THE THE STAPHYLOCOCCISTAPHYLOCOCCI

FEBRUARY 6, 2008FEBRUARY 6, 2008

CASE 1CASE 1

M.M., 17 YEAR OLD FEMALEM.M., 17 YEAR OLD FEMALE CHIEF COMPLAINT: FEVER CHIEF COMPLAINT: FEVER HPI: 2 DAYS PTA, SHE STARTED HPI: 2 DAYS PTA, SHE STARTED

EXPERIENCING HIGH-GRADE FEVER, WITH EXPERIENCING HIGH-GRADE FEVER, WITH CHILLS AND BODY MALAISE.CHILLS AND BODY MALAISE.

FOOD INTAKE WAS LIMITED, DUE TO FOOD INTAKE WAS LIMITED, DUE TO NAUSEA NAD VOMITING. SHE NOTICED NAUSEA NAD VOMITING. SHE NOTICED RASHES ON HER ABDOMEN, AND HER RASHES ON HER ABDOMEN, AND HER PERINEAL AREA WAS PAINFUL.PERINEAL AREA WAS PAINFUL.

MENSTRUAL HISTORY: SHE IS ON DAY MENSTRUAL HISTORY: SHE IS ON DAY 4 OF HER CYCLE.4 OF HER CYCLE.

PERTINENT PE FINDINGSPERTINENT PE FINDINGS

BP: 80/50 mmHgBP: 80/50 mmHg

PR:120 /MINPR:120 /MIN

T: 103 FT: 103 F BUCCAL MUCOSA AND TONGUE WERE BUCCAL MUCOSA AND TONGUE WERE

CONGESTEDCONGESTED

ERYTHEMATOUS MACULOPAPULAR ERYTHEMATOUS MACULOPAPULAR RASH SEEN ON HER ABDOMEN , RASH SEEN ON HER ABDOMEN , LOWER EXTREMITIES AND HANDSLOWER EXTREMITIES AND HANDS

GYNE EXAM SHOWED HYPEREMIC GYNE EXAM SHOWED HYPEREMIC VAGINAL WALLS, (+) TENDERNESSVAGINAL WALLS, (+) TENDERNESS

REST OF THE PE WAS NORMALREST OF THE PE WAS NORMAL

IMPRESSION?IMPRESSION?

Gram-positiveGram-positive cluster-forming coccus cluster-forming coccus

NonmotileNonmotile nonsporeforming nonsporeforming facultative anaerobe facultative anaerobe

fermentation of glucose produces mainly lactic acid fermentation of glucose produces mainly lactic acid

catalase positive catalase positive

coagulase positive coagulase positive

golden yellow colony on agar (S.aureus)golden yellow colony on agar (S.aureus) White colonies (S. epidermidis/ albicans)White colonies (S. epidermidis/ albicans)

normal flora of humans found on nasal passages, skin normal flora of humans found on nasal passages, skin and mucous membranes and mucous membranes

S. aureusS. aureus

STAPHYLOCOCCUSSTAPHYLOCOCCUS

MSAMSA

STAPH INFECTIONSSTAPH INFECTIONS suppurative infections suppurative infections superficial skin lesions such as boils, styes and superficial skin lesions such as boils, styes and

furunculosisfurunculosis PneumoniaPneumonia MastitisMastitis PhlebitisPhlebitis MeningitisMeningitis urinary tract infectionsurinary tract infections deep-seated infections, such as osteomyelitis and deep-seated infections, such as osteomyelitis and

endocarditis. endocarditis.

VIRULENCE FACTORSVIRULENCE FACTORS

1) surface proteins that promote colonization 1) surface proteins that promote colonization of host tissues; of host tissues;

(2) invasins that promote bacterial spread in (2) invasins that promote bacterial spread in tissues (leukocidin, kinases, hyaluronidase); tissues (leukocidin, kinases, hyaluronidase);

(3) surface factors that inhibit phagocytic (3) surface factors that inhibit phagocytic engulfment (capsule, Protein A); engulfment (capsule, Protein A);

(4) biochemical properties that enhance their (4) biochemical properties that enhance their survival in phagocytes (carotenoids, catalase survival in phagocytes (carotenoids, catalase production); production);

