The genus Klebsiella belongs to the tribe
Klebsiellae, a member of the family Enterobacteriaceae. The organisms are named
after Edwin Klebs, a 19th century German microbiologist. Klebsiellae are
nonmotile, rod-shaped, gram-negative bacteria with a prominent polysaccharide
capsule. This capsule encases the entire cell surface, accounts for the large
appearance of the organism on gram stain, and provides resistance against many
host defense mechanisms.
Members of the Klebsiella genus typically express 2
types of antigens on their cell surface. The first is a lipopolysaccharide (O
antigen); the other is a capsular polysaccharide (K antigen). Both of these
antigens contribute to pathogenicity. About 77 K antigens and 9 O antigens
exist. The structural variability of these antigens forms the basis for
classification into various serotypes. The virulence of all serotypes appears
to be similar.
The genus was originally divided into 3 main species based
on biochemical reactions. Today, 7 species with demonstrated similarities in
DNA homology are known. These are (1) Klebsiella pneumoniae, (2) Klebsiella
ozaenae, (3) Klebsiella rhinoscleromatis, (4) Klebsiella oxytoca,
(5) Klebsiella planticola, (6) Klebsiella terrigena, and (7) Klebsiella
ornithinolytica. K pneumoniae is the most medically important
species of the group. K oxytoca and K rhinoscleromatis have also
been demonstrated in human clinical specimens. In recent years, klebsiellae
have become important pathogens in nosocomial infections.[1]
This scanning electron micrograph (SEM) reveals some of the
ultrastructural morphologic features of Klebsiella pneumoniae. Courtesy of
CDC/Janice Carr.
Pathophysiology
Host defense against bacterial invasion depends on
phagocytosis by polymorphonuclear granulocytes and the bactericidal effect of
serum, mediated in large part by complement proteins. Both classic-pathway and
alternate-pathway complement activation have been described, but the latter,
which does not require the presence of immunoglobulins directed against
bacterial antigens, appears to be the more active pathway in K pneumoniae
infections.
Recent data from preclinical studies suggest a role for
neutrophil myeloperoxidase and lipopolysaccharide-binding protein in host
defense against K pneumoniae infection. Neutrophil myeloperoxidase is thought
to mediate oxidative inactivation of elastase, an enzyme implicated in the
pathogenesis of various tissue-destroying diseases. Lipopolysaccharide-binding
protein facilitates transfer of bacterial cell wall components to inflammatory
cells. Investigators showed higher rates of infection in experimental mice
deficient in the genes that control expression of these 2 agents.
The bacteria overcome innate host immunity through several
means. They possess a polysaccharide capsule, which is the main determinant of
their pathogenicity. The capsule is composed of complex acidic polysaccharides.
Its massive layer protects the bacterium from phagocytosis by polymorphonuclear
granulocytes. In addition, the capsule prevents bacterial death caused by
bactericidal serum factors. This is accomplished mainly by inhibiting the
activation or uptake of complement components, especially C3b. The bacteria
also produce multiple adhesins. These may be fimbrial or nonfimbrial, each with
distinct receptor specificity. These help the microorganism to adhere to host
cells, which is critical to the infectious process.
Lipopolysaccharides (LPS) are another bacterial
pathogenicity factor. They are able to activate complement, which causes
selective deposition of C3b onto LPS molecules at sites distant from the
bacterial cell membrane. This inhibits the formation of the membrane attack
complex (C5b-C9), which prevents membrane damage and bacterial cell death.
Availability of iron increases host susceptibility to K
pneumoniae infection. Bacteria are able to compete effectively for iron
bound to host proteins because of the secretion of high-affinity, low molecular
weight iron chelators known as siderophores. This is necessary because most
host iron is bound to intracellular and extracellular proteins. In order to
deprive bacteria of iron, the host also secretes iron-binding proteins.
Epidemiology
Klebsiellae are ubiquitous in nature. In humans, they may
colonize the skin, pharynx, or gastrointestinal tract. They may also colonize
sterile wounds and urine. Carriage rates vary with different studies.
Klebsiellae may be regarded as normal flora in many parts of the colon and
intestinal tract and in the biliary tract. Oropharyngeal carriage has been
associated with endotracheal intubation, impaired host defenses, and
antimicrobial use.
K pneumoniae
and K oxytoca are the 2 members of this genus responsible for most human
infections. They are opportunistic pathogens found in the environment and in
mammalian mucosal surfaces. The principal pathogenic reservoirs of infection
are the gastrointestinal tract of patients and the hands of hospital personnel.
Organisms can spread rapidly, often leading to nosocomial outbreaks.
Infection with Klebsiella organisms occurs in the
lungs, where they cause destructive changes. Necrosis, inflammation, and
hemorrhage occur within lung tissue, sometimes producing a thick, bloody,
mucoid sputum described as currant jelly sputum. The illness typically affects
middle-aged and older men with debilitating diseases such as alcoholism,
diabetes, or chronic bronchopulmonary disease. This patient population is
believed to have impaired respiratory host defenses. The organisms gain access
after the host aspirates colonizing oropharyngeal microbes into the lower
respiratory tract.
