The type of toxin plays a major role in the outcome of disease [ 94 ]. Exotoxins usually are produced by living bacteria whereas endotoxins are released by dying or dead microorganisms and as a result, prompt killing of bacteria contains some risks of rapid intoxication of the host [ 95 ].
In sepsis bacterial endotoxin triggers such serious complications as shock, adult respiratory distress syndrome, and disseminated intravascular coagulation. These events often occur when appropriate antimicrobial therapy has been instituted [ 96 ]. In some infections with bacteremia, antibiotic therapy can cause release of bacterial endotoxin-like products and cause a Jarisch—Herxheimer reaction [ 97 ]. It occurs after initiation of antibacterials in louse-borne relapsing fever, tick-borne relapsing fever, syphilis, Q fever, bartonellosis, brucellosis, tripanosomiasis, leptospirosis, etc.
In leprosy the harmful effects of dead bacteria is especially demonstrative. It suggests that many of the manifestations of leprosy erythema nodosum type, nerve damage and loss of nerve function which follow initial treatment must be due to antigens from dead organisms [ , ].
This is an illustration that a bacterium killing often is not enough and a dead microorganism may be even more harmful than a living one. Exotoxins are no less harmful than endotoxins.
Initially it was thought that the major organisms that caused bacterial sepsis were gram-negative bacteria [ ]. Some of the most frequently isolated bacteria in sepsis are Staphylococcus aureus S.
Exotoxins may fatally intoxicate the host if even infection is out of the bloodstream. For example, in tetanus and diphtheria, the infection the organism remains localized usually minor penetrating wounds and the toxin is absorbed, producing major systemic effects [ , ].
Thus, managing host intoxication by bacterial exotoxins and endotoxins is as important as killing of sepsis-causing bacteria. Oxycytosis is the main mechanism of planktonic bacteria clearing from the bloodstream [ 22 ].
Sepsis-causing planktonic pathogens survive oxycytosis by producing antioxidant enzymes catalase, superoxide dismutase, glutathione peroxidase and versatile respiration adapted to high concentrations of reactive oxygen species. Antioxidant enzymes and versatile respiration also provide bacterial survival inside erythrocytes [ 24 ]. Production of hemolysisn provides penetration of planktonic pathogens through erythrocyte membrane and forming a bacterial reservoir inside erythrocytes.
Neutralization of hemolysins or inhibition of their production prevents forming of bacterial reservoirs in erythrocytes. Encapsulated bacteria and biofilm fragments survive in the tissues and the bloodstream because of exopolymers [ 23 ]. In bacteremia exopolymers prevent oxycytosis by preventing triboelectric charging of pathogens and their attraction, fixation and oxidation on the surface of erythrocytes.
Humans have no appropriate defense mechanisms for clearing encapsulated bacteria and biofilm fragments from the bloodstream. Inhibition of exopolymer production or its depolymerization may restore the effectiveness of oxycytosis and facilitate pathogen clearing from the bloodstream. Search for new antibacterials, in particular, new antibiotics, is indispensable. Perspective antibiotics include oxazolidinones, lipopeptides, glycylcyclines, ketolides, new generations of fluoroquinolones, antistaphylococcal b-lactams, glycopeptides and others [ ].
Speaking about antibiotics for sepsis therapy, the following should be taken into account: 1. Sepsis-causing bacteria enter the bloodstream as planktonic, encapsulated, L-form and biofilm fragments and a new antibacterial should be able to dissolve in bacterial polysaccharide; 2.
In the bloodstream, the proliferation and the growth of sepsis-causing bacteria are inhibited by triboelectric charging planktonic bacteria or exopolimer insulation encapsulated bacteria and biofilm fragments.
The mechanism of action of new antibacterial medications should be different from known antibacterials and should provide killing of bacteria in the condition of low metabolic activity; 3.
In the bloodstream, sepsis-causing planktonic bacteria enter erythrocytes and form bacterial reservoirs inside erythrocytes. New medications should be fat-soluble for penetrating erythrocyte membrane and accumulating inside erythrocytes; 4. New antibacterials should be beyond the mechanisms of bacterial adaptation or should affect these mechanisms, otherwise the development of bacterial resistance will continue to be a permanent problem.
