Klebsiella pneumoniae

Last updated

Klebsiella pneumoniae
Klebsiella pneumoniae 01.png
K. pneumoniae on a MacConkey agar plate
Scientific classification OOjs UI icon edit-ltr.svg
Domain: Bacteria
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 a Gram-negative, non-motile, encapsulated, lactose-fermenting, facultative anaerobic, rod-shaped bacterium. It appears as a mucoid lactose fermenter on MacConkey agar.

Contents

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-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. [2] 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. [3]

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).[ citation needed ] 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. [4]

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. [5]

Klebsiella ranks second to E. coli for urinary tract infections in older people. [6] 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. [7]

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 abscesses, cavitation, empyema, and pleural adhesions. It has a death rate around 50%, even with antimicrobial therapy. [8]

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. [9] [10] In terms of the pathophysiology of Klebsiella pneumonia the neutrophil myeloperoxidase defense against K. pneumoniae is often seen. Oxidative inactivation of elastase is involved, while LBP helps transfer bacteria cell wall elements to the cells. [11] [12]

Signs and symptoms

Individuals with Klebsiella pneumoniae tend to cough up a characteristic sputum, as well as having fever, nausea, tachycardia, and vomiting. Klebsiella pneumoniae tends to affect people with underlying conditions, such as alcoholism. [9]

Diagnosis

In terms of the diagnosis of Klebsiella 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

Treatment for Klebsiella pneumoniae 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. [10] [13]

Streptomycin(Aminoglycoside) Streptomycin-1ntb-xtal-3D-balls.png
Streptomycin(Aminoglycoside)
Cephalosporin (core structure) Cephalosporin core structure.svg
Cephalosporin (core structure)

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, and 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. [11] [14] [15] [16] 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.[ medical citation needed ]

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. [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 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. [21] Further examinations and treatments are made on a case-by-case basis, as there are currently no international guidelines. [22]

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 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 is controversial and requires further investigation. [23] 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. [24]

Resistant strains

Multidrug-resistant Klebsiella pneumoniae Multidrug-resistant Klebsiella pneumoniaeand neutrophil.jpg
Multidrug-resistant Klebsiella pneumoniae

Klebsiella organisms are often resistant to multiple antibiotics. Current evidence implicates plasmids as the primary source of the resistance genes. [25] 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. [26]

Growth of Klebsiella pneumoniae CRE from positive blood culture on MacConkey agar in Tuscany, where an outbreak was reported starting in November 2018 of strains producing NDM carbapenemase Crescita batterica su agar.jpg
Growth of Klebsiella pneumoniae CRE from positive blood culture on MacConkey agar in Tuscany, where an outbreak was reported starting in November 2018 of strains producing NDM carbapenemase

Infection with carbapenem-resistant Enterobacteriaceae (CRE) or carbapenemase-producing Enterobacteriaceae is emerging as an important challenge in health-care settings. [28] [29] 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. [30] In the US, it was first described in North Carolina in 1996; [31] since then CRKP has been identified in 41 states; [32] 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. [33]

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%. [34] 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). [35]

In 2019, there were 192,530 global deaths attributed to resistant strains of Klebsiella pneumoniae. [36]

Global deaths (counts) attributable to bacterial antimicrobial resistance by pathogen–drug combination, 2019 [36]
3GC4GCAmino-glycosidesAmino-penicillinAnti-pseudomonalBL−BLICarbapenemsFluoro-quinolonesMacrolideMDR & XDRMeticillinMono INHMono RIFPenicillinTMP-SMXVancomycinTotal
Acinetobacter baumannii6,8603,28010,40013,30081157,70040,000132,351
Citrobacter spp1,8401,3404112,1702,3002,51010,571
Enterobacter spp53203070955015,3007,8004,65045,690
Enterococcus faecalis26,8003,42030,220
Enterococcus faecium37,20014,30051,500
Other enterococci12,2002,20014,400
Escherichia coli59,90011,70010,50021,30029,50056,00030,200219,100
Group A Streptococcus3,6303,630
Group B Streptococcus11,50013,50079925,799
Haemophilus influenzae2,4704,2906,760
Klebsiella pneumoniae50,10026,3007,93055,70029,00023,500192,530
Morganella spp168154427749
Mycobacterium tuberculosis69,81011,6003,35084,760
Proteus spp4,7308871,3302,9701,62011,537
Pseudomonas aeruginosa10,4004,3703,01010,30038,10018,30084,480
S Paratyphi4,040644,104
S Typhi17,2006,46023,660
Non-typhoidal Salmonella5,6205,620
Serratia spp1,1002,6109532,4501,0808,193
Shigella spp5,9905,990
Staphylococcus aureus2,48015,90019,600121,00018,7003,120180,800
Streptococcus pneumonia3,3302,04041,90011,20012,50012,40038,700122,070
Total140,89817,07456,73116,12037,80032,081242,950305,73749,23076,334121,00011,6003,35012,199117,37023,0401,264,514

