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Current Issues in Foodborne Illness Caused by Staphylococcus aureus

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Presented at 2013 Arkansas Association for Food Protection annual conference.

Mark E. Hart, Ph.D.
Division of Microbiology
National Center for Toxicological Research
Food and Drug Administration

Published in: Health & Medicine, Technology
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Current Issues in Foodborne Illness Caused by Staphylococcus aureus

  1. 1. Mark E. Hart, Ph.D. Division of Microbiology National Center for Toxicological Research Food and Drug Administration Current Issues in Foodborne Illness Caused by Staphylococcus aureus The views presented in this presentation do not necessarily reflect those of the United States Food and Drug Administration.
  2. 2. Presentation Outline  Introduce you to Staphylococcus aureus  General characteristics  Clinical picture  Antibiotic resistance  Virulence factors  Staphylococcus and foodborne illness  Is it a problem and why?  Is it an infection or an intoxication?
  3. 3. Staphylococcus  Gram-positive coccus (0.7 - 1.2 µm, dia.) with a marked tendency to form clusters (Gk., staphyle - “bunch of grapes”)  Staphylococcus are among the hardiest of the non-sporeforming bacteria Heat resistant (80°C for 1 hour) Salt tolerant (NaCl @ 2.5 M)
  4. 4. Staphylococcus Catalase test Coagulase test There are greater than 50 recognized species and subspecies of Staphylococcus but three are of major importance with respect to human infections; S. aureus (Coag+ ) S. epidermidis (Coag- ) S. saprophyticus (Coag- ) There are greater than 50 recognized species and subspecies of Staphylococcus but three are of major importance with respect to human infections; S. aureus (Coag+ ) S. epidermidis (Coag- ) S. saprophyticus (Coag- )
  5. 5. Too close for comfort!Too close for comfort!  Estimates suggest thatEstimates suggest that 30 - 40%30 - 40% of the humanof the human population arepopulation are asymptomaticallyasymptomatically colonized at any givencolonized at any given time on one or more oftime on one or more of their mucosal surfacestheir mucosal surfaces  Up toUp to 70%70% of people mayof people may be transiently colonizedbe transiently colonized  Anterior nares are theAnterior nares are the most common site ofmost common site of colonizationcolonization  Approximately 90% of health-care workers carry the organism People who are colonized have a higher risk of infection than noncolonized persons.
  6. 6. Predisposing Conditions  The very young and the very old  Persons with traumatic or operative wounds, burns, or other serious skin lesions  Persons with chronic debilitating disorders such as diabetes mellitus, cancer, or cystic fibrosis It is therefore, not surprising that serious staphylococcal disease is most often the result of hospital-acquired infections.
  7. 7. Staph – pathogen extraordinaire!  Each year an estimated 500,000 patients in American hospitals contract staphylococci infections  Most common cause of endocarditis nosocomial infection skin and soft tissues cellulitis, osteomyelitis, and septic arthritis  Common cause of bacteremia, nosocomial pneumonia, foodborne disease, implant infection, abscess, etc  Causes illnesses that range from minor skin infections and abscesses to life-threatening diseases such as pneumonia, meningitis, bone and joint infections and infections of the heart and bloodstream.  Toxemias such as food poisoning, scalded skin syndrome, and toxic shock syndrome.
  8. 8. Toxic epidermal necrolysisBullous impetigo Folliculitis Impetigo circinate Clinical manifestations include —
  9. 9. Necrosis of the gum tissue in an AIDS patient Toxic shock syndrome - Fatal infection with cutaneous and soft tissue involvement Clinical manifestations include —
  10. 10. Bacterial endocarditis with characteristic vegetations caused by growth of S. aureus on the heart valves. Clinical manifestations include —
  11. 11. Osteomyelitis Staphylococcal Pneumonia Clinical manifestations include —
  12. 12. So…what makes S. aureus such a “good” pathogen? Antibiotic resistance Hospital-acquired (HA) methicillin resistant Staphylococcus aureus (MRSA) endemic in most hospitals The emergence of a community-associated (CA) MRSA not seen before 2000 The emergence of livestock-associated (LA) MRSA Capacity to produce a wide variety of virulence factors (up to 40 and still growing!)
  13. 13. Evolution of Drug Resistance inEvolution of Drug Resistance in Staphylococcus aureusStaphylococcus aureus S. aureusS. aureus Penicillin-resistant S. aureus Penicillin-resistant S. aureus 1950s 1960s Methicillin (1959)Penicillin (1941) 1997 2002 Vancomycin-resistant S. aureus (VRSA) Vancomycin-resistant S. aureus (VRSA) Methicillin-resistant S. aureus (MRSA) Methicillin-resistant S. aureus (MRSA) Vancomycin intermediate-resistant S. aureus (VISA or GISA) Vancomycin (1957) MRSA first reported in UK (1961) followed by US (1968)
