Diana Miculescu

Klebsiella pneunomiae
Named after German bacteriologist, Edwin Klebs, Klebsiella are Enterobacteriacaea that
live in the mucosal surfaces mouth, skin, and intestines. Klebsiella is also found in the
environment in locations such as surface water, sewage, soil, and on plants (1). More
specifically, Klebsiella pneumoniae is found in the nasopharynx and intestines, but rarely found
on the human skin due to lack of mucosal substances (1). Klebsiella is a Gram negative, non-
motile, encapsulated, rod-shaped bacterium. The bacterium ferments lactose and is a facultative
anaerobe (1). The polysaccharide capsule characteristic of the organism assists with the invasion
of the host and therefore contributes to pathogenicity (1). Members of the Klebsiella genus
express O and K antigens on their cell surface contributing to its pathogenicity (1). The O
antigen is a component of the lipopolysaccharide, and the K antigen is a capsular polysaccharide
(1). These cell surface antigens allow the organism to attach itself to the host while impairing the
process of phagocytosis by the macrophages of the host cell (3). Another characteristic of
Klebsiella pneumoniae is the production of endotoxins which differ among strains. Exact
pathogenic mechanisms of specific species are unclear, but all three factors contribute to the
virulence of the organism in some way (3).
A major portion of Klebsiella infections occur among hospitalized patients. Known to
cause human nosocomial infections, Klebsiella species accounts for a large portion of urinary
tract infections, pneumonia, septicemias in adults and neonates, and soft tissue infections
acquired in hospital settings(1). The infections are tissue specific depending on entry of the
pathogen such as respiratory infections among those of ventilators or urinary tract infections in
patients with catheters. Klebsiella species are opportunistic pathogens and cause serious infection
of immunocompromised patients. Patients with weakened immune systems include those with
chronic pulmonary issues, diabetes, and impaired liver and kidney function (1). Specifically
Klebsiella pneumoniae infections can result in inflammation and hemorrhage of the lungs
(pathogen entry into lungs) accompanied by thick and bloody mucoid sputum. Infections of
Klebsiella have a high fatality rate is left untreated (1).
The source of infection is usually feces, since organisms inhabiting the intestinal tract
would be found in the stool, while contact with contaminated instruments or healthcare personnel
is also significant (1). The pathogen is not spread through the air. Since most infections occur in
clinical settings, detecting, treating, and containing Klebsiella caused infections within hospital
settings are important for decreasing outbreaks. However, outbreaks of Klebsiella infections
have been commonly increasing in the past years. Outbreaks of infectious Klebsiella are
typically of antibiotic resistant strains, and the occurrence of resistant strains around the world
has also increased. For example, in 2005 a patient in Israel was reported to be infected with a
Klebsiella pneumoniae carbapenemase (KPC) infection (5). This resistant strain was found to be
related to a Klebsiella pneumoniae strain from New York that was first reported in 2003 (5).
While properly treating the infection and containing the organism to a limited location is
imperative in reducing the spread of antibiotic resistant pathogens, controlling the emigration of
the pathogen is difficult. Travel of healthcare personnel, patients, and others that have come into
contact with the pathogen that could serve as reservoirs of the pathogen is difficult to control.
This aspect of disease control is quite difficult because antibiotic resistant strains are determined
through laboratory testing and it is simply impossible to test all who have come into contact with
the pathogen.
 Antibiotics used to treat Klebsiella infections are known as beta-lactam antibiotics and
include penicillin and its derivatives. These antibiotics inhibit the synthesis of the cell wall
which, as stated earlier, contributes to its pathogenicity. Another type of treatment for multiple-
drug resistant Klebsiella strains is called phage therapy. Phage therapy has been shown to kill
multiple drug-resistant Klebsiella strains. Like antibiotic resistance, phage resistance can cause
an increase in the number of microbes in environment, which is seen as being dangerous in
clinical settings (1). Instead of replacing antibiotics, phage therapy is used to supplement the
activity of antibiotics, if antibiotics are even useful (1). Probably the most alarming development
of the Klebsiella organisms is the resistance to antibiotics. Some strains acquire the ability to
hydrolyze the beta-lactam ring, which is necessary for the killing activity of the antibiotics.
Klebsiella organisms acquire this resistance to carbapenems by plasmid mediated transfer of the
gene blaKPC, which codes for carbapenemase (5). Carbapenem-resistant Enterobacteriaceae
(CREs) or carbapenemase-producing Enterobactiaceae (CPEs) are bacteria resistant to the
antibiotic class of carbapenems, as the name would suggest. Carbapenems are used to treat
infections that are caused by multidrug-resistant bacteria. Recently, organisms have acquired
resistance against these antibiotics also.
Since antibiotic use is used widely in clinical settings, multidrug-resistant bacteria pose a
threat to healthcare providers and patients. As stated earlier, carbapenems are used as “last-
resort” drugs because no other antibiotics can effectively treat the infection. The acquirement of
resistance against these last-resort drugs can be seen as a huge concern since standard treatments
with antibiotics are virtually useless for these types of organisms. Not only is the single treating
of a patient important, but the containment of the resistant strains is difficult when no effective
treatment is known. To make matters worse, the knowledge one is acting as a reservoir for the
organism can only be uncovered through a laboratory test.
Klebsiella pneumoniae carbapenemase (KPC) is the most common CRE species in the
United States seen in health settings (3). The mode of resistance is through the inactivation of the
carbapenems by enzymes produced by the pathogen (6). While antibiotics are useless when it
comes to these types of resistant organisms, efforts to find something to combat them have not
ceased. Another type of reported Carbapenasemase-producing bacteria in the United States is
known as metallo-beta-lactamases (MBLs). MBLs use a different mechanism to inactive the
beta-lactam ring. While some inhibitors of beta-lactamases are available for treatment of KPC-
types, there has been a lack of finding an inhibitor of MBL-types (6). The search for a treatment
that could reverse the resistance of the organism or assist the organism in becoming sensitive to
carbapenems are of interest (6). A natural fungal product has been identified to be an inhibitor by
Andrew King et al. In the study, King et al. found a product of a natural fungus,
aspergillomarasmine A, to be a fast acting inhibitor of the New Delhi Metallo-lactamase (NDM-
1) enzyme of MBL-types. In addition, aspergillomarasmine A was found to restore the ability of
meropenems against Enterobacteriaceae (6). King’s et al. study revealed that in mice infected
with Klebsiella pneumonia expressing NDM-1, aspergillomarasmine A was able to restore
meropenem activity (6). Studies such as King’s et al. are essential to the understanding of the
mechanisms behind the resistance of organisms. A deeper understanding of the mechanisms of
resistance could give better insight in creating or discovering a possible treatment for
antimicrobial resistant pathogens, even if the treatment can only be used to target one specific
strain or type.
Sometimes scientists reach what seems to be a “dead-end” when it comes to identifying
or discovering new organisms, products, or medicines to combat disease causing agents. In cases
such as CRE or CPE infections, the standard treatment of antibiotics fails due to resistance of
bacterial strains, and when no other treatments are available, these strains can become difficult to
not only treat but to keep contained or controlled. The increase in resistant type organisms that
cause disease demand studies dealing with finding efficient and effective treatments. Faster
pathogen detection and close surveillance of pathogens are also important, since determining if
the disease causing organism is of a resistant strain is key in deciding what type of treatment is
necessary. Even with better detection strategies, new treatment options are needed since the
continued over-use of antibiotics probably intensified this issue of antimicrobial resistance. A
decrease in the use of antibiotics may in turn decrease the rate of emerging antibiotic resistant
organisms.
 References

