|K. pneumoniae on a MacConkey agar plate|
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.
The bacterial capsule is a very large structure of many bacteria. It is a polysaccharide layer that lies outside the cell envelope, and is thus deemed part of the outer envelope of a bacterial cell. It is a well-organized layer, not easily washed off, and it can be the cause of various diseases.
Lactose is a disaccharide. It is a sugar composed of galactose and glucose subunits and has the molecular formula C12H22O11. Lactose makes up around 2–8% of milk (by weight). The name comes from lac (gen. lactis), the Latin word for milk, plus the suffix -ose used to name sugars. The compound is a white, water-soluble, non-hygroscopic solid with a mildly sweet taste. It is used in the food industry.
MacConkey agar is an indicator, a selective and differential culture medium for bacteria designed to selectively isolate Gram-negative and enteric bacilli and differentiate them based on lactose fermentation. The crystal violet and bile salts inhibit the growth of Gram-positive organisms which allows for the selection and isolation of gram-negative bacteria. Enteric bacteria that have the ability to ferment lactose can be detected using the carbohydrate lactose, and the pH indicator neutral red.
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 sputum. In the clinical setting, it is the most significant member of the Klebsiella genus 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.
Sputum is mucus and is the name used for the coughed-up material (phlegm) from the lower airways. In medicine, sputum samples are usually used for naked eye exam, microbiological investigations of respiratory infections, and cytological investigations of respiratory systems. It is critical that the patient not give a specimen that includes any mucoid material from the interior of the nose. Naked eye exam of sputum can be done at home by a patient in order to note the various colors. Any hint of yellow color suggests an airway infection. Such color hints are best detected when the sputum is viewed on a very white background such as white paper, a white pot, or a white sink surface. The more intense the yellow color, the more likely it is a bacterial infection.
Klebsiella is a genus of nonmotile, Gram-negative, oxidase-negative, rod-shaped bacteria with a prominent polysaccharide-based capsule.
A genus is a taxonomic rank used in the biological classification of living and fossil organisms, as well as viruses, in biology. In the hierarchy of biological classification, genus comes above species and below family. In binomial nomenclature, the genus name forms the first part of the binomial species name for each species within the genus.
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.
Nitrogen fixation is a process by which nitrogen in the air is converted into ammonia (NH3) or related nitrogenous compounds. Atmospheric nitrogen, is molecular dinitrogen (N2), a relatively nonreactive molecule that is metabolically useless to all but a few microorganisms. Biological nitrogen fixation converts N2 into ammonia, which is metabolized by most organisms.
Diazotrophs are bacteria and archaea that fix atmospheric nitrogen gas into a more usable form such as ammonia.
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.
Klebsiella oxytoca is a Gram-negative, rod-shaped bacterium that is closely related to K. pneumoniae, from which it is distinguished by being indole-positive; it also has slightly different growth characteristics in that it is able to grow on melezitose, but not 3-hydroxybutyrate.
The indole test is a biochemical test performed on bacterial species to determine the ability of the organism to convert tryptophan into indole. This division is performed by a chain of a number of different intracellular enzymes, a system generally referred to as "tryptophanase."
Melezitose, also spelled melicitose, is a nonreducing trisaccharide sugar that is produced by many plant sap eating insects, including aphids such as Cinara pilicornis by an enzyme reaction. This is beneficial to the insects, as it reduces the stress of osmosis by reducing their own water potential. The melezitose is part of the honeydew which acts as an attractant for ants and also as a food for bees. This is useful to the lice as they have a symbiotic relationship with ants. Melezitose can be partially hydrolyzed to glucose and turanose the latter of which is an isomer of sucrose.
The genus Klebsiella was named after the German bacteriologist Edwin Klebs (1834–1913).[ citation needed ] Also, it is 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.
Theodor Albrecht Edwin Klebs was a German-Swiss pathologist. He is mainly known for his work on infectious diseases. His works paved the way for the beginning of modern bacteriology, and inspired Louis Pasteur and Robert Koch. He was the first to identify a bacterium that causes diphtheria, which was called Klebs–Loeffler bacterium. He was the father of physician Arnold Klebs.
Carl Friedländer was a German pathologist and microbiologist who helped discover the bacterial cause of pneumonia in 1882. He also first described thromboangiitis obliterans.
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, glucocorticoid therapy, renal 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). Feces are the most significant source of patient infection, followed by contact with contaminated instruments.[ citation needed ]
Immunodeficiency is a state in which the immune system's ability to fight infectious disease and cancer is compromised or entirely absent. Most cases of immunodeficiency are acquired ("secondary") due to extrinsic factors that affect the patient's immune system. Examples of these extrinsic factors include HIV infection, extremes of age, and environmental factors, such as nutrition. In the clinical setting, the immunosuppression by some drugs, such as steroids, can be either an adverse effect or the intended purpose of the treatment. Examples of such use is in organ transplant surgery as an anti-rejection measure and in patients suffering from an overactive immune system, as in autoimmune diseases. Some people are born with intrinsic defects in their immune system, or primary immunodeficiency. A person who has an immunodeficiency of any kind is said to be immunocompromised. An immunocompromised person may be particularly vulnerable to opportunistic infections, in addition to normal infections that could affect everyone. Immunodeficiency also decreases cancer immunosurveillance, in which the immune system scans the body's cells and kills neoplastic ones.
