ICL 2.12: Corynebacterium & Actinomycetes Flashcards
what is the microbiology of corynebacterium?
gram +, pleomorphic
irregular shaped rods
do NOT form spores
non-motile
what are the characteristics of corynebacterium diphtheria?
highly toxic
noninvasive
damage from microbial products
is corynebacteria aerobic or anaerobic?
aerobic
or facultative anaerobe
what is the corynebacteria cell wall made of?
cell wall contains short-chain mycolic acids
but it’s not considered a true acid fast
how do corynebacteria grow?
grow in clumps
look like chinese letters
many contain metachromatic granules = inorganic polyphosphates that act as energy storage sites
they stain different from primary dye
what parts of the body do corynebacteria colonize?
normally colonize the skin, upper respiratory tract, GI tract, and urogenital tract
what are the 4 biotypes that C. diphtheriae is divided into?
- gravis
- mitis
- intermedium
- belfanti
which C. diphtheriae biotypes are often associated with diphtheria?
- gravis
- mitis
intermedium and belfanti are rarely associated with diphtheria
C. diphtheriae vingette
an unvaccinated 63-year-old man developed a sore throat on a week-long trip in Haiti
2 days after he returned home to Pennsylvania, he visited a local hospital with complaints of a sore throat and difficulties in swallowing; treated with antibiotics
patient returned two days later with chills, sweating, difficulty swallowing and breathing, nausea, and vomiting
he had diminished breath sounds in the left lung, and radiographs confirmed pulmonary infiltrates, as well as enlargement of the epiglottis
he went to the ICU and was treated with azithromycin, ceftriaxone, nafcillin, and steroids
over the next 4 days became hypotensive with a low-grade fever but cultures were negative for C. diphtheriae
by the eighth day of illness, a chest radiograph showed infiltrates in the right and left lung bases
white exudate consistent with C. diphtheriae pseudomembrane was observed over the supraglottic structures but cultures at this time remained negative for C. diphtheriae,
however, PCR testing for the exotoxin gene was positive
despite aggressive therapy, the patient continued to deteriorate, and on the 17th day of hospitalization developed cardiac complications and died
what race is inspired by a bacteria?
Iditarod Trail Sled Dog race!!
in 1925, 20 teams of mushers on dog sleds covered 674 miles in 6 days (127.5h) to prevent a diphtheria epidemic in alaska
that’s why there’s a statue of Balto in NY Central Park
which species can C. diphtheriae infect?
C. diphtheriae is a human specific pathogen
Immune individuals can serve as asymptomatic carriers
how is C. diphtheriae transmitted?
person-to-person transmission occurs through oral or respiratory droplets, close physical contact, and rarely by fomites
which populations are most likely to get respiratory diphtheria?
primarily a pediatric disease
however, in areas with high immunization rates, most cases are seen in the elderly population
which populations are most likely to get cutaneous diphtheria?
common in tropical countries
contact with discharge from skin lesions may play an important role in transmission of infection in these environments
which countries have endemic diphtheria?
- Africa
- South America
- Asia/South Pacific
- Middle East
- Europe
what’s the incubation period of diphtheria?
2-5 days
nasal diphtheria can be asymptomatic or mild
what is respiratory diphtheria?
gradual onset
characterized by mild fever (rarely >101° F), sore throat, difficulty in swallowing, malaise, loss of appetite, and hoarseness
which sites of the body are effected by respiratory diphtheria?
- mucous membrane of the upper respiratory tract = nose, pharynx, tonsils, larynx, and trachea
- skin = cutaneous diphtheria
- rarely, mucous membranes at other sites = eye, ear, vulva
what’s the hallmark of respiratory diphtheria?
the presence of a membrane over the mucous membrane of the tonsils, pharynx, larynx, or nares, and can extend into the trachea
that appears within 2–3 days of illness
membrane is firm, fleshy, grey, and adherent – bleeds following attempts to remove or dislodge
local complications such as life-threatening or fatal airway obstruction can result from extension of the membrane or dislodgement of a piece of the membrane into the larynx or trachea
what happens during severe respiratory diphtheria?
cervical lymphadenopathy and soft-tissue swelling in the neck give rise to a “bull-neck” appearance and obstructs airway
literally looks like a giant fat neck that is connected to the chin
what are some of the systemic complications associated with respiratory diphtheria?
- myocarditis
- polyneuropathies
often result from absorption of diphtheria toxin from the infection site and its subsequent dissemination to other organs away from the initial area of infection
*cutaneous and nasal diphtheria are localized and rarely associated with systemic toxicity
describe the diphtheria toxin
it’s the major virulence factor of C. diphteriae
diphtheria toxin is a binary toxin = classic A-B exotoxin that’s activated during secretion to form A-B proteins that remain attached via disulfide bonds
what does the B subunit of the diphtheria toxin do?
B subunit binds heparin-binding epidermal growth factor on local host cells
translocation (T) unit promotes insertion and internalization, then form pore to cytosol
what does the A subunit of the diphtheria toxin do?
the A (catalytic) subunit acts to inactivate elongation factor 2 (EF-2)
it terminates all protein synthesis and eventually kills tissue
a single molecule can inactivate all EF-2 in a cell
it’s irreversible once entering the cell
what are the effects of the diphtheria toxin on the body?
the diphtheria toxin is absorbed into the mucus membrane and can cause destruction of epithelium and inflammation
the necrotic epithelium becomes embedded with fibrin and red/white cells which results in grayish pseudomembrane that is the hallmark of diphtheria
C. diphtheriae can then invade and establish in the epithelial layers
here, it continues to produce toxin that is readily absorbed and travel to distant tissues
this can lead to damage of cardiac, nervous tissue, kidney, liver and adrenals – damage/hemmorrhage of these tissues can lead to death
what encodes the diphtheria toxin?
the diphtheria toxin is encoded by a lysogenic bacteriophage
bacteriophage = a virus that parasitizes a bacterium by infecting it and reproducing inside it
only strains infected by this phage can produce toxin and cause diphtheria
how do diagnose diphtheria?
initial treatment of diphtheria should be instituted based on clinical diagnosis rather than laboratory tests, since need to act quickly
so you base the initial treatment on epidemiologic and clinical clues like if they’re non-vaccinated and/or have visited endemic areas
even though C. diphtheriae has some characteristic growth and morphology features, they are not reliable for diagnosis
what media does diphtheria grow on?
