Emerging Infectious Diseases:
It’s a small world….
Timothy H. Dellit, MD
Associate Professor of Medicine
University of Washington School of Medicine
Associate Medical Director
Harborview Medical Center
Disclosure:
Dr. Dellit has no financial interest in any of the products or manufacturers mentioned.
Antimicrobial Resistance and HealthcareAssociated Infections
(CLA-BSI and CA-UTI)
Which of the following is NOT correct?
A. E. coli resistance to fluoroquinolones is 29-47%.
B. Pseudomonas aeruginosa resistance to
fluoroquinolones is 30-35%.
C. Pseudomonas aeruginosa resistance to carbapenems is
20-25%.
D. Acinetobacter baumannii resistance to carbapenems is
less than 10%.
Rise of Acinetobacter
1987-1996: 345 nosocomial Acinetobacter
infections per year
 By 2006-2007

◦ Fifth most common Gram-negative
nosocomial pathogen
◦ 8.4% of ventilator-associated pneumonia
◦ 29% resistant to carbapenems

2009-2011 NHSN
◦ 60-75% resistance among CLA-BSI and CA-UTI
Infect Control Hosp Epidemiol 2008;29:996-1011
Acinetobacter and Military


Most common Gram-negative bacillus recovered from traumatic
injuries to extremities during Vietnam War
102 patients with Acinetobacter bacteremia at military medical
facilities (Landstuhl and Walter Reed) between 1/02 – 8/04
◦ Service members injured in Afghanistan and the Iraq/Kuwait region

Environmental contamination of field hospitals and infection
transmission within healthcare facilities
◦ Only 1/49 soil samples positive and different PFGE pattern
◦ Sites of isolates





32% wounds
24% airway
11% blood
2% urine
31% unknown
MMWR 2004;53:1063-1066
Clin Infect Dis 2007;44:1577-84
Problematic β-lactamases
ESBL
AmpC
Bugs
E. coli, Klebsiella
SPICEM organisms
(Serratia, Pseudomonas,
Providencia,
Indole-pos Proteus,
Citrobacter, Enterobacter,
Morganella
Genetics
Plasmid
Chromosome or plasmid
Inducible Resistance
No
Yes*
Most stable β-lactams
Carbapenem
Carbapenem or cefepime
*Monotherapy with penicillin or 3rd generation cephalosporin may be
associated with inducible resistance
19 year old man s/p traumatic
open injury in India arrives at
HMC for surgical revision of his
AKA with wounds infected with
Pseudomonas, Klebsiella, E.
coli, Morganella, and
Enterococcus.
Pseudomonas aeruginosa
Escherichia coli
Colistin MIC 4 mcg/mL
Colistin MIC 2 mcg/mL
New Dehli metallo-betalactamase (NDM-1)
• Linked to receipt of
medical care in India and
Pakistan
• Encoded on a plasmid mobile genetic element
Klebsiella pneumoniae Carbapenemase
• First identified in 1996
• Encoded on a plasmid – mobile genetic element
Lancet Infect Dis
2009 Apr;9(4):228-36
Carbapenemase-Producing CRE
Carbapenem-Resistant Enterobateriaceae
Tier 1: PCR positive for carbapenemase production
(KPC, NDM-1, VIM, IMP, or OXA)
◦
Roughly 6 cases of CP-CRE per year in WA
Tier 2: CRE NOT due to carbapenemase production
◦
Roughly 80 cases per year in WA
Tier 3: Intrinsic resistance such as Proteus, Providencia,
Morganella which are ONLY imipenem non-susceptible
LTACH and KPC
Point Prevalence Survey in Chicago
• 24 acute care hospitals > 10 ICU beds
• 7 long-term acute care hospitals
LTACH: 10-54% colonization
Clin Infect Dis 2013;57:1246-52
CRE screening of samples sent for C. difficile testing
• Two NYC Hospitals
• CRE identified in
25/854 (2.9%)
patients
Infect Control Hosp
Epidemiol 2014;35:82-84
Options for Resistant Gram-Negative Bacilli
√
CarbapenemResistant
Carbapenems
• Imi/Mero/Dori
• Ertapenem
ESBL (MDR-GNR)
√
AmpC
Cefepime
Acinetobacter
Pseudomonas
Antimicrobial
√
√
√
√
√
√
Sulbactam
√
Tigecycline*
√
√
√
√
√
√
√
√
Polymixin/Colistin*
√
*Not active against Proteus
Combination therapy with
carbapenem +/- colistin +/- rifampin?
Getting to the correct therapy
Rapid Microarray Assay on
blood cultures to determine if
resistance present
Pre-matrix
Post-matrix
P
LOS
43.2
21.5
0.048
Hospital Cost
$103,075
$42,346
0.02
J Clin Microbiol 2013;51:4008-4011
Clin Infect Dis 2014;59:272-278
“MDRO Bundle”
– Catheter-associated BSI
– Ventilator-associated
pneumonia
– Catheter-associated UTI
– SCIP measures
• Active surveillance cultures
• Chlorhexidine baths
• Antimicrobial stewardship
Increased Hand Hygiene Associated with
Decreased MRSA Transmission
100
2.5
90
Hand hygiene
80
MRSA Transmission rate
2
70
60
1.5
50
40
1
30
20
0.5
10
0
0
1994
1998
Lancet 2000;356:1307-12
Transmission per 10,000 patient-days
Hand Hygiene
Contact precautions
Education
Minimize shared equipment
Environmental cleaning
Healthcare-associated
infections preventive bundles
Hand Hygiene Adherance
•
•
•
•
•
•
Influenza Viral Structure
Neuraminidase
WA: 2013-2014
Hemagglutinin
Main Types of Influenza
•A
- Humans, birds, pigs
- Antigenic drift (minor changes)
- Antigenic shift (major changes)
• Pandemic
•B
- Humans only
- Antigenic drift (minor changes)
Minor changes each year result in need for annual vaccination
Antigenic shift and reassortment with creation of novel viruses
Mayo Clin Proc. 2010;85:64-76
Antigenic Shift and Reassortment
Swine Respiratory Epithelium
Reassorted Virus
Influenza Pandemics

