| Klebsiella pneumoniae | |
|---|---|
 | |
| K. pneumoniae on aMacConkeyagar plate | |
Scientific classification | |
| Domain: | Bacteria |
| Kingdom: | Pseudomonadati |
| Phylum: | Pseudomonadota |
| Class: | Gammaproteobacteria |
| Order: | Enterobacterales |
| Family: | Enterobacteriaceae |
| Genus: | Klebsiella |
| Species: | K. pneumoniae |
| Binomial name | |
| Klebsiella pneumoniae (Schroeter 1886)Trevisan 1887 | |
| Subspecies | |
Klebsiella pneumoniae is aGram-negative, non-motile,encapsulated,lactose-fermenting,facultative anaerobic, rod-shapedbacterium. It appears as a mucoid lactose fermenter onMacConkey agar.
Although found in the normal flora of the mouth, skin, and intestines,[1] it can cause destructive changes to human and animal lungs if aspirated, specifically to the alveoli, resulting in bloody, brownish or yellow colored jelly-likesputum. In the clinical setting, it is the most significant member of thegenusKlebsiella of theEnterobacteriaceae.K. oxytoca andK. rhinoscleromatis have also been demonstrated in human clinical specimens. In recent years,Klebsiella species have become important pathogens innosocomial infections.
It naturally occurs in the soil, and about 30% of strains canfix nitrogen in anaerobic conditions.[2] As a free-livingdiazotroph, itsnitrogen-fixation system has been much-studied, and is of agricultural interest, asK. pneumoniae has been demonstrated to increase crop yields in agricultural conditions.[3]
It is closely related toK. oxytoca from which it is distinguished by beingindole-negative and by its ability to grow onmelezitose but not3-hydroxybutyrate.
The genusKlebsiella was named after the German microbiologistEdwin Klebs (1834–1913).[citation needed] It is also known as Friedlander's bacillum in honor ofCarl Friedländer, a German pathologist, who proposed that this bacterium was theetiological factor for the pneumonia seen especially inimmunocompromised individuals such as people withchronic diseases oralcoholics.
Community-acquired pneumonia caused byKlebsiella pneumoniae may occasionally be calledFriedländer's pneumonia.[4]
Illness most commonly affects middle-aged and older men more often than women with debilitating diseases. This patient population is believed to have impaired respiratory host defenses, including persons withdiabetes,alcoholism,malignancy, liver disease,chronic obstructive pulmonary disease,glucocorticoid therapy,kidney failure, and certain occupational exposures (such aspaper mill workers). Many of these infections are obtained when a person is in the hospital for some other reason (anosocomial infection).
In addition to pneumonia,Klebsiella can also cause infections in theurinary tract, lowerbiliary 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, andbacteremia, andsepsis. For patients with an invasive device in their bodies, contamination of the device becomes a risk; neonatal ward devices,respiratory support equipment, andurinary catheters put patients at increased risk. Also, the use ofantibiotics can be a factor that increases the risk of nosocomial infection withKlebsiella bacteria.Sepsis and septic shock can follow entry of the bacteria into the blood.
Research conducted at King's College, London has implicatedmolecular mimicry betweenHLA-B27 and twoKlebsiella surface molecules as the cause ofankylosing spondylitis.[5]
Klebsiella ranks second toE. coli forurinary tract infections in older people.[6] It is also anopportunistic pathogen for patients with chronic pulmonary disease, enteric pathogenicity,nasal mucosa atrophy, andrhinoscleroma.[citation needed] Newantibiotic-resistant strains ofK. pneumoniae are appearing.[7]
The most common condition caused byKlebsiella bacteria outside the hospital ispneumonia, typically in the form ofbronchopneumonia and alsobronchitis. These patients have an increased tendency to develop lungabscesses, cavitation,empyema, andpleural adhesions. It has a death rate around 50%, even withantimicrobial therapy.[8]
It is typically due toaspiration and alcoholism may be a risk factor, though it is also commonly implicated inhospital-acquired urinary tractinfections, and COPD (chronic obstructive pulmonary disease) individuals.[9][10] In terms of the pathophysiology ofKlebsiella pneumonia theneutrophilmyeloperoxidase defense againstK. pneumoniae is often seen. Oxidative inactivation ofelastase is involved, whileLBP helps transfer bacteria cell wall elements to the cells.[11][12]
Individuals withKlebsiella pneumoniae tend to cough up a characteristic "currant jelly"sputum, as well as having fever,nausea,tachycardia, andvomiting.Klebsiella pneumoniae tends to affect people with underlying conditions, such asalcoholism.[9]
