Klebsiella aerogenes

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Klebsiella aerogenes
Microscopic picture of Klebsiella aerogenes after Gram staining

Microscopic picture of Klebsiella aerogenes after Gram staining

Systematics
Department : Proteobacteria
Class : Gammaproteobacteria
Order : Enterobacterales
Family : Enterobacteriaceae
Genre : Klebsiella
Type : Klebsiella aerogenes
Scientific name
Klebsiella aerogenes
(Hormaeche & Edwards 1960)
Tindall et al. 2017 comb. nov.

Klebsiella aerogenes is a gram-negative bacterium fromthe Enterobacteriaceae family . Until 2017 it was named Enterobacter aerogenes Hormaeche & Edwards 1960, although there had been legitimate doubts about its belonging to the genus Enterobacter since the 1970s. Another synonym is Klebsiella mobilis . Klebsiella aerogenes canactively movewith the help of flagella , it is motile. This property is not typical of the Klebsiella genus. The bacterium is closely related to Klebsiella pneumoniae and Enterobacter cloacae , which is also reflected in many similar characteristics thatmake it difficult to differentiate . It is found in almost all habitats, including the intestines of humans and animals.

Of medical importance is the antibiotic resistance , which on the one hand is naturally present and on the other hand is caused by the horizontal gene transfer between different gram-negative bacterial species, which leads to an acquired antibiotic resistance. It are plasmids involved, these are small, circular DNA molecules on which the genetic information is encoded for resistance. Klebsiella aerogenes can cause infections in people who have already weakened immune systems . As a causative agent of infections acquired in hospital - nosocomial infections - it is therefore of increasing importance, especially when it comes to multi-resistant bacterial strains . However, its importance as a pathogen cannot be compared with that of Klebsiella pneumoniae . The genome of the bacterial strain Klebsiella aerogenes KCTC 2190 was completely sequenced in 2012 .

features

Appearance

Klebsiella aerogenes has small, rod-shaped cells , these are colored pink to red in the Gram stain , they are Gram- negative. A peculiarity is that they are peritrich flagellated, so by flagella are actively mobile ( motile ). This characteristic is not typical for the genus Klebsiella , but for representatives of the related genus Enterobacter . Bacterial colonies that have grown on a nutrient medium do not show any particular color.

Growth and metabolism

As usual with the representatives of the Enterobacteriaceae, the catalase test is positive and the oxidase test is negative. Klebsiella aerogenes is facultatively anaerobic , i. H. it can grow with or without oxygen . As a typical fermentation , the 2,3-butanediol fermentation is carried out to generate energy. See the Biochemical Evidence section for more information . Simple nutrient media are suitable for cultivation ; the bacteria can be grown on casein soy peptone agar (CASO agar) , for example . Often be selective media used, which are suitable for the isolation and differentiation of representatives of enterobacteria, such as MacConkey agar and eosin methylene blue agar (EMB). Klebsiella aerogenes is mesophilic , optimal growth takes place at a temperature of 30 ° C, colonies are visible after incubation for one to two days.

Chemotaxonomic Features

In addition to saturated and monounsaturated fatty acids, Klebsiella aerogenes also has fatty acids with a hydroxyl group and omega-alicyclic (ω-alicyclic) fatty acids in its membrane lipids , using the Greek lowercase ω as locant . Omega-alicyclic fatty acids are found in large quantities in representatives of the bacterial genus Alicyclobacillus . In larger proportions (percentage of membrane lipids) one finds in K. aerogenes the saturated palmitic acid C 16: 0 at 30.7% and myristic acid C 14: 0 at 9.4%; the monounsaturated omega-n fatty acids (in this case omega-7 fatty acids) vaccenic acid C 18: 1 (ω − 7) at 22.0% and palmitoleic acid C 16: 1 (ω − 7) at 16.5%; the 3-hydroxy-tetradecanoic acid C 14: 0 3-OH at 8.7% and an ω-alicyclic fatty acid C 17: 0 at 8.2%. This can be omega-cyclohexylundecanoic acid (ω-cyclohexane C17: 0), the number of carbon atoms in the ring structure was not specified. Earlier investigations from the 1960s on the bacterium, then called " Aerobacter aerogenes ", revealed the presence of larger amounts (25%) of a fatty acid with a cyclopropane ring in the carbon chain and a total of 17 carbon atoms, which was suspected to be cis -9,10-methylenehexadecanoic acid. It is homologous to lactobacillic acid ( cis -11,12-methylenoctadecanoic acid ) which also has a cyclopropane ring and a total of 19 carbon atoms; this fatty acid is also 6%. In a further study from 1968, however, the proportion of these two fatty acids was given as lower (10% and 1%, respectively).

