EPIDEMIOLOGY 200B Methods II – Prediction and Validity Scott P. Layne, MD

1. EPIDEMIOLOGY 200BMethods II – Prediction and ValidityScott P. Layne, MD

2. PART 2Staphylococcus aureus March 2010

3. Infectious Disease Agents Bacteria Gram Positive --> Staphylococcus sp. Gram Negative Zoonotic Vector Bourne Anaerobic Acid Fast Spirochetes Chlymidia Mycoplasma / Ureaplasma Viruses Prions Fungi Parasites

4. Colonization vs Infection External Host Microbe

5. Microbe Cell wall constituents Enzymes Toxins Direct destruction of tissue

6. Host Adhesion Invasion Chemotaxis (cell movement) Opsonization (C3b, IgG) Intracellular killing Genetics (HLA makeup) Integument Trauma, Foreign Bodies

7. External Contamination Exposure Traffic

8. 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

9. 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

10. Staph Related Diseases Staphylococcus epidermidis Adult bacteremia Sub-acute endocarditis Neonatal bactermia Staphylococcus saprophyticus Urinary Tract Infections

11. Skin Infections Folliculitis Boils Carbuncles Cellulitis Scalded skin syndrome Burn infections Wound infections

13. 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

14. Bioterrorism Potential ? Effects of inhaled Staph Enterotoxin B in lung Source: Textbook of Military Medicine

15. Toxic Shock Syndrome Menstrual vs Non-menstrual cases Hyperabsobable tampons Criteria T > 38.9 BP < 90 Rash with desquamation Rule out RMSF, Leptospirosis, Measles

16. 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

17. 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

18. Domains Diseases

19. Antibiotics Toxins Diseases

20. Antibiotic Testing Minimum Inhibitory Concentration (MIC) Minimum Bactericidal Concentration (MBC)

21. Antibiotic Biotypes Lower resistance Methicillin Sensitive Staph aureus (MSSA) Rx: Oxacillin Cephalexin Clindamycin Vancomycin 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

22. 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)

23. Toxins

24. 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)

26. Connection / Mystery ? Hospital Community More resistant to antibiotics More virulent from toxins

27. 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

28. 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

29. ICU: High Risk for MRSA

30. 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

31. 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

32. 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

33. Connection ? Hospital Community More resistant to antibiotics More virulent from toxins

34. 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

35. 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

36. Outbreak Reports Correctional facilities Athletic teams Men who have sex with men (MSM) Fire stations

37. Football Team Infectious Disease News December 2004

38. 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

39. 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

40. 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

41. 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

42. 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.

43. 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

44. 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.

46. % 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.

47. Proportion of Staph aureus Nosocomial Infections Resistant to Oxacillin (MRSA) In Intensive Care Unit Patients, 1989-2003 Source: NNIS System (2003 data are incomplete)

48. 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

49. 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.