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

2013 Infectious Diseases Update

David H. Spach, MD

Professor of MedicineDivision of Infectious Diseases

University of Washington, Seattle

Infectious Diseases: 2013 Update

• Central Nervous System Infections

• Respiratory Tract Infections

• Zoonotic Infections

• New Hepatitis C Testing Recommendations

• Skin and Soft Tissue Infections

Central Nervous System Infections

• 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

“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 ProphylaxisHuman Rabies Immune Globulin

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.

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.

Case History: Meningitis

What would you recommend at this point:

1. Add Ampicillin2. Change Ceftriaxone to Imipenem3. Add Clindamycin4. Add Levofloxacin

Listeria MeningoencephalitisRisk 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

Therapy for Bacterial Meningitis in Adults

Ceftriaxone#

+

Vancomycin^

+

Dexamethasone

Age 18-50 Age > 50

Ampicillin

+

Ceftriaxone#

+

Vancomycin

+

Dexamethasone

#Cefotaxime can be substituted for Ceftriaxone

^ Vancomycin trough should be maintained at 15-20 ug/ml

Ceftriaxone

Neisseria meningitidis

Haemophilus influenzae

Streptococcus pneumoniae

Drug-ResistantStreptococcus pneumoniae

Listeria monocytogenes

Vancomcycin

Ampicillin

Therapy for Bacterial Meningitis in Adults

Dexamethasone in Adults with Bacterial Meningitis

Unfavorable Response Death0

10

20

30

40

50

15

7

25

15

Dexamethasone (N = 157) Placebo (N = 144)

Pa

tie

nts

(%

)

Methods - N = 301 adults - Acute bacterial meningitis - Randomized, double-blind

Regimens - Dexamethasone* - Placebo

Study Design Outcome

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

Respiratory Tract Infections

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%

“Penicillin resistant group A streptococcus has never been documented.”

Shulman ST, et al. Clin Infect Dis 2012;55:1279-82.

Group A Streptococcal PharyngitisIDSA 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.

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.

Case History: CAP

· What antibiotic would be appropriate?

1. Azithromycin 2. Amoxicillin 3. Amoxicillin-clavulanic acid 4. Trimthoprim-sulfamethoxazole

Community-Acquired PneumoniaMost Common Pathogens

• Streptococcus pneumoniae

• Mycoplasma pneumoniae

• Chlamydia pneumoniae

• Haemophilus influenzae

2007 IDSA CAP Guidelines Out-Patient Management

Out-PatientPresence of Comorbidities

MacrolideAzithromycin

ClarithromycinErythromycin

Strong Recommendation

From: Mandell LA et al. Clin Infect Dis 2007;44:S27-42.

Out-PatientPreviously Healthy & No Risk Factors for DRSP

Doxycycline Weak Recommendation

Fluoroquinolone

MoxifloxacinGemifloxacinLevofloxacin

Strong Recommendation

Macrolide plus

Beta-Lactam Strong Recommendation

2007 IDSA CAP Guidelines Hospitalized

HospitalizedICU

Macrolideplus

Beta-Lactam

From: Mandell LA et al. Clin Infect Dis 2007;44:S27-42.

HospitalizedNon-ICU Treatment

Fluoroquinolone

MoxifloxacinGemifloxacinLevofloxacin

Beta-Lactamplus

Fluoroquinolone or Macrolide

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

Case History

Chest Radiograph Chest CT

Case History

What antimicrobial would you add:

1. Nafcillin2. Vancomycin3. Fluconazole4. Doxycycline

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 pleocytosis2. Increased hematocrit3. Increased white blood cell count with immature forms4. Thrombocytopenia

Hantavirus Pulmonary Syndrome: Reservoir

Source: CDC and Prevention

Peromyscus maniculatusDeer Mouse

Hantavirus Pulmonary Syndrome: Chest Radiograph

CDC

Early Stage

Later Stage

Severe

InterstitialSource: CDC and Prevention

Hantavirus Pulmonary SyndromeTherapy

Careful volume replacement (PAP=12-15 mm)

Vasopressors -Dopamine -Dobutamine

Good ICU care

Some experts recommend extracorporeal membrane oxygenation (ECMO) in severe cases

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.

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. Nocardiosis2. Anthrax3. Drug-Resistant Pneumococcus4. Leptospirosis

Zoonotic Infections

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 birds2. More than 50% of infections are asymptomatic3. Poliomyelitis is the most common neurologic manifestation4. In the past 10 years, the number of cases have steadily increased

West Nile Virus: Organism

• Single stranded RNA Virus

• Genus Flavirus

• 40-60 nm in size

West-Nile-Like Virus: Transmission

Picture

Birds (Reservoir)

HumansMosquitoes(Vector)

Source: CDC and Prevention.

West Nile Virus Activity in US, 2012 (through November 27)

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

West Nile Virus: Clinical Manifestations

• Asymptomatic Infection (> 70% of infections)

• West Nile Fever

• Severe Disease- Meningitis- Encephalitis- Poliomyelitis

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)

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

West Nile Virus: Prevention

• Mosquito Repellant• Remove Standing Water• Aware of Peak Mosquito

Hours

Case History

What is the most likely diagnosis?

1. Malaria2. Rocky Mountain Spotted Fever3. Babesiosis4. Anaplasmosis

Babesiosis: Transmission

Ticks- Ixodes scapularis- Ixodes pacificus

Transfusion-Associated- RBCs- Platelets

· First Line- Clindamycin plus Quinineor- Azithromycin plus Atovaquone

Babesiosis: Treatment

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.