VIRULENCE FACTORSVIRULENCE FACTORS

(5) immunological disguises (Protein A, coagulase, (5) immunological disguises (Protein A, coagulase, clotting factor); and clotting factor); and

(6) membrane-damaging toxins that lyse eukaryotic (6) membrane-damaging toxins that lyse eukaryotic cell membranes (hemolysins, leukotoxin, leukocidin; cell membranes (hemolysins, leukotoxin, leukocidin;

(7) exotoxins that damage host tissues or otherwise (7) exotoxins that damage host tissues or otherwise provoke symptoms of disease (, TSST)provoke symptoms of disease (, TSST)

(8) inherent and acquired resistance to antimicrobial (8) inherent and acquired resistance to antimicrobial agents.agents.

ALPHA-TOXINALPHA-TOXIN

most potent membrane-damaging toxin of S. most potent membrane-damaging toxin of S. aureus Iaureus I

binds to the membrane of susceptible cellsbinds to the membrane of susceptible cells Toxin subunits create a central pore through Toxin subunits create a central pore through

which cellular contents leakwhich cellular contents leak platelets and monocytesplatelets and monocytes Septic shockSeptic shock

BETA-TOXINBETA-TOXIN

sphingomyelinasesphingomyelinase damages membranes rich in this lipiddamages membranes rich in this lipid classical test for ß-toxin is lysis of sheep classical test for ß-toxin is lysis of sheep

erythrocyteserythrocytes majority of human isolates of S. aureus do not majority of human isolates of S. aureus do not

express ß-toxinexpress ß-toxin

LEUKOCIDINLEUKOCIDIN

protein toxin which creates pores in the protein toxin which creates pores in the membranesmembranes

hemolytic, but less so than alpha hemolysin. hemolytic, but less so than alpha hemolysin. Only in 2% of all of S. aureus Only in 2% of all of S. aureus 90% of the strains isolated from severe 90% of the strains isolated from severe

dermonecrotic lesions dermonecrotic lesions important factor in necrotizing skin infections. important factor in necrotizing skin infections.

COAGULASECOAGULASE

extracellular protein extracellular protein binds to prothrombin in the host to form a binds to prothrombin in the host to form a

complex called staphylothrombincomplex called staphylothrombin The protease activity characteristic of The protease activity characteristic of

thrombin thrombin result in the conversion of fibrinogen to fibrinresult in the conversion of fibrinogen to fibrin No evidence that it is a virulence factor.No evidence that it is a virulence factor.

STAPHYLOKINASESTAPHYLOKINASE

lyses fibrinlyses fibrin associated with lysogenic bacteriophagesassociated with lysogenic bacteriophages staphylokinase + plasminogen = dissolution staphylokinase + plasminogen = dissolution

of fibrin clots. of fibrin clots.

AVOIDANCE OF HOST AVOIDANCE OF HOST RESPONSERESPONSE

surface polysaccharide serotype 5 or 8surface polysaccharide serotype 5 or 8 Microcapsule: visualized only by electron Microcapsule: visualized only by electron

microscopy microscopy rapidly lose the ability when cultured in the rapidly lose the ability when cultured in the

lablab impede phagocytosis in the absence of impede phagocytosis in the absence of

complementcomplement

PROTEIN APROTEIN A

surface protein of S. aureussurface protein of S. aureus binds IgG molecules by their Fc regionbinds IgG molecules by their Fc region In serum, binding occurs in a wrong In serum, binding occurs in a wrong

orientation on the IgG orientation on the IgG disrupts opsonization and phagocytosis. disrupts opsonization and phagocytosis.

SUPERANTIGENSSUPERANTIGENS

enterotoxinsenterotoxins six antigenic typessix antigenic types

SE-A, B, C, D, E and GSE-A, B, C, D, E and G SUPERANTIGEN:activate 20% of the T cellsSUPERANTIGEN:activate 20% of the T cells (normal is 0.001%)(normal is 0.001%)

response is not specific to the antigenresponse is not specific to the antigen““useless” immune responseuseless” immune response

Superantigens evade the immune systemSuperantigens evade the immune system

STAPHYLOCOCCAL FOOD STAPHYLOCOCCAL FOOD POISONINGPOISONING

foods contaminated with toxins foods contaminated with toxins most common way: contact with food workers most common way: contact with food workers

who carry the bacteria or through who carry the bacteria or through contaminated milk and cheeses. contaminated milk and cheeses.

salt tolerant salt tolerant As the bacteria multiplies in food-produces As the bacteria multiplies in food-produces

toxins toxins resistant to heat, resistant to cooking. resistant to heat, resistant to cooking.

