Infectious Diseases Colloquium I

GASTROENTERIC INFECTIONS

Acute Infectious Diarrhea

• >3 unformed stools /24h
• increased stool volume - >300g/24h
• osmotic, secretory, motility related, mixed
• infective, non-infective
• 2ND MOST COMMON DISEASE WORLDWIDE (after acute respiratory infections)

Bacteria:
• Salmonella spp., Shigella spp., Campylobacter spp., Y. enterocolitica, E. coli, Vibrio
cholera, C. diff. & perfringens
Viruses:
• Rotavirus, Norovirus, Adenovirus, Astrovirus, Coronavirus, CMV
Parasites:
• Entamoeba hystolitica, Giardia (lamblia) intestinalis, Isospora belli, Cryptosporidium
parvum, Cyclospora cayetanesis

Host Defenses:
1. Normal bowel flora
a. Preventing colonization of potential enteric pathogens
b. More than 600 species (99% are anaerobic)
2. Gastric Acid
a. Risk for enteric infections is increased when patients have undergone gastric surgery
and treated with antacids or H2 blockers
b. Salmonella, Shigella, Giardia and helminthic infections common among those patients
c. Rotavirus highly stable in G. acid
3. Intestinal Motility
a. Normal pertistalsis is major mechanism for clearance of bacteria from the intestines
 b. Patients with anti-motility agents experience prolonged fever and shedding of organisms
+ higher frequency of bacteremia
4. Immunity
a. Cellular immunity: AIDS patients
b. Humoral immunity: IgG, IgM and secretory IgA
i) Binding of bacterial antigens to M cells in intestine and their appearance to
subepithelial lymphoid tissue, lead to proliferation of lymphocytes which populate
mucosal tissues as IgA-secreting plasma cells
VIRULANCE FACTORS
• Inoculum size
o Shigella, EHEC, Giardia and Entamoeba, 10-100 bacteria or cysts can produce
infection
o 1 million V. cholera must be ingested to cause infection
• Adherence
o Adherence to gastrointestinal mucosa
o Organisms colonize the mucosa and compete with the normal bowel flora which
is an important advantage in causing disease
• Toxin production
o Enterotoxins: cause watery diarrhea by acting directly on secretory mechanisms
§ ETEC produces heat-labile enterotoxin (LT), similar to cholera toxin, plus
heat stable enterotoxin (ST) which acts by increasing cGMP
o Cytotoxins: cause destruction of mucosal cells and associated inflammatory
diarrhea
§ Destroy intestinal mucosal cells and produce the syndrome of dysentery
(Shigella, Clostridium, E. coli)
o Neurotoxins: act directly on CNS & PNS
§ Produced outside of host and cause symptoms after ingestion (Staph.
Aureus, B. cereus, Clostridium botulinum)
o Some toxins act by more than one mechanism
o CHOLERA TOXIN – increased Cl- secretions and decreased Na+ absorption
§ A subunit: contains enzymatic activity
§ B subunit: pentamer binds toxin to enterocyte surface receptor
• Invasion
o Invasion and inflammation – of the mucosa WITH destruction of epithelial cells
(Shigella, EIEC)
o Invasion and inflammation – WITHOUT destruction of enterocytes (Salmonella)

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 o Penetration – of intact intestinal mucosa, multiplication in Peyer’s patches and
intestinal lymph nodes, dissemination to blood leading to enteric fever (S. typhi,
Y. entercolitica)

• Type of • Non- • Inflammatory • Penetrating

infection inflammatory

• Mechanisms • Toxin production • Invasion • Invasion/

• penetration

• Location • Proximal small • Colon • Distal small bowel

bowel

• Fever • No • Fever • Fever

• Abdominal • No • Abdominal • Minimal

pain cramping, abdominal pain
tenesmus

• Illness • Watery diarrhea • Dysentery (blood, • Enteric fever

mucus)

• Fecal • No • PMN • Mononuclear

leukocytes

• Microorganism • V.cholerae, • Shigella, E.coli, • S. typhi, paratyphi

E.coli, S. aureus, Campylobacter, A,B,C
Rotavirus,Giardia C.difficile,
• Yersinia
Cryptosporidium Salmonella,
E.hystolitica

LABORATORY ANALYSIS
• Blood count
• Biochemical analysis (azotemia, loss of electrolytes, acidosis)
• Inflammatory parameters (CRP, fibrinogen)
• Malabsorption (protein count, albumin, Fe)

