Klebsiella pneumoniae

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Klebsiella pneumoniae
Klebsiella pneumoniae (secondary electron microscope image, subsequently colored)

Klebsiella pneumoniae
( secondary electron microscope image, subsequently colored)

Systematics
Department : Proteobacteria
Class : Gammaproteobacteria
Order : Enterobacterales
Family : Enterobacteriaceae
Genre : Klebsiella
Type : Klebsiella pneumoniae
Scientific name
Klebsiella pneumoniae
(Schroeter 1886) Trevisan 1887

Klebsiella pneumoniae is a facultatively anaerobic , gram-negative rod bacterium from the genus Klebsiella , which is able tobreak downthe double sugar lactose (milk sugar). In addition, it can reduce the nitrogen present in the airto ammonia or ammonium ; this metabolic pathway is known as nitrogen fixation . In 1984 the species was divided into three subspecies . The bacterium is common everywhere. In humans, it belongs to the normal inhabitants of the intestine . However, itcan occuras a pathogen in other parts of the body, including animals. The genome of the bacterial strain Klebsiella pneumoniae subsp. pneumoniae DSM 30104 was completely sequenced in 2012.

Among the members of the genus, Klebsiella pneumoniae is of particular medical importance; hospital-acquired pneumonia ( nosocomial pneumonia) and other infections are typical for this species . It has several virulence factors and multi-resistant bacterial strains are known, i. H. they are against many antibiotic resistant so that the drug during an infection with these strains of bacteria are not effective. People with a weakened immune system or with acute infections are at risk; the level of contamination can also be decisive.

features

Appearance

The cells of Klebsiella pneumoniae appear in the light microscope image as short rods with a length of 1–2  µm and a width of 0.5–0.8 µm. They are present individually or in pairs and are surrounded by a mucous capsule ( glycocalyx ). In the Gram staining they are colored pink to red, they are Gram negative. As is typical for the genus Klebsiella , they are not actively mobile ( motile ), i.e. they have no flagella (flagella). However, the cell surface is covered with fimbriae . Bacterial colonies that have grown on a nutrient medium do not show any particular coloring, they are convex, round on top and rather large with a diameter of 3–4 mm; their slimy appearance is typical. This is caused by the accumulation of extracellular polysaccharides , which together with the water present form a biofilm .

Growth and metabolism

Colonies of Klebsiella pneumoniae (right half) and Escherichia coli on MacConkey agar , they are each colored pink due to the breakdown of lactose, whereas the colonies of K. pneumoniae look slimy.

As usual with the representatives of the Enterobacteriaceae, the catalase test is positive and the oxidase test is negative. Klebsiella pneumoniae is facultatively anaerobic ; H. it can grow with or without oxygen . It is able to utilize the disaccharide lactose . See the Biochemical Evidence section for more information .

It is also one of the nitrogen-fixing microorganisms; it can reduce elemental, molecular nitrogen (N 2 ) to ammonia (NH 3 ) or ammonium (NH 4 + ) and thus make it biologically available . This takes place with the help of the enzyme complex nitrogenase in an anoxic environment, since the enzyme complex is inactivated by oxygen. Klebsiella pneumoniae is diazotrophic , so it can grow with N 2 as a nitrogen source in order to build up cell-specific substances such as amino acids .

For the cultivation of simple culture media are suitable, for example, trypticase soy agar (TSA agar) on Columbia blood agar , the bacteria can be cultured. Selective culture media which are suitable for the isolation and differentiation of representatives of enterobacteria are often used , for example MacConkey agar and eosin methylene blue agar (EMB), both of which contain lactose. For a further selection, a nutrient medium is recommended that contains only citrate and inositol as a carbon source ( organic compound for energy production ) ; it is based on Simmons citrate agar with an addition of 1% inositol. Klebsiella pneumoniae is mesophilic , optimal growth takes place at a temperature of 30–37 ° C, colonies are visible after incubation for one to two days. Growth also takes place at 41 ° C, but not at 5 ° C. Bacterial strains isolated from medical test material usually grow optimally at 37 ° C, but various detection reactions for identification run better at an incubation temperature of 30 ° C.