Alcoholism, also known as alcohol use disorder (AUD), is a broad term for any drinking of alcohol that results in mental or physical health problems. The disorder was previously divided into two types: alcohol abuse and alcohol dependence. In a medical context, alcoholism is said to exist when two or more of the following conditions are present: a person drinks large amounts over a long time period, has difficulty cutting down, acquiring and drinking alcohol takes up a great deal of time, alcohol is strongly desired, usage results in not fulfilling responsibilities, usage results in social problems, usage results in health problems, usage results in risky situations, withdrawal occurs when stopping, and alcohol tolerance has occurred with use. Risky situations include drinking and driving or having unsafe sex, among other things. Alcohol use can affect all parts of the body, but it particularly affects the brain, heart, liver, pancreas and immune system. This can result in mental illness, Wernicke–Korsakoff syndrome, irregular heartbeat, liver cirrhosis and increased cancer risk, among other diseases. Drinking during pregnancy can cause damage to the baby resulting in fetal alcohol spectrum disorders. Women are generally more sensitive than men to the harmful physical and mental effects of alcohol.
Malignancy is the tendency of a medical condition to become progressively worse.
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.
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, 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.[ citation needed ] It is also an opportunistic pathogen for patients with chronic pulmonary disease, enteric pathogenicity, nasal mucosa atrophy, and rhinoscleroma.[ citation needed ] New antibiotic-resistant strains of K. pneumoniae are appearing.
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.
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 USA, 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, 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 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:
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.
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:
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.
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, ertapenem and ciprofloxacin. 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.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.
Beta-lactamases are enzymes produced by bacteria that provide multi-resistance to β-lactam antibiotics such as penicillins, cephalosporins, cephamycins, and carbapenems (ertapenem), although carbapenems are relatively resistant to beta-lactamase. Beta-lactamase provides antibiotic resistance by breaking the antibiotics' structure. These antibiotics all have a common element in their molecular structure: a four-atom ring known as a β-lactam. Through hydrolysis, the lactamase enzyme breaks the β-lactam ring open, deactivating the molecule's antibacterial properties.
The term broad-spectrum antibiotic can refer to an antibiotic that acts on the two major bacterial groups, gram-positive and gram-negative, or any antibiotic that acts against a wide range of disease-causing bacteria. These medications are used when a bacterial infection is suspected but the group of bacteria is unknown or when infection with multiple groups of bacteria is suspected. This is in contrast to a narrow-spectrum antibiotic, which is effective against only a specific group of bacteria. Although powerful, broad-spectrum antibiotics pose specific risks, particularly the disruption of native, normal bacteria and the development of antimicrobial resistance. An example of a commonly used broad-spectrum antibiotic is ampicillin.
A hospital-acquired infection (HAI), also known as a nosocomial infection, is an infection that is acquired in a hospital or other health care facility. To emphasize both hospital and nonhospital settings, it is sometimes instead called a health care–associated infection. Such an infection can be acquired in hospital, nursing home, rehabilitation facility, outpatient clinic, or other clinical settings. Infection is spread to the susceptible patient in the clinical setting by various means. Health care staff can spread infection, in addition to contaminated equipment, bed linens, or air droplets. The infection can originate from the outside environment, another infected patient, staff that may be infected, or in some cases, the source of the infection cannot be determined. In some cases the microorganism originates from the patient's own skin microbiota, becoming opportunistic after surgery or other procedures that compromise the protective skin barrier. Though the patient may have contracted the infection from their own skin, the infection is still considered nosocomial since it develops in the health care setting.
Multiple drug resistance (MDR), multidrug resistance or multiresistance is antimicrobial resistance shown by a species of microorganism to multiple antimicrobial drugs. The types most threatening to public health are MDR bacteria that resist multiple antibiotics; other types include MDR viruses, parasites. Recognizing different degrees of MDR, the terms extensively drug resistant (XDR) and pandrug-resistant (PDR) have been introduced. The definitions were published in 2011 in the journal Clinical Microbiology and Infection and are openly accessible.
Carbapenems are a class of highly effective antibiotic agents commonly used for the treatment of severe or high-risk bacterial infections. This class of antibiotics is usually reserved for known or suspected multidrug-resistant (MDR) bacterial infections. Similar to penicillins and cephalosporins, carbapenems are members of the beta lactam class of antibiotics, which kill bacteria by binding to penicillin-binding proteins, thus inhibiting bacterial cell wall synthesis. However, these agents individually exhibit a broader spectrum of activity compared to most cephalosporins and penicillins. Furthermore, carbapenems are typically unaffected by emerging antibiotic resistance, even to other beta-lactams.