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DIAGNOSIS
• Stool culture (selective growth medium)
• Fresh stool examination for parasites
• Rapid ELISA stool tests (C. diff toxin A & B) (Rotavirus)
• Stool test for Shiga-toxin
• PCR
• Serologic blood testing (E. hystolitica)
• Blood culture (S. typhi)

TREATMENT
• REHYDRATION – oral (mild diarrhea), IV (severe)
• Antimicrobial drugs – dysentery, inflammatory diarrhea with high fever, bacteremia
• Probiotics

BACTERIAL FOOD POISONING

STAPHYLOCOCCUS AUREUS
• Source: nose, mouth, skin
• Food contamination: ham, poultry, mayonnaise, ice cream
• TOXIN: heat-stable staphylococcal enterotoxin B
• Pathogenesis: symptoms are mediated through the ANS
Clinical presentation:
o Incubation period 1-6 hours
o Nausea, vomiting, diarrhea, abdominal cramps
o No fever
o Illness lasts under 24 hours
DIAGNOSIS
• Generally based on sign and symptoms of the disease
• Staph. aureus can be identified from stool or vomit and bacteria and toxin in food
o Testing usually reserved for outbreaks

THERAPY
• Adequate rehydration

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BACILLUS CEREUS
• Gram (+), facultative aerobic spore forming bacteria
• Emetic form: caused by a LOW molecular weight, heat-stable peptide (like staph.
enterotoxin B)
o Source: rice (heat-resistant spores, heat-stable toxin)
o Incubation: 1-6 hours
o Clinical presentation: same as Staph. food poisoning
• Diarrheal form: LARGE molecular weight protein (like E. coli enterotoxin)
o Sources: meat, vegetables, beans, cereals
o Incubation: 8-16 hours
o Clinical presentation: diarrhea, abdominal cramps (fever and vomiting
uncommon)
o Illness is self-limiting, not lasting in excess of 24hrs
DIAGNOSIS
• Isolation of B. cereus serotype known to cause foodborne illness from feces or vomitus of
patient
• Non-specific rehydration for treatment

CLOSTRIDIUM PERFRINGENS
• Gram (+) anaerobic, spore forming bacteria
• Sources: beef, poultry, legumes
• CPE – clostridium perfringens enterotoxin produced in intestinal tract
o Incubation: 8-14 hours
o Clinical presentation: diarrhea, abdominal cramps
DIAGNOSIS
• Testing contaminated food or stool for C. perfringens and CPE
TREATMENT
• Adequate rehydration

VIBRIO PARAHEMOLYTICUS
• Source: raw seafood, summer months
• Clinical presentation: diarrhea and abdominal cramps, sometimes dysentery-like illness
• Treatment: adequate rehydration, in serious cases; antibiotics

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 VIRAL GATROENTERITIS

Virus type Genome Risk groups Seasonality Diagnosis Therapy

structure

Rotavirus RNA Children<3 years Winter ELISA Oral

rehydration

Adenovirus DNA Children<3 years Year-round ELISA Oral

rehydration

Calicivirus RNA Children - EM Oral

rehydration

Astrovirus RNA Children, Winter EM Oral

immunocompromised rehydration
pt.

Norwalk-like RNA Children, adults Winter EM Oral

rehydration

Parvovirus DNA - Year-round EM None

Picornavirus RNA - - Culture,EM None

Coronavirus RNA - - EM None

ROTAVIRUS (RNA)
• Most important cause of severe diarrhea in infants and children <3 years
• Pathogenesis: spread through fecal-oral route
o Kills epithelial mature villus cells in small intestine
o Lack of absorption of nutrients = osmotic diarrhea
• Clinical presentation:
o Vomiting, diarrhea
o Fever >39 degrees
• Diagnosis: ELISA – detection of rotavirus antigen in fecal specimens
• Treatment: standard oral rehydration, multivalent rotavirus vaccine (children under 6 mon)

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NOROVIRUS
• Waterborne epidemics on cruise ships, nursing homes, camps
• Pathogenesis: infects epithelial cells of small intestine
o Carb malabsorption, mild steatorrhea, decreased levels of brush border enzymes
• Clinical presenation:
o Incubation: 18-72 hours
o Nausea, vomiting, cramps, diarrhea
o Fever, headache, myalgias
o Illness is mild and self-limited
• Diagnosis: ELISA and PCR based assays
DYSENTERY
Acute infectious inflammatory colitis characterized by frequent passage of small volume
stools consisting of blood and mucus.

