: United States, 1988-1994 and 1999-2002 Prevalence of HCV Antibody, by Year of Birth Year of Birth HCV Prevalence(%) 1910 1988–19941999–2002 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0 19201930 1940 19501960197019801990

61. Source: Armstrong GL, et al. Ann Intern Med. 2006;144:705-14. NHANES Survey: United States, 1988-1994 and 1999-2002 Prevalence of HCV Antibody, by Year of Birth Year of Birth HCV Prevalence(%) 1910 1988–19941999–2002 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0 19201930 1940 19501960197019801990 1945-1965

62. Sources: Armstrong GL, et al. Ann Intern Med. 2006;144:705-14. Chak E, et al. Liver Int. 2011;31:1090-101. Hepatitis C: Progression of Disease 25-30 years Normal Liver Chronic Hepatitis HCC ESLD Death HCV Infection 20-25 years Cirrhosis Time

63. Source: Ly KN, et al. Ann Intern Med. 2012:156:271-8. Age-Adjusted Mortality Rates from HBV, HCV, & HIV United States, 1999-2007 Rate per 100,000 PY Year HIV 19992000 2001 2002 2003 2004 20062007 2005 5 4 3 2 1 0 7 6 Hepatitis C Hepatitis B

64. Source: Rein DR, et al. Dig Liver Dis. 2011:43:66-72. Age-Adjusted Mortality Rates from HBV, HCV, & HIV United States, 1999-2007 Peak

65. Source: CDC and Prevention. MMWR. 2012;RR61:1-32.  All persons identified with HCV infection should receive: - A brief alcohol screening and intervention as indicated, - Referral to appropriate care and treatment services for HCV, - Post-test counseling 2012 CDC Birth Cohort HCV Testing Recommendations

66. Source: Armstrong GL, et al. Ann Intern Med. 2006;144:705-14. Therapy for Hepatitis C: Historical Milestones 198 6 199 8 200 1 200 2 Timeline 201 1 201 4

67. Skin and Soft Tissue Infections

68. Case History: Skin & Soft Tissue A 22-year-old woman presents with a 5 x 5 cm boil on her back. She has no know known medical problems. She is afebrile and the lesion is erythematous, slightly tender, and soft in the middle.

69. Case History: Skin & Soft Tissue You suspect MRSA. How would you manage this? A. Hot compresses B. Antibiotics C. Incision and drainage D. Incision and drainage + antibiotics

70. Source: Liu C, et al. Clin Infect Dis. 2011:52:1-38.

71. 2010 IDSA Practice Guidelines Therapy for CA-MRSA Skin & Soft Tissue Infection Simple Abscess or Boil - Incision and Drainage Source: Liu C, et al. Clin Infect Dis. 2011:52:1-38. “For simple abscesses or boils incision and drainage alone is likely to be adequate, but additional data are needed to further define the role of antibiotics, if any, in this setting.”

72. Incision and Drainage +/- TMP-SMX for CA-MRSA Abscess Study DesignTreatment Failures Source: Schmitz GR, et al. Ann Emerg Med. 2010;56:283-7.  Methods - 212 adults randomized - F/U: 190 at day 7, 96 at day 30 - Uncomplicated CA-MRSA abscess - Setting: emergency room  Treatment Arms - I & D + Placebo: 2 bid x 7d - I & D + TMP-SMX: 2 DS bid x 7d  Follow-Up - Recheck at days 2 and 7 P = 0.12P = 0.02

73. Case History: Skin & Soft Tissue A 28-year-old man presents with an abscess on his hand and fever (T = 38.6°C). He has diabetes, but no other medical problems. The patient says this is a spider bite, but he has a history of 2 prior MRSA infections.