Chemotaxonomy

Components of the bacterial cell act as antigens , in Klebsiella there are 77 different K antigens (K refers to the capsule), as well as 9 somatic O antigens. Of diagnostic importance are the K-antigens by serological examination the various let serotypes distinguish what u. a. is applied in the clarification of epidemiological connections. However, there is also an ELISA method for the detection of the O-antigens. The determination can also be made with the help of genetic tests.

genetics

The GC content , i.e. the proportion of the nucleobases guanine and cytosine in the bacterial DNA , is 57.0 mol percent in the bacterial strain DSM 30104 (from the strain collection DSM German Collection of Microorganisms and Cell Cultures )  . DSM 30104 is the type strain of the subspecies Klebsiella pneumoniae subsp. pneumoniae and with it the species , it was isolated from human blood . The genome was completely sequenced in 2012 .

It is a ring-shaped bacterial chromosome and has a size of 5,512 kilobase pairs (kb), which is roughly comparable to the size of the genome of Escherichia coli . There are 5,425 coding genes and 77 tRNAs were identified. The genes were the Antibiotic Resistance Genes Database (ARDB, antibiotic resistance - genetic database ) are compared, there were 15 genes are identified that confer resistance, u. a. for a class A beta-lactamase and an efflux pump . Ten other genes code for gene products that extend the β-lactamase capabilities of the bacterium, including the gene called ampC , which codes for the enzyme called AmpC-beta-lactamase (in this case a cephalosporinase) and the gene called gloB , which codes for an enzyme called metallo-β-lactamase (in this case a carbapenemase). Since then, over 4,200 genomes (based on the circular bacterial chromosome) of this species have been sequenced, and 913 annotations of plasmids have been carried out (as of 2018).

Plasmids often carry the genetic information for antibiotic resistance (see below) of the bacterium, the gene products are enzymes that change a certain chemical structure of an antibiotic and thereby prevent the drug from working. In Klebsiella pneumoniae these are plasmid-coded beta-lactamases, such as SHV-1, TEM-1, TEM-2 or other ESBL ( Extended Spectrum β-Lactamases ). Since the beginning of the 21st century, resistance to carbapenems caused by carbapenemases ( carbapenem-hydrolyzing beta-lactamase ), which are called KPC ( Klebsiella pneumoniae carbapenemases) after the producing bacterium , different variants are KPC-1, KPC-2 or called KPC-3. The specialty of plasmids is that they are exchanged between different types of bacteria by horizontal gene transfer and thus the antibiotic resistance is "transferred". A clinical case report of the transfer of a plasmid with the resistance gene bla KPC-3 from K. pneumoniae to K. aerogenes is described there in the article .

The investigation of the nucleotide sequence of individual genes showed that the species Klebsiella pneumoniae is very diverse. Further genetic investigations, for example a modification of the PCR method with randomly amplified polymorphic DNA ( RAPD ), confirm the occurrence of three different phylogenetic groups, which are referred to as KpI, KpII and KpIII. They are not identical to the three subspecies. Further genetic investigations in recent years, such as sequencing the 16S ribosomal RNA (rRNA) and multi- locus sequence analysis (MLSA) of certain genes, have led to the representatives of the KpII group being classified as Klebsiella quasipneumoniae and the strains of the phylogenetic group KpIII as Klebsiella variicola .

Pathogenicity

The three subspecies of K. pneumoniae are  assigned to risk group 2 by the Biological Agents Ordinance in conjunction with the TRBA ( Technical Rules for Biological Agents) 466 . In K. pneumoniae subsp. pneumoniae and K. pneumoniae subsp. rhinoscleromatis there is also the comment ht , which indicates that the bacterium is pathogenic for humans and vertebrates , but that there is usually no transmission between the two host groups .

