Epidemiology
: the true incidence of staphylococcal food poisoning is unknown for a
number of reasons, including poor responses from victims during interviews
with health officials; misdiagnosis of the illness, which may be symptomatically
similar to other types of food poisoning (such as vomiting caused by Bacillus
cereus toxin); inadequate collection of samples for laboratory analyses;
and improper laboratory examination. Of the bacterial pathogens causing
foodborne illnesses in the USA (127 outbreaks, 7082 cases recorded in 1983),
14 outbreaks, involving 1257 cases, were caused by S. aureus. These
outbreaks were followed by 11 outbreaks (1153 cases) in 1984, 14 outbreaks
(421 cases) in 1985, 7 outbreaks (250 cases) in 1986, and one reported
outbreak (100 cases) in 1987. 367 food-related outbreaks were registered
in USA during 1973 to 1987. Isolates of CA-MRSA were found in :
USA
Japan
Australia : these are truly community strains (they are sensitive to most
non-betalactam antibiotics). They were 1st described in 1986 as originating
from remote Western Australian settlements (Brisbane, Canberra, Melbourne,
and Sydney and cases were reported in Perth and Darwinref).
By MLST/SCCmec typing, there are currently 18 different (unrelated) community
MRSA clones throughout Australia, only a limited number of which are PVL
positive. In Western Australia, most MRSA isolates are non-multiresistant
and originate in the community. Epidemic MRSA is not endemic in any of
the state's hospitals unlike the hospitals in Eastern Australia. Initially,
these strains were the Western Samoan types, which appear to have been
imported from the Pacific Islands to NZ and then Australia. More recently,
the Queensland clone has emerged (the Ipswich strain). Australian strains
seemed multiply resistant (like hospital strains), whereas many of the
USA strains were resistant only to b-lactam
antimicrobials). ST30 isolates from Fiji include the "South West Pacific"
group of MRSAs (PVL positive, SCCmec Type IV).
Proteomics : 3 phagotypes
(I-III) and 1 non lysable group. Chapman medium+. Microcapsule
in
vivo (usually serotypes 5 or 8). Carothenoids production (=> "aureus")
depends on growth conditions.
Endotoxins :
some strains are capsulated.
p42protein A binds to :
CH3 domains of soluble IgG1, IgG2, Gm3
s+t+ IgG3 and IgG4, preventing
their binding to FcgRs or C1q. It may be used
in affinity chromatography
to purify IgGs or replace secondary Ab in immunological assays
p33a-toxin (= 3S + 12S subunits)
: pore-forming (7 protomers) but no hemolytic activity on human RBCs, toxic
effects on many cell kinds (keratinocytes, endothelial cells, monocytes,
macrophages, platelets and WBCs).
b-toxin : no hemolytic activity on human
RBCs. It acts as a sphingomyelinase.
g-toxin / leukotoxin : b-hemolytic
activity on human RBCs, macrophages, lymphocytes and PMNs. Agar-inhibited.
d-toxin : b-hemolytic
activity on human RBCs. It acts as a PL-C on PI in sebum allowing diffusion.
Leukotoxic.
Panton-Valentine leukocidin
(PVL) (F and S subunits) alters membrane permeability in macrophages
and PMNs and prevents cell motility => pus (sometimes a criterion for defining
virulent strains). PVL was produced by < 1.6% of strains of Staphylococcus
aureus found in the UK. The evidence that PVL is, in fact, the major
virulence factor in CA-MRSA is largely circumstantial, but there are substantial
links between PVL and virulence. It is possible that PVL is only a marker
for other virulence factors such as a gamma-hemolysin, enterotoxin, toxic
shock toxin, or other toxins similar to PVLref.