1918 Spanish H1N1 (Avian Virus)
◦ 40-50 million deaths worldwide
◦ 500,000 deaths in US with case mortality 2.5%

1957 Asian H2N2 (Re-assorted Virus)
◦ 70,000 deaths in US

1968 Hong Kong H3N2 (Re-assorted Virus)
◦ 34,000 deaths in US


1977 Russian H1N1
2009 Triple-reassorted H1N1 (Swine-origin)
◦ 42,000 lab-confirmed hospitalizations in US
◦ 2,125 lab-confirmed deaths in US
◦ Case mortality < 0.1%
Importance of Early Recognition and
Clinical Judgment

Early treatment associated with better outcomes
 Co-morbidities
 All hospitalized patients, even if symptoms > 48 hours

First 15 deaths in King County during 2009 pandemic
◦ Time from symptom onset to treatment
 Mean 5.8 days (2-12 days)
◦ 5 patients with predisposing risk factors presented with ILI and were not
treated initially

Testing challenges
◦
◦
◦
◦
Rapid point of care tests 10-50% sensitive
FA and “inconclusive results”
Movement towards PCR testing
Upper vs. lower tract testing
Epi-Log Dec 2009: Public Health Seattle & King County
Critical Care 2009;13:R148
J Infect Dis 2011;203;1739-47
World Distribution of H5N1 (Avian Flu)
Through Nov 29, 2011
571 Cases
335 Deaths (59%)
2011
Egypt (34)
Indonesia (11)
Cambodia (8)
Bangladesh (2)
January 2014
Resident of Alberta
Canada died after
returning from Beijing
Primarily contact with infected birds; very rare
reports of possible human to human transmission
450 cases
145 deaths (32%)
Avian Influenza Virus
J Infect 2014 epub
Healthcare worker returns from Saudia Arabia to
Orlando FL and in route develops fever, muscle aches,
cough. Which precautions should be implemented?
A.
B.
C.
D.
Patient should be placed in droplet
precautions for influenza-like illness.
Patient should be placed in airborne isolation
with use of N95 respirator
Patient should be placed in contact
precautions due to concern for MRSA
pneumonia.
Patient should be placed in airborne plus
contact precautions with use of gown, gloves,
and N95 respirator with eye protection.
MERS Corona Virus
Through June 13, 2014
• 701 cases
• 249 deaths (27.1%)
2 US Cases
(Indiana, Florida)
MERS-CoV Characteristics
Clin Infect Dis 2014;59:160-165
Chikungunya
Aedes mosquito
Fever, joint pains, headache, muscle pain, rash
Ebola Hemorrhagic Fever
Outbreak in West Africa
March – July 2014
1,323 cases
729 Deaths (56%)
Incubation: 2 to 21 days
Ebola (VHF) Precautions