genetics

Already in the 1970s it was shown with the help of DNA hybridization that the bacterial species is more closely related to Klebsiella pneumoniae (about 55% structural relationship) than to Enterobacter cloacae (about 45%). The GC content , ie the proportion of nucleic bases guanine and cytosine in the bacterial DNA lies with the bacterial strain KCTC 2190 (from the strain collection Korean Collection for Type Cultures ) 54.8  mole percent . KCTC 2190 was the first strain of the species, then still called Enterobacter aerogenes , whose genome was completely sequenced in 2012 . It is the type strain that was isolated from sputum . The genome is a ring-shaped bacterial chromosome and has a size of 5,280 kilobase pairs (kb), which is roughly comparable to the genome size of Escherichia coli . There are 4,912 coding genes , 3,824 of which are presumed genes with regard to annotation for proteins . In addition, 84 tRNAs and 25 rRNAs were identified. Since then, 150 genomes (based on the circular bacterial chromosome) of this species have been sequenced, as well as 13 different plasmids (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. Examples are the plasmid-coded penicillinase or the plasmid-coded extended spectrum β-lactamase ( ESBL ). 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". This will u. a. in gram-negative bacteria, as observed in representatives of the genus Klebsiella , Escherichia and Enterobacter . In a case from Italy, this could be documented in vivo in 2016 : A patient in the intensive care unit of a hospital in Rome was regularly examined for carbapenem- resistant Enterobacteriaceae (CRE). After a neurosurgical operation, he was infected with multi-resistant Klebsiella pneumoniae , which led to sepsis and later to an abscess in the groin , where a dialysis catheter for hemodialysis ("blood washing") was attached. All K. pneumoniae isolates obtained from the patient were resistant to carbapenems. A short time later, K. aerogenes was also found in the abscess , albeit sensitive to the carbapenemes. In the next sample taken three weeks later, a carbapenem-resistant K. aerogenes strain was identified. The subsequent genetic analysis by means of PCR ( polymerase chain reaction ), and other methods showed that the two resistant strains of bacteria are each a plasmid with the IncFII K - replicon and the bla KPC-3 exhibited gene. The gene coding for the latter as KPC-3 designated carbapenemase after K. pneumoniae was named, but is not limited to these bacteria. The plasmids of each resistant K. pneumoniae and K. aerogenes isolate were identified as a known plasmid (pK-pQIL IncFII K ) after transformation by means of PCR ; they were 100% identical to this. The plasmids were also compared by restriction fragment length polymorphism (RFLP) analysis , the lengths of the restriction fragments being indistinguishable. It can therefore be assumed that the plasmid was transferred from K. pneumoniae to K. aerogenes while the bacteria colonized or infected the patient.

Pathogenicity

K. aerogenes is  assigned to risk group 2 by the Biological Agents Ordinance in conjunction with the TRBA ( Technical Rules for Biological Agents) 466 . The entry is made as Enterobacter aerogenes = Klebsiella mobilis . The comment ht indicates that the bacterium is pathogenic for humans and vertebrates , but that there is usually no transmission between the two host groups .

In the specialist literature, common statements are often made for E. cloacae and E. aerogenes , as the representatives of the Enterobacter genus , which can cause infections in humans. After the last-mentioned bacterial species was transferred to the genus Klebsiella (2017), it will probably take some time for the medical community to take notice, similar to the assignment of E. sakazakii to the genus Cronobacter as Cronobacter sakazakii (2008). Compared to K. pneumoniae , the pathogenicity of K. aerogenes is less pronounced, which u. a. This is due to the widespread multi-resistance of K. pneumoniae , hospital-acquired pneumonia ( nosocomial pneumonia) is typical for this species . Furthermore, K. pneumoniae has more virulence factors . Infections caused by K. aerogenes (or E. aerogenes ) described in the literature are also often nosocomial, mostly bacteremia . K. aerogenes produces hemagglutinins , which lead to visible clumping (agglutination) of erythrocytes .