SHIGELLOSIS
• Gram (-), non-motile bacilli, members of Enterobacteriae family, four species:
o S. dysenteriae
o S. flexneri
o S. sonnei
o S. boydii
• Natural pathogen for humans
• Transmission: fecal-oral route
• INFECTIVE DOSE: 10-100 bacteria
o Oral ingestion, passing gastric acid barrier
o Attachment to colonic cells (M cells), entry by endocytic mechanism, movement
into cell membrane, then cell-to-cell spread of infection
o Intracellular multiplication causes cell damage and death resulting in mucosal
ulcerations
• Virulence factors
o Plasmid responsible for invasion and spreading of bacteria among colonic cells
o Shiga enterotoxins ShET-1 & 2 alter electrolyte transport and cause fluid
secretion and act as cytotoxins by destroying epithelial cells
o SHIGA-TOXIN – produced y S. dysenteriae type 1, plays a role in
microangiopathic complications

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• Clinical presentation
o Incubation: 24-48 hours
o 25% of patients have no symptoms
§ 25% mild fever, or fever and self-limited watery diarrhea, or have fever
and water diarrhea that progresses to dysentery
o Abdominal cramps, tenesmus
o Complications: toxic megacolon and perforation
• Extraintestinal manifestations
o HUS – hemolytic uremic syndrome
o Anemia with CHF
o Anuria with renal failure
o Thrombocytopenia
o Encephalopathy
§ Seizures in young children with high fever
§ Reiter’s syndrome – reactive arthritis
• Diagnosis:
o Stool culture: MacConkey agar, Salmonella-Shigella agar
§ Typical UNCOLOURED colonies of shigella (Salmonella-Shiga)
o Enzyme immunoassay for detection of Shiga-toxin in stool
o Endoscopy: mucosa is hemorrhagic with mucus discharge, focal ulcerations and
exudate in distal colon
o (+) fecal leukocytes – leukocytosis
o anemia, due to blood loss
o Pre-renal azotemia and acidosis (dehydration)
• THERAPY
o Dysentery: antibiotics
§ 4-fluoroquinolones (Ciprofloxacin), Azithromycin, Ceftriaxone
o Toxic megacolon: colectomy
o HUS: dialysis

ENTAMOEBA HYSTOLITICA
• Transmission: fecal-oral route
• Cysts are infective and trophozoites are responsible for invasion and inflammation of the
mucosa

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• Clinical presentation:
o Mild diarrhea
o Dysentery
o Chronic diarrhea with weight loss
• Extraintestinal manifestation: LIVER ABSCESS
• THERAPY
o For invasive amebiasis and abscess:
§ Metronidazole
o Eradication of cysts:
§ Paromomycine
CAMPYLOBACTERIOSIS
• Gram (-) rods
• Found in GIT of animals and pets
• Humans infected by using raw, undercooked food products (poultry, milk) or through direct
contact with animals
• Clinical presentation:
o Incubation: 1-7 days
o Fever, headache, myalgia (first 12-48 hr)
o Cramping
o Diarrhea varies from several watery stools to bloody stools
• Complications:
o Bacteremia & hypogammaglobinemia (AIDS)
o Cholecystits, pancreatitis, endocarditis, reactive arthritis
o Guillain-Barré syndrome (triggered 20-40% of all cases)
• DIAGNOSIS
o Stool culture in campylobacter-specific media
o Blood culture
o Direct microscopic examination of stool: organisms with vibroid morphology
• TREATMENT
o High fever and dysentery longer than a week = erythromycin, clarithromycin
ciprofloxacin
o Systemic infections = gentamycin, imipenem, ciprofloxacin

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E. COLI

• Pathotype • Epidemiolog • Clinical • Defining • Responsible

a
y Syndromeb Molecular Trait Genetic
Elementc

• EHEC • Food, water, • Hemorrhagi • Shiga toxin • Lambda-like

person-to- c colitis, Stx1- or
person; all hemolytic- Stx2-
ages, uremic encoding
industrialized syndrome bacteriophag
countries e