Local outbreaks

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. [37]

Nevada 2016. 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. [38] 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. [39] [40] [41]

Antimicrobial resistance gene transfer

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 from Klebsiella pneumoniae is Salmonella .[ 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 in Klebsiella pneumoniae are plasmid-borne. An example of a niche would be soil, often considered a hotspot for gene transfer.[ citation needed ]

Horizontal gene transfer of AMR genes by Klebsiella pneumoniae Klebsiella Penumoniae Horizontal Gene Transfer.jpg
Horizontal gene transfer of AMR genes by Klebsiella pneumoniae
Total AMR genes per sppAverage plasmids
Acinetobacter baumannii 2781.5
Pseudomonas aeruginosa 2630
Klebsiella pneumoniae4102.5
Enterobacter cloacae 2772.2
Escherichia coli 2041

The table shows the number of AMR genes and plasmids (per strain or subspecies) compared to other common bacteria species. [42]

Prevention

To prevent spreading Klebsiella infections between patients, healthcare personnel must follow specific infection-control precautions, [24] 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) [43] 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. [24]

To prevent the spread of infections, patients also should clean their hands very often, including:

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. [24] 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. [44]

Research

Multiple drug-resistant K. pneumoniae strains have been killed in vivo by intraperitoneal, intravenous, or intranasal administration of phages in laboratory tests. [45] 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. [46]

Vaccine development

New data sources outlining the global burden of K. pneumoniae and drug-resistant forms are expected to build momentum into prophylactic vaccine development. [47] The recent 2022 IHME study showed that in 2019 K. pneumoniae was responsible for 790,000 deaths [571,000–1,060,000] in all age groups across 11 infectious syndromes. Importantly, in Sub-saharan Africa K. 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 invasive K. pneumoniae disease in both vulnerable persons but also as a maternal vaccine to prevent neonatal sepsis and global demand assessments have been published. [48] As of June 2023, one single clinical development program for a K. 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. [49] 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.

Related Research Articles

<span class="mw-page-title-main">Beta-lactamase</span> Class of enzymes

Beta-lactamases (β-lactamases) are enzymes produced by bacteria that provide multi-resistance to beta-lactam antibiotics such as penicillins, cephalosporins, cephamycins, monobactams 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 beta-lactam (β-lactam) ring. Through hydrolysis, the enzyme lactamase breaks the β-lactam ring open, deactivating the molecule's antibacterial properties.

<span class="mw-page-title-main">Enterobacteriaceae</span> Family of bacteria

Enterobacteriaceae is a large family of Gram-negative bacteria. It includes over 30 genera and more than 100 species. Its classification above the level of family is still a subject of debate, but one classification places it in the order Enterobacterales of the class Gammaproteobacteria in the phylum Pseudomonadota. In 2016, the description and members of this family were emended based on comparative genomic analyses by Adeolu et al.

<span class="mw-page-title-main">Cephalosporin</span> Class of pharmaceutical drugs

The cephalosporins are a class of β-lactam antibiotics originally derived from the fungus Acremonium, which was previously known as Cephalosporium.

<span class="mw-page-title-main">Hospital-acquired infection</span> Infection that is acquired in a hospital or other health care facility

A hospital-acquired infection, also known as a nosocomial infection, is an infection that is acquired in a hospital or other healthcare facility. To emphasize both hospital and nonhospital settings, it is sometimes instead called a healthcare-associated infection. Such an infection can be acquired in a hospital, nursing home, rehabilitation facility, outpatient clinic, diagnostic laboratory or other clinical settings. A number of dynamic processes can bring contamination into operating rooms and other areas within nosocomial settings. Infection is spread to the susceptible patient in the clinical setting by various means. Healthcare staff also 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. Nosocomial infection tends to lack evidence that it was present when the patient entered the healthcare setting, thus meaning it was acquired post-admission.

<i>Klebsiella</i> Genus of gram-negative bacteria

Klebsiella is a genus of Gram-negative, oxidase-negative, rod-shaped bacteria with a prominent polysaccharide-based capsule.