Biochemical evidence

The close relationship between K. aerogenes and K. pneumoniae and E. cloacae can also be seen in biochemical features such as the enzymes present and the resulting metabolic properties . Investigations based on this in the 1970s already led to the proposal to place E. aerogenes in the genus Klebsiella. These biochemical features can be used in a colorful series to identify K. aerogenes or to differentiate it from other species, provided that there are enough distinguishing features. A systematic study of representatives of the Enterobacteriaceae was published in 1985. Some of the results from these two studies are shown in the table below:

Table: Results of various tests to differentiate
Test method, feature Klebsiella aerogenes Klebsiella pneumoniae Enterobacter cloacae
Motility at 36 ° C + ( 1 ) - ( 1 ) +
Indole formation - - -
Methyl red sample - - -
Acetoin formation (VP test) + + +
Citrate utilization + + +
H 2 S formation - - -
Urease - + d ( 1 )
Hydrolysis of gelatin - - -
Aesculin splitting + + d
Gas formation from glucose ( 2 ) + + +
Acid formation from arabinose + + +
Acid formation from glucose + + +
Acid formation from rhamnose + + +
Acid formation from xylose + + +
Acid formation from cellobiose + + +
Acid formation from lactose + + d
ONPG test ( 3 ) + + +
Acid formation from maltose + + +
Acid formation from sucrose + + +
Acid formation from adonitol + + d
Acid formation from dulcitol - d d
Acid formation from glycerol + + d
Acid formation from inositol + + -
Acid formation from mannitol + + +
Acid formation from sorbitol + + +
Arginine dihydrolase (ADH) - - +
Lysine decarboxylase (LDC) + + -
Ornithine decarboxylase (ODC) + - +

Remarks:

  1. + stands for a positive, - for a negative result, the specification d (for different) means "variable", d. that is, there are strains that can produce a positive result as well as strains that do not; or the positive reaction is too weak to be seen clearly.
  2. Reactions in which the utilization of carbohydrates is checked are highlighted in color ; monosaccharides , disaccharides and sugar alcohols are listed . When carbohydrates are used, a pH indicator is used to check whether acids are formed during the breakdown. Gas formation can be demonstrated with the aid of a Durham tube, in which the gas is collected, or with the OF test .
  3. The ONPG test is a biochemical test for the enzyme β-galactosidase and serves as a confirmation reaction for the utilization of the disaccharide lactose.

These examinations can be used for miniaturized test systems . Typical results for K. aerogenes can be viewed in the freely accessible database BacDive of the DSMZ ( German Collection of Microorganisms and Cell Cultures ).

Systematics and taxonomy

The close relationship of Klebsiella , Enterobacter , Serratia and some other genera means that the systematics of the Enterobacteriaceae has been changing constantly for decades, as it is adapted to the knowledge of science. The genus Enterobacter was defined in 1960 by Hormaeche and Edwards and contained the then recognized species " Aerobacter aerogenes " and " Aerobacter cloacae ". Its aim was to enable the scientists working in the field to clearly classify newly described species by describing the typical characteristics. The genus previously referred to as " Aerobacter " contained both motile and non-motile bacteria, the latter being assigned to the genus Klebsiella . Systematic biochemical investigations of species belonging to the Klebsielleae tribe , with numerical evaluation by computer programs, showed in 1971 that E. aerogenes is more closely related to Klebsiella species than to E. cloacae . The logical consequence would have been to transfer Enterobacter aerogenes to the genus Klebsiella and to designate it as Klebsiella aerogenes . However, this was not possible in 1971 because a bacterium with the name “ Klebsiella aerogenes ” ( Kruse ) Taylor et al. 1956 was known. As a result, a new epithet was chosen, and the designation as K. mobilis was used to draw attention to the fact that this species, unlike the representatives of the genus Klebsiella , is motile, i.e. capable of active movement through flagella. The strain CDC 819-56 (= NCTC 10006 = ATCC 13048) was chosen as the type strain because it was proposed as a neotype for E. aerogenes .

