Endocarditis, Meningitis, and Bloodstream Infections

1
Endocarditis, Meningitis, and Bloodstream
Infections
2
Infective Endocarditis

• Infective endocarditis is an infection of the
  endocardial surface of the heart.
• Although heart valves are most often involved,
  the wall of the heart may be involved or
  infection may occur at the site of structural
  defects.
• Patients with prosthetic valves and other foreign
  materials are particularly susceptible.

3
Infective Endocarditis

• Infections may be
• acute (presenting within 6 weeks),
• subacute (presenting from 6 weeks to 3 months),
• chronic (presenting after more then 3 months).

4
Epidemiology of Endocarditis

• Infective endocarditis is relatively rare
  approximately 20 cases per year would be seen at
  the QEII.
• Endocarditis takes place on normal and abnormal
  heart valves, and on congenitally abnormal
  hearts.
• Only highly virulent bacteria, e.g. S. aureus,
  infect normal valves.

5
Epidemiology (contd)

• Low virulence, oral and skin microorganisms are
  more likely to cause infection on abnormal valves
  (e.g. Viridans streptococci and coagulase
  negative staphylococci).
• Prosthetic valves are most susceptible and may be
  infected by all of the above in addition to
  bacteria attaching to the valve at the time of
  its insertion.

6
Pathogenesis

• Mucous membranes and skin are colonized.
• Trauma results in bacteremia.
• Organisms adhere to roughened endocardial
  surfaces.
• Adherence is promoted by fibrin, platelet
  aggregation, and endothelial damage.
• Further platelet fibrin deposition takes place.
• Bacterial division begins and vegetations
  develop.
• Vegetations develop with dormant organisms at the
  center.

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Consequences of Infection

• Heart.
• Cauliflower shaped vegetations may develop
• These may impair normal valve function or may
  break off into the systemic circulation.
• Ongoing inflammation may destroy the valve and
  produce valvular insufficiency.
• Small emboli many enter the coronary arteries and
  cause myocardial infarction.
• Abscesses may develop which impair electrical
  conduction.

8
Consequences (contd)

• Brain
• The cortex may be showered with multiple
  micro-emboli, resulting in confusion or coma.
• Large emboli may produce stroke.
• Large emboli may occasionally result in one or
  more brain abscesses.
• Meningitis may occur from ongoing bactermia.

9
Consequences (contd)

• Kidney
• Large emboli may break off and obstruct renal
  arteries.
• Immune complexes (bacterial antigens, complement
  and immunoglobulin) may cause renal kidney
  inflammation.
• Other
• Emboli from large vegatations may go to spleen,
  extremities, eye and other organs.
• Occasionally, involved blood vessels will weaken,
  stretch or burst.

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Diagnosis

• Usually, risk factors can be identified.
• Previously recognized valvular heart disease
• Preceding dental or other surgical procedures
• Intravenous drug use
• Recent heart surgery
• A long stranding indwelling lines

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Diagnosis (contd)

• Blood cultures
• Blood cultures are positive in approximately 90
  of cases
• Negative cultures may occur with prior treatment
  or with unusual or slow growing organisms
• Echocardiography
• Removal of an embolus

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Treatment of Bacterial Endocarditis

• Treatment is customized for every patient and
  depends on
• the organism, its susceptibility pattern,
• the presence of foreign material,
• the feasibility of surgery,
• allergies, and convenience.
• Almost all cases are treated for at least 4
  weeks.
• Combination treatments are common, especially
  penicillin and aminoglycoside combinations which
  act synergistically.

13
Prevention

• The American Heart Association has published
  guidelines for prophylactic antibiotics for at
  risk dental and surgical procedures.
• Prophylactic antibiotics are normally given
  immediately before and for several hours after
  the procedure when a bacteremia is considered
  likely.
• Likely antibiotics interfere with bacterial
  adherence so infection does not become
  established.