Early detection of pathogens and their sensitivity to bactericidal medications remain indispensable. Mass spectrometry also enables to distinguish drug-resistant from drug-susceptible isolates [ ]. An effective treatment must comprise the neutralization of endotoxins. LPS can trigger systemic hyper-inflammatory response with multiple organ failure and lethality.
An acute exposure to endotoxin can result in life-threatening sepsis while chronic exposure has been implicated in several diverse disease states involving the gastrointestinal, nervous, metabolic, vascular, pulmonary and immune systems [ ]. Humans have several mechanisms for inactivating LPS including lipid A-neutralizing proteins bactericidal permeability-increasing protein, lactoferrin, lysozyme, collectins, etc.
Intestinal alkaline phosphatase can inactivate LPS [ ], but its role in LPS inactivation in humans has not been established. AOAH is a 2-subunit lipase which selectively hydrolyzes the secondary acyloxyacyl-linked fatty acyl chains from the lipid A region of bacterial LPS.
Novel types of endotoxin neutralizing compounds include peptides modified by lipophilic moieties and non-peptidic molecules, particularly lipopolyamines [ ]. Some synthetic LPS-neutralizing agents also have been developed. They include synthetic peptides, based on the endotoxin-binding domains of natural binding proteins such as lactoferrin, Limulus anti-LPS factor, NK-lysin, cathelicidins [ ].
Anti-TNF antibodies have shown to help in the treatment of septic shock [ ]. Endotoxin recognition molecules MD-2 and toll-like receptor 4 also may be considered as potential targets for therapeutic intervention in endotoxin shock [ ].
Extracorporeal endotoxin removal or endotoxoid based vaccines have additional medical applications [ ]. A variety of gram-positive organisms are capable of causing sepsis.
Those most often implicated are, in descending order of frequency, Staphylococcus aureus, Streptococcus pneumoniae , coagulase-negative staphylococci, beta-hemolytic streptococci, and enterococci, but virtually any gram-positive organism may be involved [ ]. Gram-positive bacteria, such as Staphylococcus aureus , cause serious human illnesses through combinations of surface virulence factors and secretion of exotoxins.
SAgs are one of the most potent toxins produced by bacteria. They are non-glycosylated proteins that have a relatively low molecular weight [ ]. SAgs are the most powerful T cell mitogens ever discovered. Concentrations of less than 0. SAgs produced by S. These toxins produce a massive cellular immune response that could lead to a fatal toxic shock [ ].
Classical toxic shock syndrome TSS caused by S. STSS, caused by S. The clinical symptoms are very similar to those in TSS, but STSS is often associated with bacteraemia, myositis or necrotizing fasciitis [ ]. This interaction triggers the release of high amounts of various cytokines and other effectors by immune cells [ ]. For developing potential therapies for conditions mediated by SAgs, toxoids have been explored [ ].
In addition, monoclonal antibodies that cross-react with more than one exotoxin there have been generated [ ], although it remains difficult to generate a broad-spectrum neutralizing approach because of the structural diversity of these toxins [ ].
At present some different neutralizing agents against individual exotoxins have been tested and offered. Advances in selection technologies have sped up the process of generating antibodies with exquisitely tailored characteristics. In particular, synthetic antibody libraries, in which the antigen-binding sites are entirely man-made now rival or even exceed the potential of natural immune repertoires [ ].
Recently, efforts have aimed to circumvent the limitations of developing antibodies in animals by developing wholly in vitro techniques for designing antibodies of tailored specificity [ ].
This has been realized with the advent of synthetic antibody libraries that possess diversity outside the scope of natural immune repertoires and are thus capable of yielding specificities not otherwise attainable [ ]. A number of synthetic peptides corresponding to different regions of various superantigens including SEA and TSST-1 have been studied [ , ].
For example, it has been shown that synthetic peptide and antibody to the peptide can independently block the proliferative effects of all of the staphylococcal and streptococcal superantigens and that this inhibition is specific for the peptide, besides, the anti-peptide antibody can provide passive protection against toxic shock [ ].
Taking into account that SAgs binding to variable domains of T cell receptor beta chains Vbeta leads to massive release of inflammatory molecules, soluble forms of different Vbeta domains with a high affinity for binding superantigens have been generating [ ]. Glycerol monolaurate GML , a 12 carbon fatty acid monoester has been offered as a promising therapy in toxic shock syndrome.
