|K. pneumoniae on a MacConkey agar plate|
Although found in the normal flora of the mouth, skin, and intestines, it can cause destructive changes to human lungs if aspirated, specifically to the alveoli resulting in bloody sputum. In the clinical setting, it is the most significant member of the Klebsiella genus of Enterobacteriaceae. K oxytoca and K rhinoscleromatis have also been demonstrated in human clinical specimens. In recent years, klebsiellae have become important pathogens in nosocomial infections.
It naturally occurs in the soil, and about 30% of strains can fix nitrogen in anaerobic conditions. As a free-living diazotroph, its nitrogen fixation system has been much-studied, and is of agricultural interest, as K. pneumoniae has been demonstrated to increase crop yields in agricultural conditions.
Members of the Klebsiella genus typically express two types of antigens on their cell surfaces. The first, O antigen, is a component of the lipopolysaccharide (LPS), of which 9 varieties exist. The second is K antigen, a capsular polysaccharide with more than 80 varieties. Both contribute to pathogenicity and form the basis for serogrouping.
The genus Klebsiella was named after the German bacteriologist Edwin Klebs (1834–1913).
Also known as Friedlander's Bacillum in honor of Carl Friedlander, a German pathologist, who proposed that this bacteriae was the etiological factor for the pneumonia seen specially in immunocompromised individuals such as suferers of chronic diseases or alcoholics.
K. pneumoniae can cause destructive changes to human lungs via inflammation and hemorrhage with cell death (necrosis) that sometimes produces a thick, bloody, mucoid sputum (currant jelly sputum). These bacteria gain access typically after a person aspirates colonizing oropharyngeal microbes into the lower respiratory tract.
As a general rule, Klebsiella infections are seen mostly in people with a weakened immune system. Most often, illness affects middle-aged and older men with debilitating diseases. This patient population is believed to have impaired respiratory host defenses, including persons with diabetes, alcoholism, malignancy, liver disease, chronic obstructive pulmonary diseases (COPD), glucocorticoid therapy, renal failure, and certain occupational exposures (such as paper mill workers). Many of these infections are obtained when a person is in the hospital for some other reason (a nosocomial infection). Feces are the most significant source of patient infection, followed by contact with contaminated instruments.
The most common infection caused by Klebsiella bacteria outside the hospital is pneumonia, typically in the form of bronchopneumonia and also bronchitis. These patients have an increased tendency to develop lung abscess, cavitation, empyema, and ural adhesions. It has a high death rate of about 50%, even with antimicrobial therapy. The mortality rate can be nearly 100% for persons with alcoholism and bacteremia.
In addition to pneumonia, Klebsiella can also cause infections in the urinary tract, lower biliary tract, and surgical wound sites. The range of clinical diseases includes pneumonia, thrombophlebitis, urinary tract infection, cholecystitis, diarrhea, upper respiratory tract infection, wound infection, osteomyelitis, meningitis, and bacteremia and septicemia. For patients with an invasive device in their bodies, contamination of the device becomes a risk; for example, respiratory support equipment and urinary catheters put patients at increased risk. Also, the use of antibiotics can be a factor that increases the risk of nosocomial infection with Klebsiella bacteria. Sepsis and septic shock can follow entry of the bacteria into the blood.
Two unusual infections of note from Klebsiella are rhinoscleroma and ozena. Rhinoscleroma is a chronic inflammatory process involving the nasopharynx. Ozena is a chronic atrophic rhinitis that produces necrosis of nasal mucosa and mucopurulent nasal discharge.
Klebsiella ranks second to E. coli for urinary tract infections in older persons. It is also an opportunistic pathogen for patients with chronic pulmonary disease, enteric pathogenicity, nasal mucosa atrophy, and rhinoscleroma.