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Meningitis

• Inflammation of the meninges surrounding the
  brain and spinal cord.
• Acute meningitis is associated with
• sudden onset
• headache
• neck stiffness
• confusion (occasionally)
• Meningitis can be acute or chronic, the latter
  being relatively rare

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Causes of Meningitis

• Bacteria
• S. pneumoniae
• N. meningitidis
• H. influenzae
• Other bacteria, including Listeria (Streptococci
  and gram negative bacilli)

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Causes of Meningitis (contd)

• Viral causes
• Enteroviruses
• Arboviruses
• Herpesviruses
• Other
• Syphilis
• Tuberculosis
• Fungi

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Pathogenesis of Bacterial Meningitis

• Nasal pharyngeal colonization
• Local invasion
• Bacteremia
• Meningeal invasion
• Bacterial replication in the subarachnoid space
• Release of bacterial cell wall components

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Pathogenesis (contd)

• Release of bacterial call components
• Activates macrophages to release cytokines
• Subarachnoid space inflammation
• Increased CSF outflow resistance
• Cerebral vasculitis
• Increased blood brain barrier permeability
• Increase brain edema
• Confusion and coma

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Epidemiology of Meningitis

• S. pneumoniae occurs in both young children and
  adults with no epidemic potential.
• N. meningitidis occurs primarily in infants,
  younger children, and teenagers both sporadic
  and epidemic cases occur.
• H. influenzae affects children between 3 months
  and 5 years. Now virtually eliminated by HI
  vaccine.

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Epidemiology (contd)

• Listeria monocytogenes may affect the young and
  the elderly most cases are likely food related
  and epidemics can occur.
• Enteroviruses usually responsible for mild cases
  during summer and may occur in clusters.
• Arboviruses seen primarily in localized areas of
  the world where the virus, mosquitoes and birds
  encounter optimal conditions.

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Diagnosis

• Clinical features
• CAT scan showing no evidence of a mass
• Cloudy spinal fluid with increased numbers of
  white cells, high protein and low glucose
• Organisms seen on gram stain (may be negative
  when antibiotics have been administered)
• CSF culture
• Throat and stool culture for suspected viral
  meningitis

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Treatment

• Treatment is usually given empirically (before
  the organism have been identified)
• Definitive treatment
• Usually a single antibiotic based on
  identification and susceptibilities
• S. pneumoniae (penicillin or a third-generation
  cephalosporin)
• Neisseria meningitidis (penicillin)
• Hemophilus influenzae (a third-generation
  cephalosporin)

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Prevention of Meningitis

• Secondary cases of both N. meningitidis and H.
  influenzae do occur, but are rare.
• Immediate household contacts and others with
  close personal contact may be infected.
• Antibiotic prophylaxis may be used for
  susceptible contacts.
• In larger outbreaks, N. meningitidis vaccine may
  be administered.

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Diarrhea and Intra-Abdominal Infections
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Objectives Abdominal and Enteric Infections

• To understand the nature of the normal flora in
  the GI tract.
• To become familiar with the major enteric
  pathogens
• To become familiar with the mechanisms of
  disease.
• To have an understanding of the role of gut flora
  in intra abdominal infections.

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GI Tract - Normal Flora

• Oral cavity
• Respiratory flora (Mixed Gram positives, gram
  negative coccobacilli, anaerobes. Coliforms are
  rare.)
• Stomach
• As for oral cavity, (flora has low numbers
  because of acidity).
• Small bowel/colon
• Fecal flora (Mixed gram negative rods
  (coliforms), enterococci, many species and large
  numbers of anaerobes gram positive and negative.)

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GI Tract Fluid Shifts

• 1.5 L/day oral intakeSaliva1/5 L
• Gastric secretions 3 L Bile 0.5
  LPancreas 2 L DuodenumSmall
  bowel 50 L
  Colon 0.15 L/day lost in
  stool

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Tract - Anatomy and GI Functioning

• Oral Cavity Food chewed and mixed.
• Stomach Acid bath and further mixing stage.
• Duodenum Neutralized, and mixed with bile and
  digesting enzymes from pancreas
• Small Bowel Absorption of nutrients.Colon Absorp
  tion of fluid, and electrolytes

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Types of enteric disease caused by microbes

• Food poisoning Intoxication, no infection.
• Infection with toxin producers.
• Infection with no toxin produced.
• Infection with superficial invasion/destruction.
• Infection with deep invasion.