<span class="mw-page-title-main">Carbapenem</span> Class of highly effective antibiotic agents

Carbapenems are a class of very effective antibiotic agents most commonly used for treatment of severe 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 antibiotics drug class, 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.

Ampicillin/sulbactam is a fixed-dose combination medication of the common penicillin-derived antibiotic ampicillin and sulbactam, an inhibitor of bacterial beta-lactamase. Two different forms of the drug exist. The first, developed in 1987 and marketed in the United States under the brand name Unasyn, generic only outside the United States, is an intravenous antibiotic. The second, an oral form called sultamicillin, is marketed under the brand name Ampictam outside the United States, and generic only in the United States. Ampicillin/sulbactam is used to treat infections caused by bacteria resistant to beta-lactam antibiotics. Sulbactam blocks the enzyme which breaks down ampicillin and thereby allows ampicillin to attack and kill the bacteria.

<span class="mw-page-title-main">Temocillin</span> Chemical compound

Temocillin is a β-lactamase-resistant penicillin introduced by Beecham, marketed by Eumedica Pharmaceuticals as Negaban. It is used primarily for the treatment of multiple drug-resistant, Gram-negative bacteria.
It is a 6-methoxy penicillin; it is also a carboxypenicillin.

<i>Klebsiella oxytoca</i> Species of bacterium

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. It was first described in 1886 when it was isolated from sour milk and named Bacillus oxytocus perniciosus.

<i>Acinetobacter baumannii</i> Species of bacterium

Acinetobacter baumannii is a typically short, almost round, rod-shaped (coccobacillus) Gram-negative bacterium. It is named after the bacteriologist Paul Baumann. 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.

<span class="mw-page-title-main">Cefoxitin</span> Chemical compound

Cefoxitin is a second-generation cephamycin antibiotic developed by Merck & Co., Inc. from Cephamycin C in the year following its discovery, 1972. It was synthesized in order to create an antibiotic with a broader spectrum. It is often grouped with the second-generation cephalosporins. Cefoxitin requires a prescription and as of 2010 is sold under the brand name Mefoxin by Bioniche Pharma, LLC. The generic version of cefoxitin is known as cefoxitin sodium.

β-Lactamase inhibitor Family of enzymes

Beta-lactamases are a family of enzymes involved in bacterial resistance to beta-lactam antibiotics. In bacterial resistance to beta-lactam antibiotics, the bacteria have beta-lactamase which degrade the beta-lactam rings, rendering the antibiotic ineffective. However, with beta-lactamase inhibitors, these enzymes on the bacteria are inhibited, thus allowing the antibiotic to take effect. 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.

<span class="mw-page-title-main">New Delhi metallo-beta-lactamase 1</span> Enzyme

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 sensitive only to polymyxins and tigecycline.

<span class="mw-page-title-main">Plasmid-mediated resistance</span> Antibiotic resistance caused by a plasmid

Plasmid-mediated resistance is the transfer of antibiotic resistance genes which are carried on plasmids. Plasmids possess mechanisms that ensure their independent replication as well as those that regulate their replication number and guarantee stable inheritance during cell division. By the conjugation process, they can stimulate lateral transfer between bacteria from various genera and kingdoms. Numerous plasmids contain addiction-inducing systems that are typically based on toxin-antitoxin factors and capable of killing daughter cells that don't inherit the plasmid during cell division. 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 family Enterobacteriaceae. The global spread of MDR plasmids has been enhanced by selective pressure from antimicrobial medications used in medical facilities and when raising animals for food.

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". Examples of enzymes found in certain types of CRE are 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.

<span class="mw-page-title-main">Ceftazidime/avibactam</span> Combination antibiotic medication

Ceftazidime/avibactam, sold under the brand name Avycaz among others, is a fixed-dose combination medication composed of ceftazidime, a cephalosporin antibiotic, and avibactam, a β-lactamase inhibitor. It is used to treat complicated intra-abdominal infections, urinary tract infections, and pneumonia. It is only recommended when other options are not appropriate. It is given by infusion into a vein.