K. pneumoniae has several virulence factors . The capsule (glycocalyx) protects against phagocytosis by the phagocytes , cells of the immune system . It disrupts the complement system involved in the defense against microorganisms by preventing its activation or the uptake of polypeptides that have already been released , such as C3b . Adhesins enable attachment to the host cells. Some adhesins from K. pneumoniae also act as hemagglutinins and can be assigned to the fimbriae ( pili ). The type 1 fimbriae lead to visible clumping (agglutination) of erythrocytes from guinea pigs, they attach to human epithelial cells of the intestine or epithelial cells of the urinary tract . K. pneumoniae isolates from medical samples form more type 1 fimbriae than isolates from environmental samples. Type 3 fimbriae also occur; they mediate the attachment of bacteria to the plant root system , and in humans to endothelial cells , epithelial cells of the alveoli and the urinary tract, and to type V collagen . What role does type 3 fimbriae in the Infection of humans is still the subject of research. It is believed that they are responsible for colonizing invasive medical devices that remain in the body for long periods of time.

The lipopolysaccharides (LPS) of the outer membrane act as antigens, the outwardly directed polysaccharide chains are referred to as O-antigens (compare the Kauffmann-White scheme used in Salmonella ). K. pneumoniae has nine different O antigens, with O1 being the most common. The O-antigens also disrupt the reaction cascade of the complement system. In addition, O1 is involved in the necrosis of infected tissue . The bacterial siderophores are also important for the pathogenicity. They serve to supply the cells with iron ions that are essential for the metabolism by binding Fe 3+ ions. K. pneumoniae produces enterobactin (Enterochelin), while only some strains also produce aerobactin . In the serotypes K1 and K2, a plasmid was found on which the genetic information for the hydroxamate aerobactin is encoded. If these genes are transferred into a strain without a plasmid with the help of the transformation , the transformed cells have a virulence increased by a factor of 100. Also yersiniabactin , one for Yersinia typical TYPES siderophore is formed by some tribes.

Biochemical evidence

K. pneumoniae is closely related to K. aerogenes (formerly part of the Enterobacter genus ) and Enterobacter cloacae . The bacteria show a pronounced versatility with regard to the utilization of various carbohydrates and, with a few exceptions, have the same biochemical characteristics, such as the enzymes present and the resulting metabolic properties .

Representatives of the genus Klebsiella , as an typical fermentation the 2,3-butanediol fermentation by for energy in the Voges-Proskauer test is acetoin , an intermediate of 2,3-butanediol fermentation demonstrated. Representatives of the related genera Enterobacter and Klebsiella react positively here. In principle, this also applies to K. pneumoniae , but the subspecies or individual bacterial strains show different reactions, i.e. also a negative result in the VP test. In contrast to the description of the species, the type strain DSM 30104 is VP-negative (i.e. it does not produce acetoin from pyruvate ), but it shows a positive result in the methyl red test , which is typical for representatives of mixed acid fermentation . These differences in physiological phenotype reflect the genetic diversity of the bacterial species. Further biochemical characteristics cannot be clearly defined within the species. The indole test is basically suitable as a distinguishing feature between K. pneumoniae (indole negative) and Klebsiella oxytoca (indole positive), but there are also some indole positive strains of K. pneumoniae .

Further evidence

Instead of detecting the bacterium, one often limits oneself to the determination of the serotype or the detection of individual virulence factors or resistance genes . The K and O antigens can be determined both “conventionally” serologically (referred to as serotyping in the English-language literature ) as well as by these methods since the spread of molecular biological methods, for example with the help of multi-locus sequence analysis (MLSA). By comparison with the numerous sequenced genomes of the species, it could be shown that the serotype O1 almost always occurs in strains with the capsule antigens K1 or K2. The serotypes K1 and K2 are considered to be hypervirulent. The capsule antigens can also be determined by multiplex PCR (more than one genome segment is detected) and pulsed field gel electrophoresis (PFGE).

Identification using the MALDI-TOF method in combination with mass spectrometry (MS) is generally suitable for detecting Klebsiella , but is not always reliable in terms of distinguishing closely related genera, for example to Raoultella . The spectra of many gram-negative species belonging to the enterobacteria show great agreement (as of 2013), which makes identification difficult. Another systematic study of bacteria cultivated in a liquid, blood-containing nutrient solution showed that especially bacteria are not correctly identified with a capsule. Of antibiotic resistance MALDI-TOF can be other hand, in the detection are applied to the absence or reduced presence of proteins in the outer membrane (English: outer membrane proteins , OMP) to be detected. In the case of K. pneumoniae , OmpK36 is important, an important membrane porin through which β-lactam antibiotics enter the cell. In the case of resistant strains it is absent or is only developed in small numbers.

