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.
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.
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 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.
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
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
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
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
Source: Armstrong GL, et al. Ann Intern Med. 2006;144:705-14.
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.
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
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
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.”
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
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.
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
2010 IDSA Practice GuidelinesTherapy 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
2010 IDSA Practice GuidelinesTherapy 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.
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
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.
Case HistorySkin & Soft Tissue
• How would you manage this?
A. Ciprofloxacin
B. TMP-SMX
C. Amoxicillin-clavulanic acid + TMP-SMX
D. TMP-SMX + Ciprofloxacin
2010 IDSA Practice GuidelinesTherapy 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.
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
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?
2010 IDSA Practice GuidelinesTherapy 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.
2010 IDSA Practice GuidelinesMRSA 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
End