In terms of the diagnosis ofKlebsiella pneumoniae the following can be done to determine if the individual has this infection, with the addition of susceptibility testing to identify drug-resistant organisms:[11][9]
Treatment forKlebsiella pneumoniae is byantibiotics such asaminoglycosides,piperacillin/tazobactam, andcephalosporins, the choice depending uponantibiotic susceptibility testing, the person's health condition, medical history and severity of the disease.[10][13]
Klebsiella possessesbeta-lactamase giving it resistance toampicillin. Many strains have acquired anextended-spectrum beta-lactamase with additional resistance tocarbenicillin,amoxicillin, and ceftazidime. The bacteria remain susceptible toaminoglycosides and somecephalosporins, and varying degrees of inhibition of thebeta-lactamase withclavulanic acid have been reported. Infections due to multidrug-resistantgram-negative pathogens in theICU have invoked the re-emergence ofcolistin. However, colistin-resistant strains ofK. pneumoniae have been reported in ICUs.[11][14][15][16] In 2009, strains ofK. pneumoniae with gene calledNew Delhi metallo-beta-lactamase (NDM-1) that even gives resistance against intravenous antibioticcarbapenem, were discovered inIndia andPakistan.Klebsiella cases in Taiwan have shown abnormal toxicity, causing liver abscesses in people withdiabetes mellitus (DM); treatment consists of third generationcephalosporins.[medical citation needed]
Hypervirulent (hvKp) is a rather recentK pneumoniae variant that is significantly more virulent than classicalK. pneumoniae (cKp). While cKp is an opportunistic pathogen responsible for nosocomial infections that usually affect immunocompromised patients, hvKp is clinically more concerning since it also causes disease in healthy individuals and can infect virtually every site of the body. The genetic traits that lead to this pathotype are included in a large virulence plasmid and potentially on additional conjugative elements.[17]
These newly identified strains were described to overproduce capsule components and siderophores for iron acquisition, among other factors.[18] Although initial studies showed that hvKp is rather susceptible to antibiotic treatment, it has been recently shown that such strains can acquire resistance plasmids and become multiresistant to a variety of antibiotics.[18][19][20]
It originated fromAsia, having a high mortality rate among the population. It often spreads tocentral nervous system andeye causingendophthalmitis, nonhepatic abscesses,pneumonia,necrotizing fasciitis, andmeningitis. One visual trait of these strains is hypermucoviscous phenotype and a string test can be used to help the diagnosis.[21] Further examinations and treatments are made on a case-by-case basis, as there are currently no international guidelines.[22]
HypervirulentK. pneumoniae (hvKp) can also colonize the gastrointestinal tract of healthy individuals, facilitating its spread within communities. A study on Carbapenem-resistant hypervirulentKlebsiella pneumoniae (CR-hvKp) found that its infection leads to significant alterations in the gut microbiota, disrupting its structure and composition.[23] The disruption of the gut microbiota undermines the host's immune defenses, making it more susceptible to systemic infections. The compromised gut barrier facilitates the translocation of CR-hvKp into the bloodstream, increasing the risk of systemic infections. The combination of gut microbiota disruption and compromised immunity contributes to higher mortality rates in CR-hvKp infections. These findings underscore the importance of maintaining gut microbiota integrity to prevent systemic dissemination of CR-hvKp and reduce associated mortality. Strategies aimed at preserving or restoring gut microbiota balance could be pivotal in managing CR-hvKp infections.
Studies have identified hvKp carriage in approximately 5–6% of healthy adults in Asia, suggesting a significant reservoir outside healthcare settings. Once colonized, person-to-person transmission, particularly via the fecal–oral route, is a plausible mechanism for community dissemination, especially in regions where hvKp is endemic.[24]
Environmental Sources:
Beyond human carriers, hvKp has been isolated from various environmental sources, indicating potential non-human reservoirs.[25] Notably, hvKp strains have been detected in:
These findings underscore the importance of environmental surveillance and suggest that food and water sources could play roles in hvKp transmission.