Standard, Droplet, and Contact Precautions
◦ Single room, door closed
◦ All persons entering the patient room should wear at least:




Gloves
Gown (fluid resistant or impermeable)
Eye protection (goggles or face shield)
Facemask
◦ Additional PPE might be required in certain situations (e.g.,
copious amounts of blood, other body fluids, vomit, or feces
present in the environment), including but not limited to:
 Double gloving
 Disposable shoe covers

Aerosol generating procedures
◦ N95 respirator or PAPR
1943: routine use of whole-cell
pertussis vaccine
Pertussis Outbreak
• Respiratory Etiquette
• Droplet Precautions
• Tdap
ACIP 2012: Tdap with every pregnancy
• Optimally between weeks 27-36
• May prevent:
- 906 infant cases
- 462 hospitalizations
- 9 deaths
2005: Tdap at age 11 or 12
J Infect Dis 2014;209;978-985
45 y o woman is hospitalized because of the acute onset of headache,
malaise, chest pain, sore throat, abdominal pain, myalgias, and a dry,
nonproductive cough preceded by a 2-day prodrome of coryza and some
diarrhea. The US has been on a Code Red advisory alert for several weeks.
T 40 C, HR 64, RR 24
Bilateral course rhonchi
Blood cultures grow Francisella tularensis
In addition to standard precautions, which type of isolation is most
appropriate for this patient?
A. Contact precautions
B. Droplet precautions
C. Airborne precautions
D. No additional isolation precautions are required
27 y o veterinarian presents to ED in New Mexico because of dyspnea,
fever, malaise, nausea, vomiting, and increased watery sputum that
began last night followed by hemoptysis this morning. His mother, with
whom he lives, died of pneumonia 4 days ago. US on Code Red
advisory for past 10 days.
T 39.8 HR 118 RR 32 BP 92/48
Lungs dull to percussion throughout left lung field with egophany
CXR with LLL infiltrate
Blood cultures later grow a Gram-negative rod
Which of the following pathogen is MOST likely with the correct precautions?
A. Bacillus anthracis – droplet precautions
B. Bacillus anthracis – airborne precautions
C. Yersinia pestis – droplet precautions
D. Yersinia pestis – airborne precautions
Pneumonic Plague


Usually 2-4 d incubation
period
Fever, cough, dyspnea
◦ Bloody, watery, or (less
commonly) purulent sputum
◦ GI symptoms may occur:
N/V/D/pain

Rapidly progressive
pneumonia
JAMA (2000) 283:2281
Inhalational Anthrax
• Bacteria release toxin
- Edema, hemorrhage, necrosis
• Early symptoms: Fever, dyspnea,
cough, H/A, emesis, abd/chest pain
• Hemorrhagic mediastinitis
• Hemorrhagic meningitis: 50%
• Cyanosis, hypotension, death
JAMA (1999) 281:1735
Match the Precaution
(In addition to Standard Precautions)
MRSA
Influenza
Tuberculosis
Disseminated varicella
Tularemia
Cutaneous anthrax
Inhalational anthrax
Pneumonic plague
Viral Hemorrhagic Fever
Prion (CJD)
Rabies
Standard only
Contact
Droplet
Airborne
Summary

Continued emergence of antimicrobial resistance
 Multidrug-resistant Gram negative rods
 Carbapenem Resistant Enterobateriaceae (CRE)

Emergence of novel viruses
 Importance of travel history as the world gets smaller
 Appropriate precautions (airborne vs. droplet)

Bioterrorism