EPIDEMIOLOGY 200B
Methods II – Prediction and
Validity
Scott P. Layne, MD
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PART 2
Staphylococcus aureus
March 2010
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Infectious Disease Agents
Bacteria
Gram Positive --> Staphylococcus sp.
Gram Negative
Zoonotic
Vector Bourne
Anaerobic
Acid Fast
Spirochetes
Chlymidia
Mycoplasma / Ureaplasma
Viruses
Prions
Fungi
Parasites
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Colonization
vs
Infection
External
Host
Microbe
4
Microbe
Cell wall constituents
Enzymes
Toxins
Direct destruction of tissue
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Host
Adhesion
Invasion
Chemotaxis (cell movement)
Opsonization (C3b, IgG)
Intracellular killing
Genetics (HLA makeup)
Integument
Trauma, Foreign Bodies
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External
Contamination
Exposure
Traffic
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Staphylococcus aureus
Transmission & Ecology
Carried in nasal membranes and skin of warn-blooded
animals
Colonizes one-third of humans at any one time
Spread by close contacts
Spread by contaminated hands and surfaces
Spread enhanced by sneezing
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Staph Related Diseases
Staphylococcus aureus
Skin Infections
Food Poisoning
Toxic Shock Syndrome
Osteomyelitis
Infective Arthritis
Acute Endocarditis
Pneumonia
Sepsis
Parotitis
High probability of blood borne spread leading to
multiple sites of infection
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Staph Related Diseases
Staphylococcus epidermidis
Adult bacteremia
Sub-acute endocarditis
Neonatal bactermia
Staphylococcus saprophyticus
Urinary Tract Infections
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Skin Infections
Folliculitis
Boils
Carbuncles
Cellulitis
Scalded skin syndrome
Burn infections
Wound infections
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Food Poisoning
Enterotoxin A effects
Fever and Myalgias
Respiratory symptoms
Headache
Gastrointestinal symptoms, vomiting, diarrhea
Short incubation periods (2 - 6 hours)
Epidemic outbreaks
#2 cause (20%) of food borne outbreaks
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Bioterrorism Potential ?
Effects of inhaled Staph Enterotoxin B in lung
Source: Textbook of Military Medicine
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Toxic Shock Syndrome
Menstrual vs Non-menstrual cases
Hyperabsobable tampons
Criteria
T > 38.9
BP < 90
Rash with desquamation
Rule out RMSF, Leptospirosis,
Measles
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Toxic Shock Syndrome
Involvement of three or more of the
following organs
Gut: vomiting, diarrhea
Muscle: myalgias, elevated CPK
Kidney: pyuria, elevated creatinine
Liver: hepatitis
Blood: thrombocytopenia
CNS: disorientation
Overall ~5% case fatality
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Other Infections
Osteomyelitis
#1 causative organism
caused by trauma or blood borne spread
Infective Arthritis
#1 causative organism
Acute Endocarditis
#1 causative organism
Infects normal, abnormal, prosthetic valves
Post Viral Lobar Pneumonia
Especially after influenza
Bacteremia and Sepsis
#1 causative organism
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Domains
Diseases
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Antibiotics
Toxins
Diseases
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Antibiotic Testing
Minimum Inhibitory Concentration (MIC)
Minimum Bactericidal Concentration (MBC)
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Antibiotic Biotypes
Methicillin Sensitive Staph aureus (MSSA)
Rx: Oxacillin
Cephalexin
Clindamycin
Vancomycin
Lower
resistance
Methicillin Resistant Staph aureus (MRSA)
Rx: Vancomycin
Vancomycin Intermediate Staph aureus (VISA)
Vancomycin Resistant Staph aureus (VRSA)
Rx: Teichoplanin
Fusidic acid
Quinupristin-dalfopristin (Synercid)
Linezolid (Zyvox)
Rifampin
Bactrim
Minocycline
Daptomycin (Cubicin)
Higher
resistance
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Toxins
Hemolysins (RBC)
Alpha toxin
Beta toxin
Delta toxin
Gamma toxin
Panton-Valentine Leukocidin (WBC)
Enterotoxins (food poisoning)
Toxin A
Toxin F
Toxic Shock Syndrome Toxin (superantigen)
Exfoliatin (intraepidermal separation)
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Toxins
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Strain Typing
Electrophoresis of proteins
Multilocus enzyme electrophoresis
Plasmid analysis
Restriction endonuclease analysis of chromosomal DNA
Restriction fragment length polymorphisms
Ribotyping
Nucleotide sequence analysis
Whole genome sequencing
2,872,769 bp & 2,560 genes (USA300)
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Connection / Mystery ?
Hospital
Community
More resistant
to antibiotics
More virulent
from toxins
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Two Overall Patterns
Hospital-acquired MRSA (h-MRSA)
Community-acquired MRSA (c-MRSA)
h-MRSA has more antibiotic resistance
genes than c-MRSA
c-MRSA has more virulence genes than hMRSA
c-MRSA is causing serious and fatal
infections in healthy people
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Hospital-acquired MRSA
In 1960s, MRSA began to appear in
hospitalized patients
In 1970s, MRSA became the main cause of
nosocomial infections worldwide
In 1996, VISA was first isolated with 8 cases
to date
In 1997, VRSA was first isolated with 4
cases to date
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ICU: High Risk for MRSA
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Risk Factors for
Nosocomial Infection
Severity of illness
Previous exposure to antimicrobial agents
Underlying diseases or conditions
Chronic renal disease
Insulin-dependent diabetes mellitus
Peripheral vascular disease
Dermatitis
Skin lesions
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Risk Factors (cont.)