Staph food poisoningStaph food poisoning

highest risk of contamination: highest risk of contamination:

sliced meat,sliced meat,

puddingspuddings

pastriespastries

sandwiches sandwiches

SIGNS AND SYMPTOMSSIGNS AND SYMPTOMS

fast acting toxinsfast acting toxins cause illness in as little as 30 minutescause illness in as little as 30 minutes Average: one to six hours after eating Average: one to six hours after eating

contaminated food. contaminated food. nausea, vomitingnausea, vomiting Crampy abdominal pain Crampy abdominal pain diarrhea. diarrhea.

Staph food poisoningStaph food poisoning

Lab diagnosis:Lab diagnosis: Identification of the bacteria in stool and Identification of the bacteria in stool and

vomitusvomitus toxin can be detected in food itemstoxin can be detected in food items generally based only on the signs and generally based only on the signs and

symptomssymptoms High index of suspicionHigh index of suspicion Testing is usually reserved for outbreaks Testing is usually reserved for outbreaks

involving several persons involving several persons

Staph food poisoningStaph food poisoning

The illness is mild The illness is mild recover after one to three daysrecover after one to three days Supportive treatmentSupportive treatment Antibiotics are not useful Antibiotics are not useful Patients with this illness are not contagiousPatients with this illness are not contagious

SUPERANTIGEN :TSST-1SUPERANTIGEN :TSST-1

CAUSES TOXIC SHOCK SYNDROMECAUSES TOXIC SHOCK SYNDROME TSST-1 is responsible for 75% of TSS, TSST-1 is responsible for 75% of TSS,

including all menstrual cases including all menstrual cases enterotoxins B and C cause 50% of non-enterotoxins B and C cause 50% of non-

menstrual cases of TSS. menstrual cases of TSS.

TOXIC SHOCK SYNDROMETOXIC SHOCK SYNDROME

Mostly in femalesMostly in females Cases reported also in males (e.g.surgical site Cases reported also in males (e.g.surgical site

infection)infection) Menstrual-related TSSMenstrual-related TSS Non-mentrual related TSSNon-mentrual related TSS

TSSTSS

SIGNS AND SYMPOTOMS :TSSSIGNS AND SYMPOTOMS :TSS

Prodromal period of 2-3 days Prodromal period of 2-3 days Pain at site of infection Pain at site of infection Fever and/or chills Fever and/or chills Nausea and/or vomiting Nausea and/or vomiting

SIGNS AND SYMPTOMS:TSSSIGNS AND SYMPTOMS:TSS

Profuse watery diarrhea with abdominal pain Profuse watery diarrhea with abdominal pain Lightheadedness and/or syncope Lightheadedness and/or syncope Myalgias and/or arthralgias Myalgias and/or arthralgias Pharyngitis and/or headache Pharyngitis and/or headache Confusion (more common with staphylococcal Confusion (more common with staphylococcal

TSS than with streptococcal TSS) TSS than with streptococcal TSS)

The Centers for Disease Control and The Centers for Disease Control and Prevention (CDC) criteria for the diagnosis of Prevention (CDC) criteria for the diagnosis of

staphylococcal TSS staphylococcal TSS

Fever, hypotension, and rash Fever, hypotension, and rash Involvement of 3 or more organ systems Involvement of 3 or more organ systems Absence of serologic evidence of Rocky Absence of serologic evidence of Rocky

Mountain spotted fever, leptospirosis, measles, Mountain spotted fever, leptospirosis, measles, hepatitis B, antinuclear antibody, positive hepatitis B, antinuclear antibody, positive Venereal Disease Research Laboratory Venereal Disease Research Laboratory (VDRL) test results, and antibodies at (VDRL) test results, and antibodies at Monospot testing Monospot testing

SKIN RASHSKIN RASH

Diffuse rash, occasionally patchy and Diffuse rash, occasionally patchy and erythematous, with desquamation occurring erythematous, with desquamation occurring approximately 1-2 weeks later approximately 1-2 weeks later