Recombinant monoclonal antibodies that target staphylococcal enterotoxin B SEB and block receptor interactions can be of therapeutic value as well. Human monoclonal antibodies possess high affinity, target specificity, and toxin neutralization qualities essential for any therapeutic agent [ ]. Intravenous polyspecific immunoglobulin G IVIG neutralizes the activity of a wide spectrum of superantigens [ ]. Planktonic bacteria grow and proliferate because their thin capsule does not interfere respiration and metabolic exchange.
Rapidly proliferating, planktonic bacteria are short of time to produce a thick capsule. Antibacterial medications, particularly antibiotics, are not soluble in capsular polysaccharids and cannot penetrate capsule and reach bacterial wall, besides, low metabolic activity prevents absorption of antibacterial agents.
On the other hand, depolymerization of bacterial capsule may re-start bacterial rapid growth and proliferation. Capsule contains antigens and virulence factors that may be released during capsule depolymerization. Capsule polysaccharides CPS are not only fundamental virulence factors for a wide range of Gram-negative e. Klebsiella pneumonia , Escherichia coli and others and Gram-positive e.
Streptococcus pneumonia , Staphylococcus aureus, etc. The biosynthesis of bacterial capsules is regulated by a system involving a protein tyrosine phosphatase PTP and a protein tyrosine kinase [ , ].
Inhibition of these proteins may stop capsule production. As a result, bacterial virulence decreases and bacteria killing by oxidation in the bloodstream increases. Fascioquinol E inhibits PTP activity both in vitro and in vivo [ ]. Capsule inhibitory drugs may become an important addition to anti-sepsis therapies.
Biofilm-associated infections are very difficult to treat with conventional antibiotics, therefore, the development of antibiofilm agents is indispensable. A potential antibiofilm drug that can either facilitate the dispersion of preformed biofilms or inhibit the formation of new biofilms in vivo is needed. So far, a plethora of potential antibiofilm agents with unique structures, mainly inspired by biosolutions enzymes, phages, interspecies interactions and antimicrobial molecules from microbial origin and natural products, have been developed and shown promise in dispersing existing biofilms or preventing bacteria from forming them [ ].
The majority of the recently developed antibiofilm molecules do not directly affect bacterial survival and thus the expectation is that resistance to these molecules will not occur. It is hoped that some of these lead compounds would be translated into antibiofilm drugs [ ]. To date, many antibiofilm compounds have been identified from diverse natural sources, for example, brominated furanones [ ], ursine triterpenes [ ], corosolic acid and asiatic acid [ ], ginseng [ ] and 3-indolylacetonitrile [ ].
Indole, which is generated by the degradation of tryptophan by tryptophanase [ ] is an intercellular signal molecule that can affect multiple aspects of some bacterial species [ ] inhibiting biofilm formation and motility [ ]. N-acyl homoserine lactones, cationic molecules that contain an excess of lysine and arginine residues, d - amino acids, monomeric trimethylsilane TMS , 1-alkylquinolinium bromide ionic liquids exhibit antimicrobial and antibiofilm properties [ — ].
Nucleases such as DNase and RNase affect integrity of biofilms by degrading nucleic acid scaffold components of the extracellular matrix [ ]. Nonbiocidal antibiofilm molecules for example, serine proteases, can target matrix-associated proteins [ ].
Dispersin B degrades poly- N -acetylglucosamine PNAG , a major polysaccharide component of many bacterial extracellular matrices [ ]. The important biological messenger, nitric oxide NO is a signal for biofilm dispersal, inducing the transition from the biofilm mode of growth to the free swimming planktonic state.
Moreover, biofilms exposed to low doses of NO are more susceptible to antimicrobial treatments than untreated biofilms [ ]. Unfortunately, till now no antibiofilm drug has been registered and used in clinical practice. As a result, the treatment of biofilm-related infections is not effective. Antibiotics should be combined with antibiofilm agents.
Antibiofilm agents that can both disperse and kill biofilm bacteria could have some useful applications, but remain rare [ , ].