Invasive procedures
Surgery
Dialysis
Presence of invasive devices
Urinary catheterization
Repeated contact with healthcare system
Colonization by multidrug-resistant organism
Advanced age
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Infection Control Strategies
Bacterial surveillance (laboratory)
Antibiotic use pattern (pharmacy)
Antibiotic use intervention (alter Rx)
Hand washing
Gloves
Gowns
Face masks
Patient isolation, cohorting
Traffic control
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Connection ?
Hospital
Community
More resistant
to antibiotics
More virulent
from toxins
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Community-acquired MRSA
Reproduction, Mutation, Selection
In 1999, MSRA associated with 4 fatal
cases in infants, with all carrying the
gene for Panton-Valentine (PVL)
toxin
Today, there are multiple clones
and/or strains
USA300
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C-MRSA Case Definition
Positive culture, sensitivity testing
Outpatient setting or within 48 hours after hospitalization
Person no medical history of MRSA infection or
colonization
Person has no medical history in the past year of
Hospitalization
Nursing home, skilled facility, hospice
Dialysis
Surgery
Person has no permanent indwelling catheters or
medical devices that pass through the skin into the
body
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Outbreak Reports
Correctional facilities
Athletic teams
Men who have sex with men (MSM)
Fire stations
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Football Team
Infectious Disease News
December 2004
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LA County Jail
Outbreak 2002 - 2003
928 inmates with MRSA infections
66 inmates hospitalized
10 inmates had invasive disease
bacteremia, endocarditis, osteomyelitis
Predominant strain identified (PFGE)
Largest jail worldwide
165,000 persons per year
20,000 per day
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Transmission Factors
Crowding
Many outbreaks occur in settings where
people are in close proximity.
Frequent contacts
Football linemen often have skin infections
in sites where they have skin abrasions
Compromised skin
Broken skin is more likely to be an infection
site than intact skin
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Transmission Factors
Contaminated surfaces, shared items
Includes towels, razors, toothbrushes
Lack of cleanliness
Transmission is more likely in places where
people cannot achieve appropriate hand
and body hygiene
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Intervention Program
2003, Fencers, Colorado
Increased hand hygiene
Showering with soap after every practice or tournament
Covering cuts and abrasions with a bandage until
healed
Laundering personal items such as towels and
supporters after each use
Cleaning or laundering shared athletic equipment such
as pads or helmets at least once a week but ideally
after each use
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Intervention Program
2003, Fencers, Colorado
Establishing a routine cleaning schedule for the sensor
wires
Consulting a health-care provider for wounds that do
not heal or appear infected.
No further infections have been reported.
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Community Surveillance
In 2000, CDC began working closely with four states,
with a combined population of about 12 million persons,
to study the epidemiology of CA-MRSA infections. The
information from these studies is helping CDC
understand the nature of the disease, why people get
infected, and to develop future studies designed to
improve our ability to prevent these infections. These
data are being collected in Connecticut, Minnesota,
Georgia, and Maryland as part of CDC's Emerging
Infections Program, Active Bacterial Core surveillance
(ABCs). This program is being expanded to six states in
2004.
http://www.cdc.gov/ncidod/hip/ARESIST/mrsa_comm_faq_print.htm
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At nine Emerging Infections Program sites (EIPs),
surveillance is conducted for invasive bacterial diseases
due to pathogens of public health importance. For each
case of invasive disease in the study population, a case
report with basic demographic information is filed and, in
most cases, bacterial isolates from a normally sterile site
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from patients are sent to CDC for laboratory study.
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% Staph aureus Isolates Resistant to Methicillin
100
80
60
40
20
0
1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000
Sources: National Nosocomial Infections Surveillance System. Am J Infect
Control. 1999;27:520-532; Am J Infect Control. 2000;28:429-448; Am J
Infect Control. 2001;29:404-421.
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Proportion of Staph aureus Nosocomial
Infections Resistant to Oxacillin (MRSA) In
Intensive Care Unit Patients, 1989-2003
Percent Resistance
70
60
50
40
30
20
10
0
1989
1991
1993
1995
1997
1999
2001
2003
Year
Source: NNIS System (2003 data are incomplete)
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Staphylococcus aureus
(MRSA)
Examples of questions that can be addressed
Risk factors associated with transmission
Optimal schedules for utilizing antibiotics
Impacts of hand washing or other control measures
Are there super-spreaders
What governs spread of virulent clones
What determines ecological fitness
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Reading
Emily Kajita, Justin Okano, Erin N. Bodine, Scott P. Layne,
Sally Blower. 2007. Modeling an outbreak of an emerging
pathogen. Nature Reviews Microbiology 5, 1 – 10.
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