Emerging Infectious Diseases:It’s a small world….

Timothy H. Dellit, MDAssociate Professor of MedicineUniversity of Washington School of MedicineAssociate Medical DirectorHarborview Medical Center

Disclosure: Dr. Dellit has no financial interest in any of the products or manufacturers mentioned.

Antimicrobial Resistance and Healthcare-Associated 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 Acinetobacter1987-1996: 345 nosocomial

Acinetobacter infections per yearBy 2006-2007

◦ Fifth most common Gram-negativenosocomial 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

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

Problematic β-lactamases

Colistin MIC 4 mcg/mL

Pseudomonas aeruginosa

Escherichia coli

Colistin MIC 2 mcg/mL

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.

New Dehli metallo-beta-lactamase (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 CRECarbapenem-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

*Not active against Proteus

Options for Resistant Gram-Negative Bacilli

Combination therapy with carbapenem +/- colistin +/- rifampin?

Getting to the correct therapy

Pre-matrix

Post-matrix

P

LOS 43.2 21.5 0.048

Hospital Cost

$103,075 $42,346 0.02

Rapid Microarray Assay on blood cultures to determine if resistance present

J Clin Microbiol 2013;51:4008-4011Clin Infect Dis 2014;59:272-278

“MDRO Bundle”

Increased Hand Hygiene Associated with Decreased MRSA Transmission

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Lancet 2000;356:1307-12

• Hand Hygiene• Contact precautions• Education• Minimize shared equipment• Environmental cleaning• Healthcare-associated

infections preventive bundles– Catheter-associated BSI– Ventilator-associated

pneumonia– Catheter-associated UTI– SCIP measures

• Active surveillance cultures • Chlorhexidine baths• Antimicrobial stewardship

Influenza Viral Structure

Mayo Clin Proc. 2010;85:64-76

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

HemagglutininNeuraminidase

WA: 2013-2014

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 H1N12009 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 CountyCritical Care 2009;13:R148J Infect Dis 2011;203;1739-47

World Distribution of H5N1 (Avian Flu)

Through Nov 29, 2011571 Cases335 Deaths (59%)

2011Egypt (34)Indonesia (11)Cambodia (8)Bangladesh (2)

Primarily contact with infected birds; very rare reports of possible human to human transmission

January 2014 Resident of Alberta Canada died after returning from Beijing

450 cases145 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. Patient should be placed in droplet precautions for influenza-like illness.

B. Patient should be placed in airborne isolation with use of N95 respirator

C. Patient should be placed in contact precautions due to concern for MRSA pneumonia.

D. Patient should be placed in airborne plus contact precautions with use of gown, gloves, and N95 respirator with eye protection.

MERS Corona VirusThrough June 13, 2014• 701 cases• 249 deaths (27.1%)

2 US Cases(Indiana, Florida)

MERS-CoV Characteristics

Clin Infect Dis 2014;59:160-165

ChikungunyaAedes mosquitoFever, joint pains, headache, muscle pain, rash

Ebola Hemorrhagic Fever Outbreak in West Africa

March – July 20141,323 cases729 Deaths (56%)

Incubation: 2 to 21 days

Ebola (VHF) PrecautionsStandard, 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

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

J Infect Dis 2014;209;978-985

1943: routine use of whole-cell pertussis vaccine

2005: Tdap at age 11 or 12

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)

MRSAInfluenzaTuberculosisDisseminated varicellaTularemiaCutaneous anthraxInhalational anthraxPneumonic plagueViral Hemorrhagic FeverPrion (CJD)Rabies

Standard onlyContactDropletAirborne

Summary

Continued emergence of antimicrobial resistanceMultidrug-resistant Gram negative rodsCarbapenem Resistant Enterobateriaceae (CRE)

Emergence of novel virusesImportance of travel history as the world gets

smallerAppropriate precautions (airborne vs. droplet)

Bioterrorism