ESKAPE is an acronym comprising the scientific names of six highly virulent and antibiotic resistant bacterial pathogens including: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. The acronym is sometimes extended to ESKAPEE to include Escherichia coli. This group of Gram-positive and Gram-negative bacteria can evade or 'escape' commonly used antibiotics due to their increasing multi-drug resistance (MDR). As a result, throughout the world, they are the major cause of life-threatening nosocomial or hospital-acquired infections in immunocompromised and critically ill patients who are most at risk. P. aeruginosa and S. aureus are some of the most ubiquitous pathogens in biofilms found in healthcare. P. aeruginosa is a Gram-negative, rod-shaped bacterium, commonly found in the gut flora, soil, and water that can be spread directly or indirectly to patients in healthcare settings. The pathogen can also be spread in other locations through contamination, including surfaces, equipment, and hands. The opportunistic pathogen can cause hospitalized patients to have infections in the lungs, blood, urinary tract, and in other body regions after surgery. S. aureus is a Gram-positive, cocci-shaped bacterium, residing in the environment and on the skin and nose of many healthy individuals. The bacterium can cause skin and bone infections, pneumonia, and other types of potentially serious infections if it enters the body. S. aureus has also gained resistance to many antibiotic treatments, making healing difficult. Because of natural and unnatural selective pressures and factors, antibiotic resistance in bacteria usually emerges through genetic mutation or acquires antibiotic-resistant genes (ARGs) through horizontal gene transfer - a genetic exchange process by which antibiotic resistance can spread.

<span class="mw-page-title-main">Cefiderocol</span> Antibiotic

Cefiderocol, sold under the brand name Fetroja among others, is an antibiotic used to treat complicated urinary tract infections when no other options are available. It is indicated for the treatment of multi-drug-resistant Gram-negative bacteria including Pseudomonas aeruginosa. It is given by injection into a vein.