In 1980, the implementation of the Approved Lists of Bacterial Names according to the Bacteriological Code ( International Code of Nomenclature of Bacteria , ICNB) led to both K. mobilis and E. aerogenes being listed as valid bacterial names; they are homotypical synonyms , da both species have the same type stem. In contrast, the name " Klebsiella aerogenes " ( Kruse ) Taylor et al. Declared invalid in 1956. In fact, the designation as E. aerogenes was still preferred in the professional world , although the new possibility of genetic investigations has also confirmed that the bacterium belongs to the genus Klebsiella . With the help of the DNA hybridization it was shown that the bacterial species is more closely related to Klebsiella pneumoniae (about 55% structural relationship) than to Enterobacter cloacae (about 45%). F. Grimont and PAD Grimont pointed out in 2006 that it was sensible to place E. aerogenes in the genus Klebsiella , the only problem being the implementation in the nomenclature . Brian J. Tindall, Granger Sutton and George M. Garrity implemented this in 2017 with their specialist article, in which it was proven, citing all the appropriate rules of the International Code of Nomenclature of Bacteria (ICNB), that the epithet K. mobilis chosen in 1971 is inadmissible and the bacterial species is to be named as Klebsiella aerogenes .

Klebsiella aerogenes ( Hormaeche & Edwards 1960) Tindall et al. 2017 comb. nov. is defined by the type trunk NCTC 10006 (= ATCC 13048 = CCUG 1429 = DSM 30053 = JCM 1235 = KCTC 2190 = LMG 2094 = NBRC 13534,). Synonyms are:

  • “ Aerobacter aerogenes ” Hormaeche & Edwards 1958 → this designation is not listed in the 1980 Approved Lists and is therefore invalid
  • Enterobacter aerogenes Hormaeche & Edwards 1960 → as a basonym
  • Klebsiella mobilis Bascomb et al. 1971 (Approved Lists 1980) → this synonym may no longer be used because the epithet is not allowed

Klebsiella aerogenes ( Hormaeche & Edwards 1960) Tindall et al. 2017 comb. nov. is not identical with " Klebsiella aerogenes " ( Kruse ) Taylor et al. 1956. This bacterium was assigned to the taxon Klebsiella pneumoniae subsp. pneumoniae . The epithet K. aerogenes is the Latinized combination of the ancient Greek words for 'air' and 'produce' and means 'gas-producing'. This draws attention to the production of carbon dioxide (CO 2 ) and hydrogen (H 2 ) during the fermentative breakdown of glucose.

meaning

Occurrence

K. aerogenes is ubiquitous. Their natural habitats are bodies of water , sewage , soil , raw milk and the intestines of humans and animals . Medical test material in which it has been detected includes urine , faeces , blood , sputum , wounds and cerebrospinal fluid ( cerebrospinal fluid ).

biotechnology

The formation of hydrogen (H 2 ) during the fermentation of Klebsiella aerogenes can be used biotechnologically to produce biohydrogen . Rice straw can be used as the starting material. Compared to strictly anaerobic bacteria, such as clostridia , which also produce hydrogen, fermentation with the facultative anaerobic K. aerogenes is easier because oxygen does not have to be completely removed. Another product of the fermentation of K. aerogenes is 2,3-butanediol , which is important as a raw material for the chemical industry. As a cheap raw material for the fermentative degradation can bagasse are used, which in the sugar production from sugar cane is applicable. To increase the yield , a genetically modified bacterial strain is used that can utilize xylose better.

Antibiotic resistance

K. aerogenes has a natural antibiotic resistance to benzylpenicillin , oxacillin and ampicillin (all of which are β-lactam antibiotics ). In the case of acquired resistances, K. aerogenes , like E. cloacae, is problematic as an opportunistic pathogen ; both types are of increasing importance as pathogens for nosocomial infections. Resistance to the beta-lactam antibiotics (e.g. carbenicillin ) and ureidopenicillins (e.g. mezlocillin ) as well as 3rd generation cephalosporins (e.g. cefotaxime ) can be determined by a plasmid-coded Extended Spectrum β- Lactamase ( ESBL ). A case report is described in the Genetics section . A K. aerogenes isolate was discovered there that produces a carbapenemase (KPC-3) and is therefore resistant to carbapenems. 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, while E. cloacae and K. aerogenes are rarely found. However, there have been isolated reports from different countries (e.g. Italy, Portugal, China) about the occurrence of K. aerogenes with carbapenem resistance.