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Food Poisoning

• Associated with errors in food handling (e.g.
  excess time standing at room temperature,
  contamination).
• Preformed toxin ingested organisms. (Symptoms
  are caused by the toxin - no organisms may be
  viable.)
• Organisms ingested and initiate infection.

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Food Poisoning (contd)

• Most common types are short lived (24-48 hrs)
• e.g. Staph aureus (vomiting, diarrhea)
• Bacillus cereus (vomiting, diarrhea)
• Clostridium perfringens (diarrhea)
• Botulism (paralysis, death)

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Infection with toxin producers

• Toxin causes outflow of fluid in small bowel
  (bowel wall is undamaged)
• Diarrhea is watery, no blood, no pus (cells are
  stimulated to secrete fluid)
• Mediated by cytotonic toxins
• e.g. E. coli - Traveller's diarrhea
• Cholera - severe watery diarrhea

33
Infection with non toxin producer

• Bowel wall may be coated with organisms (coating
  prevents absorbtion of nutrients)
• Malabsorption may be chronic, leading to bulky
  stools.
• e.g. Giardia - "Beaver fever

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Infection with superficial invasion and/or gut
wall destruction

• Bowel wall has ulcerations at areas of invasion,
  and bleeds. (Toxin kills cells in gut wall)
• Diarrhea passed in small volumes, blood, pus,
  may be present. dysentery (in severe disease
  perforation of the gut wall can occur)

35
Infection with superficial invasion and/or gut
wall destruction (contd)

• Mediated by cytotoxic toxins.
• e.g. Shigella E. coli 0157
  Clostridium difficile

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Infection with deep invasion

• Organisms invade bloodstream (may seed infection
  to other body sites)
• Diarrhea may be bloody, with fever (ulcerations
  occur at site of invasion)
• "Enteric fever,
• e.g. Salmonella, including typhoid
  Yersinia (may mimic appendicitis)

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Common organisms causing diarrhea in Canada

• Bacteria
• E. coli 0157
• Shigella
• Salmonella
• Campylobacter
• Yersinia
• Clostridium difficile
• Parasites - see later lecture
• Viral causes - see later lecture

38
Shigella spp

• 4 species (most severe is S. dysenteriae).
• Travel history is common to areas having poor
  sewage disposal.
• Person to person spread occurs as few organisms
  are required to spread infection (Low infective
  dose). Can be in food/water.

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Shigella spp (contd)

• Cytotoxic toxins produced with superficial
  invasion.
• Diarrhea/dysentery result which can be severe.
• Antibiotics are used for treatment.
• Diagnosis by stool culture.

40
E. coli 0157 and Verotoxin Producing E. coli

• Toxin produced which destroys cultures of vero
  cells. (O157 is the most common serotype to
  produce verotoxin, and attacks the colon.
• Acquired from food (especially undercooked
  hamburger, unpasteurized milk).

41
E. coli 0157 and Verotoxin Producing E. coli
(contd)

• Diarrhea, abdominal pain, and in severe cases
  hemorrhagic colitis (passing blood per rectum),
  in some cases renal disease can follow infection.
• Most severe disease occurs at extremes of life.
  Antibiotics are contra-indicted and should not be
  used for treatment.

42
Campylobacter spp.

• 2 common species of microaerophilic curved rods,
  that produce toxins.
• Acquired from poultry, especially if poorly
  cooked, unpasteurized milk, water, pets.
• Diarrhea may be watery or bloody, and is
  occasionally severe enough to cause dehydration.
• Usually settles without treatment, but can be
  treated with erythromycin if severe.