Klebsiella organisms are often resistant to multiple antibiotics. Current evidence implicates plasmids as the primary source of the resistance genes. Klebsiella with the ability to produce extended-spectrum beta-lactamases ESBL are resistant to many classes of antibiotics. The most frequent resistances include resistance to aminoglycosides, fluoroquinolones, tetracyclines, chloramphenicol, and trimethoprim/sulfamethoxazole.
Infection with carbapenem-resistant Enterobacteriaceae (CRE) or carbapenemase-producing Enterobacteriaceae is emerging as an important challenge in health-care settings. One of many CREs is carbapenem-resistant Klebsiella pneumoniae (CRKP). Over the past 10 years, a progressive increase in CRKP has been seen worldwide; however, this new emerging nosocomial pathogen is probably best known for an outbreak in Israel that began around 2006 within the healthcare system there. In the USA, it was first described in North Carolina in 1996; since then CRKP has been identified in 41 states; and is recovered routinely in certain hospitals in New York and New Jersey. It is now the most common CRE species encountered within the United States.
CRKP is resistant to almost all available antimicrobial agents, and infections with CRKP have caused high rates of morbidity and mortality, in particular among persons with prolonged hospitalization and those critically ill and exposed to invasive devices (e.g., ventilators or central venous catheters). The concern is that carbapenem is often used as a drug of last resort when battling resistant bacterial strains. New slight mutations could result in infections for which there is very little, if anything, healthcare professionals can do to treat patients with resistant organisms.
A number of mechanisms cause carbapenem resistance in Enterobacteriaceae. These include hyperproduction of ampC beta-lactamase with an outer membrane porin mutation, CTX-M extended-spectrum beta-lactamase with a porin mutation or drug efflux, and carbapenemase production. The most important mechanism of resistance by CRKP is the production of a carbapenemase enzyme, blakpc. The gene that encodes the blakpc enzyme is carried on a mobile piece of genetic material (a transposon; the specific transposon involved is called Tn4401), which increases the risk for dissemination. CRE can be difficult to detect because some strains that harbor blakpc have minimal inhibitory concentrations (MICs) that are elevated but still within the susceptible range for carbapenems. Because these strains are susceptible to carbapenems, they are not identified as potential clinical or infection control risks using standard susceptibility testing guidelines. Patients with unrecognized CRKP colonization have been reservoirs for transmission during nosocomial outbreaks.
The extent and prevalence of CRKP within the environment is currently unknown. The mortality rate is also unknown, but is suspected to be within a range of 12.5% to 44%. The likelihood of an epidemic or pandemic in the future remains uncertain. The Centers for Disease Control and Prevention released guidance for aggressive infection control to combat CRKP:
- Place all patients colonized or infected with CRE or carbapenemase-producing Enterobacteriaceae on contact precautions. Acute-care facilities are to establish a protocol, in conjunction with the guidelines of the Clinical and Laboratory Standards Institute to detect nonsusceptibility and carbapenemase production in Enterobacteriaceae, in particular Klebsiella spp. and Escherichia coli, and immediately alert epidemiology and infection control staff members if identified. All acute-care facilities are to review microbiology records for the preceding 6-12 months to ensure that there have not been previously unrecognized CRE cases. If they do identify previously unrecognized cases, a point prevalence survey (a single round of active surveillance cultures) in units with patients at high risk (e.g., intensive-care units, units where previous cases have been identified, and units where many patients are exposed to broad-spectrum antimicrobials) is needed to identify any additional patients colonized with carbapenem-resistant or carbapenemase-producing Klebsiella spp. and E. coli. When a case of hospital-associated CRE is identified, facilities should conduct a round of active surveillance testing of patients with epidemiologic links to the CRE case (e.g., those patients in the same unit or patients having been cared for by the same health-care personnel).