• ETEC • Food, water; • Traveler's • Heat-stable and - • Virulence

young diarrhea labile plasmid(s)
children in enterotoxins,
and travelers colonization
to developing factors
countries

• EPEC • Person-to- • Watery • Localized • EPEC

person; diarrhea adherence, adherence
young attaching and factor
children and effacing lesion on plasmid
neonates in intestinal pathogenicity
developing epithelium island (locus
countries for
enterocyte
effacement)

• EIEC • Food, water; • Dysentery • Invasion of • Multiple

children in colonic epithelial genes
and travelers cells, intracellular contained
to developing multiplication, primarily in
countries cell-to-cell spread large
virulence
plasmid

• EAEC • ? Food, • Traveler's • Aggregative/diffus • Chromosom

water; diarrhea, e adherence, al or
children in acute virulence factors plasmid-
and travelers diarrhea, regulated by associated
to developing persistent AggR adherence
countries; all diarrhea and toxin
ages, genes
industrialized
countries

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TRAVELLER’S DIARRHEA
• Causes: Enterotoxic E.coli, Shigella, salmonella, campylobacter, Vibrio spp., Giardia,
Entamoeba hystolitica, Cryptosporidium, Cyclospora, Rotavirus
• Self limited for 1-5 days
• Abdominal cramps and watery diarrhea

EHEC 0157:H7
• Fecal-oral route, contaminated mainly through water and food
• Source: digestive tract of cattle and wild animals (deer, swine)
• Pathogenesis:
o Bacteria produces Shiga-like toxin
o Incubation: 3-4 days
• Clinical presentation:
o Abdominal cramps, dysentery
• Complications:
o HUS (10%), mortality 3-5%
• Therapy:
o Symptomatic
o Use of antibiotics is CONTRAINDICATORY
o Dialysis (HUS)

CHOLERA
Acute diarrheal disease, results in rapidly progressive dehydration (then death) within a matter
of hours.
Discovered in 1883 by Robert Koch
• Vibrio cholera
o Gram (-), highly motile, facultative anaerobic curved rod, with one or more
flagella
o Antigenic structure: flagellar H antigen, and a somatic O antigen
o 200 serotypes recognized
o Serogroup O1 = most exclusive cause of cholera epidemics
o Two biotypes of V. cholera O1 : Classical and El Tor
• Epidemiology

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 o Habitat: coastal salt water
o Ingestion of water or food contaminated by human feces
o Infective dose is high, but markedly reduced in hypochlorhydric persons
o Susceptibility to cholera is significantly higher in people with O-blood type!
• Pathogenesis:
o TCP- toxin-co-regulated pilus is essential for V. cholera intestinal colonization
o Cholera toxin consists of monomeric enzymatic A subunit, and a pentameric
binding B subunit (binds toxin to enterocyte surface receptor)
o Accumulation of NaCl in intestinal lumen
o Water moves passively to maintain osmolality, isotonic fluid then accumulates in
intestines
o When the volume of the gut exceeds the capacity to resorb it, water diarrhea
occurs
o Hypovolemic shock (profound dehydration) and acidosis (loss of bicarbonate)
follow
• Clinical presentation:
o Incubation: 24-48 hours
o Asymptomatic, mild diarrhea
o Full-blown syndrome: most rapidly fatal disease
o Cholera sicca: abdominal distention and ileus with accumulation of fluid in
intestinal lumen
o Painless, watery diarrhea that may become voluminous and followed by vomiting
o NO FEVER
o Muscle cramps due to electrolyte disturbances
• Rice Water diarrhea:
o Very little fecal matter, appears within 24 hours
o Gray, slightly cloudy with flecks of mucus (no blood)
o Sweet, fishy odour
• 3-5% loss of body weight = thirst develops
• 5-8% loss = postural hypotension, weakness, tachycardia and decreased skin turgor
• >10% loss = oliguria, weak or absent pulses, sunken eyes, wrinkled (washerwoman) skin,
somnolence and coma
• LAB FINDING
o Hemocrit (elevated)
o Mild neutrophilic leukocytosis