43
Salmonella spp.

• Genus of coliforms that colonize birds and
  reptiles. gt7000 serotypes have been recorded.
  These can be used to help trace outbreaks.
• Acquired from poorly cooked poultry eggs, pet
  reptiles, contaminated food, water.
• Diarrhea can be bloody. Invasive disease can
  occur (enteric fever).

44
Salmonella spp. (contd)

• S. typhi causes typhoid. A few other serotypes
  can cause enteric fever also.
• If mild infection is treated with antibiotics,
  chronic carriage of the organism can develop.
• Treatment can be required in severe cases with
  fever.

45
Yersinia spp.

• Coliform that is associated with pigs. Tends to
  be slow growing. Able to grow well at
  refrigerator temperatures.
• Diarrhea may be bloody. Abdominal pain mimicking
  appendicitis can occur. Enteric fever can occur
  in severe cases.
• Antibiotics are used for treatment in severe
  cases.

46
Clostridium difficile

• Anaerobic gram positive rod, which forms spores
  that can persist in the environment.
• Can colonize healthy people, found commonly in
  healthy babies and in about 2 of adults in the
  community, but up to 30 of patients in hospital.
• Most common agent causing infective diarrhea in
  hospitals especially after antibiotic therapy.

47
Clostridium difficile (contd)

• Diarrhea can be watery and if severe, can cause
  colonic distention and rupture.
• Diagnosed by toxin detection in stool.
• Treated with antibiotics if necessary.

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Diagnosis of enteric illness

• Stool Specimens
• For aerobes stool should be sent using a
  transport medium for culture on media that allows
  pathogens to grow and suppresses the growth of
  flora.
• For detection of C. difficile, stool without
  transport media should be sent for toxin
  detection.
• WBC in stool may indicate the mechanism of
  infection.(e.g. invasion present).

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Intra-abdominal infection

• Release of fecal flora into the abdominal cavity
  occurs when the gut is perforated and results in
• Initially peritonitis, which may develop into
  life threatening sepsis.
• Development of abscess if the host survives,
  which must be drained - may be multiple and occur
  at a variety of sites. Organisms involved
  include a mixture of aerobes and anaerobes.

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Intra-abdominal infection (contd)

• Peritonitis can also occur when a single species
  infects the peritoneum or as a complication of
  peritoneal dialysis when skin or environmental
  organisms may be involved.

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Helicobacter pylori

• Microaerophilic spiral gram negative rod, very
  fastidious, colonizes gastric mucosa.
• Route of transmission not well defined.
• Causes gastritis, and in chronic infection causes
  ulcers and can lead to some types of stomach
  cancer.

52
Helicobacter pylori (contd)

• Detected by serology, histology or culture of
  stomach biopsy.
• Can be treated with antibiotics.

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Sexually Transmitted Disease
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Sexually Transmitted Diseases - Syphilis

• Causative agent Treponema pallidum
• Described in 1905 by Schaudinn and Hoffman
• tightly coiled organism (5-15 ?m length, 0.09-0.5
  ?m diameter)
• Increasing prevalence since mid-1980s
• Transmitted through sexual contact or
  transplacetally

55
Syphilis - Clinical Presentation

• Primary syphilis (localized)
• Produces a chancre (painless ulceration)
• Presents 1-4 weeks post infectious contact
• Heals spontaneously within weeks
• Secondary syphilis (systemic)
• Lesions on skin, central nervous system, liver
• Latent infection (asymptomatic)
• Tertiary syphilis (late)
• Gumma )(late cutaneous, bony, or visceral
  lesions)
• Cardiovascular and neurological
• Congenital

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Syphilis - Diagnosis and Treatment

• Dark field microscopy
• Nonspecific tests
• VDRL (Venereal Disease Research Laboratory)
• RPR (Rapid Plasma Reagin)
• Specific tests
• FTA-Abs (fluorescnet treponemal absorption)
• MHA-TP (microhemagglutination for T. pallidum)
• Treatment
• Contact tracing
• Penicillin is treatment of choice, tetracycline
  or erythromycin if pen allergic