74. Case History Skin & Soft Tissue You suspect MRSA. How would you manage this? A. Hot compresses B. Antibiotics C. Incision and drainage D. Incision and drainage + antibiotics

76. 2010 IDSA Practice Guidelines Therapy for CA-MRSA Skin & Soft Tissue Infection Simple Abscess or Boil - Incision and Drainage Complicated Abscess - Incision and drainage + antimicrobial therapy Source: Liu C, et al. Clin Infect Dis. 2011:52:1-38. Antibiotic therapy recommended for abscesses associated with the following conditions: - Severe or extensive disease or rapid progression in presence of associated cellulitis - Signs and symptoms of systemic illness - Associated comorbidities or immunosuppression - Extremes of age - Abscess in an area difficult to drain (eg, face, hand, and genitalia) - Associated septic phlebitis - Lack of response to incision and drainage alone

77. 2010 IDSA Practice Guidelines Therapy for CA-MRSA Skin & Soft Tissue Infection Empiric Therapy for Out-Patient Management - TMP-SMX: 1-2 DS tabs PO BID - Clindamycin: 300-450 mg PO TID - Doxycycline: 100 mg PO BID - Minocycline: 200 mg x1, then 100 mg PO BID - Linezolid: 600 mg PO BID If Also Covering for Group A Streptococcus - TMP-SMX + Amoxicillin: 500 mg PO TID - Clindamycin - Doxycycline/Minocycline + Amoxicillin: 500 mg PO TID - Linezolid Source: Liu C, et al. Clin Infect Dis. 2011:52:1-38.

78. Beta-Lactams: Mechanism of Action Cell Wall Cell Membrane Penicillin Binding Proteins Beta-Lactam Transpeptidation Carboxypeptidation DNA Staphylococcus aureus

79. Cell Wall Cell Membrane Penicillin Binding Proteins Cell Wall Synthesis DNA Beta-Lactam Beta-Lactams: Mechanism of Action Staphylococcus aureus

80. MRSA: Resistance to Beta-Lactams Altered Penicillin Binding Protein Beta-Lactam DNA mecA PBP 2a MRSA

81. Case History: Skin & Soft Tissue A 31-year-old man presents with an cellulitis on his left hand and low-grade fever (T = 38.4°C). On examination, there is no focal abscess identified. He had no known medical problems.

82. Case History Skin & Soft Tissue How would you manage this? A. Ciprofloxacin B. TMP-SMX C. Amoxicillin-clavulanic acid + TMP-SMX D. TMP-SMX + Ciprofloxacin

83. 2010 IDSA Practice Guidelines Therapy for CA-MRSA Skin & Soft Tissue Infection Simple Abscess or Boil - Incision and Drainage Complicated Abscess - Incision and drainage + antimicrobial therapy Nonpurulent Cellulitis (and no abscess) - Empiric therapy for beta-hemolytic streptococci Source: Liu C, et al. Clin Infect Dis. 2011:52:1-38.

84. Cephalosporins and MRSA Which one of the following cephalosporins has good activity against MRSA? A. Ceftaroline B. Ceftriaxone C. Cefepime D. Cefazolin E. Cefastopamrsa

85. MRSA: Mechanism of Action Altered Penicillin Binding Protein Beta-Lactam DNA mecA PBP 2a

86. Ceftaroline and MRSA: PBP2a Binding Altered Penicillin Binding Protein Ceftaroline DNA PBP 2a

87. Case History: Skin & Soft Tissue A 42-year-old man presents feeling very ill with an abscess on his right hip and fever (T = 38.8°C). He has a history of 3 prior MRSA infections. You decide to admit him to the hospital for incision and drainage and antibiotics. What IV antibiotics could you use? What can you do to prevent this?

88. 2010 IDSA Practice Guidelines Therapy for CA-MRSA Skin & Soft Tissue Infection Empiric Therapy for Hospitalized Patient - Vancomycin: 15-20 mg/kg IV q 8-12 h - Linezolid: 600 mg IV or PO BID - Daptomycin: 4 mg/kg IV QD - Telavancin: 10 mg/kg IV QD - Clindamycin: 600 mg IV or PO TID Source: Liu C, et al. Clin Infect Dis. 2011:52:1-38. Note: after IDSA guidelines developed, FDA-approved Ceftaroline: 600 mg IV q12 h for acute SSTI, including MRSA.

89. 2010 IDSA Practice Guidelines MRSA Decolonization Source: Liu C, et al. Clin Infect Dis. 2011:52:1-38. Nasal Decolonization - Mupirocin: bid x 5-10 days Topical Body Decolonization - Chlorhexidine: once daily x 5-14 days - Dilute bleach bath*: 2x/week x 3 months *Dilute bleach bath = 1 teaspoon per gallon of water [or ¼ cup per ¼ tub or 13 gallons of water] for 15 minutes

90. End