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 o Blood urea, nitrogen and creatinine (elevated) – consistent with pre-renal
azotemia
o Dehydration and bicarbonate loss leads to metabolic acidosis (arterial pH ~7.2)
• Identification of V. cholera in stool
o Directly: dark-field microscopy on wet mount of fresh stool
§ Serotype can be diagnosed by immobilization with specific anti-serum
o Selective medium: thiosulfate-citrate-bile salts-sucrose (TCBS) agar
§ Organism grows as flat yellow colony
• Diagnosis
o Monoclonal antibody based kits and methods based on PCR have been
developed
• TREATMENT:
o Rapid and adequate replacement of fluids, electrolytes and base required
o Mortality rate for appropriately treated disease is less than 1%
o Due to profound acidosis, Ringer’s lactate is best (base)
§ Must be given with K+
o Antibiotics: single dose tetracycline (2g), doxycycline (300mg)

SALMONELLOSIS
• Gram (-) bacilli, non spore forming, facultative anaerobic, motile by peritrichous flagella
• S. typhi and S. paratyphi cause enteric (typhoid) fever and restricted to growth in human
hosts
• Non-typhoidal salmonella are inhabitants of the GIT of animals (mammals, reptiles, birds
and insects)
• Antigenic determinants:
o Somatic O antigen (lipopolysaccharide cell wall components)
o Surface Vi antigen (restricted to S. typhi and paratyphi)
o Flagellar H antigen
o Salmonellae are divided into serogroups based on reactivity to somatic O-antigen
anti-sera (A, B, C1, C2, D and E)
• Epidemiology:
o Transmitted by contaminated food and water, fecal-oral route
o Infective dose 103-106 bacteria

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• Pathogenesis
o Salmonellae penetrate mucus layer
o Enter intestine through the phagocytic M-cells or by bacteria mediated
endocytosis

NON-TYPHIODAL SALMONELLOSIS
• Morbidity and mortality is highest among elderly, infants and immunocompromised patients
• CAUSES: S. enteritidis, S. typhimurium, S. hadar
• Pathogenesis:
o Intestinal cells secrete IL-8; a strong neutrophil chemotactic factor
o Massive PMN infiltration and degranulation with release of toxic substances by
PMNs may result in damage to intestinal mucosa = inflammatory diarrhea
o Infection is localized in terminal ileum
• Clinical presentation
o Gastroenteritis
o Bacteremia
o Localized infections
o Chronic carriage
• Gastroenteritis
o Incubation: 6-48 hours
o Nausea, vomiting, abdominal cramps
o Fever (resolves in 48-72 hours)
o Diarrhea – loose, greenish stools (resolves 3-7 days)
• Bacteremia
o 5% of patients
o prolonged fever with (+) blood culture
o if 3 or more blood cultures are positive, endovascular infection should be
considered (endocarditis, arteritis)
• Localized infections
o Splenic abscess
o Cholecystitis
o Pancreatitis
o CNS: meningitis, cerebral abscess
o Pulmonary: pneumonia, lung abscess, empyema, pleural effusion

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 o Urinary: cystitis, pyelonephritis, ovarian and testicular abscess, prostatitis,
epididimytis
o Axial: osteomyelitis, septic arthritis, reactive arthritis (Reiter’s syndrome)
• Chronic carriage
o Stool cultures remain postitive for 4-5 weeks after infection
o Antibiotic therapy can be associated with prolonged gastrointestinal carriage
• DIAGNOSIS
o Stool culture – MacConkey agar, SS agar (black culture)
o Blood culture (grey colonies)
o Endoscopy and biopsy
o Serological test: Widal agglutination test
§ Agglutinating antibodies to O, H and Vi antigens
• Treatment
o Dehydration should be treated with fluid and electrolyte replacement
o Antibiotics not recommended!!! – only infants and >50 yrs
o Probiotics
o Bacteremia = 3rd gen. cephalosporin / quinolone

ENTERIC (typhoid) FEVER

Typhoid fever is a systemic disease characterized by abdominal pain caused by dissemination
of Salmonella typhi or paratyphi.
13-17 million cases worldwide, 600,000 deaths per year.
• Transmission person-person, caused by ingestion of contaminated food or water
• Pathogenesis:
o Crossing epithelial layer for small intestine, salmonellae undergo phagocytosis by
macrophages
o In macrophages they are protected from PMN’s complement and antibodies
o Salmonellae have mechanisms to avoid killing by macrophages
o Disseminate in macrophages via the lymphatics and colonize reticuloendothelial
tissues (liver, spleen, lymph nodes and bone marrow)
o They also enter the circulation (via d. thoracicus) causing bacteremia and
metastatic localized infections
o Endotoxin of S. typhi contribute to systemic symptoms, such as cytokines
released from infected mononuclear phagocytes
o Small bowel mucosa is infiltrated by mononuclear cells