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STDs - Gonorrhea

• Causative agent Neisseria gonorrhoeae
  (gonococcus)
• Gram-negative diplococcus
• Requires enriched medium to grow as well as CO2
• susceptible to dessication - must be transported
  in charcoal medium or brought immediately to the
  laboratory

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Gonorrhea - Clinical Presentation

• Incidence is dropping significantly in Canada
• Most common in 20-25 age group
• Transmitted through contact of mucous membranes
  (sexually or perinatally)
• Clinical manifestations
• mucopurulent urethritis
• mucopurulent cervicitis, pelvic inflammatory
  disease
• pharangitis, conjunctivitis
• disseminated gonococcal infection
• gonorrheal ophthalmia neonatorum

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Gonorrhea - Diagnosis and Treatment

• Culture of urethral or cervical swabs
• Confirmation
• direct fluorescent antibody test
• sugar fermentation
• Amplification such as polymerase chain reaction
  (PCR)

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Gonorrhea - Diagnosis and Treatment (contd)

• Treatment
• contact tracing
• penicillin NO longer the treatment of choice 2ry
  to penicillinase production
• cefixime or ceftriaxone ciprofloxacin or
  ofloxacin if ?-lactam allergic

61
STDs - Chlamydia

• Causative agent Chlamydia trachomatis
• Obligate intracellular bacteria devoid of a cell
  wall (cannot be gram-stained)
• Cannot be grown on artificial media, requires
  cellular culture

62
STDs - Chlamydia (contd

• Complex life cycle
• reticulate body actively replicates within cells
• elementary body infectious particle
• Infects urethral, cervical, and conjunctival
  epithelial cells

63
Chlamydia - Clinical Presentation

• Transmitted through sexual contact or perinatally
• Most common in 15-25 age group, femalesgtmales
• Asymptomatic carriers - common
• Incidence increases as number of partners increase

64
Chlamydia - Clinical Presentation (contd)

• Clinical manifestations
• nongonococcal mucopurulent urethritis and
  cervicitis
• pelvic inflammatory disease
• Reiters syndrome (urethritis, conjunctivitis,
  and arthritis)
• conjunctivitis (especially in neonates) and
  trachoma

65
Chlamydia - Diagnosis and Treatment

• Men urethral swabs, urine samples
• Women endocervical swabs (not vagina), urine?
• Must be transported in sucrose-phosphate medium

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Chlamydia - Diagnosis and Treatment (contd)

• Detection
• culture on cellular medium
• enzyme immunoassay (EIA), direct fluorescent
  antibody, or amplification methods
• Treatment
• contact tracing
• erythromycin, doxycycline, or azithromycin

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STDs - Genital Herpes

• Causative agent herpes simplex virus (HSV) type
  1 or 2
• Linear double-stranded DNA virus, neorotropic
• Primary, latent, and recurrent infection
• Occurs in all population groups
• Prevalence of antibody increases with age and
  correlates with SES
• Seroprevalence studies of HSV-2 20-80 have
  antibodies
• Transmitted through close contact with person
  shedding virus

68
Genital Herpes - Clinical Presentation

• Primary infection
• constitutional symptoms (fever, headache,
  malaise, myalgia)
• painful lesions
• dysurea (males 44, females 88)
• vaginal or urethral discharge
• tender inguinal adenopathy
• Latent - shedding of virus without any lesions

69
Genital Herpes - Clinical Presentation (contd)

• Recurrent infection - HSV-2gtHSV-1
• usually localized to genital area
• 50 have prodromal symptoms (tingling, pain)
• Congenital infection (localized, CNS,
  disseminated)

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Genital Herpes - Diagnosis and Treatment

• Swabs of local lesions
• electron microscopy (EM)
• culture on cellular medium
• Serology is not useful for diagnosis
• Treatment
• antivirals (acyclovir, valaciclovir, famciclovir)
• long term prophylaxis may be necessary in
  recurrent disease