Klebsiellae have also been incriminated in nosocomial
infections. Common sites include the urinary tract, lower respiratory tract,
biliary tract, and surgical wound sites. The spectrum of clinical syndromes
includes pneumonia, bacteremia, thrombophlebitis, urinary tract infection
(UTI), cholecystitis, diarrhea, upper respiratory tract infection, wound
infection, osteomyelitis, and meningitis. The presence of invasive devices,
contamination of respiratory support equipment, use of urinary catheters, and
use of antibiotics are factors that increase the likelihood of nosocomial
infection with Klebsiella species. Sepsis and septic shock may follow
entry of organisms into the blood from a focal source.
Rhinoscleroma and ozena are 2 other infections caused by Klebsiella
species. These diseases are rare. Rhinoscleroma is a chronic inflammatory
process involving the nasopharynx, whereas ozena is a chronic atrophic rhinitis
characterized by necrosis of nasal mucosa and mucopurulent nasal discharge.
K oxytoca
has been implicated in neonatal bacteremia, especially among premature infants
and in neonatal intensive care units. Increasingly, the organism is being
isolated from patients with neonatal septicemia.
Extensive use of broad-spectrum antibiotics in hospitalized
patients has led to both increased carriage of klebsiellae and, subsequently,
the development of multidrug-resistant strains that produce extended-spectrum
beta-lactamase (ESBL). These strains are highly virulent, show capsular type
K55, and have an extraordinary ability to spread. Most outbreaks are due to a
single clone or single gene; the bowel is the major site of colonization with
infection of the urinary tract, respiratory tract, and wounds. Bacteremia and
significant increased mortality have resulted from infection with these
species.
In addition to prior antibiotic use, risk factors for
infection include the presence of an indwelling catheter, feeding tube, or
central venous catheter; poor health status; and treatment in an intensive care
unit or nursing home. Acquisition of these species has become a major problem
in most hospitals because of resistance to multiple antibiotics and potential
transfer of plasmids to other organisms.
Epidemiology
Frequency
United States
In some parts of the world, K pneumoniae is an
important cause of community-acquired pneumonia in elderly persons. Studies
conducted in Malaysia and Japan estimate the incidence rate in elderly persons
to be 15-40%, which is equal to, if not greater than, that of Haemophilus
influenzae. However, in the United States, these figures are different.
Persons with alcoholism are the main population at risk, and they constitute
66% of people affected by this disease. Mortality rates are as high as 50% and
approach 100% in persons with alcoholism and bacteremia.
Klebsiellae are also important in nosocomial infections
among adult and pediatric populations. Klebsiellae account for approximately 8%
of all hospital-acquired infections. In the United States, depending on the
study reviewed, they comprise 3-7% of all nosocomial bacterial infections,
placing them among the top 8 pathogens in hospitals. Klebsiellae cause as many
as 14% of cases of primary bacteremia, second only to Escherichia coli
as a cause of gram-negative sepsis. They may affect any body site, but
respiratory infections and UTIs predominate.
Of 145 reported epidemic outbreaks of nosocomial bacteremias
during 1983-1991, 13 were attributed to Klebsiella organisms. The US
Centers for Disease Control and Prevention report that Klebsiella
strains were responsible for 3% of all pathogenic epidemic outbreaks.
An investigation of Klebsiella pneumoniae
carbapenemase (KPC)-producing Enterobacteriaceae among patients of acute
and long-term acute care hospitals was conducted in 2011. The investigation
found extensive spread of KPC-producing Enterobacteriaceae throughout 4
adjacent counties in Indiana and Illinois over a 1-yr period. Long-term acute
care hospitals played a central role in the outbreak, suggesting that
guidelines for controlling KPC should be expanded to include long-term care facilities.
Education of personnel and coordinated regional efforts among health care
facilities are crucial for KPC control.[2]
K oxytoca
is among the top 4 pathogens that cause infection in patients in neonatal
intensive care units. It is the second most frequent cause of gram-negative
neonatal bacteremia.
International
Outbreaks of neonatal septicemia occur worldwide. Infection
with K pneumoniae also has a worldwide distribution. Infection with K
rhinoscleromatis is not common in the United States, although it has a
worldwide distribution and is usually observed in areas of eastern Europe,
southern Asia, central Africa, and Latin America.
Mortality/Morbidity
- Klebsiella pneumonia is a necrotizing process with a predilection
for debilitated people. It has a high mortality rate of approximately 50%
even with antimicrobial therapy. The mortality rate approaches 100% for
persons with alcoholism and bacteremia.
- Klebsiella bacteremia and sepsis produce clinical manifestations
similar to those caused by other gram-negative enteric organisms.
Morbidity and mortality rates are comparable to those for other
gram-negative organisms that cause sepsis and septic shock. In neonatal
units, outbreaks caused by ESBL-producing strains present a more serious
problem and may be associated with increased mortality.
Age
- Community-acquired
Klebsiella (Friedlãnder) pneumonia is a disease of debilitated
middle-aged and older men with alcoholism.
- Nosocomial
infections may affect adults or children, and they occur more frequently
in premature infants, patients in neonatal intensive care units, and
hospitalized individuals who are immunocompromised.
Sumber : http://emedicine.medscape.com/article/219907-overview#showall
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