CORYNEBACTERIUM AND

LISTERIA (NON-SPORE-
FORMING RODS)
Corynebacterium diphtheriae and Listeria monocytogenes. Both of
these gram-positive rods infect patients in the pediatric age group.
CORYNEBACTERIUM DIPHTHERIAE
• Corynebacterium diphtheriae is the pathogen responsible for
diphtheria. It colonizes the pharynx, forming a grayish
pseudomembrane composed of fibrin, leukocytes, necrotic epithelial
cells, and Corynebacterium diphtheriae cells. From this site, the
bacteria release a powerful exotoxin into the bloodstream, which
specifically damages heart and neural cells by interfering with protein
synthesis.
• While working in the pediatric emergency room, you see a child with
a sore throat and fever. There is a dark inflammatory exudate on the
child's pharynx, which appears darker and thicker than that of strep
throat. Although you may feel the urge to scrape off this tightly
adherent pseudomembrane, you must resist this temptation, because
bleeding will occur and the systemic absorption of the lethal exotoxin
will be enhanced.
• Being the brightest medical student in the pediatric emergency room,
you immediately recognize that this child probably has diphtheria.
Realizing that you are dealing with an extremely powerful exotoxin,
you quickly send the throat and nasopharynx swabs for culture on
potassium tellurite agar and Loeftler's coagulated blood serum media.
However, these culture results will not be ready for days!!! You may
try a Gram stain of a specimen from the pseudomembrane, but
grampositive rods are not always seen. Since there is no time to loaf
with diphtheria, it is often best to proceed rapidly to treatment via
the following 3-step method.
1) Antitoxin: The diphtheria antitoxin only inactivates circulating toxin,
which has not yet reached its target tissue, so this must be administered
quickly to prevent damage to the heart and nervous system.
2) Penicillin or erythromycin: Either antibiotic will kill the bacteria, preventing
further exotoxin release and rendering the patient non-contagious.
3) DPT vaccine: The child must receive the DPT vaccine, as infection by
Corynebacterium diphtheriae does not always result in immunity to future
infection by this organism. The DPT vaccine stands for: D = Diphtheria; P =
Pertussis (Whooping Cough); and T = Tetanus. The diphtheria portion
contains formalin inactivated diphtheria toxin .
• Now that therapy has been administered, we can sit back, relax, and
confirm our clinical suspicion of diphtheria. On the potassium-tellurite
plate, colonies of Corynebacterium diphtheriae become gray to black
within 24 hours. With Loeffier's coagulated blood serum, incubation
for 12 hours followed by staining with methylene blue will reveal rod-
shaped pleomorphic bacteria.
• Fortunately for nonimmunized children, not all Corynebacterium
diphtheriae secrete this exotoxin. Just as Group A beta-hemolytic
streptococci must first be lysogenized by a temperate bacteriophage
to produce the erythrogenic toxin that causes scarlet fever,
Corynebacterium diphtheriae first must be lysogenized by a
temperate bacteriophage which codes for the diphtheria exotoxin.
• This powerful exotoxin contains two subunits. The B subunit binds to
target cells and allows the A subunit to enter the cell. Once inside the
cell, the A subunit blocks protein synthesis by inactivating elongation
factor (EF2), which is involved in translation of eucaryotic mRNA into
proteins . Notice an interesting comparison: Anti-ribosomal antibiotics
are specifically designed to inhibit protein synthesis in bacterial
(procaryotic) cells. Similarly, this exotoxin specifically inhibits protein
synthesis in humans (eucaryotes). Thus this exotoxin can be
considered a "human antibiotic," because its damage to heart and
neural cells can be lethal.
Other Coryneform bacteria (also called the
diphtheroids)
• The Greek word ''koryne" means "club" and the word ''bacterion" means "little
rod"; other bacteria that share these morphological features with Corynebacterium
diphtheriae have been called either the Coryneform bacteria or the diphtheroids.
These bacteria include the genera Corynebacterium, Arcanubacterium,
Breuibacterium, Microbacterium and others. These Coryneform bacteria are
normal inhabitants of water, soil and the human skin and mucous membranes.
They are frequently isolated as "contaminants" in cultures in hospitalized patients
and you will often receive a report from the micro lab on one of your patients
stating that the early culture is growing a diphtheroid or gram positive rod. While
this usually does not indicate an active infection, one must be careful because
these bacteria are increasingly causing both community acquired infections (native
valve endocarditis, urinary tract infections, prostatitis, and periodontal infections)
and nosocomial (hospital acquired) infections.
• In hospitalized patients, these bacteria can cause surgical wound
infections, catheter and prosthetic device related infections, and
native and prosthetic valve endocarditis. Common nosocomial
pathogens include Corynebacterium jeikeium, Corynebacterium
urealyticum, Corynebacterium amycolatum, and Corynebacterium
striatum. Another thing that sets the Coryneform bacteria apart from
Corynebacterium diptheriae is that they are usually quite resistant to
antibiotics and require treatment with intravenous vancomycin.
Consultation with an infectious diseases physician is advised to help
determine if an actual infection exists and to guide antibiotic therapy.
