Klebsiella Infections

''Klebsiella pneumoniae'' is a Gram-negative, non-motile, encapsulated, lactose- fermenting, facultative anaerobic, rod-shaped bacterium. It appears as a mucoid lactose fermenter on MacConkey agar.

Although found in the normal flora of the mouth, skin, and intestines, it can cause destructive changes to human and animal lungs if aspirated, specifically to the alveoli resulting in bloody, brownish or yellow colored jelly like sputum. In the clinical setting, it is the most significant member of the genus '' Klebsiella'' of the Enterobacteriaceae. ''K. oxytoca'' and ''K. rhinoscleromatis'' have also been demonstrated in human clinical specimens. In recent years, ''Klebsiella'' species 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.

It is closely related to '' K. oxytoca'' from which it is distinguished by being indole-negative and by its ability to grow on melezitose but not 3-hydroxybutyrate.

History

The genus ''Klebsiella'' was named after the German microbiologist Edwin Klebs (1834–1913). It is also known as Friedlander's bacillum in honor of Carl Friedländer, a German pathologist, who proposed that this bacterium was the etiological factor for the pneumonia seen especially in immunocompromised individuals such as people with chronic diseases or alcoholics.

Community-acquired pneumonia caused by ''Klebsiella pneumoniae'' may occasionally be called ''Friedländer's pneumonia''.

Epidemiology

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 with diabetes, alcoholism, malignancy, liver disease, chronic obstructive pulmonary diseases, glucocorticoid therapy, kidney failure, and certain occupational exposures (such as papermill workers). Many of these infections are obtained when a person is in the hospital for some other reason (a nosocomial infection).

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 sepsis. For patients with an invasive device in their bodies, contamination of the device becomes a risk; neonatal ward devices, 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.

Research conducted at King's College, London has implicated molecular mimicry between HLA-B27 and two ''Klebsiella'' surface molecules as the cause of ankylosing spondylitis.

''Klebsiella'' ranks second to ''E. coli'' for urinary tract infections in older people. It is also an opportunistic pathogen for patients with chronic pulmonary disease, enteric pathogenicity, nasal mucosa atrophy, and rhinoscleroma. New antibiotic-resistant strains of ''K. pneumoniae'' are appearing.

''Klebsiella'' pneumonia

The most common condition 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 pleural adhesions. It has a death rate around 50%, even with antimicrobial therapy.

Pathophysiology

It is typically due to aspiration and alcoholism may be a risk factor, though it is also commonly implicated in hospital-acquired urinary tract infections, and COPD (chronic obstructive pulmonary disease) individuals

In terms of the pathophysiology of ''Klebsiella'' pneumonia we see neutrophil myeloperoxidase defense against ''K. pneumoniae''. Oxidative inactivation of elastase is involved, while LBP helps transfer bacteria cell wall elements to the cells.

Signs and symptoms

Individuals with ''Klebsiella'' pneumonia tend to cough up a characteristic sputum, as well as having fever, nausea, tachycardia, and vomiting. ''Klebsiella'' pneumonia tends to affect people with underlying conditions, such as alcoholism.

Diagnosis

In terms of the diagnosis of ''Klebsiella'' pneumonia the following can be done to determine if the individual has this infection, including ''susceptibility testing'' for (ESBL) ''Extended Spectrum β-Lactamase'', as well as:
* Blood culture
* CBC
*Sputum(culture)
* Radiography(chest)
*CT scan

Treatment

Treatment for ''Klebsiella'' pneumonia is by antibiotics such as aminoglycosides pipercillin tazobactam, and cephalosporins, the choice depending upon antibiotic susceptibility testing, the person's health condition, medical history and severity of the disease.