One specific example of this containment policy could be seen in Israel in 2007. This policy had an intervention period from April, 2007 to May, 2008. A nationwide outbreak of CRE (which peaked in March, 2007 at 55.5 cases per 100,000 patient days) necessitated a nationwide treatment plan. The intervention entailed physical separation of all CRE carriers and appointment of a task force to oversee efficacy of isolation by closely monitoring hospitals and intervening when necessary. After the treatment plan (measured in May, 2008), the number of cases per 100,000 patient days decreased to 11.7. The plan was effective because of strict hospital compliance, wherein each was required to keep detailed documentation of all CRE carriers. In fact, for each increase in compliance by 10%, incidence of cases per 100,000 patient days decreased by 0.6. Therefore, containment on a nationwide scale requires nationwide intervention.
In the United States, the reasons the CDC is recommending the detection of carbapenem resistance or carbapenemase production only for Klebsiella spp. and E. coli are: this facilitates performing the test in the microbiology laboratory without the use of molecular methods, and these organisms represent the majority of CREs encountered in the United States. Effective sterilization and decontamination procedures are important to keep the infection rate of this antibiotic resistant strain, CRKP as low as possible.
As with many bacteria, the recommended treatment has changed as the organism has developed resistances. The choice of a specific antimicrobial agent or agents depends on local susceptibility patterns and on the part of the body infected. For patients with severe infections, a prudent approach is the use of an initial short course (48-72 h) of combination therapy, followed by a switch to a specific monotherapy once the susceptibility pattern is known for the specific patient.
If the specific Klebsiella in a particular patient does not show antibiotic resistance, then the antibiotics used to treat such susceptible isolates include ampicillin/sulbactam, piperacillin/tazobactam, ticarcillin/clavulanate, ceftazidime, cefepime, levofloxacin, norfloxacin, gatifloxacin, moxifloxacin, meropenem, and ertapenem. Some experts recommend the use of meropenem for patients with ESBL producing Klebsiella. The claim is that meropenem produces the best bacterial clearing.
The use of antibiotics is usually not enough. Surgical clearing (frequently done as interventional radiology drainage) is often needed after the patient is started on antimicrobial agents.
Multiple drug-resistant K. pneumoniae strains have been killed in vivo by intraperitoneal, intravenous, or intranasal administration of phages in laboratory tests. While this treatment has been available for some time, a greater danger of bacterial resistance exists to phages than to antibiotics. Resistance to phages may cause a bloom in the number of the microbes in environment, as well as among humans (if not obligate pathogenic). This is why phage therapy is used only in conjunction with antibiotics, to supplement their activity instead of replacing it altogether.
Preventing Klebsiella from spreading
To prevent spreading Klebsiella infections between patients, healthcare personnel must follow specific infection control precautions. These precautions may include strict adherence to hand hygiene and wearing gowns and gloves when they enter rooms where patients with Klebsiella–related illnesses are housed. Healthcare facilities also must follow strict cleaning procedures to prevent the spread of Klebsiella.
To prevent the spread of infections, patients also should clean their hands very often, including:
- Before preparing or eating food
- Before touching their eyes, nose, or mouth
- Before and after changing wound dressings or bandages
- After using the restroom
- After blowing their nose, coughing, or sneezing
- After touching hospital surfaces such as bed rails, bedside tables, doorknobs, remote controls, or the phone
- Ryan, KJ; Ray, CG, eds. (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. ISBN 0-8385-8529-9.
- Postgate, J (1998). Nitrogen Fixation (3rd ed.). Cambridge University Press. ISBN 978-0521640473.
- Riggs, PJ; Chelius MK; Iniguez AL; Kaeppler SM; Triplett EW (2001). "Enhanced maize productivity by inoculation with diazotrophic bacteria". Australian Journal of Plant Physiology 29 (8): 829–836. doi:10.1071/PP01045.
- Podschun, R; Ullmann, U (October 1998). "Klebsiella spp. as Nosocomial Pathogens: Epidemiology, Taxonomy, Typing Methods, and Pathogenicity Factors". Clinical Microbiology Reviews 11 (4): 589–603. PMC 88898.
- Rashid, T; Ebringer, A (June 2007). "Ankylosing spondylitis is linked to Klebsiella--the evidence". Clinical Rheumatology 26 (3): 858–864. doi:10.1007/s10067-006-0488-7. PMID 17186116.