  14. 14. Dancer, S. J. J. Antimicrob. Chemother. 2008 61:246-253; doi:10.1093/jac/dkm465 Mortality rates of staphylococcal bacteraemia over time (1941) (1959) Vancomycin (1957)
  15. 15. Objective: To describe the incidence and distribution of invasive MRSA disease in 9 US communities and to estimate the burden of invasive MRSA infection in the United States in 2005. Conclusions: It is estimated after adjusting for age, race, and sex to the US population, that 18,650 in-hospital deaths occurred in 2005 as a result of invasive MRSA infections. By comparison, that same year, roughly 16,000 people in the US died from AIDS. How serious are MRSA infections? JAMA, October 17, 2007 - Vol. 298, No. 15
  16. 16. A new “kid in town,” community-associated (CA) MRSA
  17. 17. Outbreaks of CA-MRSA have occurred among: Athletic teams - football, wrestling, rugby, fencing Correctional facilities Military barracks Daycares and schools Dormitories
  18. 18. Year Sport No. infected (attack rate) Infection and transmission factors 19941 High School Wrestling 6 (19%) Close contact 20002 College Football 10 (14%) Close contact, shared items, skin trauma 20033 College Football 10 (10%) Close contact, skin trauma, poor hygiene 20034 Pro Football 5 (9%) Close contact, skin trauma, poor hygiene 20035 College Football 11 (10%) Close contact, shared items, skin trauma 1 Lindenmayer JM, et al. Arch Intern Med 1998;158:895-9. 2 Kainer MA. MRSA among college football team. (CDC unpublished) 3 Begier EM, et al. Clin Infect Dis. 2004;39:1446-53. 4 Kazakova SV, et al. New Engl J Med. 2005;352:468-75. 5 Nguyen DM, et al.Emerg Infect Dis. 2005;11:526-532. MRSA Outbreaks among U.S. Sports Teams (1994-2004)
  19. 19. A new “kid in town,” community-associated (CA) MRSA
  20. 20.  Survey of 11 EDs throughout US in Aug 2004Survey of 11 EDs throughout US in Aug 2004  422 patients with skin & soft tissue infections422 patients with skin & soft tissue infections  75% (320/422) caused by75% (320/422) caused by S. aureusS. aureus  59% were MRSA (15% - 74%) and of these 97% were59% were MRSA (15% - 74%) and of these 97% were pulse-field type USA-300pulse-field type USA-300 KC -KC - 74%74% Atlanta - 72%Atlanta - 72% Charlotte, NC - 68%Charlotte, NC - 68% New Orleans - 67%New Orleans - 67% Albuquerque - 60%Albuquerque - 60% Phoenix - 60%Phoenix - 60%  Philadelphia - 55%Philadelphia - 55%  Portland, OR - 54%Portland, OR - 54%  Los Angeles - 51%Los Angeles - 51%  Minneapolis - 39%Minneapolis - 39%  New York -New York - 15%15% Prevalence of CA-MRSAPrevalence of CA-MRSA
  21. 21. Clinical Presentation of CA-MRSAClinical Presentation of CA-MRSA Cellulitis 75 - 80% of CA-MRSA infections are of the skin and soft tissues
  22. 22. A new “kid in town,” community-associated (CA) MRSA • Numerous community outbreaks by predominantly two PFGE types - USA300 and USA400 • Most notably in  health care settings in Canada, Native Americans, children in day care, and a maternity ward in New York (USA400)  children, correctional facility inmates, participants in sports teams, men who have sex with men, and military recruits (USA300) • CA-MRSA is not an archetype to HA-MRSA • Fatal infections in otherwise healthy individuals (USA400)  Four pediatric deaths – Minnesota and North Dakota, 1997-1999. MMWR 1999, 48:707-710 • These isolates all produced Panton-Valentine leukocidin (PVL) • Genomic analysis of one of these isolates (MW2) revealed 19 novel genes for virulence factors as compared to 5 hospital strains • Carry the SCCmec type IVa mobile element • Susceptible to non β-lactam antibiotics other than erythromycin
  23. 23. Extracellular Proteins of S. aureus (toxins, enzymes, and cell wall-associated proteins) • Coagulase • Enterotoxins • Hemolysins (α-δ) • Lipase • Toxic shock syndrome toxin • Leukocidin • Collagenase • Hyaluronidase • Acid phosphatase • Endopeptidase • Metalloprotease • Penicillinase • Microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) • Nuclease • Exfoliative toxins (A, B) • Staphylokinase • Phospholipase • Pyrogenic exotoxin • Fibrinolysin • Elastase • Protein A • Alkaline phosphatase • Serine protease • Thiol protease • Capsule and biofilm formation Includes cell wall-associated binding proteins for collagen, fibrinogen, fibronectin, and bone-sialo protein
  24. 24. What about StaphylococcalWhat about Staphylococcal Food Poisoning?Food Poisoning? Taken from Gladwin and Trattler,Taken from Gladwin and Trattler, Clinical microbiology madeClinical microbiology made ridiculously simpleridiculously simple, Edition 2 (1999), MedMaster Inc., Miami, Edition 2 (1999), MedMaster Inc., Miami