- selective media include cysteine-tellurite blood agar = CTBA or Tinsdale; best to diagnose
- colistin-nalidixic agar = CNA; allows growth, but not diagnostic
Tellurite inhibits most respiratory tract and Gram-negative bacteria
C. diphtheriae reduce tellurite to form gray-black color on agar
what test is used to detect diphtheria toxin?
most important assay is for production of
diphtheria toxin or possess phage
- Elek test was used historically to detect toxin – see precipitate formed when toxin binds to antitoxin
PCR tests for presence of tox gene – Get false positive if toxin not expressed
how do you treat diphtheria?
the most important treatment for diphtheria is early administration of antitoxin – it’s most effective when administered within 3 days of disease development
but it can’t neutralize toxin that has already entered host cells
Equine diphtheria antitoxin (DAT) is the mainstay of treatment!! but you have to perform sensitivity test before administering horse serum to prevent serum sickness
you also need to make sure airway is clear since pseudomembrane can extend into the nasopharnyx or down the larnyx and swelling of lymphatics in neck can also occlude breathing
why do you give antibiotics during diphtheria infection? which antibiotic do you give?
- prevent further exotoxin production
- prevent carrier status
penicillin or erythromycin is DOC
is there a vaccine for diphtheria?
yup
there’s an extremely effective and safe vaccine is available for preventing diphtheria
what is the immunization schedule for diphtheria?
it’s actually a diphtheria and tetanus toxoids and accellular pertusis vaccine = DTaP
4 doses needed initially and then another final dose around 4-6 years old
what two types of diphtheria vaccines are there?
- DTaP
2. Tdap
what is the DTap vaccine?
combined vaccine against diphtheria, tetanus, and pertussis – pertussis component is acellular
children receive 4 doses at normal or “catch-up” schedule
the acellular vaccine is safer to administer and there’s fewer side-effects, such as local pain and redness, and/or fever
what’s the Tdap vaccine?
acronym for the collective vaccines preventing tetanus, diphtheris, and pertussus in adolescents and adults
differ from the childhood DTaP vaccines in that the concentration of diphtheria and pertussis toxoid has been reduced (lowercase d and p)
it’s the booster for “adolescents” and “adults” of all ages who have already received the initial vaccine series – given every 10 years
can be given more frequently in certain situations like a pertussis outbreak or if in the catch up program
FLASHCARD: microbiology, pathology, epidemiology, clinical, diagnosis, treatment of corynebacterium diphtheria
MICROBIOLOGY: Gram + pleomorphic rods, facultative anaerobe, non-motile, short-chain mycolic acid in cell wall, grow in clumps (Chinese letters), contain metachromatic granules
PATHOLOGY: Causes diphtheria. Start in nasal cavity. Gradual onset. Production of binary toxin encoded by bacteriophage that terminates protein synthesis and kills cells. Toxin causes formation of pseudomembrane in throat-associated tissues. Dead tissue provides environment for bacteria to grow and release more toxin, and may block breathing. Initial illness is mild with sore throat, but progresses to severe as toxin affects heart, nervous tissue, kidney, liver, and adrenals.
EPIDEMIOLOGY: Can live in throat without causing disease. Even vaccinated can be carrier, since antibodies are against toxin, not actual bacteria. Most cases seen in countries with poor vaccine coverage, but visitors can pick up and carry back to affect unvaccinated in developed countries.
CLINICAL: Initial illness is mild with sore throat. See formation of pseudomembrane in throat tissues 2-3 days after symptoms start, which can block breathing, but also a site for bacterial growth. As toxin spreads, see severe symptoms heart, nervous tissue, kidney, liver, and adrenals. Often fatal.
DIAGNOSIS: Initial treatment is quickly initiated based on clinical symptoms and epidemiology. Bacteria growth on cysteine-tellurite blood agar (CTBA or Tinsdale) is selective and best to diagnose. CAN agar allows growth, but not diagnostic. Can perform Elek test to detect toxin or use PCR to identify the presence of the toxin gene (but not proved toxin is being produced).
TREATMENT: Most important is early administration of antitoxin to neutralize effects. Also, must assess pseudomembrane to prevent patient choking. DTaP vaccine is very effective. Penicillin or erythromycin is DOC
what are the other corynebacterium species other than corynebacterium diphtheria?
- C. jeikeium
- C. urealyticum
- C. amycolatum
- C. ulcerans
- C. pseudotuberculosis
what is C. jeikeium?
opportunistic in immunocompromised patients – uncommon in healthy people
seen on skin of hospitalized patients (40%) regardless of immune status
VERY RESISTANT to antibiotics
what is C. urealyticum?
uncommon in healthy people
strong urease producer
forms struvite calculi or renal stones
risk factors = immunosuppression, genitourinary disorders, urologic procedure, antibiotic therapy
resistant to most antibiotics
what is C. amycolatum?
found on the skin but not oropharynx
opportunistic pathogen
most commonly isolated Corynebacterium in clinical specimens but often misidentified
resistant to many antibiotics
what is C. ulcerans?
can carry the diphtheria gene
disease indistinguishable from diphtheria