To get aK. pneumoniae infection, a person must be exposed to thebacteria. In other words,K. pneumoniae must enter therespiratory tract to cause pneumonia, or the blood to cause a bloodstream infection.In healthcare settings,K. pneumoniae bacteria can be spread through person-to-person contact (for example, contaminated hands of healthcare personnel, or other people via patient to patient) or, less commonly, by contamination of the environment; the role of transmission directly from the environment to patients iscontroversial and requires further investigation.[26] However, the bacteria are not spread through the air.[16]Patients in healthcare settings also may be exposed toK. pneumoniae when they are onventilators, or haveintravenouscatheters or wounds. These medical tools and conditions may allowK. pneumoniae to enter the body and cause infection.[27]
Klebsiella organisms are often resistant to multiple antibiotics. Current evidence implicatesplasmids as the primary source of the resistance genes.[28]Klebsiella species with the ability to produce extended-spectrum beta-lactamases (ESBL) are resistant to virtually all beta-lactam antibiotics, except carbapenems. Other frequent resistance targets includeaminoglycosides,fluoroquinolones,tetracyclines,chloramphenicol, andtrimethoprim/sulfamethoxazole.[29]
Infection withcarbapenem-resistant Enterobacteriaceae (CRE) orcarbapenemase-producing Enterobacteriaceae is emerging as an important challenge in health-care settings.[31][32] One of many CREs is carbapenem-resistantKlebsiella 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.[33] In the US, it was first described in North Carolina in 1996;[34] since then CRKP has been identified in 41 states;[35] and is routinely detected 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 healthcare professionals can do very little, if anything, to treat patients with resistant organisms.
A number of mechanisms cause carbapenem resistance in the Enterobacteriaceae. These include hyperproduction of ampCbeta-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 theblaKPC enzyme is carried on a mobile piece of genetic material (atransposon; the specific transposon involved is called Tn4401), which increases the risk for dissemination. CRE can be difficult to detect because some strains that harborblaKPC haveminimum inhibitory concentrations 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.[36]
The extent and prevalence of CRKP within the environment is currently unknown. Themortality rate is also unknown, but has been observed to be as high as 44%.[37] TheCenters for Disease Control and Prevention released guidance for aggressive infection control to combat CRKP:
In 2019, there were 192,530 global deaths attributed to resistant strains ofKlebsiella pneumoniae.[39]
| 3GC | 4GC | Amino-glycosides | Amino-penicillin | Anti-pseudomonal | BL−BLI | Carbapenems | Fluoro-quinolones | Macrolide | MDR & XDR | Meticillin | Mono INH | Mono RIF | Penicillin | TMP-SMX | Vancomycin | Total | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Acinetobacter baumannii | 6,860 | 3,280 | 10,400 | 13,300 | 811 | 57,700 | 40,000 | 132,351 | |||||||||
| Citrobacter spp | 1,840 | 1,340 | 411 | 2,170 | 2,300 | 2,510 | 10,571 | ||||||||||
| Enterobacter spp | 5320 | 3070 | 9550 | 15,300 | 7,800 | 4,650 | 45,690 | ||||||||||
| Enterococcus faecalis | 26,800 | 3,420 | 30,220 | ||||||||||||||
| Enterococcus faecium | 37,200 | 14,300 | 51,500 | ||||||||||||||
| Other enterococci | 12,200 | 2,200 | 14,400 | ||||||||||||||
| Escherichia coli | 59,900 | 11,700 | 10,500 | 21,300 | 29,500 | 56,000 | 30,200 | 219,100 | |||||||||
| Group AStreptococcus | 3,630 | 3,630 | |||||||||||||||
| Group BStreptococcus | 11,500 | 13,500 | 799 | 25,799 | |||||||||||||
| Haemophilus influenzae | 2,470 | 4,290 | 6,760 | ||||||||||||||
| Klebsiella pneumoniae | 50,100 | 26,300 | 7,930 | 55,700 | 29,000 | 23,500 | 192,530 | ||||||||||
| Morganella spp | 168 | 154 | 427 | 749 | |||||||||||||
| Mycobacterium tuberculosis | 69,810 | 11,600 | 3,350 | 84,760 | |||||||||||||
| Proteus spp | 4,730 | 887 | 1,330 | 2,970 | 1,620 | 11,537 | |||||||||||
| Pseudomonas aeruginosa | 10,400 | 4,370 | 3,010 | 10,300 | 38,100 | 18,300 | 84,480 | ||||||||||
| Salmonella Paratyphi | 4,040 | 64 | 4,104 | ||||||||||||||
| Salmonella Typhi | 17,200 | 6,460 | 23,660 | ||||||||||||||
| Non-typhoidalSalmonella | 5,620 | 5,620 | |||||||||||||||
| Serratia spp | 1,100 | 2,610 | 953 | 2,450 | 1,080 | 8,193 | |||||||||||
| Shigella spp | 5,990 | 5,990 | |||||||||||||||
| Staphylococcus aureus | 2,480 | 15,900 | 19,600 | 121,000 | 18,700 | 3,120 | 180,800 | ||||||||||
| Streptococcus pneumoniae | 3,330 | 2,040 | 41,900 | 11,200 | 12,500 | 12,400 | 38,700 | 122,070 | |||||||||
| Total | 140,898 | 17,074 | 56,731 | 16,120 | 37,800 | 32,081 | 242,950 | 305,737 | 49,230 | 76,334 | 121,000 | 11,600 | 3,350 | 12,199 | 117,370 | 23,040 | 1,264,514 |