Until the advent of CA-MRSA, PVL had been found only in methicillin-susceptible
strains of S. aureus. Initially discovered by Van de Velde, PVL
was distinguished from hemolysins in 1932 by Panton and Valentine. In the
1930s, PVL-containing strains were associated with cutaneous and invasive
staphylococcal infections, as
is the case in the current CA-MRSA infection spectrum. Currently in
the USA, > 95% of infections are skin-related. Invasive infections such
as those referred to in the posting are, as stated, quite rare. PVL is
a bicomponent cytotoxin made up of class S and class F proteins which together
act to create holes in the cellular membrane. The toxin is referred to
as synergohymenotropic, as it consists of 2 proteins working synergistically
to puncture a membrane as a
octomeric unit
staphylococcal enterotoxins
(SEs) (bacteriophage-coded, in phagotype III, heat-stable => food-borne
toxinfections). Below 6-7°C toxin production is poor. They resist
30' at 100°C.
SE-A (produced by 75% of strains; bacteriophage encoded)
SE-B (encoded by chromosome, defective bacteriophage or episome).
It is considered by CDC as a category B biological
weapon.
SE-C1 (plasmid encoded)
SE-C2 (plasmid encoded)
SE-C3
SE-D (plasmid encoded)
SE-E (bacteriophage encoded)
SE-F / pyrogenic toxin / TSST-1 (only in some strains) => Th1
polarization
p24exfoliatin / epidermolysin / epidermolytic
or exfoliative toxin (ET) : an erythrogenic, epidermolytic, heat-stabile,
acid-labile exotoxin produced by certain strains of Staphylococcus aureus
ET-A (from phagotype II, chromosome coded)
ET-B (from non-II phagotypes, plasmid coded)
They are Ser proteases that destroy desmosomes between cells in the stratum
granulosum of epidermis without inducing inflammation and cause intraepidermal
separation to give rise to the clinical manifestations of the scalded skin
syndrome
A pool of virulence and antibiotic resistance genes in the form of large
mobile "accessory elements" is available for transfer between strains :
no single strain has all these elements, but the ease of exchange is probably
why the organism is so globally successful. A good deal of similarity and
a surprisingly high level of variation exist between epidemic MRSA (EMRSA)-16
clone (MRSA252) and an isolate of an invasive CA-MSSA (MSSA476). The development
of endemic populations and the occurrence of sudden outbreaks at previously
MRSA-free hospitals are more likely to be due to changes in the community
reservoir : although the proportion of people in the community carrying
MRSA is very low—about 1% - and the hospitals that have the big problems
with MRSA are geographically clustered, that's gradually going to spread
to the neighboring hospitals via the community reservoir and by direct
transfer between hospitals
Transmission
: found ...
over skin
in oropharynx of ill or healthy carriers (commensal in > 20% anterior nasal
vestibuli) : outbreaks have been associated with skin colonization or viral
upper respiratory tract infection (URI) in a phenomenon of airborne dispersal
called the "cloud" phenomenon. Nasal carriage is common among health
care workers, but outbreaks caused by such carriers are relatively uncommon.
Physiciansref
and nursesref
may become a "cloud adult", analogous to the "cloud babies"
who shed S. aureus into the air in association with viral URIsref1,
ref2,
ref3,
ref4,
ref5,
ref6.
in perineum
reservoir : Oryctolagus
cuniculus.
Growth at pH 4.2÷9.3 and T = 6.5÷46 °C. Community-associated
MRSA in horses and humans who work with horses. J Am Vet Med Assoc. 2005;226:
580-83. To evaluate the prevalence of nasal colonization with methicillin-resistant
Staphylococcus aureus (MRSA) in horses and
horse personnel, nasal swab specimens were collected from 972 horses
and 107 humans on equine farms in Ontario, Canada and New York state with
(targeted surveillance) and without (non-targeted surveillance) a history
of MRSA colonization or infection in horses during the preceding year.
Selective culture for MRSA was performed. Isolates were typed via pulsed-field
gel electrophoresis, and antibiograms were determined. MRSA was isolated
from 46 of 972 (4.7%) horses (0/581 via non-targeted surveillance and 46/391
-- 12% -- via targeted surveillance). Similarly, MRSA was isolated from
14 of 107 (13%) humans (2/41 -- 5% -- from non-targeted surveillance and
12/66 -- 18% -- from targeted surveillance). All isolates were subtypes
of Canadian epidemic MRSA-5, an uncommon strain in humans. All isolates
were resistant to at least one antimicrobial class in addition to beta-lactams.