Systematics

The German microbiologist Carl Friedländer first described these bacteria in 1883 as the causative agent of a rare form of pneumonia ( Friedländer pneumonia ). At that time he still called it " Diplococcus ". Shortly thereafter, the "Friedländer bacteria" were described as " Bacterium pneumoniae crouposae " Zopf 1885, " Hyalococcus pneumoniae " Schroeter 1886 and " Bacillus pneumoniae " ( Schroeter 1886) Flügge 1886.

In 1984 the species was divided into three subspecies :

  • Klebsiella pneumoniae subsp. ozaenae ( Abel 1893) Ørskov 1984, comb. nov. → Basonym : Klebsiella ozaenae ( Abel 1893) Bergey et al. 1925 (Approved Lists 1980)
  • Klebsiella pneumoniae subsp. pneumoniae ( Schroeter 1886) Ørskov 1984, subsp. nov.
  • Klebsiella pneumoniae subsp. rhinoscleromatis ( Trevisan 1887) Ørskov 1984, comb. nov. → Basonym: Klebsiella rhinoscleromatis Trevisan 1887 (Approved Lists 1980)

Klebsiella pneumoniae ( Schroeter 1886) Trevisan 1887 is defined by the type strain ATCC 13883 (= CCUG 225 = CIP 82.91 = DSM 30104 = HAMBI 450 = IAM 14200 = IFO (NBRC) 14940 = JCM 1662 = LMG 2095 = NCTC 9633), according to the Division into three subspecies, this is also the type strain for K. pneumoniae subsp. pneumoniae ( Schroeter 1886) Ørskov 1984.

The division into three subspecies is based on characteristics of the pathogenesis and not on the sufficient distinguishability of the DNA sequence . Genetic studies in 2003 showed that at least three different phylogenetic groups exist within the species, but these are not the subspecies mentioned here. In pneumonia caused by K. pneumoniae , strains belonging to the phylogenetic group KpI are predominant, but representatives of the groups KpII ( K. quasipneumoniae ) and KpIII ( K. variicola ) also occur.

meaning

Occurrence and ecology

Klebsiella pneumoniae is ubiquitous . Their natural habitats are bodies of water , waste water (especially from industrial plants for paper production and fruit processing ), soil and plants, especially the roots there. The bacteria attach themselves to the root hairs of the rhizodermis with the help of their fimbriae (especially the type 3 fimbriae) in order to fix nitrogen there. In contrast to rhizobia ( nodule bacteria ), which live exclusively in symbiosis with plants from the legume family, nitrogen fixation takes place in K. pneumoniae associatively with various higher plants ( vascular plants ), sometimes as endophytes . Thus, K. pneumoniae and from leaves of the rice plant , the tissue of the stalks of Zea mays ( maize ) and rotting wood isolated. In the case of literature references on occurrence, however, it should be noted that the identification was not always reliable, so that isolated isolates can also be assigned to other Klebsiella species or representatives of the genus Raoultella (which were previously included in the genus Klebsiella ).

The bacterium also colonizes animals and humans, u. a. the intestine , K. pneumoniae has been isolated from numerous representatives of mammals and insects . In mares (female domestic horses ) it can cause metritis , an inflammation of the uterus . This applies to strains with the capsule antigens K1, K2 and K5, which have caused epidemics . On the other hand, strains with the capsule antigen K7 are viewed more as opportunistic pathogens . In addition to the human intestine, where it is part of the intestinal flora , the bacterium can also be found in the nasopharynx ( nasopharynx ). Prior to the emergence of multiresistant strains, it was assumed that colonization of patients or hospital staff was the reservoir through which infection with K. pneumoniae could be caused. Investigations of epidemic outbreaks in hospitals - i.e. nosocomial infections - with the help of serological (determination of K antigens) or molecular biological methods show a different picture. Often a certain antibiotic-resistant clone that was responsible for the infection can later be identified. If the patients are screened at admission and at regular intervals with regard to colonization with K. pneumoniae , it can be proven that this clone was not originally found in the patient. Investigations in Italian hospitals in 2012 revealed the distribution of the multi-resistant clones ST101, ST258 and ST512.