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 o Peyer’s patches of the small intestine are hyperplastic, infiltrated with MN cells
o Perforation results from necrosis of the intestinal wall
o Intestinal bleeding results from erosion of blood vessls
• Clinical presentation
o Incubation: 3-21 days
o Fever
o Abdominal pain
o Diarrhea, constipation
• Physical findings:
o Abdominal tenderness
o “rose spots” – maculo-papular rash localized on the trunk and chest
§ salmonella can be cultured from punch biopsies from the lesions
o Heptosplenomegaly
o Bradycardia
o Epitaxis
o Typhoid state: abnormal state of consciousness such as apathy, confusion,
delirium, stupor or coma
• Complications
o Local complications (3rd/4th week of infection)
§ Intestinal perforation
§ Gastrointestinal bleeding
§ Peritonitis
§ Shock
o Extraintestinal complications
§ Cholecystits, pancreatitis, hepatic and splenic abscesses, hepatitis
§ Myocarditis, pericarditis, endocarditis, nephritis, pneumonia, meningitis
• Laboratory findings
o Anemia
o Leukopenia and neutropenia
o Elevated liver function tests (ALT, AST, alkaline phosphatase, lactate
dehydrogenase)
• DIAGNOSIS
o “gold standard” – culture positive for S. typhi
o blood culture = (+) in first week

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 o stool culture = (-) in first week, becomes (+) in week 3
o Widal serologic test (positive in 3rd week)
• TREATMENT
o Ceftriaxon (IV) or quinolones (ciprofloxacin) orally/IV for 10-14 days

YERSINA ENTERCOLITICA
• Gram (-) bacilli, pleomorphic
• Isolated from soil, water, contaminated food and wide variety of wild and domestic animals
• Clinical presentation
o Enteritis/enterocolitis: diarrhea with low-grade fever, cramping, nausea, vomiting
o Y. entercolitica septicemia: presents as severe illness with fever and
leukocytosis, with abdominal pain
o Mesenteric adenitis and terminal ileitis: confused with appendicitis
§ Low grade fever and right-lower quadrant pain, tenderness, guarding
o Erythema nodosum: 15-20%
• Diagnosis:
o Selective cefsulodin-Irgasan-novobiocin (CIN) agar
o Typical “bull’s eye” colonies
o Agglutination tests or ELISA used most commonly
• Treatment
o 3rd generation cephalosporins, quinolones and TMP-SMX

STAPHYLOCOCCI INFECTIONS
S. AUREUS, S. EPIDERMIDIS, S. SAPROPHYTICUS
• Staph can infect animate and inanimate objects
o Mucous membranes of skin are the favoured spot for adhesion
o Spreading of staph cause local abscesses
o Toxin liberation to the skin and other organs =skin rashes, toxic shock syndrome,
bacteremia etc…
• Gram (+) cocci, clustered
• Aerobic and Anaerobic growers

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CLINICAL CLASSIFICATION
• Methicillin-resistant S. aureus (MRSA)
o CA-MRSA
o HA-MRSA
• Methicilln-resistant S. epidermidis (MRSE)

INFECTION FACTORS
• >1 million organisms to trigger infection
• Susceptible hosts (diabetes, IV drug abusers)
• Viral diseases predispose a primary staph. invasion of the lung
• SPREADING FROM CUTANEOUS FOCI (>50%)
o Or direct inoculation into blood stream (IV drugs, catheters)
• Direct person-person contact
• Indirect person-person
• Asymptomatic nasal carriers – airborne transmission?