Rash initially appearing on trunk, spreading Rash initially appearing on trunk, spreading to arms and legs, and involving palms and to arms and legs, and involving palms and soles soles

SKIN RASH: TSSSKIN RASH: TSS

SKIN RASH: TSSSKIN RASH: TSS

MULTI-ORGAN INVOLVEMENT: MULTI-ORGAN INVOLVEMENT: TSSTSS

ventricular arrhythmias, renal failure, or hepatic ventricular arrhythmias, renal failure, or hepatic failure failure

Disseminated intravascular coagulation (DIC) Disseminated intravascular coagulation (DIC) Acute respiratory distress syndrome Acute respiratory distress syndrome Necrotizing fasciitis and/or myositis Necrotizing fasciitis and/or myositis Altered consciousness (CNS involvement) Altered consciousness (CNS involvement)

Mucosal inflammation (eg, vaginitis, Mucosal inflammation (eg, vaginitis, conjunctivitis, pharyngitisconjunctivitis, pharyngitis

STRAWBERRY TONGUE:TSSSTRAWBERRY TONGUE:TSS

TSSTSS

Fever higher than 102°F Fever higher than 102°F Systolic BP less than 90 mm Hg Systolic BP less than 90 mm Hg orthostatic decrease in systolic BP of 15 orthostatic decrease in systolic BP of 15

mm Hg mm Hg

LAB EXAMS:TSSLAB EXAMS:TSS

The CBC: leukocytosis , mild anemia, and/or The CBC: leukocytosis , mild anemia, and/or thrombocytopenia. thrombocytopenia.

ElectrolyteS:hyponatremia, hypokalemia, ElectrolyteS:hyponatremia, hypokalemia, hypocalcemia out of proportion to hypoalbuminemia, hypocalcemia out of proportion to hypoalbuminemia, hypophosphatemia, and hypomagnesemia. hypophosphatemia, and hypomagnesemia.

Liver function test: hyperbilirubinemia , elevated Liver function test: hyperbilirubinemia , elevated aspartate aminotransferase (SGOT) level , and an aspartate aminotransferase (SGOT) level , and an elevated alanine aminotransferase (SGPT) elevated alanine aminotransferase (SGPT)

Coagulation studies:elevated activated partial Coagulation studies:elevated activated partial thromboplastin time (aPTT) and fibrin split products. thromboplastin time (aPTT) and fibrin split products.

LAB EXAMS:TSSLAB EXAMS:TSS

Azotemia and/or acute tubular necrosis Azotemia and/or acute tubular necrosis Urinalysis:sterile pyuria, myoglobinuria, and Urinalysis:sterile pyuria, myoglobinuria, and

red cell casts. red cell casts. Increased Creatine kinase Increased Creatine kinase

levels:rhabdomyolysis levels:rhabdomyolysis ABG: metabolic acidosis secondary to ABG: metabolic acidosis secondary to

hypotension and/or hypoxia. hypotension and/or hypoxia.

Lab exams :TSSLab exams :TSS

Culture all potentially infected sites (including Culture all potentially infected sites (including blood)blood)

CXR: pulmonary edema. CXR: pulmonary edema. XRAYS: soft-tissue swelling. XRAYS: soft-tissue swelling. 2D ECHO: wall-motion abnormality, toxic 2D ECHO: wall-motion abnormality, toxic

cardiomyopathy. cardiomyopathy.

TREATMENT :TSSTREATMENT :TSS

Fluid resuscitation Fluid resuscitation Crystalloids may be administered. As much as Crystalloids may be administered. As much as

10-20 L/d often is necessary. 10-20 L/d often is necessary. Administer supplemental oxygen therapy to Administer supplemental oxygen therapy to

maximize tissue oxygenation and to correct maximize tissue oxygenation and to correct hypoxia and/or acidosis. hypoxia and/or acidosis.

Assisted ventilation may be required if acute Assisted ventilation may be required if acute respiratory distress syndrome develops. respiratory distress syndrome develops.

