Current Issues in Foodborne Illness Caused by Staphylococcus aureus
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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. ...

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

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  • Folliculitis – inflammation of a follicle or follicles; used ordinarily in reference to hair follicles but sometimes in relation to follicles of other kinds. Impetigo circinate - impetigo of bullous (staphylococcal) type, in which several lesions may become confluent or in which a large bulla ruptures, leaving circinate, raw, often crusted lesions. Confluent yellow crusted papules, vesicles, and crusts Comments: A blistering crusted eruption continued to spread over the face of this healthy 1-year-old boy who was treated with a topical cream by a local quack. He cleared when he was started on an oral antistaphylococcal antibiotic. Bullous impetigo – a staphylococcal skin infection, occurring in infants and children, or rarely in sweaty flexures of adults, and characterized by rapid formation of fragile bullae up to 2 or 3 cm. in diameter, which break early and heal centrally, leaving crusted arcuate or annular erosions. Toxic epidermal necrolysis – an exfoliative skin disease in which erythema rapidly spreads over the entire body, followed by the formation of large flaccid bullae and later by skin that appears scalded and separates from the body in sheets, much as in a second degree burn.
  • Osteomyelitis – patchy decalcification and periosteal reaction with deposition of new bone. Pneumonia – The radiograph of the child ’s chest shows collapse of the lung on the right and marked displacement of the mediastinum to the left as a result of a pyopneumothorax (a collection of pus and air or gas in the pleural cavity) on the right side.
  • Introduction of every new class of antimicrobial drug is followed by emergence of resistance. By the 1950s, penicillin-resistant S. aureus were a major threat in hospitals and nurseries. By the 1970s, methicillin-resistant S. aureus had emerged and spread, a phenomenon that encouraged widespread use of vancomycin. Meticillin (INN, BAN) or methicillin (USAN) is a narrow spectrum beta-lactam antibiotic of the penicillin class. It was developed by Beecham in 1959. It was previously used to treat infections caused by susceptible Gram-positive bacteria, particularly beta-lactamase-producing organisms such as Staphylococcus aureus that would otherwise be resistant to most penicillins, but is no longer clinically used. Its role in therapy has been largely replaced by flucloxacillin and dicloxacillin, however the term methicillin-resistant Staphylococcus aureus (MRSA) continues to be used to describe Staphylococcus aureus strains resistant to all penicillins. Methicillin is no longer manufactured because the more stable and similar penicillins such as oxacillin (used for clinical antimicrobial susceptibility testing), flucloxacillin and dicloxacillin are used medically. In the 1990s, vancomycin-resistant enterococci emerged and rapidly spread; most of these organisms are resistant to other traditional first-line antimicrobial drugs. At the end of the century, the first S. aureus strains with reduced susceptibility to vancomycin were documented, prompting concerns that S. aureus fully resistant to vancomycin may be on the horizon. In June 2002 the first case of vancomycin-resistant S. aureus was detected. Early preparations of vancomycin were both nephrotoxic and neurotoxic. Vancomycin preparations today are purer so toxicity is now uncommon but serum levels and renal function have to be monitored and the appropriate dose administered.
  • Figure 1 . Mortality rates of staphylococcal bacteraemia over time. Data taken from Rubin et al ., 1 Cosgrove et al . 3 and Fridkin et al . 6
  • Cellulitis is a skin infection caused by bacteria. Normally, your skin helps protect you from infection. But if you have a cut, sore, or insect bite, bacteria can get into the skin and spread to deeper tissues. If it is not treated with antibiotics, the infection can spread to the blood or lymph nodes. This can be deadly. Some people can get cellulitis without having a break in the skin. These include older adults and people who have diabetes or a weak immune system. These people are also more likely to develop dangerous problems from cellulitis. And they are more likely to get cellulitis again.
  • In the United States, sporadic illnesses caused by B. cereus , C. perfringens , and S. aureus are not reportable (Bennett et al., Clin. Infect. Dis. 2013). Thus estimates of the annual number of illnesses and descriptive epidemiology rely on illnesses that occur in outbreaks. Data reported to a national outbreak surveillance system provides a unique opportunity to examine the epidemiologic and clinical characteristics of outbreaks caused by these pathogens. A foodborne disease outbreak is defined as the occurrence of ≥2 similar illnesses resulting from the ingestion of a common food. 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 tempterature during hot holding (33%), and inadequate cold holding temperature (22%).
  • The SE-like proteins either lack emetic activity or have not been tested. Several, including SE-l H, Se-l K, Se-l L, and Se-l Q have been tested and are nonemetic; the remaining SE-l proteins have not been tested. Recent reports of CNS of animal origin (

Current Issues in Foodborne Illness Caused by Staphylococcus aureus Current Issues in Foodborne Illness Caused by Staphylococcus aureus Presentation Transcript

  • 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.
  • 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?
  • 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)
  • 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- )
  • 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.
  • 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.
  • 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.
  • Toxic epidermal necrolysisBullous impetigo Folliculitis Impetigo circinate Clinical manifestations include —
  • Necrosis of the gum tissue in an AIDS patient Toxic shock syndrome - Fatal infection with cutaneous and soft tissue involvement Clinical manifestations include —
  • Bacterial endocarditis with characteristic vegetations caused by growth of S. aureus on the heart valves. Clinical manifestations include —
  • Osteomyelitis Staphylococcal Pneumonia Clinical manifestations include —
  • 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!)
  • 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)
  • 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)
  • 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
  • A new “kid in town,” community-associated (CA) MRSA
  • Outbreaks of CA-MRSA have occurred among: Athletic teams - football, wrestling, rugby, fencing Correctional facilities Military barracks Daycares and schools Dormitories
  • 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)
  • A new “kid in town,” community-associated (CA) MRSA
  •  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
  • Clinical Presentation of CA-MRSAClinical Presentation of CA-MRSA Cellulitis 75 - 80% of CA-MRSA infections are of the skin and soft tissues
  • 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
  • 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
  • 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
  • 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.
  • 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!
  •  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%)
  • 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!
  • 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)
  • Mom says, “Wash your hands!!!