References

  1. ↑ Ryan KJ, Ray CG, eds. (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. ISBN   978-0-8385-8529-0.
  2. ↑ Postgate J (1998). Nitrogen Fixation (3rd ed.). Cambridge University Press. ISBN   978-0-521-64047-3.
  3. ↑ 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.
  4. ↑ Zander DS, Farver CF (2016). Pulmonary Pathology: A Volume in Foundations in Diagnostic Pathology Series. Elsevier Health Sciences. p. 169. ISBN   978-0-323-46119-1 . Retrieved 14 January 2017.
  5. ↑ Rashid T, Ebringer A (June 2007). "Ankylosing spondylitis is linked to Klebsiella--the evidence". Clinical Rheumatology. 26 (6): 858–864. doi:10.1007/s10067-006-0488-7. PMID   17186116. S2CID   43456525.
  6. ↑ "Female Urinary Tract Infection" (PDF). Medical Diagnostic Laboratories, L.L.C. Archived from the original (PDF) on 2020-10-15. Retrieved 2020-05-06.
  7. ↑ Groopman J (2008-08-11). "Superbugs". The New Yorker . Retrieved 2013-07-07. The new generation of resistant infections is almost impossible to treat.
  8. ↑ Setiawan A, Widodo AD, Endraswari PD (December 2022). "Comparison of ciprofloxacin, cotrimoxazole, and doxycycline on Klebsiella pneumoniae: Time-kill curve analysis". Annals of Medicine and Surgery. 84: 104841. doi:10.1016/j.amsu.2022.104841. PMC   9758284 . PMID   36536710.
  9. 1 2 3 "Aspiration Pneumonia Symptoms. Treatment and Information | Patient". Patient. Retrieved 13 January 2017.
  10. 1 2 "Klebsiella species – GOV.UK". www.gov.uk. Retrieved 13 January 2017.
  11. 1 2 3 Klebsiella Infections at eMedicine
  12. ↑ Li B, Zhao Y, Liu C, Chen Z, Zhou D (2014). "Molecular pathogenesis of Klebsiella pneumoniae". Future Microbiology. 9 (9): 1071–1081. doi:10.2217/fmb.14.48. PMID   25340836.
  13. ↑ Wilson WC, Grande CM, Hoyt DB (2007). Trauma critical care. New York: Informa Healthcare. p. 444. ISBN   978-1-4200-1684-0 . Retrieved 13 January 2017.
  14. ↑ Sanchez GV, Master RN, Clark RB, Fyyaz M, Duvvuri P, Ekta G, Bordon J (January 2013). "Klebsiella pneumoniae antimicrobial drug resistance, United States, 1998-2010". Emerging Infectious Diseases. 19 (1): 133–136. doi:10.3201/eid1901.120310. PMC   3557979 . PMID   23260464.
  15. ↑ Antoniadou A, Kontopidou F, Poulakou G, Koratzanis E, Galani I, Papadomichelakis E, et al. (April 2007). "Colistin-resistant isolates of Klebsiella pneumoniae emerging in intensive care unit patients: first report of a multiclonal cluster". The Journal of Antimicrobial Chemotherapy. 59 (4): 786–790. doi: 10.1093/jac/dkl562 . PMID   17307769.
  16. ↑ "Klebsiella pneumoniae in Healthcare Settings". Centers for Disease Control and Prevention. Retrieved 13 January 2017.
  17. ↑ Russo TA, Marr CM (June 2019). "Hypervirulent Klebsiella pneumoniae". Clinical Microbiology Reviews. 32 (3). doi:10.1128/cmr.00001-19. PMC   6589860 . PMID   31092506.
  18. 1 2 Zhu J, Wang T, Chen L, Du H (2021). "Virulence Factors in Hypervirulent Klebsiella pneumoniae". Frontiers in Microbiology. 12: 642484. doi: 10.3389/fmicb.2021.642484 . PMC   8060575 . PMID   33897652.
  19. ↑ Tang M, Kong X, Hao J, Liu J (2020). "Epidemiological Characteristics and Formation Mechanisms of Multidrug-Resistant Hypervirulent Klebsiella pneumoniae". Frontiers in Microbiology. 11. doi: 10.3389/fmicb.2020.581543 . PMC   7714786 . PMID   33329444. 581543.
  20. ↑ Liu C, Du P, Xiao N, Ji F, Russo TA, Guo J (2020). "Hypervirulent Klebsiella pneumoniae is emerging as an increasingly prevalent K. pneumoniae pathotype responsible for nosocomial and healthcare-associated infections in Beijing, China". Virulence. 11 (1): 1215–1224. doi: 10.1080/21505594.2020.1809322 . PMC   7549996 . PMID   32921250.
  21. ↑ Hagiya H, Watanabe N, Maki M, Murase T, Otsuka F (October 2014). "Clinical utility of string test as a screening method for hypermucoviscosity-phenotype Klebsiella pneumoniae". Acute Medicine & Surgery. 1 (4): 245–246. doi:10.1002/ams2.40. PMC   5997228 . PMID   29930857.
  22. ↑ Russo TA, Marr CM (June 2019). "Hypervirulent Klebsiella pneumoniae". Clinical Microbiology Reviews. 32 (3). doi:10.1128/CMR.00001-19. PMC   6589860 . PMID   31092506.
  23. ↑ "Carbapenem-resistant Enterobacteriaceae (CRE) Infection: Clinician FAQs". Cdc.gov. Retrieved 25 October 2017.
  24. 1 2 3 4 5 "Guideline for Isolation Precautions: Preventing Transmission of Infectious Agents in Healthcare Settings 2007". Centers for Disease Control and Prevention. 19 February 2021.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  25. ↑ Hudson CM, Bent ZW, Meagher RJ, Williams KP (June 6, 2014). "Resistance determinants and mobile genetic elements of an NDM-1-encoding Klebsiella pneumoniae strain". PLOS ONE. 9 (6): e99209. Bibcode:2014PLoSO...999209H. doi: 10.1371/journal.pone.0099209 . PMC   4048246 . PMID   24905728.