PATHOGENESIS
a) Staph usually invades hair follicles and sebaceous glands
b) Breached skin allows local microbial multiplication with inflammation and tissue necrosis
c) PML rapidly enter area and ingest large number of staph.
d) Thrombosis of surrounding capillaries
e) Fully developed staph lesion consists of:
a. Central core of dead leukoctyes and bacteria, gradually liquefying to form
characteristic thick, creamy pus surrounded by fibroblastic wall
f) Staph may enter bloodstream (failure of host cutaneous immune mechanisms)

IMMUNITY
• Pathogenic Staph can survive within human leukocytes
• Intact PML are the main protective mechanisms against staph.
• Role of humoral immunity is uncertain, however 100% of adults have antibodies to staph
antigens

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MANIFESTATIONS
• Skin and soft tissue infections
o Folliculitis
o Carbuncul, furuncul
o Cellulitis
o Impetigo
• Pulmonary infections
• Bacteremia
o Complications: meningitis, endocarditis
• Endocarditis
• Food poisoning
• Osteoarticular infections
• Genitourinary infections
• Toxic-shock-syndrome***
• Kawasaki syndrome (multisystem vasculitis)

TOXIC SHOCK SYNDROME

Acute-onset multi-organ illness (associated with use of tampons and packing of surgical
wounds), mainly caused by Staph. aureus.
• Diagnosis:
o High fever >38.8
o Low blood pressure <90mmHg
o Diffuse macular rash with desquamation
o 3 of following organ systems involved:
§ Liver (increased AST, ALT, bilirubin)
§ Blood (platelets <100,000/m3)
§ Renal (polyuria, increased blood-urea-nitrogen and creatinine)
§ GIT (diarrhea, vomiting)
§ Muscular (myalgia, increased CPK – creatinine protein kinase)
§ CNS (disorientation)
• Treatment
o Dependent on host setting (hospital, community)
o Rapid necrosis of tissue produced by staph (surgical drainage required)

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 o Sluggish response to AB therapy – continued longer than many other bacterial
infections
o Antimicrobial resistance – importance of confirming AB susceptibility
o ANTIBIOTICS:
§ Nafcillin, Cefazolin, Vancomycin, Clindamycin – IV, 10-14 days

RESISTANCE
Mechanisms of resistance in S. aureus:
• Genetic variation in S. aureus is very extensive
• Lateral gene transfer has played a fundamental role in the evolution
• The mecgene has been horizontally transferred into distinct S. aureus chromosomal
backgrounds at least 5 times, showing that methicillin-resistant strains have evolved
multiple independent times, rather than from a single ancestral strain

STREPTOCCOCAL INFECTIONS
GROUP A STREPTOCOCCI (GAS)
• Most common group of infections
• Toxins: streptolysins (S&O), hyaluronic acid (protection from phagocytosis), protein M
(complement activation and phagocytosis inhibition)
PHARYNGITIS
o 20-40% exudative cases in children over 3 years
o transmitted through respiratory droplets
o Incubation: 1-4 days
• Clinical presentation:
o Sore throat, fever, chills, malaise and sometimes abdominal complaints (in
children)
o Physical findings: erythema and swelling of pharyngeal mucosa
§ Purulent exudate over posterior pharyngeal wall and tonsils
§ Enlarged, tender cervical lymph nodes
• Diagnosis:
o Differentiate from viral infection: blood testing (WBC count, PMN=bacteria)
o Culturing to see which antibiotic is useful
• Treatment:
o Benzathine penicillin G for 10 days
o Cephalosporins or clindamycin for hypersensitive patients

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SCARLET FEVER = pharyngitis + scarlet fever exanthema (rash)
GAS ANGINA (Vincent’s angina) = similar presentation to mononucleosis, acute leukemia,
candidiasis => blood test to differentiate!!! Throat swab is “gold standard”

ERYSIPELAS (cellulitis)
• Local infection of skin with associated lymphatic vessels with superficial bullae (2-3 days
after onset)
• Clinical presenation:
o Clearly demarcated border of intense red skin
o Lesion is warm, tender and has a glossy appearance and swollen
• Treatment:
o Penicillin 14 days
• **** if facial vein triangle affected = connected to brain = meningitis!!

NECROTIZING FASCITIS (deep-soft tissue infection)

Aka: streptococcal hemolytic gangrene
• necrosis and inflammatory fluid along fascial planes, between muscle groups without
infecting muscles (usually = strep. myositis)
• Treatment: surgical drainage + high dose of penicillin

GROUP B STREPTOCOCCI (GBS)

Major cause of sepsis and meningitis
• 1/3 women are carriers (if pregnant need to be treated with penicillin until delivery)

GROUP C&D STREPTOCOCCI

• similar to GAS infections
• less sensitive to penicillin (requiring higher doses)

ENTEROCOCCI
2nd leading cause of UTIs (1st is E. coli)

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