Lavoro svolto da Roberta Clari ed Alessio Testore.
Description
Klebsiella is a gram negative, nonmotile, usually encapsulated rod-shaped bacterium; this genus belongs to the tribe Klebsiellae, a member of the family Enterobacteriaceae.
Members of the Klebsiella genus typically express 2 types of antigens on their cell surface: a lipopolysaccharide (O antigen) and a capsular polysaccharide (K antigen). About 77 K antigens and 9 O antigens exist. The structural variability of these antigens forms the basis for classification into various serotypes with similar virulence.
The genus was originally divided into 3 main species based on biochemical reactions.
Today, 7 species with demonstrated similarities in DNA homology are known. These are Klebsiella pneumoniae, Klebsiella ozaenae, Klebsiella rhinoscleromatis, Klebsiella oxytoca, Klebsiella planticola, Klebsiella terrigena, and Klebsiella ornithinolytica. K pneumoniae is the most important one.
Epidemiology
Klebsiella spp. are ubiquitous in nature and probably have two common habitats: the environment (surface water, sewage, soil and plants), and the mucosal surfaces of mammals such as humans, horses, or swine, which they colonize. In fact they are saprophytes in human nasopharynx and intestinal tract. They may also colonize sterile wounds and urine; oropharyngeal carriage has been associated with endotracheal intubation, impaired host defenses, and antimicrobial use.
Klebsiella is related to a variety of diseases such as atypical community-acquired pneumonia, occurring particularly in chronic alcoholics, and urinary tract infections (Klebsiella pneumoniae), atrophic rhinitis called ozaena (Klebsiella ozaenae), rhinoscleroma (Klebsiella rhinoscleromatis).
Community-Acquired Klebsiella pneumoniae Bacteremia: Global Differences in Clinical Patterns. 2002
Effect of alcohol consumption on host release of interleukin-17 during pulmonary infection with Klebsiella pneumoniae. 2001
The vast majority of Klebsiella infections, however, are associated with hospitalization.
Predictors of carbapenem-resistant Klebsiella pneumoniae acquisition among hospitalized adults and effect of acquisition on mortality. 2008
The spectrum of clinical syndromes includes pneumonia, bacteremia, thrombophlebitis, urinary tract infection (UTI), cholecystitis, diarrhea, upper respiratory tract infection, wound infection, osteomyelitis, and meningitis.Sepsis and septic shock may follow entry of organisms into the blood from a focal source.The principal pathogenic are the gastrointestinal tract of patients and the hands of hospital personnel.
There are many risk factors related to these infections: the presence of invasive devices, contamination of respiratory support equipment, use of urinary catheters, and use of antibiotics.
In particular the extensive use of broad-spectrum antibiotics in hospitalized patients has led to both increased carriage of Klebsiella and, subsequently, the development of multidrug-resistant strains that produce extended-spectrum beta-lactamase (ESBL). These strains are highly virulent, show capsular type K55, and have an extraordinary ability to spread.
Pathogenicity factors
Klebsiella have several virulence factors that oppose host defenses which depend mainly on phagocytosis by polymorphonuclear granulocytes and the bactericidal effect of serum, mediated in large part by complement proteins.
First of all bacteria possess a polysaccharide capsule, composed of complex acidic polysaccharides, which is the main determinant of their pathogenicity. It protects the bacterium from phagocytosis by polymorphonuclear granulocytes and prevents bacterial death caused by bactericidal serum factors probably by inhibiting the activation or uptake of complement components, especially C3b. In addition capsule polysaccharides have been reported to inhibit the differentiation and functional capacity of macrophages in vitro.
The bacteria also produce multiple adhesins. These may be fimbrial or nonfimbrial, each with distinct receptor specificity. These help the microorganism to adhere to host cells, which is critical to the infectious process.
Lipopolysaccharides (LPS) are another bacterial pathogenicity factor. They are able to activate complement, which causes selective deposition of C3b onto LPS molecules at sites distant from the bacterial cell membrane (the longest O-polysaccharide side chains). This inhibits the formation of the membrane attack complex (C5b-C9), which prevents membrane damage and bacterial cell death.
Finally Klebsiella such as the others bacteria require iron for their growth using it mainly as a redox catalyst in proteins participating in oxygenand electron transport processes. In human free iron is very low because of its binding intracellularly to proteins such as hemoglobin,ferritin, hemosiderin, and myoglobin and extracellularly to high-affinityiron-binding proteins such as lactoferrin and transferrin; so the bacteria must compete with host for it secreting high-affinity, low-molecular-weight iron chelators,called siderophores.
Virulent Clones of Klebsiella pneumoniae: Identification and Evolutionary Scenario Based on Genomic and Phenotypic Characterization. 2009
Treatment and Resistance
Treatment of Klebsiella infection depends on the patient’s health condition, medical history and severity of the disease.
An empirical therapy can be implemented by using broad-spectrum antibiotics such as aminoglycosides and cephalosporins; however these bacteria are resistant to multiple antibiotics cause of their beta-lactamase production which is thought to be a plasmid-mediated property.
Spreading and mechanisms of antibiotic resistance of microorganisms, producing beta-lactamases. Molecular mechanisms of resistance to beta-lactams of Klebsiella spp. strains, isolated in cases of nosocomial infections. 2008
Nowadays there are many strains which have acquired an extended-spectrum beta-lactamase that is related to lots of risk factors such as pre-infection hospital stay, nosocomial origin, central venous catheterization, surgical intervention, antibiotic use longer than one week, and previous hospitalization.
Epidemiology and risk factors for ESBL-producing Klebsiella pneumoniae: a case control study. 2010
Third-generation cephalosporins (eg, cefotaxime, ceftriaxone), carbapenems (eg, imipenem/cilastatin), aminoglycosides (eg, gentamicin, amikacin), and quinolones are highly specific against Klebsiella and can be used as monotherapy or combination therapy.
Resistance of Klebsiella pneumoniae strains producing and not producing ESBL (extended-spectrum beta-lactamase) type enzymes to selected non-beta-lactam antibiotics. 2002
So generally speaking antibiotic therapy should be preceded by isolation of the pathogen from biological samples and antibiogram.
Klebsiella Infections: Treatment & Medication. 2009
Tigecyclin
Mortality/Morbidity
Klebsiella pneumonia has a predilection for debilitated people. It has a high mortality rate of approximately 50% even with antimicrobial therapy. The mortality rate approaches 100% for persons with alcoholism and bacteremia.
Klebsiella bacteremia and sepsis produce clinical manifestations similar to those caused by other gram-negative enteric organisms. Morbidity and mortality rates are comparable to those for other gram-negative organisms that cause sepsis and septic shock. In neonatal units, outbreaks caused by ESBL-producing strains present a more serious problem and may be associated with increased mortality.