''Klebsiella'' possesses beta-lactamase giving it resistance to ampicillin, many strains have acquired an extended-spectrum beta-lactamase with additional resistance to carbenicillin, amoxicillin, and ceftazidime. The bacteria remain susceptible to aminoglycosides and some cephalosporins, varying degrees of inhibition of the beta-lactamase with clavulanic acid have been reported. Infections due to multidrug-resistant gram-negative pathogens in the ICU have invoked the re-emergence of colistin. However, colistin-resistant strains of ''K. pneumoniae'' have been reported in ICUs. In 2009, strains of ''K. pneumoniae'' with gene called New Delhi metallo-beta-lactamase ( NDM-1) that even gives resistance against intravenous antibiotic carbapenem, were discovered in India and Pakistan. ''Klebsiella'' cases in Taiwan have shown abnormal toxicity, causing liver abscesses in people with diabetes mellitus (DM), treatment consists of third generation cephalosporins.

Hypervirulent ''Klebsiella pneumonia''

Hypervirulent (hvKp) is a rather recent ''K pneumoniae'' variant that is significantly more virulent than classical ''K. 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.

These newly identified strains were described to overproduce capsule components and siderophores for iron acquisition, among other factors. 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.

It is originated from Asia, having a high mortality rate among the population. It often spreads to central nervous system and eye causing endophthalmitis, nonhepatic abscesses, pneumonia, necrotizing fasciitis, and meningitis. One visual trait of these strains is hypermucoviscous phenotype and a string test can be used to help the diagnosis. Further examinations and treatments are made on a case-by-case basis, as there are currently no international guidelines.

Transmission

To get a ''K. pneumoniae'' infection, a person must be exposed to the bacteria. In other words, ''K. pneumoniae'' must enter the respiratory tract to cause pneumoniae, 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 is controversial and requires further investigation. However, the bacteria are not spread through the air.
Patients in healthcare settings also may be exposed to ''K. pneumoniae'' when they are on ventilators, or have intravenous catheters or wounds. These medical tools and conditions may allow ''K. pneumoniae'' to enter the body and cause infection.

Resistant strains

''Klebsiella'' organisms are often resistant to multiple antibiotics. Current evidence implicates plasmids as the primary source of the resistance genes. ''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 include 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 US, it was first described in North Carolina in 1996; since then CRKP has been identified in 41 states; 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 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, ''blak''pc. The gene that encodes the ''blak''pc 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 ''blak''pc have minimum 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.

The extent and prevalence of CRKP within the environment is currently unknown. The mortality rate is also unknown, but has been observed to be as high as 44%. The Centers for Disease Control and Prevention released guidance for aggressive infection control to combat CRKP:

:''Place all patients colonized or infected with 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.

In mid-August 2016, a resident of Washoe County was hospitalized in Reno due to a CRE (specifically ''Klebsiella 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 resort colistin. 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.

Prevent from spreading

To prevent spreading'' Klebsiella'' infections between patients, healthcare personnel must follow specific infection-control precautions, 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) 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

Treatment

''K. pneumoniae'' can be treated with antibiotics if the infections are not drug-resistant. Infections by ''K. 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. More specific treatments of ''Klebsiella'' pneumonia are given in its section above. For urinary tract infections with multidrug-resistant ''Klebsiella'' species, a combination therapy with amikacin and meropenem has been suggested.

Research

Multiple drug-resistant ''K. pneumoniae'' strains have been killed ''in vivo'' by intraperitoneal, intravenous, or intranasal administration of phages in laboratory tests. 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.

References

External links

Virtual museum of bacteria page on ''K. pneumoniae''


What're the complications of pneumonia?
(health-cares.net)


(emedicine.com)
Klebsiella Genome Projects
fro
Genomes OnLine Database

Klebsiella pneumoniae-Associated Vertebral Osteomyelitis After Laparoscopic CholecystectomyType strain of ''Klebsiella pneumoniae'' at Bac''Dive'' – the Bacterial Diversity Metadatabase

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Enterobacteriaceae
Gram-negative bacteria
Pathogenic bacteria
Polysaccharide encapsulated bacteria
Bacteria described in 1886