Antibiotic resistance is determined in the laboratory by an antibiogram , often using the Kirby-Bauer method on Müller-Hinton agar . A suspension of the bacterium is distributed on or in this nutrient medium and small, circular filter plates that contain various antibiotics in a defined amount are placed on top. If the antibiotic is effective, circular zones of inhibition appear in the bacterial lawn after incubation , the diameter of which is determined. If the bacterium is resistant to the drug, the zone of inhibition is missing and the diameter is given as 0 mm. Typical results for antibiograms of K. aerogenes can be viewed in the database BacDive of the DSMZ (German Collection of Microorganisms and Cell Cultures).

Monitoring programs , the so-called Surveillances, serve to collect epidemiologically useful information about infectious diseases and the possibly resistant pathogens involved. In 2015, the Robert Koch Institute (RKI) published an overview of the surveillance systems for pathogens and resistance for Germany. In the programs surveillance of antibiotic use and bacterial resistance in intensive care units (SARI) and antibiotic resistance monitoring in Lower Saxony (ARMIN), however , K. aerogenes is not recorded, whereas K. pneumoniae and E. cloacae are. Reports from the ECDC ( European Center for Disease Prevention and Control ), for example the European survey on carbapenemase-producing Enterobacteriaceae (EuSCAPE) and The European Surveillance System (TESSy), provide data on the antibiotic resistance of Enterobacter spp. (see there), without specifying the individual species in more detail.

Medical importance

The importance of K. aerogenes as a causative agent of infections, especially of nosocomial infections, cannot be compared with that of K. pneumoniae . However, it should be noted that the three related species K. pneumoniae , K. aerogenes and E. cloacae belong to the human intestinal flora and thus there is the possibility that the bacteria can colonize other parts of the body and thus cause infections in immunosuppressed patients. Other ways of spreading are contamination through the hands of the nursing staff in the event of poor hygiene or cross-contamination through objects. The main risk factors for an infection are a long stay in the intensive care unit of a hospital, diseases of the gastrointestinal tract , in which, for example, a breakthrough of the intestine occurs, burns and the use of invasive medical procedures , e.g. B. when inserting catheters . With regard to multi-resistant K. aerogenes or E. cloacae , long and intensive antibiotic therapy is discussed as a risk factor, since the use of beta-lactam antibiotics promotes the development of resistance by selecting the bacterial species that are identified via an inducible gene segment (this is called ampC ), whose gene product is the enzyme cephalosporinase.

Nosocomial infections are monitored by the Hospital Infection Surveillance System (KISS). The hospitals involved in the system provide data on the identified pathogens; these include the pathogen groups 3MRGN and 4MRGN (multi-resistant gram-negative bacteria), however, in the reference data from 2013 to 2016, K. aerogenes is not recorded, in contrast to K. pneumoniae and E. cloacae .

