Ministry of Higher Education

Subject: Microbiology II
& Scientific Research
Al Muthanna University Grade: 3
College of Veterinary Medicine Lecture : 10
Branch of Microbiology

Microbiology II/ ENTEROBACTERIACEAE

NAME: Klebsiella spp.

SYNONYM OR CROSS REFERENCE: Human pathogens include K. pneumoniae subspecies

pneumoniae, ozaenae, and rhinoscleromatis; K. oxytoca; K.
granulomatis; K. variicola; and K. singaporensis.

CHARACTERISTICS: Klebsiella spp. are Gram-negative, nonmotile, usually encapsulated rod-

shaped bacteria, belonging to the family Enterobacteriaceae. These bacteria produce lysine
decarboxylase but not ornithine decarboxylase and are generally positive in the Voges-
Proskauer test. Members of the Enterobacteriaceae family are generally facultative anaerobic,
and range from 0.3 to 1.0 μm in width and 0.6 to 6.0 μm in length. Klebsiella spp. often occur in
mucoid colonies. The genus consists of 77 capsular antigens (K antigens), leading to different
serogroups.

PATHOGENICITY/TOXICITY:
Klebsiella spp. have been identified as important common pathogens for nosocomial
pneumonia (7 to 14% of all cases), septicaemia (4 to 15%), urinary tract infection (UTIs; 6 to
17%), wound infections (2 to 4%), intensive care unit (ICU) infections (4 to 17%), and neonatal
septicaemias (3 to 20%). Klebsiella spp. can also cause bacteremias and hepatic infections, and
have been isolated from a number of unusual infections. They are also important opportunistic
pathogens, particularly among the immunocompromised. Pathogenicity factors of Klebsiella
spp. include adhesins, siderophores, capsular polysaccharides (CPLs), cell surface
lipopolysaccharides (LPSs), and toxins, each of which plays a specific role in the pathogenesis of
these species. Depending on the type of infection and the mode of infectivity, cells of Klebsiella
spp. may adhere and attack upper respiratory tract epithelial cells, cells in gastrointestinal tract,
endothelial cells, or uroepithelial cells, followed by colonization of mucosal membranes.
Common underlying conditions include alcoholism, diabetes mellitus, chronic liver disease
(cirrhosis), chronic renal failure, cancer, transplants, burns, and/or use of catheters.

Respiratory disease:
- K. pneumonia; a leading cause of community-acquired and nosocomial pneumonia and lung
abscesses. Infection of the upper lobe is more common. Symptoms include: fevers, chills, and
leukocytosis with red currant jelly-like sputum. Rare complications include lung infection
involving necrosis and sloughing of the entire lobe.
- K. ozaenae – causes ozena, a primary atrophic rhinitis (AR) which involves chronic
inflammation of the nose.
- K. rhinoscleromatis – causes rhinoscleroma (RS), a chronic granulomatous infection which
predominantly affects the cavity of the nose. Central nervous system (CNS) infections: K.
pneumoniae and K. oxytoca – cause community-acquired meningitis and brain abscesses.
Clinical symptoms include: headaches, fever, altered conciousness, seizures, and septic shock.
- K. ozaenae – associated with rare cases of cerebral abscess and meningitis. Urinary tract
infections (UTIs):
Klebsiella spp. are a frequent cause of UTIs. Significant bacteriuria has been ascribed to K.
ozaenae.

Hepatic disease:
- K. pneumoniae – an important causative pathogen for pyogenic liver abscesses with
symptoms including fever, right-upper-quadrant pain, nausea, vomiting, diarrhea or
 abdominal pain, and leukocytosis. Abscesses occur predominantly in the right lobe and
are solitary.
Other infections:
K. granulomatis – causes donovanosis or granuloma, a chronic ulcerative disease that primarily
affects the genitalia. Symptoms include development of small papule or ulcer at the site of
inoculation that later develop into large red ulcers (lesions) that extend along the moist folds of
the genitalia.
.
EPIDEMIOLOGY:
Klebsiella spp. occur worldwide, particularly in tropical and subtropical regions, and are
ubiquitous, including forest environments, vegetation soil, water, and mucosal membranes of
host species. Although they are common pathogens for communityacquired pneumonias and
bacteremias, the majority of the infections are nosocomial (hospital-acquired; ~56% of all
Klebsiella infections). Adult males are more susceptible to infection with Klebsiella spp. than
adult females; however, Klebsiella spp. demonstrate higher colonization rates among neonates
and may survive up to months as compared to a few days to weeks in adults. Risk of infection
and carriage rates of Klebsiella spp. increases with increase in duration of stay within a hospital.
Infection and carriage rates also increase with antimicrobial use.