Medical importance

Diseases caused by Klebsiella pneumoniae ( Klebsiella pneumoniae subsp. Pneumoniae ) are often infections of the lower urinary tract ( urinary tract infection , UTI or CTI as an abbreviation in English) or respiratory tract ( pneumonia ). Pneumonia (including Friedländer pneumonia) is mainly caused by serotypes with the K1 antigen, but K2, K3, K4, K5 and K6 can also be involved. The bacterium is increasingly known to cause nosocomial pneumonia in immunocompetent inpatients.

Nosocomial infections ("hospital infections") in immunocompromised patients are often caused by the use of invasive medical procedures , such as B. caused when inserting catheters or intensive care ventilation . In addition to pneumonia, nosocomially acquired infectious diseases also include urinary tract infections, wound infections , bacteremia up to sepsis and cholecystitis . In addition to immunocompromised patients, newborns are at risk. In recent years there have been several epidemic outbreaks in newborn intensive care units , with fatal consequences. The clinical significance of (nosocomial) infections with K. pneumoniae is linked to the bacterium's widespread multi-resistance . K. pneumoniae is one of the five most common pathogens of bacterial sepsis (6.7% of cases, published in 2006) and nosocomially acquired pneumonia (10.1% of cases, published in 2010). She belongs to the so-called ESKAPE group.

A current approach to differentiate the Klebsiella pneumoniae bacterial strains with regard to their medical relevance, which is also confirmed by genetic tests, is the division into the following three groups: opportunistic, hypervirulent and multi-resistant strains. The opportunistic pathogens infect particularly patients with a weakened immune system and are typical of nosocomial infections (see above). Hypervirulent K. pneumoniae are so-called community acquired strains that colonize or infect healthy people outside of health care facilities. They cause serious infections, such as pyogenic liver abscess , endophthalmitis (infection in the eye) and meningitis (meningitis), these have been increasingly reported from Asia and the Pacific countries since the 1990s . The serotypes K1 and K2 in particular are referred to as hypervirulent. Genetic comparative studies show that they have a particularly large number of virulence factors. a. a large number of siderophores, the formation of colibactin (damages the DNA) and the regulatory gene rmpA ( mucosity regulator , refers to the mucous capsule). The production of carbapenemases is typical for multi-resistant K. pneumoniae , making the treatment of the infection increasingly difficult (see following sections).

Klebsiella pneumoniae and autoimmune diseases

There are studies that indicate that by natural defense mechanisms against educated and pneumoniae Klebsiella directed IgA antibodies with structures of the human cell surface protein HLA-B27 cross-react . HLA-B27 regulates important functions of the human immune system. Klebsiella pneumoniae is suspected of also causing autoimmune reactions such as B. Ankylosing spondylitis (Bechterew's disease).

Antibiotic resistance

K. pneumoniae has a natural antibiotic resistance to benzylpenicillin , aminopenicillins (e.g. ampicillin and amoxicillin ) and carboxypenicillins (e.g. carbenicillin and ticarcillin ), all of which are β-lactam antibiotics . The resistance is based on the class A beta-lactamase encoded in the bacterial chromosome. Acquired resistances that occur in addition are often caused by plasmid-coded ESBL ( Extended Spectrum β-Lactamases ) such as SHV-1, TEM-1 or TEM-2 (see section Genetics ). This makes K. pneumoniae resistant to other penicillins as well as 3rd generation cephalosporins (e.g. cefotaxime and ceftazidime ). In the late 1990s, 24% of K. pneumoniae strains in the United States were resistant to ceftazidime. Intensive care units involved in the German epidemiological surveillance program Surveillance of Antibiotic Use and Bacterial Resistance in Intensive Care Units (SARI) reported an increase in resistance to 3rd generation cephalosporins from 2.2% (2000) to 16.8% (2010). Since the beginning of the 21st century, resistance to carbapenems caused by carbapenemases (another group of β-lactamases), which are called KPC ( Klebsiella pneumoniae carbapenemases) after the producing bacterium (see next section) , has also been observed .