1. Podschun R, Ullmann U. Klebsiella spp. as nosocomial pathogens: epidemiology, taxonomy,

typing methods, and pathogenicity factors. Clinical Microbiology Reviews [serial on the
Internet]. (1998, Oct), [cited December 2, 2015]; 11(4): 589-603. Available from:
MEDLINE with Full Text.
2. Highsmith A, Jarvis W. Klebsiella pneumoniae: Selected Virulence Factors That Contribute to
Pathogenicity. Infection Control [serial on the Internet]. (1985), [cited December 2,
2015]; (2): 75. Available from: JSTOR Journals.
3. Limbago B, Rasheed J, Anderson K, Zhu W, Kitchel B, Kallen A, et al. IMP-producing
carbapenem-resistant Klebsiella pneumoniae in the United States. Journal Of Clinical
Microbiology [serial on the Internet]. (2011, Dec), [cited December 2, 2015]; 49(12):
4239-4245. Available from: MEDLINE with Full Text.
4. Hudson C, Bent Z, Meagher R, Williams K. Resistance Determinants and Mobile Genetic
Elements of an NDM-1-Encoding Klebsiella pneumoniae Strain. Plos ONE [serial on the
Internet]. (2014, June), [cited December 2, 2015]; 9(6): 1-14. Available from: Academic
Search Complete.
5. McKenna M. Antibiotic resistance: the last resort. Nature [serial on the Internet]. (2013, July
25), [cited December 2, 2015]; 499(7459): 394-396. Available from: MEDLINE with
Full Text.
6. King A, Reid-Yu S, Wang W, King D, De Pascale G, Wright G, et al. Aspergillomarasmine A
overcomes metallo-β-lactamase antibiotic resistance. Nature [serial on the Internet].
(2014, June 26), [cited December 1, 2015]; 510(7506): 503-506. Available from:
MEDLINE with Full Text.