- Groopman, J (2008-08-11). "Superbugs". The New Yorker. Retrieved 2013-07-07. "The new generation of resistant infections is almost impossible to treat."
- Hudson, Corey; Bent, Zachary; Meagher, Robert; Williams, Kelly (June 6, 2014). "Resistance Determinants and Mobile Genetic Elements of an NDM-1-Encoding Klebsiella pneumoniae Strain". PLoS One. doi:10.1371/journal.pone.0099209.
- Nathisuwan, S; Burgess, DS; Lewis, JS (August 2001) [Epub 2012-01-07]. "Extended-Spectrum β-Lactamases: Epidemiology, Detection, and Treatment". Pharmacotherapy 21 (8): 920–928. doi:10.1592/phco.21.11.920.34529.
- Limbago, BM; Rasheed, JK; Anderson, KF; Zhu, W et al. (December 2011) [Epub 2011-10-12]. "IMP-Producing Carbapenem-Resistant Klebsiella pneumoniae in the United States". Journal of Clinical Microbiology 49 (12): 4239–4245. doi:10.1128/JCM.05297-11. PMC 3233008. PMID 21998425.
- Berrie, C (2007-04-04). "Carbapenem-resistant Klebsiella pneumoniae outbreak in an Israeli hospital". Medscape. Medical News. WebMD. Retrieved 2013-07-07.
- Yigit, H; Queenan, AM; Anderson, GJ; Domenech-Sanchez, A et al. (April 2001). "Novel carbapenem-hydrolyzing beta-lactamase, KPC-1, from a carbapenem-resistant strain of Klebsiella pneumoniae". Antimicrobial Agents and Chemotherapy 45 (4): 1151–1161. doi:10.1128/AAC.45.4.1151-1161.2001. PMC 90438.
- Vastag, Brian (2012-08-22). "‘Superbug’ stalked NIH hospital last year, killing six". The Washington Post. Retrieved 2013-07-07.
- Lledo, W; Hernandez, M; Lopez, E; Molinari, OL et al. (2009-03-20). "Guidance for Control of Infections with Carbapenem-Resistant or Carbapenemase-Producing Enterobacteriaceae in Acute Care Facilities". Morbidity and Mortality Weekly Report (CDC) 58 (10): 256–260.
- Schwaber, MJ; Lev, B; Israeli, A; Solter, E et al. (2011-04-01) [Epub 2011-02-11]. "Containment of a country-wide outbreak of carbapenem-resistant Klebsiella pneumoniae in Israeli hospitals via a nationally implemented intervention". Clinical Infectious Diseases 52 (7): 848–855. doi:10.1093/cid/cir025. PMID 21317398.
- Bogovazova, GG; Voroshilova, NN; Bondarenko, VM (April 1991). "The efficacy of Klebsiella pneumoniae bacteriophage in the therapy of experimental Klebsiella infection". Zhurnal mikrobiologii, epidemiologii, i immunobiologii (in Russian) (Russia: Moskva) (4): 5–8. ISSN 0372-9311. PMID 1882608.
- Chanishvili, N, ed. (2012). A Literature Review of the Practical Application of Bacteriophage Research. Hauppauge, NY: Nova Science. ISBN 9781621008514.
- "Guideline for Isolation Precautions: Preventing Transmission of Infectious Agents in Healthcare Settings 2007". Centers for Disease Control and Prevention.
|Wikispecies has information related to: Klebsiella pneumoniae|
|Wikimedia Commons has media related to Klebsiella pneumoniae.|
- Virtual museum of bacteria page on K. pneumoniae
- What're the complications of pneumonia? (health-cares.net)
- Klebsiella Infection (emedicine.com)
- Klebsiella Genome Projects from Genomes OnLine Database
- Klebsiella pneumoniae-Associated Vertebral Osteomyelitis After Laparoscopic Cholecystectomy