HOST RANGE:
Humans, mammals (including horses, bovines, rhesus and squirrel monkeys, guinea pigs,
muskrats, lemurs, and bats), aquatic animals (including elephant seals, California sea lions, and
harbor seals), reptiles (including snakes, crocodiles, and American alligators), birds, insects, and
plants (banana, rice sugar cane and maize).

INFECTIOUS DOSE:
Unknown. According to one source, 108 Klebsiella organisms per gram of feces are required to
produce damage.
MODE OF TRANSMISSION:
Klebsiella spp. can be transmitted through skin contact with environmentally contaminated
surfaces and/or objects. Fecal transmission has also been suggested for some cases of
bacteremia caused by Klebsiella spp.

INCUBATION PERIOD: Not clearly understood.

COMMUNICABILITY:
Members of Klebsiella spp. can be transmitted from person-toperson; however, the
communicability period is unknown. Approximately one-third of people carry Klebsiellae in
their stools. Hospital personnel have been shown to frequently carry Klebsiellae on their hands.

DISSEMINATION
- RESERVOIR: Infected humans (with or without symptoms of disease) are the primary
reservoir for Klebsiella spp. E.g., infected infants (usually asymptomatic) colonized with
invasive strains of Klebsiella spp., and hospital patients (for nosocomial infections).
Other sources include certain plants.
- ZOONOSIS: None.
- VECTORS: None

EXPOSURE CONTROLS / PERSONAL PROTECTION

- RISK GROUP CLASSIFICATION: Risk Group 2. The risk group associated with “Klebsiella
spp.” reflects the genus as a whole, but does not necessarily reflect the risk group
classification of every species within the genus.
- CONTAINMENT REQUIREMENTS: Containment Level 2 facilities, equipment, and
operational practices for work involving infectious or potentially infectious materials,
animals, or cultures. The containment and operational requirements may vary with the
species, subspecies, and/or strains.
 - PROTECTIVE CLOTHING: Lab coat. Gloves when direct skin contact with infected
materials or animals is unavoidable. Eye protection must be used where there is a
known or potential risk of exposure to splashes.
- OTHER PRECAUTIONS: All procedures that may produce aerosols, or involve high
concentrations or large volumes should be conducted in a biological safety cabinet
(BSC). The use of needles, syringes, and other sharp objects should be strictly limited.
Additional precautions should be considered with work involving animals or large scale
activities.