Carbapenem- resistant Klebsiella pneumoniae strains (KPC)

The formation of a carbapenemase ( carbapenem-hydrolyzing beta-lactamase ) was observed for the first time in 2001 in a certain Klebsiella pneumoniae strain : This causes the Klebsiella to be resistant to certain antibiotics, the carbapenemes. These include B. the drugs imipenem and meropenem . However, the activity of carbapenemase is suppressed in the presence of clavulanic acid . The investigated carbapenem -resistant Klebsiella pneumoniae strain ( carbapenem-resistant Klebsiella pneumoniae , CRKP) "1534" continued to show resistance to all cephalosporins and aztreonam and is therefore largely insensitive to many modern antibiotics. Different variants of the Klebsiella pneumoniae carbapenemases are known, such as KPC-1, KPC-2 and KPC-3.

Multi-resistant strains

Carbapenemase-producing Enterobacteriaceae (CPE) are classified in Germany as 3 MRGN or 4MRGN (multi-resistant gram-negative bacteria). In the pathogen group CPE, K. pneumoniae is disproportionately represented, but through horizontal gene transfer the KPC can also be found in related species of enterobacteria, for example in Escherichia coli , Serratia marcescens , Enterobacter cloacae , Citrobacter freundii as well as in K. oxytoca and K. aerogenes . Since resistance to fluoroquinolones usually also occurs when an ESBL or a carbapenemase occurs, these strains are resistant to all four antibiotic classes defined in the MRGN system and are referred to as 4MRGN. In 2012, the Robert Koch Institute (RKI) reported on the first case from Germany in which a multi-resistant strain was isolated from the surgical wound on a patient's hip. The antibiogram confirmed the isolate as 4MRGN, and resistance to colistin , which is actually used as a reserve antibiotic in such cases , was also demonstrated .

In 2012, the KRINKO (Commission for Hospital Hygiene and Infection Prevention ) set up at the RKI warned "(...) that Germany is just at the beginning of a development in which there is an increase in carbapenem-resistant K. pneumoniae strains." Internationally, CPE are already widespread, or at least an increasing problem. This is shown, for example, by the international monitoring system European survey on carbapenemase-producing Enterobacteriaceae (EuSCAPE). The 28 member states of the European Union , seven (potential) candidate countries , Iceland , Norway and Israel are involved in this surveillance system . An interim report published in 2013 indicates that 29 of these 38 states maintain a national surveillance system for carbapenemase-producing Enterobacteriaceae (CPE), and Klebsiella pneumoniae is also monitored in all national programs . 33 of the “national experts” stated that K. pneumoniae is the type of bacteria that is most frequently detected among CPE in their country .

Examples of infections with multi-resistant strains

In Washoe County , Nevada , USA , a multi-resistant strain of Klebsiella pneumoniae was discovered in a patient who had previously been hospitalized in India several times . The bacterium was resistant to all approved antibiotics. In the laboratory, only fosfomycin showed an effect, but it could only be taken orally, as it was not approved in the USA for intravenous treatment, as required by the patient. The patient died after receiving all 26 US-approved antibiotics, including a. even fosfomycin in oral form, had no effect. In May 2017, the pathogen Klebsiella pneumoniae 4MRGN was found in five patients at the Frankfurt University Hospital , the largest hospital in Hesse . In 2011 and 2012 there were several deaths in the newborn intensive care unit in the Bremen-Mitte Clinic from multi-resistant strains.