  26. ↑ Nathisuwan S, Burgess DS, Lewis JS (August 2001). "Extended-spectrum beta-lactamases: epidemiology, detection, and treatment". Pharmacotherapy. 21 (8): 920–928. doi:10.1592/phco.21.11.920.34529. PMID   11718498. S2CID   73938823.
  27. ↑ "Superbatterio New Delhi: salgono a 147 i casi in Toscana" (in Italian). Il Tirreno. 13 December 2019. Retrieved 14 December 2019.
  28. ↑ Limbago BM, Rasheed JK, Anderson KF, Zhu W, Kitchel B, Watz N, et al. (December 2011). "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.
  29. ↑ Ghaith DM, Mohamed ZK, Farahat MG, Aboulkasem Shahin W, Mohamed HO (March 2019). "Colonization of intestinal microbiota with carbapenemase-producing Enterobacteriaceae in paediatric intensive care units in Cairo, Egypt". Arab Journal of Gastroenterology. 20 (1): 19–22. doi:10.1016/j.ajg.2019.01.002. PMID   30733176. S2CID   73444389.
  30. ↑ Berrie C (2007-04-04). "Carbapenem-resistant Klebsiella pneumoniae outbreak in an Israeli hospital". Medscape . Medical News. WebMD . Retrieved 2013-07-07.
  31. ↑ Yigit H, Queenan AM, Anderson GJ, Domenech-Sanchez A, Biddle JW, Steward CD, 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 .
  32. ↑ Vastag B (2012-08-22). "'Superbug' stalked NIH hospital last year, killing six". The Washington Post . Archived from the original on 2012-12-23. Retrieved 2013-07-07.
  33. ↑ "Public Health Agency of Canada (PHAC) – Agence de la sante publique du Canada (ASPC)". Phac-aspc.gc.ca. 2004-09-24. Retrieved 25 October 2017.
  34. ↑ Schwaber MJ, Klarfeld-Lidji S, Navon-Venezia S, Schwartz D, Leavitt A, Carmeli Y (March 2008). "Predictors of carbapenem-resistant Klebsiella pneumoniae acquisition among hospitalized adults and effect of acquisition on mortality". Antimicrobial Agents and Chemotherapy. 52 (3): 1028–1033. doi:10.1128/AAC.01020-07. PMC   2258527 . PMID   18086836.
  35. ↑ Centers for Disease Control Prevention (CDC) (March 2009). "Guidance for control of infections with carbapenem-resistant or carbapenemase-producing Enterobacteriaceae in acute care facilities". MMWR. Morbidity and Mortality Weekly Report. 58 (10): 256–260. PMID   19300408.
  36. 1 2 Murray, Christopher J L.; et al. (February 12, 2022). "Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis". The Lancet. 399 (10325): 629–655. doi:10.1016/S0140-6736(21)02724-0. PMC   8841637 . PMID   35065702 . Retrieved 23 December 2023.
  37. ↑ Schwaber MJ, Lev B, Israeli A, Solter E, Smollan G, Rubinovitch B, et al. (April 2011). "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.
  38. ↑ Gallagher J (13 January 2017). "Bug resistant to all antibiotics kills woman". BBC News. Retrieved 16 January 2017.
  39. ↑ "Nevada woman dies of superbug resistant to all available US antibiotics". STAT. 12 January 2017. Retrieved 13 January 2017.
  40. ↑ Belluz J. "A woman died from a superbug that outsmarted all 26 US antibiotics". Vox. Retrieved 13 January 2017.
  41. ↑ "Superbug Killed Nevada Woman". Yahoo! News. Retrieved 13 January 2017.
  42. 1 2 .Wyres, Kelly L; Holt, Kathryn E (2018-10-01). "Klebsiella pneumoniae as a key trafficker of drug resistance genes from environmental to clinically important bacteria". Current Opinion in Microbiology. Antimicrobials * Microbial systems biology. 45: 131–139. doi: 10.1016/j.mib.2018.04.004 . ISSN   1369-5274. PMID   29723841.
  43. ↑ "Guidance : Infection Prevention and Control Measures for Healthcare Workers in All Healthcare Settings" (PDF). Phac-aspc.gc.ca. Retrieved 25 October 2017.
  44. ↑ Yasin F, Assad S, Talpur AS, Zahid M, Malik SA (July 2017). "Combination Therapy for Multidrug-Resistant Klebsiella Pneumoniae Urinary Tract Infection". Cureus. 9 (7): e1503. doi: 10.7759/cureus.1503 . PMC   5608481 . PMID   28948123.
  45. ↑ 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) (4): 5–8. PMID   1882608.
  46. ↑ Chanishvili N, ed. (2012). A Literature Review of the Practical Application of Bacteriophage Research. Hauppauge, NY: Nova Science. ISBN   978-1-62100-851-4.
  47. ↑ Institute of Health Metrics and Evaluation. Global Research on Antimicrobial Resistance, University of Washington. 2022. Accessed: https://vizhub.healthdata.org/microbe/?settings=eyIxIjoiYW1yIiwiMiI6ImJhciIsIjMiOiJhbXIiLCI0IjoyMiwiNSI6MSwiNiI6MSwiNyI6MSwiOCI6MSwiOSI6MSwiMTIiOjEsIjEzIjoxLCIxNCI6MSwiMTUiOjEsIjE2IjoyLCIxNyI6MywiMTgiOjIwMTksIjE5IjpmYWxzZSwiMjAiOnRydWUsIjIyIjoxfQ==
  48. ↑ VacZine Analytics. MarketVIEW: Klebsiella pneumoniae vaccines. https://www.vaczine-analytics.com/products-marketviewVAMV087_klebsiella_pneumoniae_vaccines.asp
  49. ↑ Trautmann M et al. O antigen seroepidemiology of Klebsiella clinical isolates and implications for immunoprophylaxis of Klebsiella infections. Vaccine. 22(7), 818–21 (2004)
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.