On all farms with colonized horses, at least one human was colonized with
an indistinguishable subtype. For horses, residing on a farm that housed
> 20 horses was the only factor significantly associated with MRSA colonization.
For humans, regular contact with > 20 horses was the only identified risk
factor. Results confirm a reservoir of colonized horses on a variety of
farms in Ontario and New York and provide evidence that one MRSA strain
is predominantly involved in MRSA colonization in horses and humans that
work with horsesref.
MRSA is an emerging equine pathogen. To attempt to control nosocomial and
zoonotic transmission, an MRSA screening program was established for all
horses admitted to the Ontario Veterinary College Veterinary Teaching
Hospital, whereby nasal screening swabs were collected at admission, weekly
during hospitalization, and at discharge. MRSA was isolated from 120 (5.3%)
of 2283 horses: 61 (50.8%) at the time of admission, 53 (44.2%) during
hospitalization, and 6 from which the origin was unclear because an admission
swab had not been collected. Clinical infections attributable to MRSA were
present or developed in
14 (11.7%) of 120 horses. The overall rate of community-associated
colonization was 27 per 1000 admissions. Horses colonized at admission
were more likely to develop clinical MRSA infection than those not colonized
at admission (OR 38.9, 95% CI 9.49-160, P < 0.0001). The overall nosocomial
MRSA colonization incidence rate was 23 per 1000 admissions. The incidence
rate of nosocomial MRSA infection was at the rate of 1.8 per 1000 admissions,
with an incidence density of 0.88 per 1000 patient days. Administration
of ceftiofur or aminoglycosides during hospitalization was the only risk
factor associated with nosocomial MRSA
colonization. MRSA screening of horses admitted to a veterinary hospital
was useful for identification of community-associated and nosocomial colonization
and infection and for monitoring of infection control practicesref.
MRSA infection was identified in 2 horses treated at a veterinary hospital
in 2000, prompting a study of colonization rates of horses and associated
persons. 79 horses and 27 persons colonized or infected with MRSA were
identified from October 2000 to November 2002; most isolations occurred
in a 3-month period in 2002. 27 (34%) of the equine isolates were from
the veterinary hospital, while 41 (51%) were from one thoroughbred farm
in Ontario. 17 (63%) of 27 human isolates were from the veterinary hospital,
and 8 (30%) were from the thoroughbred farm. 13 (16%) horses and one (4%)
person were clinically infected. 96 percent of equine and 93% of human
isolates were subtypes of Canadian epidemic MRSA-5, spa type 7, and possessed
SCCmecIV. All tested isolates from clinical infections were negative for
the Panton-Valentine leukocidin genesref.
Equine MRSA infection may be an important emerging zoonotic and veterinary
disease. Europe has also reported this findingref => clinical manifestations :
erysipela
after 6-7 days incubation : sometimes relapsing even after years.
botryomycosis : a chronic purulent granulomatous
bacterial infection usually caused by Staphylococcus aureus, originally
thought to be due to fungi called “botryomycetes,” characterized by lesions
containing sulfur granules composed of a central mass of bacteria
surrounded by a capsule, and histologically resembling actinomycosis or
mycetoma. Human infection is usually localized to the skin but may involve
other organs such as the viscera and lymph nodes, especially in debilitated
patients; infection in domestic animals most often occurs as chronic, localized
or spreading abscesses of the skin.