• Rhodococcus equi (formerly Corynebacterium equi)
• This gram positive, aerobic nonmotile, bacillary bacteria (rod-like that can grow long,
curved, clubbed and even form branching short filaments) typically infects animals like
cattle, sheep, deer, bears, dogs and cats. It has been isolated in manure and soil and if
inhaled by an immunocompromised person (organ transplant recipient or HIV
infected) it can form a necrotizing pneumonia that looks like that caused by
Mycobacterium tuberculosis or Nocardia: the infection forms infiltrates, single or
multiple nodules that cavitate and pleural effusions.
• Clinical Pearl: Upper lobe lung nodules and cavities that form air-fluid levels are
characteristic of Rhodococcus infection, while the upper lung cavities caused by
Mycobacterium tuberculosis rarely form air-fluid levels. Also, Rhodococcus may stain
partially acid-fast, leading to even more diagnostic confusion when trying to
differentiate from tuberculosis.
LISTERIA MONOCYTOGENES
• Listeria monocytogenes is a small facultatively anaerobic, non-spore
forming gram-positive rod that when isolated in blood is often first
identified by the micro lab as a diphtheroid (be careful because you
might think this is just a contaminant!). It has 1-5 flagella and when
grown at 25 °C exhibits a tumbling motility. Because it can grow at low
temperatures, it is often cultured at 4-10 °C, so called cold-enrichment,
to differentiate it from other bacteria. It has a major virulence factor,
listeriolysin 0, that allows it to escape the phagolysosomes of
macrophages and avoid intracellular killing. To remember why this bug
Listeriosis is bad, think of this List: Pregnant women, neonates, and
meningitis in the elderly and immunocompromised.
1) The first group at high risk of infection is pregnant women. Infection
usually occurs in the third trimester, when the cell-mediated immunity
decreases. Interestingly, meningitis is unusual in pregnant women who
usually suffer from bacteremia and sepsis. The bacteria infects the fetus
and 22% of these infections result in neonatal death; surviving babies
are often born prematurely with active infection. Because Listeria is
acquired from ingestion of contaminated foods (infected coleslaw, milk,
soft cheeses, butter and deli meats) pregnant women are often told to
avoid soft cheese and cold cuts.
2) The second group at risk is the fetus and neonate. Infection is acquired in
utero as described above and can also be contracted from an asymptomatic
mother, with vaginal colonization with Listeria, during vaginal birth. This mode of
infection results in neonatal meningitis presenting about 2 weeks post-partum.
Since the advent of Haemophilus infiuenzae vaccination (HiB vaccine, Listeria
monocytogenes now causes about 20% of all neonatal meningitis.
Clinical Pearl: Three bacteria are responsible for most meningitis acquired by
the baby coming out of the birth canal (within first 3 months of age): Listeria
monocytogenes, Escherichia coli, and Group B Streptococcus. Two bacteria
cause meningitis later in life after the maternal antibodies passively given to
fetus wane and before new antibodies develop: Neisseria meningitides and
Haemophilus infiuenzae.
3) The third group of patients at risk for Listeria meningitis is the elderly
and the immunocompromised. In fact, Listeria is the second most
common cause of meningitis, after Pneumococcus, in people >50 years
of age and is the most common cause of meningitis in patients with
lymphoma, on corticosteroids or receiving organ transplantation. It also
causes meningitis frequently in patients with AIDS.
• You may wonder why this organism invades neonates and certain immunosuppressed
patients but not an immune competent host. The main reason is that Listeria
monocytogenes is a resistant fellow, able to hide out and survive within certain immune
cells, such as macrophages and neutrophils that can phagocytose, or engulf, foreign
objects such as bacteria. Since they can survive either outside or within cells, Listeria
monocytogenes is called a facultative intracellular organism . However, in immune
competent hosts, the immune system can release factors that activate the macrophage,
so that these cells can now destroy the "vagrant" bacteria within them. Immunologists
refer to this immune system-mediated method of destroying Listeria as cell-mediated
immunity. However, neonates (up to 3 months of age) and immunosuppressed patients
are unable to activate their phagocytic cells, thus allowing Listeria monocytogenes to
flourish and in’fect the meninges. Since pregnancy may also depress cell-mediated
immunity, Listeria monocytogenes can infect pregnant women as well, who may develop
meningitis or remain asymptomatic carriers.
• when meningitis develops in a patient who is at high risk for Listeria
monocytogenes, it is important to treat it empirically with antibiotics that
will cover this bacterium. After a lumbar puncture confirms that this is a
bacterial meningitis (cerebrospinal fluid analysis reveals a high number of
neutrophils, a high protein level, a low glucose, and the Gram stain of the
cerebrospinal fluid may demonstrate gram-positive rods), we must add
either ampicillin or trimethoprimsulfamethoxazole to the antibiotic regimen.
These are 2 antibiotics that cover Listeria monocytogenes.
• Clinical Pearl: In all adults over 50 years of age and in immunocompromised
patients who develop an acute meningitis, add ampicillin or trimethoprim
sulfamethoxazole to empirically cover Listeria monocytogenes!