Web links

 Wikispecies: Klebsiella  - Species Directory

swell

literature

Individual evidence

  1. ↑ a b c d e E. Hormaeche, PR Edwards: A proposed genus Enterobacter. In: International Bulletin of Bacteriological Nomenclature and Taxonomy. Volume 10, No. 2, April 1960, pp. 71-74. ISSN  0096-266X . doi : 10.1099 / 0096266X-10-2-71 .
  2. ↑ a b c d e f g h i F. Grimont, PAD Grimont: The Genus Enterobacter. Introduction. In: The Prokaryotes. A Handbook on the Biology of Bacteria, Volume 6. 2006, pp. 197-214.
  3. ↑ a b c Shoshana Bascomb, Stephen P. Lapage, WR Willcox, MA Curtis: Numerical Classification of the Tribe Klebsielleae. In: Journal of General Microbiology. Volume 66, No. 3, 1971, pp. 279-295, doi : 10.1099 / 00221287-66-3-279 .
  4. ↑ a b c Sang Heum Shin, Sewhan Kim u. a .: Complete Genome Sequence of Enterobacter aerogenes KCTC 2190. In: Journal of Bacteriology. Volume 194, No. 9, May 2012, pp. 2373-2374, doi : 10.1128 / JB.00028-12 , PMID 22493190 , PMC 3347075 (free full text).
  5. ↑ a b c d e f g German Collection of Microorganisms and Cell Cultures (DSMZ): Klebsiella aerogenes, Type Strain. In: Website BacDive . Retrieved May 28, 2018 .
  6. ↑ a b c d e f B. J. Tindall, G. Sutton, GM Garrity: Enterobacter aerogenes Hormaeche and Edwards 1960 (Approved Lists 1980) and Klebsiella mobilis Bascomb et al. 1971 (Approved Lists 1980) share the same nomenclatural type (ATCC 13048) on the Approved Lists and are homotypic synonyms, with consequences for the name Klebsiella mobilis Bascomb et al. 1971 (Approved Lists 1980). In: International Journal of Systematic and Evolutionary Microbiology. Volume 67, 2017, pp. 502-504, doi : 10.1099 / ijsem.0.001572 .
  7. ↑ William M. O'Leary: S-adenosylmethionine in the biosynthesis of bacterial fatty acids. In: Journal of Bacteriology. Volume 84, No. 5, November 1962, pp. 967-972, PMID 16561975 , PMC 277996 (free full text).
  8. ^ John I. Gallin, William M. O'Leary: Lipoidal Components of Bacterial Lipopolysaccharides: Nature and Distribution of Fatty Acids in Aerobacter aerogenes. In: Journal of Bacteriology. Volume 96, No. 3, September 1968, pp. 660-664, PMID 5732501 , PMC 252356 (free full text).
  9. ↑ Klebsiella aerogenes. In: National Center for Biotechnology Information (NCBI) Genome website . Retrieved May 25, 2018 .
  10. ↑ a b c 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 .
  11. ↑ TRBA (Technical Rules for Biological Agents) 466: Classification of prokaryotes (Bacteria and Archaea) into risk groups. In: Website of the Federal Institute for Occupational Safety and Health (BAuA). August 25, 2015, pp. 115, 164 , accessed on March 29, 2018 (last change on March 31, 2017).
  12. ↑ a b c d Subhash Chandra Parija: Coliforms: Klebsiella, Enterobacter (Chapter 31) . In: Textbook of Microbiology and Immunology . 2nd Edition. Elsevier India, Haryana 2012, ISBN 978-81-312-2810-4 , pp. 261-264 .
  13. ↑ a b J. J. Farmer III, BR Davis u. a .: Biochemical identification of new species and biogroups of Enterobacteriaceae isolated from clinical specimens. In: Journal of Clinical Microbiology. Volume 21, No. 1, January 1985, pp. 46-76, ISSN  0095-1137 . PMID 3881471 , PMC 271578 (free full text) (review).
  14. ↑ Approved Lists of Bacterial Names . In: VBD Skerman, Vicki McGowan, PHA Sneath (Eds.): International Journal of Systematic Bacteriology . tape 30 , no. 1 , 1980, p. 362 , doi : 10.1099 / 00207713-30-1-225 .
  15. ^ A b Jean Euzéby, Aidan C. Parte: Genus Klebsiella. In: List of Prokaryotic names with Standing in Nomenclature, Systematics of Bacteria (LPSN) . Retrieved May 24, 2018 .
  16. ↑ Nooshin Asadi, Hamid Zilouei: Optimization of organosolv pretreatment of rice straw for enhanced biohydrogen production using Enterobacter aerogenes. In: Bioresource Technology. 227, March 2017, pp. 335-344, doi : 10.1016 / j.biortech.2016.12.073 .
  17. ↑ Jaeyong Um, Duck Gyun Kim and a .: Metabolic engineering of Enterobacter aerogenes for 2,3-butanediol production from sugarcane bagasse hydrolysate. In: Bioresource Technology . Volume 245, Part B, December 2017, pp. 1567–1574, doi : 10.1016 / j.biortech.2017.05.166 , PMID 28596073 .
  18. ↑ a b c Recommendation of the Commission for Hospital Hygiene and Infection Prevention (KRINKO) at the Robert Koch Institute (RKI): Hygiene measures in the event of infections or colonization with multi-resistant Gram-negative rods. In: Federal Health Gazette - Health Research - Health Protection. Volume 55, 2012, pp. 1311-1354, ISSN  1437-1588 . doi : 10.1007 / s00103-012-1549-5 .
  19. ↑ Robert Koch Institute (ed.): Overview of the surveillance systems for pathogens and resistance . January 29, 2015, p. 1–3 ( Online + PDF; 141 KB [accessed March 30, 2018]).
  20. ↑ KISS Hospital Infection Surveillance System - Pathogen Surveillance in the ITS-KISS module. (PDF; 559 KB) Reference data 2013–2016, stratification: all stations. In: National Reference Center for Surveillance of Nosocomial Infections. May 2, 2017, pp. 1–157 , accessed May 27, 2018 .