Laboratory examinations : Bollinger's
granules (small, yellowish white granules in mulberry-like masses,
containing micrococci, seen in the granulation tissue of botryomycosis)
In cases where the food may have been treated to kill the staphylococci,
as in pasteurization or heating, direct microscopic observation of the
food may be an aid in the diagnosis. A number of serological methods for
determining the enterotoxigenicity of S. aureus isolated from foods,
as well as methods for the separation and detection of toxins in foods,
have been developed, and used successfully, to aid in the diagnosis of
the illness. Phage typing may also be useful when viable staphylococci
can be isolated from the incriminated food, from victims, and from suspected
carriers, such as food handlers. the onset of symptoms in staphylococcal
food poisoning is usually rapid, and, in many cases, acute, depending on
individual susceptibility to the toxin, the amount of contaminated food
eaten, the amount of toxin in the food ingested, and the general health
of the victim. Some individuals may not always demonstrate all the symptoms
associated with the illness. In more severe cases, headache, muscle cramping,
and transient changes in blood pressure and pulse rate may occur. Recovery
generally takes 2 days. However, it is not unusual for complete recovery
to take 3 days and sometimes longer in severe cases. A toxin dose <
1.0 mg in contaminated food will produce symptoms
of staphylococcal intoxication. This toxin level is reached when S.
aureus populations exceed 100 000 per gram. Foods that are frequently
incriminated in staphylococcal food poisoning include long conserved meat
and meat products (usually with high salt concentration that inhibits growth
of symbiontic bacteria); poultry and egg products; salads such as egg,
tuna, chicken, potato, and macaroni; bakery products such as cream-filled
pastries, cream pies, and chocolate eclairs; sandwich fillings; and milk
and dairy products. Foods that require considerable handling during preparation,
and that are kept at slightly elevated temperatures after preparation,
are frequently involved in staphylococcal food poisoning.
Laboratory
examinations : direct diagnosis.
Therapy : ==plamid
b-lactamase==>
broad-spectrum b-lactam resistance (penicillin-resistant
Staphylococcus
aureus (PRSA)), but still sensitive to methicillin
(methicillin-sensitive Staphylococcus aureus (MSSA)) > oxacillin
> dicloxacillin
==point mutation in PBP==>
methicillin-resistant Staphylococcus aureus
(MRSA) (90% of nosocomial infections and 20-30% of communitary ones
: outbreaks of community-acquired MRSA (CA-MRSA) occur in various
populations, including children attending child care, prison inmates, men
who have sex with men, players of competitive sports (wrestlers and rugby
and football players due to skin trauma and contact with lesions of other
players; but also those sports that involve little skin-to-skin contact
among players, such as fencing, due to sharing equipment or personal items
and protective clothing that can be hot and might chafe skin, resulting
in abrasions and lacerations) : in CA-MRSA strains, the mec IV gene,
which causes resistance to all b-lactams (antistaphylococcal
penicillins,
cephalosporins)
like the hospital strains by a change in penicillin binding proteins, is
contained in a gene cassette substantially smaller than any of the 3 associated
with hospital strains. Panton-Valentine
leucocidin (PVL) appears to be frequently if not uniformly associated
with CA-MRSA strains, as compared with hospital-acquired MRSAs,
which could produce increased virulence in CA-MRSA. Although CA-MRSA is
often referred to as a "superbug", unlike hospital strains, CA-MRSA isolates
are often resistant only to monobactams
and retain sensitivity to other agents including clindamycin,
macrolides,
minocycline,
rifampin,
fusidic
acid,
quinolones
and vancomycin.
MRSA has mortality = 21% vs. 8% in MSSAref.
Most clinical isolates of S aureus are now methicillin-resistant
in the UK, which has one of the highest rates of MRSA in the world. The
number of deaths attributed to MRSA infection increased each year from
1993 to 2003, according to figures compiled from death certificates. Between
2002 and 2003, mentions of MRSA on death certificates increased by 19%,
although laboratory reports of MRSA show an increase of only 7%, indicating
that improved reporting might underlie some of the rise. Although usually
involving the skin as cutaneous abscesses -- invasive, life-threatening
infection can occur. One article reports on the epidemiology of the infection
in 3 cities in the USA (Atlanta, Baltimore, and Atlanta) and found incidence
rates of 18.0 to 25.7 cases per 100,000 annually with a 23% hospitalization
rateref.