Hospital-acquired pneumonia (HAP) or nosocomial pneumonia refers to any pneumonia contracted by a patient in a hospital at least 48–72 hours after being admitted. It is thus distinguished from community-acquired pneumonia. It is usually caused by a bacterial infection, rather than a virus.
Acinetobacter baumannii is a typically short, almost round, rod-shaped (coccobacillus) Gram-negative bacterium. It can be an opportunistic pathogen in humans, affecting people with compromised immune systems, and is becoming increasingly important as a hospital-derived (nosocomial) infection. While other species of the genus Acinetobacter are often found in soil samples, it is almost exclusively isolated from hospital environments. Although occasionally it has been found in environmental soil and water samples, its natural habitat is still not known.
Enterobacter cloacae is a clinically significant Gram-negative, facultatively-anaerobic, rod-shaped bacterium.
Beta-lactamases are a family of enzymes involved in bacterial resistance to beta-lactam antibiotics. They act by breaking the beta-lactam ring that allows penicillin-like antibiotics to work. Strategies for combating this form of resistance have included the development of new beta-lactam antibiotics that are more resistant to cleavage and the development of the class of enzyme inhibitors called beta-lactamase inhibitors. Although β-lactamase inhibitors have little antibiotic activity of their own, they prevent bacterial degradation of beta-lactam antibiotics and thus extend the range of bacteria the drugs are effective against.
Klebsiella pneumonia (KP) is a form of bacterial pneumonia associated with Klebsiella pneumoniae. 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 individuals
New Delhi metallo-beta-lactamase 1 (NDM-1) is an enzyme that makes bacteria resistant to a broad range of beta-lactam antibiotics. These include the antibiotics of the carbapenem family, which are a mainstay for the treatment of antibiotic-resistant bacterial infections. The gene for NDM-1 is one member of a large gene family that encodes beta-lactamase enzymes called carbapenemases. Bacteria that produce carbapenemases are often referred to in the news media as "superbugs" because infections caused by them are difficult to treat. Such bacteria are usually susceptible only to polymyxins and tigecycline.
Plasmid-mediated resistance is the transfer of antibiotic resistance genes which are carried on plasmids. The plasmids can be transferred between bacteria within the same species or between different species via conjugation. Plasmids often carry multiple antibiotic resistance genes, contributing to the spread of multidrug-resistance (MDR). Antibiotic resistance mediated by MDR plasmids severely limits the treatment options for the infections caused by Gram-negative bacteria, especially Enterobacteriaceae family. The global spread of MDR plasmids has been enhanced by selective pressure from antibiotic usage in human and veterinary medicine.
Multidrug resistant Gram-negative bacteria are a type of Gram-negative bacteria with resistance to multiple antibiotics. They can cause bacteria infections that pose a serious and rapidly emerging threat for hospitalized patients and especially patients in intensive care units. Infections caused by MDR strains are correlated with increased morbidity, mortality, and prolonged hospitalization. Thus, not only do these bacteria pose a threat to global public health, but also create a significant burden to healthcare systems.
Carbapenem-resistant Enterobacteriaceae (CRE) or carbapenemase-producing Enterobacteriaceae (CPE) are Gram-negative bacteria that are resistant to the carbapenem class of antibiotics, considered the drugs of last resort for such infections. They are resistant because they produce an enzyme called a carbapenemase that disables the drug molecule. The resistance can vary from moderate to severe. Enterobacteriaceae are common commensals and infectious agents. Experts fear CRE as the new "superbug". The bacteria can kill up to half of patients who get bloodstream infections. Tom Frieden, former head of the Centers for Disease Control and Prevention has referred to CRE as "nightmare bacteria". Types of CRE are sometimes known as KPC and NDM. KPC and NDM are enzymes that break down carbapenems and make them ineffective. Both of these enzymes, as well as the enzyme VIM have also been reported in Pseudomonas.
Ceftolozane is a novel cephalosporin antibiotic, developed for the treatment of infections with gram-negative bacteria that have become resistant to conventional antibiotics. It was studied for urinary tract infections, intra-abdominal infections and ventilator-associated bacterial pneumonia. Ceftolozane is combined with the β-lactamase inhibitor tazobactam, which protects ceftolozane from degradation. Ceftolozane-tazobactam is indicated for the treatment of complicated urinary tract infections and complicated intra abdominal infections.
Ceftazidime/avibactam is a combination drug composed of ceftazidime, a cephalosporin antibiotic, and avibactam, a β-lactamase inhibitor. It is used for the treatment of serious bacterial infections.
ESKAPE is an acronym encompassing the names of six bacterial pathogens commonly associated with antimicrobial resistance: ESKAPE is an acronym for their names and a reference to their ability to escape the effects of commonly used antibiotics through evolutionarily developed mechanisms, and also because it is a acronym made from the first letters of their scientific names:
The new generation of resistant infections is almost impossible to treat.
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