Proteus infection
Proteus is a member of the Enterobacteriaceae family. The genus of Proteus consists of motile,
aerobic and facultatively anaerobic, Gram-negative rods. Proteus is a member of the
tribe Proteeae, which also includes Morganella and Providencia. The genus Proteus currently
consists of five named species: P. mirabilis, P. vulgaris, P. penneri, P. myxofaciens and P.
hauseri and three unnamed genomospecies: Proteus genomospecies 4, 5, 6 . However, a recent
study indicated that P. myxofaciens may represent a separate genus with low similarity to
tribe Proteeae, and it has been suggested that this organism be renamed Cosenzaea
myxofaciens .
A striking microbiologic characteristic of Proteus species is their swarming activity. Swarming
appears macroscopically as concentric rings of growth emanating from a single colony or
inoculum. On a cellular level, swarming results from bacterial transformation from "swimmer
cells" in broth to "swarmer cells" on a surface such as agar, in a process involving cellular
elongation and increased flagellin synthesis. The genus name Proteus originates from the
mythological Greek sea god Proteus, who was an attendant to Poseidon . Proteus could change
his shape at will. This attribute reminded early microbiologists of the morphologic variability of
the Protei on subculture, including their ability to swarm.
EPIDEMIOLOGY
Members of the genus Proteus are widespread in the environment and are found in the human
gastrointestinal tract . The most common infections caused by Proteus spp. are urinary tract
infections (UTIs). Proteus spp. can be found to colonize the vaginal introitus prior to onset of
bacteruria. Therefore, like Escherichia coli, Proteus spp. causes urinary tract infections by
ascending from the rectum to the periurethra and bladder.
P. mirabilis is by far the most common species identified in clinical specimens. P. mirabilis is a
common cause of both community-acquired and catheter-associated UTI, cystitis,
pyelonephritis, prostatitis, wound infections, and burn infections, and occasionally causes
respiratory tract infections, chronic suppurative otitis media, eye infections (endophthalmitis),
meningitis, and meningoencephalitis. It is a common cause of bacteremia following catheter-
associated UTI (90), and in rare cases has been reported to cause cellulitis, endocarditits,
mastoiditis, empyema, and osteomyelitis. It has also been suggested that P. mirabilis could
have a role in the etiology of rheumatoid arthritis .
P. vulgaris, previously considered biogroup 2, has been reported to cause UTIs, wound
infections, burn infections, bloodstream infections, and respiratory tract infections . There has
also been one case study of P. vulgaris causing bacteremia and brain abscesses, with the
suspected point of entry being the digestive tract.>
P. penneri, previously biogroup 1, generally causes UTIs, wound infections, burn infections,
bloodstream infections, and respiratory tract infections.There has been one case study ofP.
penneri Fournier's gangrene in a child with congenital genitourinary anomalies . There has also
been one recent report of P. penneri causing "red body disease" of the Pacific white
shrimp Penaeus vannamei . Notably, P. penneri may be incorrectly identified as P. mirabilis due
to being indole-negative , and it cannot be clearly resolved from P. vulgaris by 16S sequencing
unless using the 16S-23S internal transcribed spacer . Thus, the burden of human infections
caused by this organism may be underestimated.P. myxofaciens was originally isolated from a
gypsy moth and has been isolated from UTIs in India .
P. hauseri, previously considered biogroup 3, has not been associated with infections in
humans.
CLINICAL MANIFESTATIONS
The clinical manifestations of infections with Proteus spp. are, in the main, non-specific.
However, urinary tract infections involving struvite stones are characteristic. By producing
urease, Proteus spp. can hydrolyze urea into ammonia and carbon dioxide, and therefore raise
urinary pH. Alkalinization of urine promotes precipitation of magnesium-ammonium phosphate
salts leading to the formation of struvite stones, which may serve as a nidus for the persistence
of infection or may directly obstruct the urinary tract, thereby promoting infection.

PATHOGENESIS
Proteus spp. possess several virulence factors that explain their uropathogenic potential, many
of which have been investigated in a murine model of UTI (>9). They have pili or fimbriae for
adherence to uroepithelium. Additionally, they elaborate cytotoxic hemolysins that lyse red
cells and release iron, a bacterial growth factor. Proteus isolates possess flagella for motility. As
noted above they produce urease, leading to the formation of struvite stones.

Special Infections
Meningitis:
Proteus meningitis usually follows neurosurgical procedures . Third generation cephalosporins
are indicated in the treatment of P. mirabilis meningitis only if the organism is proven not to be
an ESBL producer. Aztreonam has also been successfully used in the treatment
of Proteus meningitis, and may be an option in penicillin allergic patients . Meropenem (2 grams
every 8 hours intravenously, in adult patients with normal renal function) should be regarded as
the therapy of choice for meningitis due to >P. vulgaris, P. penneri and ESBL producing P.
mirabilis. Although only a single case report of failure exists, ceftriaxone or > cefotaxime should
probably be avoided for >P. vulgaris or P. penneri meningitis. Removal of neurosurgical
hardware should be considered wherever possible.
Endocarditis:
Infective endocarditis due to P. mirabilis has been rarely reported. The few cases that have
been reported appear to have been related to prosthetic valves . Therefore early surgical
intervention is likely the key to successful outcome. Therapeutic options would appear to be an
appropriate beta-lactam (see section on therapy of bacteremia above) plus an aminoglycoside.
Underlying Diseases
The therapeutic recommendations are not different for those patients with
immunosuppression.

Alternate Therapy
Serious infections in patients with life-threatening allergies to beta-lactam antibiotics could
comprise aminoglycosides or possibly either quinolones or cotrimoxazole. Nitrofurantoin is not
an option nor is tetracycline or the glycylcycline class.

Dr. Naer Alkaabi