  25. 25. It is estimated (Scallan et al., Emerg. Infect. Dis., 2011)It is estimated (Scallan et al., Emerg. Infect. Dis., 2011) that of the 48 million foodborne illnesses (1 in 6that of the 48 million foodborne illnesses (1 in 6 Americans) that occur in the United States each year, 9.4Americans) that occur in the United States each year, 9.4 million are caused by known pathogens.million are caused by known pathogens. Is staphylococcal foodborne illness a problem?Is staphylococcal foodborne illness a problem? 1998 – 2008 surveillance data recorded 6,795 outbreak-1998 – 2008 surveillance data recorded 6,795 outbreak- associated illnesses resulting in 333 hospitalizations, and 3associated illnesses resulting in 333 hospitalizations, and 3 deaths rankingdeaths ranking S. aureusS. aureus 44thth behind norovirus,behind norovirus, SalmonellaSalmonella,, andand Clostridium perfringens.Clostridium perfringens.
  26. 26. Infection or intoxication?  Staphylococcal food poisoning (SFP) is caused byStaphylococcal food poisoning (SFP) is caused by preformed toxin, known aspreformed toxin, known as staphylococcal enterotoxinsstaphylococcal enterotoxins (SE), production in improperly handled foods,(SE), production in improperly handled foods, therefore, SFP is a toxemia!therefore, SFP is a toxemia!  Utilizing the MMWR surveillance report (06/28/2013)Utilizing the MMWR surveillance report (06/28/2013) for 1998 – 2008 which recorded 458 outbreaksfor 1998 – 2008 which recorded 458 outbreaks consisting of 6,741 confirmed and suspected illnesses,consisting of 6,741 confirmed and suspected illnesses,  illnesses most often occurred in persons ≥ 20 yearsillnesses most often occurred in persons ≥ 20 years of age (85%)of age (85%)  had a median incubation period of 4 hourshad a median incubation period of 4 hours  diarrhea was commonly reported (≥ 86%)diarrhea was commonly reported (≥ 86%)  abdominal cramps (median of ≥ 61%) and vomitingabdominal cramps (median of ≥ 61%) and vomiting (median of 87%)were reported and(median of 87%)were reported and  median duration of illness was 15 hoursmedian duration of illness was 15 hours  How much toxin does it take?How much toxin does it take? In humans and nonhuman primates, 24- to 48-h episodes of retching, vomiting, and diarrhea every 15 to 30 minutes without fever resulted when nanogram quantities of SEs were ingested!
  27. 27.  Meat or poultry dishes were the most commonMeat or poultry dishes were the most common foods reported accounting for 55% of allfoods reported accounting for 55% of all S. aureusS. aureus outbreaks; primarily pork of the ham variety.outbreaks; primarily pork of the ham variety.  Foods implicated were most often prepared in aFoods implicated were most often prepared in a restaurant or deli (44%)restaurant or deli (44%)  The most common factors contributing to theThe most common factors contributing to the occurrence of an outbreak were errors in foodoccurrence of an outbreak were errors in food processing and preparation and contamination by aprocessing and preparation and contamination by a food workerfood worker Infection or intoxication? (cont) Reported errors included – allowing foods to remain at room or outdoor temperature for several hours (58%) insufficient time or temperature during reheating (57%) slow cooling of prepared foods (44%) insufficient time or temperature during the initial cooking process (40%) preparing foods more than one-half day in advance of serving (33%) insufficient time or temperature during hot holding (33%) and inadequate cold holding temperature (22%)
  28. 28. Characteristics of staphylococcal enterotoxins (SE) Molecular sizes ranging from 22 – 29 kDa Unusually resistant to heat (biologically active despite boiling for 1 h) Generally resistant to proteolysis (trypsin and pepsin) and acids (such as stomach acid) and slightly resistant to desiccation. They are secreted by all human-pathogenic S. aureus Currently S. aureus strains can secret from 1 to 23 of at least 23 serologically distinct enterotoxins SEs are defined by emetic activity when ingested by humans or when given orally to nonhuman primates Almost all of the SEs are encoded on variable genetic DNA elements Note: Schlievert et al., Clin. Infect. Dis. (2008) reports a strain that expresses all 23!
  29. 29. Over half of theOver half of the SEs are encodedSEs are encoded on mobileon mobile genetic elementsgenetic elements (plasmid,(plasmid, bacteriophages,bacteriophages, transposons, andtransposons, and pathogenicitypathogenicity islands)islands)
  30. 30. Mom says, “Wash your hands!!!

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