Web links

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literature

Individual evidence

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  13. ↑ Jane F. Turton, Hatice Baklan, LK Siu, Mary E. Kaufmann, Tyrone L. Pitt: Evaluation of a multiplex PCR for detection of serotypes K1, K2 and K5 in Klebsiella sp. and comparison of isolates within these serotypes. In: FEMS Microbiology Letters. Volume 284, No. 2, July 2008, pp. 247-252, doi: 10.1111 / j.1574-6968.2008.01208.x .
  14. ↑ a b Andrew E. Clark, Erin J. Kaleta, Amit Arora, Donna M. Wolk: Matrix-assisted laser desorption ionization-time of flight mass spectrometry: a fundamental shift in the routine practice of clinical microbiology. In: Clinical Microbiology Reviews . Volume 26, No. 3, July 2013, pp. 547-603, doi: 10.1128 / CMR.00072-12 , PMID 23824373 , PMC 3719498 (free full text) (review).
  15. ↑ a b Carolina Venditti, Laura Villa u. a .: Isolation of KPC 3-producing Enterobacter aerogenes in a patient colonized by MDR Klebsiella pneumoniae. In: New Microbiologica . Volume 39, No. 4, October 2016, pp. 310-313, PMID 27284988 .
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  17. ^ A b Rebekah M. Martin, Michael A. Bachman: Colonization, Infection, and the Accessory Genome of Klebsiella pneumoniae. In: Frontiers in Cellular and Infection Microbiology . Volume 8, 2018, p. 4, doi: 10.3389 / fcimb.2018.00004 , PMID 29404282 , PMC 5786545 (free full text) (review).
  18. ↑ M. Ogasawara, DH Kono, DT Yu: Mimicry of human histocompatibility HLA-B27 antigens by Klebsiella pneumoniae. In: Infection and Immunity . Volume 51, Number 3, March 1986, pp. 901-908, PMC 260984 (free full text).
  19. ^ H. Yigit, AM Queenan et al. a .: Novel carbapenem-hydrolyzing beta-lactamase, KPC-1, from a carbapenem-resistant strain of Klebsiella pneumoniae. In: Antimicrobial Agents and Chemotherapy . Volume 45, Number 4, April 2001, pp. 1151-1161, doi: 10.1128 / AAC.45.4.1151-1161.2001 . PMID 11257029 . PMC 90438 (free full text).
  20. ↑ Ashfaque Hossain et al. a .: Plasmid-Mediated Carbapenem-Hydrolyzing Enzyme KPC-2 in an Enterobacter sp. In: Antimicrob Agents Chemother. Volume 48, number 11, November 2004, pp. 4438-4440, doi: 10.1128 / AAC.48.11.4438-4440.2004 , PMC 525415 (free full text).
  21. ↑ Ben M. Lomaestro: The Spread of Klebsiella pneumoniae Carbapenemase - Producing K. pneumoniae to Upstate New York. In: Clinical Infectious Diseases . Volume 43, 2006, pp. E26 – e28.
  22. ↑ Case report of the detection of a multi-resistant Klebsiella pneumoniae isolate in a patient . In: Robert Koch Institute (Ed.): Epidemiologisches Bulletin . No.  45 , November 12, 2012, p. 453–455 ( rki.de [PDF; 94 kB ; accessed on July 2, 2018]).
  23. ^ Hajo Grundmann, Corinna Glasner, Anna-Pelagia Magiorakos, Liselotte Högberg-Diaz, Dominique L. Monnet, Barbara Albiger: Carbapenemase-producing bacteria in Europe. (PDF; 3.3 MB) ECDC Technical Report. European Center for Disease Prevention and Control (ECDC), November 2013, pp. 1–18 , accessed on May 24, 2018 .
  24. Jump up ↑ L. Chen, R. Todd, J. Kiehlbauch, M. Walters, A. Kallen: Notes from the Field: Pan-Resistant New Delhi Metallo-Beta-Lactamase-Producing Klebsiella pneumoniae - Washoe County, Nevada, 2016. In: Morbidity and Mortality Weekly Report (MMWR), number 66, 2017, p. 33, doi: 10.15585 / mmwr.mm6601a7 .
  25. ↑ After Klebsiella infestation: Intensive care unit at the University Hospital is still closed. faz.net , May 8, 2017, accessed July 1, 2018 .
  26. ↑ Klebsiella - the germ of death in the premature baby ward. welt.de , November 3, 2011, accessed July 1, 2018 .