Israel 2007–2008. A nationwide outbreak of CRE in Israel peaked in March 2007 at 55.5 cases per 100,000 patient days and 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.[40]
Nevada 2016. In mid-August 2016, a resident ofWashoe County was hospitalized inReno due to a CRE (specificallyKlebsiella pneumoniae) infection. In early September of the same year, she developed septic shock and died. On testing by CDC an isolate from the patient was found to be resistant to all 26 antibiotics available in the US, including drug of last resortcolistin.[41] It is believed she may have picked up the microbe while hospitalized in India for two years due to a broken right femur and subsequent femur and hip infections.[42][43][44]
Klebsiella pneumoniae carries a large number of anti-microbial resistance genes (AMR genes). These genes are transferred via plasmids from and to other human pathogens. One human pathogen that commonly acquires AMR genes fromKlebsiella pneumoniae isSalmonella.[citation needed] This could help with treatment of salmonella infections due to having knowledge of possible antibiotic resistance data.[citation needed]
The majority of AMR genes inKlebsiella pneumoniae are plasmid-borne. An example of a niche would be soil, often considered a hotspot for gene transfer.[citation needed]
| Total AMR genes per spp | Average plasmids | |
|---|---|---|
| Acinetobacter baumannii | 278 | 1.5 |
| Pseudomonas aeruginosa | 263 | 0 |
| Klebsiella pneumoniae | 410 | 2.5 |
| Enterobacter cloacae | 277 | 2.2 |
| Escherichia coli | 204 | 1 |
The table shows the number of AMR genes and plasmids (per strain or subspecies) compared to other common bacteria species.[45]
To prevent spreading Klebsiella infections between patients, healthcare personnel must follow specific infection-control precautions,[27] which may include strict adherence to hand hygiene (preferably using an alcohol based hand rub (60–90%) or soap and water if hands are visibly soiled. Alcohol based hand rubs are effective against these Gram-negative bacilli)[46] and wearing gowns and gloves when they enter rooms where patients withKlebsiella-related illnesses are housed. Healthcare facilities also must follow strict cleaning procedures to prevent the spread ofKlebsiella.[27]
To prevent the spread of infections, patients also should clean their hands very often, including:
K. pneumoniae can be treated with antibiotics if the infections are notdrug-resistant. Infections byK. pneumoniae can be difficult to treat because fewer antibiotics are effective against them. In such cases, a microbiology laboratory must run tests to determine which antibiotics will treat the infection.[27] More specific treatments ofKlebsiella pneumonia are given in its section above. Forurinary tract infections with multidrug-resistantKlebsiella species, a combination therapy withamikacin andmeropenem has been suggested.[47]
Multiple drug-resistantK. pneumoniae strains have been killedin vivo by intraperitoneal, intravenous, or intranasal administration ofphages in laboratory tests.[48] Resistance to phages is not likely to be as troublesome as to antibiotics as new infectious phages are likely to be available in environmental reservoirs. Phage therapy can be used in conjunction with antibiotics, to supplement their activity instead of replacing it altogether.[49]
New data sources outlining the global burden ofK. pneumoniae and drug-resistant forms are expected to build momentum into prophylactic vaccine development.[50] The recent 2022 IHME study showed that in 2019K. pneumoniae was responsible for 790,000 deaths [571,000–1,060,000] in all age groups across 11 infectious syndromes. Importantly, in Sub-saharan AfricaK. pneumoniae was responsible for 124,000 [89,000–167,000] neonatal deaths due to bloodstream infections. Based on these and other data, a newly developed prophylactic vaccine would ideally be designed to prevent invasiveK. pneumoniae disease in both vulnerable persons but also as a maternal vaccine to prevent neonatal sepsis and global demand assessments have been published.[51] As of June 2023, one single clinical development program for aK. pneumoniae vaccine [Kleb4V/GSK4429016A] was in a Phase 1/2 study in healthy adults aged 18–70 yrs (n=166) [Clinical trials identifier: NCT04959344]. The vaccine is an O-antigen based conjugate where the specific O-antigens in the vaccine remain undisclosed [Michael Kowarik, LimmaTech Biologics, World Vaccine Congress EU, 2022] although only a limited number of O-serotypes can account for a high proportion of clinical isolates.[52] A recent Q1 2024 GSK Corporate R&D pipeline update showed that Kleb4V/GSK4429016A had been removed. The status of the program is now subject to verification.
The new generation of resistant infections is almost impossible to treat.
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