Case History

The most appropriate course of action is:

1. Give PO Doxycycline for 14-21 days2. Reassure and don’t give antibiotics3. Draw serology and treat if positive4. Give IV Ceftriaxone for 14-21 days

Erythema Migrans Rash

From: Steere AC. N Engl J Med. 2001;345:115-25.

National Lyme Disease Risk

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

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

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 infection4. Pseudomonas is the most likely cause of the infection

Case History: Animal Bite

Microbiology of Infected Cat Bites

From: Talan DA, et al. NEJM 1999;340:85-92.


• 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.


• 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 Amoxicillin4. Pasturella is one of the most common organisms isolated

Microbiology of Infected Dog Bites

From: Talan DA, et al. NEJM 1999;340:85-92.

Dog & Cat Bites Wound InfectionsTherapy

Therapy (Oral) - Amoxicillin-CA x 7-14 days

Therapy (Intravenous - Ampicillin-sulbactam - Ertapenem

Therapy (Penicillin-Allergic) - Clindamycin plus Fluoroquinolone

New Hepatitis C Testing Recommendations

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 1965D. Test all persons born from 1955 to 1975

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


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.

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

Source: Armstrong GL, et al. Ann Intern Med. 2006;144:705-14.

NHANES Survey: United States, 1988-1994 and 1999-2002Prevalence of HCV Antibody, by Year of Birth

Year of Birth

HC

V P

revale

nce(%

)

1910

1988–1994 1999–20027.0

6.0

5.0

4.0

3.0

2.0

1.0

01920 1930 1940 1950 1960 1970 1980 1990


NHANES Survey: United States, 1988-1994 and 1999-2002Prevalence of HCV Antibody, by Year of Birth

Year of Birth

HC

V P

revale

nce(%

)

1910

1988–1994 1999–20027.0

6.0

5.0

4.0

3.0

2.0

1.0

01920 1930 1940 1950 1960 1970 1980 1990

1945-1965

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

HCCESLDDeath

HCV Infection

20-25 years

Cirrhosis

Time

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

100,0

00 P

Y

Year

HIV

1999 2000 2001 2002 2003 2004 2006 20072005

5

4

3

2

1

0

7

6

Hepatitis C

Hepatitis B

Source: Rein DR, et al. Dig Liver Dis. 2011:43:66-72.

Age-Adjusted Mortality Rates from HBV, HCV, & HIV United States, 1999-2007

Nu

mb

er

Year

2010

Deaths

2014 2018 2022 2026 2030 2034 2038 2042 2046 2050 2054 2058

40,000

35,000

30,000

25,000

20,000

15,000

10,000

5,000

0

45,000Peak


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


Therapy for Hepatitis C: Historical Milestones

0

20

40

60

80

100

6

16

3442 39

55

70

90

Su

sta

ine

d V

iro

log

ic R

es

po

ns

e (

%)

1986

1998

2001

2002

Timeline2011

2014

Skin and Soft Tissue Infections

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.


• You suspect MRSA. How would you manage this?

A. Hot compresses

B. Antibiotics

C. Incision and drainage

D. Incision and drainage + antibiotics

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

2010 IDSA Practice GuidelinesTherapy for CA-MRSA Skin & Soft Tissue Infection

• Simple Abscess or Boil - Incision and Drainage


“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.”

Treatment Failure (at day 7)

New Lesions (within 30 days)

0

10

20

30

40

2728

17

9

I & D Alone I & D + TMP-SMX

Pa

tie

nts

(%

)

Incision and Drainage +/- TMP-SMX for CA-MRSA Abscess

Study Design Treatment 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 = 0.12 P = 0.02


• 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.

Case HistorySkin & Soft Tissue

• You suspect MRSA. How would you manage this?

A. Hot compresses

B. Antibiotics

C. Incision and drainage

D. Incision and drainage + antibiotics



• Complicated Abscess - Incision and drainage + antimicrobial therapy


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


• 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


Beta-Lactams: Mechanism of Action

Cell WallCell Membrane

Penicillin Binding Proteins Beta-Lactam

TranspeptidationCarboxypeptidation

DNA

Staphylococcus aureus

Cell WallCell Membrane

Penicillin Binding Proteins

Cell Wall Synthesis

DNA

Beta-Lactam

Beta-Lactams: Mechanism of Action

Staphylococcus aureus

MRSA: Resistance to Beta-Lactams

Altered Penicillin Binding Protein Beta-Lactam

DNA

mecAPBP 2a

PBP 2a

PBP 2a

MRSA


• 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.

Case HistorySkin & Soft Tissue

• How would you manage this?

A. Ciprofloxacin

B. TMP-SMX

C. Amoxicillin-clavulanic acid + TMP-SMX

D. TMP-SMX + Ciprofloxacin



• Complicated Abscess - Incision and drainage + antimicrobial therapy

• Nonpurulent Cellulitis (and no abscess)- Empiric therapy for beta-hemolytic streptococci


Cephalosporins and MRSA

• Which one of the following cephalosporins has good

activity against MRSA?

A. Ceftaroline

B. Ceftriaxone

C. Cefepime

D. Cefazolin

E. Cefastopamrsa

MRSA: Mechanism of Action

Altered Penicillin Binding Protein Beta-Lactam

DNA

mecA

PBP 2a

PBP 2a

PBP 2a

Ceftaroline and MRSA: PBP2a Binding

Altered Penicillin Binding Protein Ceftaroline

DNA

PBP 2a

PBP 2a


• 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?


• 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


Note: after IDSA guidelines developed, FDA-approved

Ceftaroline: 600 mg IV q12 h for acute SSTI, including MRSA.

2010 IDSA Practice GuidelinesMRSA Decolonization


• 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

End

Documents

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