TREATMENT:TSSTREATMENT:TSS

Hyperbaric oxygen therapy: necrotizing soft-Hyperbaric oxygen therapy: necrotizing soft-tissue infectionstissue infections

Cardiac monitoring Cardiac monitoring Foley catheterFoley catheter Tampons and packing materials, if present, Tampons and packing materials, if present,

should be removed. should be removed. menstruation-related TSS:irrigation of vagina menstruation-related TSS:irrigation of vagina

with isotonic sodium chloride solution or with isotonic sodium chloride solution or povidone-iodine solution povidone-iodine solution

EXFOLIATIN TOXINEXFOLIATIN TOXIN

separation within the epidermis, through the separation within the epidermis, through the stratum granulosum of the epidermis. stratum granulosum of the epidermis.

Staphylococcal exfoliative toxin B has been Staphylococcal exfoliative toxin B has been shown to specifically cleave desmoglein 1, a shown to specifically cleave desmoglein 1, a cadherin that is found in desmosomes in the cadherin that is found in desmosomes in the epidermis. epidermis.

SCALDED SKIN SCALDED SKIN SYNDROME(SSS)SYNDROME(SSS)

Ritter DiseaseRitter Disease affects infants and children under the age of 5.affects infants and children under the age of 5.

SIGNS AND SYMPTOMS: SSSSIGNS AND SYMPTOMS: SSS

fever fever Generalized erythemaGeneralized erythema skin slips off with gentle pressure leaving wet skin slips off with gentle pressure leaving wet

red areas (Nikolsky sign) red areas (Nikolsky sign) exfoliation or desquamation exfoliation or desquamation painful skinpainful skin

SSSSSS

SSSSSS

SSSSSS

LAB EXAMS: SSSLAB EXAMS: SSS

Complete blood count Complete blood count cultures of the skin and throat cultures of the skin and throat skin biopsy skin biopsy Serum electrolytes Serum electrolytes

TREATMENT: SSSTREATMENT: SSS

Fluid rehydration is initiated with Lactated Fluid rehydration is initiated with Lactated Ringer solution at 20 cc/kg initial bolus. Ringer solution at 20 cc/kg initial bolus. Repeat the initial bolus as clinically indicated Repeat the initial bolus as clinically indicated

maintenance therapy with consideration for maintenance therapy with consideration for fluid losses from exfoliation of skin being fluid losses from exfoliation of skin being similar to a burn patient. similar to a burn patient.

TREATMENT:SSSTREATMENT:SSS

Topical wound care: saline AND topical Topical wound care: saline AND topical antibiotic ointment. antibiotic ointment.

A chest radiograph should be considered to A chest radiograph should be considered to rule out pneumonia as the original focus of rule out pneumonia as the original focus of infection. infection.

Steroids are not indicated at this time.Steroids are not indicated at this time.

PROGNOSIS:SSSPROGNOSIS:SSS

Healing begins in about 10 days following treatment.Healing begins in about 10 days following treatment. A full recovery is expected. A full recovery is expected. Possible Complications   Possible Complications   

septicemia septicemia

dehydration or electrolyte imbalance dehydration or electrolyte imbalance

poor temperature control (in young infants) poor temperature control (in young infants) cellulitiscellulitis

The disorder may not be preventable; Prompt The disorder may not be preventable; Prompt treatmenttreatment

COAGULASE-NEGATIVE STAPHCOAGULASE-NEGATIVE STAPH

S. epidermidis;75% of clinical isolatesS. epidermidis;75% of clinical isolates S, haemolyticusS, haemolyticus S. hominisS. hominis S. capitisS. capitis S. saprophyticusS. saprophyticus

increased use of implants such as CSF shunts, increased use of implants such as CSF shunts, IV lines, cardiac valves, pacemakers, artificial IV lines, cardiac valves, pacemakers, artificial joints, urinary catheters joints, urinary catheters

increasing number of severely debilitated increasing number of severely debilitated patients in the hospitals.patients in the hospitals.

morphologically similar to S.aureus, however morphologically similar to S.aureus, however they form white colonies, and are coagulase they form white colonies, and are coagulase negative.negative.

S.epidermidisS.epidermidis

DISEASE CAUSED BY DISEASE CAUSED BY COAGULASE-NEGATIVE STAPHCOAGULASE-NEGATIVE STAPH

Prosthetic valve endocarditisProsthetic valve endocarditis MeningitisMeningitis PeritonitisPeritonitis UTI in pregnant women(S. saprophyticus)UTI in pregnant women(S. saprophyticus) Treatment is with Vancomycin, if not resistant. Treatment is with Vancomycin, if not resistant.