The other reported on necrotizing fasciitis/myositis caused by CA-MRSAref
and found 14 cases among the 843 CA-MRSA infections. The letters reported
on 4 cases of pyomyositis from CA-MRSA in Washington DCref
and laboratory spread of the organism to a microbiologist in Franceref.
USA300, the predominant epidemic clone in numerous outbreaks in closed
communities in the USA, is also increasingly seen in Europe. International
travel and the increasing trend of training or working abroad among health
care workers probably contribute to its global spreadref.
vancomycin- or glycopeptide-intermediate Staphylococcus
aureus (VISA / GISA)
vancomycin-resistant
Staphylococcus
aureus (VRSA)ref1,
ref2
(MIC >32 mg/mL) (e.g. via resistance plasmid
acquired from Enterococcus faecalis,
co-infectant in diabetic ulcers) : first isolated in 1996 in a Japan patient
patient who had contracted a post-operative wound infection. Subsequent
isolation of several VRSA strains from USA (3 cases since 2002ref1,
ref2
: Michigan, Pennsylvania and New Yorkref1,
ref2),
France, Korea, South Africa, and Brazil has confirmed that emergence of
vancomycin resistance is a global issue. Hetero-VRSA frequently
generate VRSA upon exposure to vancomycin. Vancomycin resistance is acquired
by mutation and thickening of cell wall due to accumulation of excess amounts
of peptidoglycan. The isolate was susceptible to chloramphenicol,
linezolid,
minocycline,
pristinamycin
(quinupristin + dalfopristin),
rifampin,
and cotrimoxazole.
Although the New York isolate contained the vanA resistance gene,
the vancomycin MIC of the isolate appeared low when tested initially by
an automated method. Additional testing at CDC indicated that Microscan
and Vitek (bioMerieux, Hazelwood, Missouri) testing panels and cards available
in the US did not detect vancomycin resistance in this VRSA isolate. Consequently,
additional VRSA infections might have occurred but were undetected by laboratories
using automated methods. Potential VRSA isolates should be saved for confirmatory
testing, and clinical microbiology laboratories must ensure that they are
using susceptibility testing methods that will detect VRSA. The most accurate
form of vancomycin susceptibility testing for staphylococci is a nonautomated
MIC method (for example, broth microdilution, agar dilution, or agar-gradient
diffusion) in which the organisms are incubated for a full 24 hours before
reading results. Therefore, when performing automated susceptibility testing
of S. aureus strains, particularly MRSA, laboratories should include
a vancomycin-agar screening plate containing 6 mg/mL
of vancomycin and examine the plate for growth after 24 hour incubation.
CDC recommends contact precautions when caring for patients with these
infections, including 1) placing the patient in a private room; 2) wearing
gloves and a gown during patient contact; 3) washing hands after contact
with the patient, infectious body tissues, or fluids; and 4) limiting the
use of patient-care items to individual patients. In addition, the number
of people caring for a patient with VRSA or VISA should be minimized (for
example, by assigning dedicated staff to care for the patient). Isolation
of S. aureus with confirmed or presumptive vancomycin resistance
should be reported immediately through state and local health departments.
VRSA is already developing resistance to linezolid
and pristinamycin (quinupristin
+ dalfopristin),
and is expected to develop immunity to daptomycin
=> need for antibiogram.
Salicylic acid
activates the stress response gene sigB to reduce the expression
of the a-hemolysin gene promoter, hla,
and the fibronectin-binding protein (FnBP) gene promoter, fnbA,
2 important virulence factors
Prevention :
resistant to antiseptics and disinfectants, such as quaternary ammonium
compounds. Protect wounds, use goloves, do not cough or sneeze over foods.
Follow correct rules of cooling and refrigeration.
Web resources
: Network for Antimicrobial
Resistance in Staphycoccus aureus (NARSA)
to purify IgGs or replace secondary Ab in immunological assays
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