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EPIDEMIOLOGY 200BMethods II – Prediction and

Validity

Scott P. Layne, MD

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PART 2

Staphylococcus aureus

March 2010

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Infectious Disease AgentsBacteria

Gram Positive --> Staphylococcus sp.Gram NegativeZoonoticVector BourneAnaerobicAcid FastSpirochetesChlymidiaMycoplasma / Ureaplasma

VirusesPrionsFungiParasites

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Colonizationvs

Infection

Host Microbe

External

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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 aureusSkin InfectionsFood PoisoningToxic Shock SyndromeOsteomyelitisInfective ArthritisAcute EndocarditisPneumoniaSepsisParotitis

High probability of blood borne spread leading to multiple sites of infection

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Staph Related Diseases

Staphylococcus epidermidisAdult bacteremiaSub-acute endocarditisNeonatal bactermia

Staphylococcus saprophyticusUrinary Tract Infections

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Skin InfectionsFolliculitis

Boils

Carbuncles

Cellulitis

Scalded skin syndrome

Burn infections

Wound infections

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Food PoisoningEnterotoxin 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 ?

Source: Textbook of Military Medicine

Effects of inhaled Staph Enterotoxin B in lung

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Toxic Shock SyndromeMenstrual vs Non-menstrual cases

Hyperabsobable tampons

CriteriaT > 38.9BP < 90Rash with desquamation

Rule out RMSF, Leptospirosis, Measles

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Toxic Shock Syndrome

Involvement of three or more of the following organsGut: vomiting, diarrheaMuscle: myalgias, elevated CPKKidney: pyuria, elevated creatinineLiver: hepatitisBlood: thrombocytopeniaCNS: disorientation

Overall ~5% case fatality

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Osteomyelitis#1 causative organismcaused by trauma or blood borne spread

Infective Arthritis#1 causative organism

Acute Endocarditis #1 causative organismInfects normal, abnormal, prosthetic valves

Post Viral Lobar PneumoniaEspecially after influenza

Bacteremia and Sepsis #1 causative organism

Other Infections

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Domains

Diseases

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Diseases

Antibiotics Toxins

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Antibiotic Testing

Minimum Inhibitory Concentration (MIC)Minimum Bactericidal Concentration (MBC)

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Antibiotic BiotypesMethicillin Sensitive Staph aureus (MSSA)

Rx: OxacillinCephalexinClindamycinVancomycin

Methicillin Resistant Staph aureus (MRSA)Rx: Vancomycin

Vancomycin Intermediate Staph aureus (VISA)Vancomycin Resistant Staph aureus (VRSA)

Rx: TeichoplaninFusidic acidQuinupristin-dalfopristin (Synercid)Linezolid (Zyvox)RifampinBactrimMinocyclineDaptomycin (Cubicin)

Lowerresistance

Higherresistance

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ToxinsHemolysins (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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Hospital Community

Connection / Mystery ?

More resistantto antibiotics

More virulentfrom 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 h-MRSA

c-MRSA is causing serious and fatal infections in healthy people

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Hospital-acquired MRSAIn 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 StrategiesBacterial surveillance (laboratory)

Antibiotic use pattern (pharmacy)Antibiotic use intervention (alter Rx)

Hand washingGlovesGownsFace masksPatient isolation, cohortingTraffic control

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Hospital Community

Connection ?

More resistantto antibiotics

More virulentfrom 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 DefinitionPositive 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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Infectious Disease NewsDecember 2004

Football Team

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LA County JailOutbreak 2002 - 2003

928 inmates with MRSA infections

66 inmates hospitalized

10 inmates had invasive disease

bacteremia, endocarditis, osteomyelitis

Predominant strain identified (PFGE)

Largest jail worldwide165,000 persons per year

20,000 per day

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Transmission Factors

CrowdingMany outbreaks occur in settings where people are in close proximity.

Frequent contactsFootball linemen often have skin infections in sites where they have skin abrasions

Compromised skinBroken skin is more likely to be an infection site than intact skin

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Transmission Factors

Contaminated surfaces, shared itemsIncludes towels, razors, toothbrushes

Lack of cleanlinessTransmission is more likely in places where people cannot achieve appropriate hand and body hygiene

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Intervention Program

2003, Fencers, ColoradoIncreased 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, ColoradoEstablishing 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 SurveillanceIn 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 from patients are sent to CDC for laboratory study.

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% Staph aureus Isolates Resistant to Methicillin

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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20

40

60

80

100

1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000

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Proportion of Staph aureus Nosocomial Infections Resistant to Oxacillin (MRSA) In

Intensive Care Unit Patients, 1989-2003

Source: NNIS System (2003 data are incomplete)

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10

20

30

40

50

60

70

1989 1991 1993 1995 1997 1999 2001 2003

Year

Percent Resistance

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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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ReadingEmily 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.