S. saprophyticus responds to trimethoprim or S. saprophyticus responds to trimethoprim or to quinolones.to quinolones.

ENDOCARDITISENDOCARDITIS

STAPH DRUG RESISTANCESTAPH DRUG RESISTANCE

(1) mutation in chromosomal genes followed (1) mutation in chromosomal genes followed by selection of resistant strains by selection of resistant strains

(2) acquisition of resistance genes as (2) acquisition of resistance genes as extrachromosomal plasmids, transducing extrachromosomal plasmids, transducing particles, transposons, or other types of DNA particles, transposons, or other types of DNA inserts. inserts.

MRSAMRSA

occur in otherwise healthy people who have occur in otherwise healthy people who have not been recently (within the past year) not been recently (within the past year) hospitalized hospitalized

had a medical procedure (such as dialysis, had a medical procedure (such as dialysis, surgery, catheters)surgery, catheters)

community-associated (CA)-MRSA infections community-associated (CA)-MRSA infections skin infections: abscesses, boils, and other skin infections: abscesses, boils, and other pus-filled lesionspus-filled lesions

MRSA RESERVOIRSMRSA RESERVOIRS

In hospitals, the most important reservoirs of In hospitals, the most important reservoirs of MRSA are infected or colonized patientsMRSA are infected or colonized patients

HOSPITAL PERSONNEL: commonly HOSPITAL PERSONNEL: commonly identified as a link for transmission between identified as a link for transmission between colonized or infected patients.colonized or infected patients.

MODE OF MODE OF TRANSMISSION:MRSATRANSMISSION:MRSA

via hands (especially health care workers' via hands (especially health care workers' hands) which may become contaminated by hands) which may become contaminated by contact with contact with

a) colonized or infected patientsa) colonized or infected patients b) colonized or infected body sites of the b) colonized or infected body sites of the

personnel themselves, personnel themselves, c) devices, items, or environmental surfaces c) devices, items, or environmental surfaces

contaminated with body fluids containing contaminated with body fluids containing MRSA.MRSA.

Hospital-associated MRSA isolate is resistant to :Hospital-associated MRSA isolate is resistant to :

erythromycinerythromycin

clindamycinclindamycin

tetracyclinetetracycline community-associated MRSA isolates resistant:community-associated MRSA isolates resistant:

ß-lactam agentsß-lactam agents

erythromycin. erythromycin.

TREATMENT: MRSATREATMENT: MRSA

vancomycin vancomycin in Georgia, Texas, and California, the in Georgia, Texas, and California, the

prevalence of CA-MRSA is widespread. prevalence of CA-MRSA is widespread.

VRSAVRSA

1996, MRSA strains with decreased 1996, MRSA strains with decreased susceptibility to vancomycin susceptibility to vancomycin

VISA: if the MIC for vancomycin is 4-8µg/ml, VISA: if the MIC for vancomycin is 4-8µg/ml, VRSA :MIC is >16µg/ml. VRSA :MIC is >16µg/ml.

VISA, VRSAVISA, VRSA

several underlying health conditions (such as several underlying health conditions (such as diabetes and kidney disease)diabetes and kidney disease)

previous infections with methicillin-resistant previous infections with methicillin-resistant Staphylococcus aureus (MRSA)Staphylococcus aureus (MRSA)

intravenous [IV] catheters)intravenous [IV] catheters) recent hospitalizationsrecent hospitalizations recent exposure to vancomycin and other recent exposure to vancomycin and other

antimicrobial agents. antimicrobial agents.

TREATMENT FOR VRSATREATMENT FOR VRSA

limited treatment options for VISA/VRSA limited treatment options for VISA/VRSA infectionsinfections

rifampin, gentamicin, imipenem, rifampin, gentamicin, imipenem, chloramphenicol, trimethoprim-chloramphenicol, trimethoprim-sulfamethoxazole, and tetracycline sulfamethoxazole, and tetracycline

IMPRESSION FOR CASE 1IMPRESSION FOR CASE 1