Iron is an essential nutrient for nearly all known life forms. Its capacity to readily donate or accept electrons makes it essential for important cellular redox processes [ ]. Iron is the single most important micronutrient bacteria need to survive [ ]. The proliferative capability of many invasive pathogens is limited by the bioavailability of iron and so pathogens have developed strategies to obtain iron from their host organisms.
In turn, host defense strategies have evolved to sequester iron from invasive pathogens and human immune system has evolved ways to deprive microorganisms of this vital element [ ]. During infection and inflammation, iron is withdrawn from the circulation and is redirected to hepatocytes and macrophages, thereby reducing the availability of iron to invading pathogens [ ]. The ability of pathogens to acquire iron in a host is an important determinant of both their virulence and the nature of the infection produced.
Bacteria utilize various iron sources which include the host proteins transferrin and lactoferrin, heme, and low molecular weight iron chelators termed siderophores [ ].
Ferrous iron can also be directly imported by the G protein-like transporter, FeoB [ ]. In sepsis, infection from the tissues enters to venous blood. Erythrocytes in the venous blood are lack of oxygen and sepsis-causing bacteria easily survive oxycytosis by producing antioxidant enzymes. Pathogens penetrate erythrocyte membrane by hemolysins and form a bacterial reservoir inside erythrocytes. High concentrations of iron inside erythrocytes are toxic for many bacteria because iron promotes the formation of damaging oxidative radicals, but sepsis-causing bacteria overcome iron toxicity by producing antioxidant enzymes.
Inhibition of bacterial hemolysins may prevent pathogen penetration into erythrocytes. Human serum lipids have inhibitory effect on staphylococcal alpha, beta and delta hemolysins, but the effect is weak [ ].
Hence, inhibiting the heptamer formation is of considerable interest. However, both natural and chemical inhibitors reported so far has difficulties related to toxicity, bioavailability, and solubility, which necessitate in identifying some alternatives. A silkworm hemolymph protein, apolipophorin ApoLp , binds to the cell surface of Staphylococcus aureus and inhibits expression of the saePQRS operon encoding a two-component system, SaeRS, and hemolysin genes.
The pore-forming toxin alpha-hemolysin may be also inhibited by cAMP [ ]. Antioxidant enzymes of sepsis-causing bacteria provide bacterial survival during phagocytosis in the tissues and oxycytosis oxidation on the surface and inside erythrocytes in the bloodstream. Catalase may function by preventing the formation of excessive concentrations of H 2 O 2 and by using H 2 O 2 in the peroxidatic oxidation of compounds such as methanol and formic acid.
Glutathione peroxidase catalyzes the reduction of H 2 O 2 , organic hydroperoxides, and lipid peroxides in the presence of glutathione, the hydrogen donor.. The biochemical function of glutathione peroxidase is to reduce lipid hydroperoxides to their corresponding alcohols and to reduce free hydrogen peroxide to water [ ]. Inhibition of bacterial catalase production increases the effectiveness of bacteria killing by phagocytes and erythrocytes.
However, available bacterial catalase inhibitors are not safe [ — ] and new inhibitors are needed. The manganese and zinc binding protein calprotectin CP reduces bacterial superoxide dismutase activity resulting in increased sensitivity of pathogens to oxidative stress.
The inhibition of superoxide defenses by CP increases bacterial sensitivity to neutrophil-mediated killing [ , ] and oxycytosis [ 22 ].
Glutathione peroxidase makes an important contribution to bacterial virulence [ — ]. It has been detected in all sepsis-causing bacteria [ , ]. Glutathiones have relatively recently been discovered in bacteria and hence little is known about their properties. Understanding of antibiotic interaction with bacterial GSTs may be useful in treating bacterial resistance towards antibiotics [ ]. A gene with homology to glutathione peroxidase was shown to contribute to the antioxidant defenses of Streptococcus pyogenes group A streptococcus.
Successful pathogens have evolved effective systems for defense against oxidative stress that include combinations of reducing enzymes, molecular scavengers, and protein and DNA repair enzymes [ , ]. Bacterial mutants defective for resistance to oxidative stress are often avirulent [ ]. Bacteria which are characterized by absence of glutathione, produce other low molecular weight thiols which fulfill the same functions as glutathione [ ].
Unfortunately, at present glutathione peroxidase inhibitors are not available. Sepsis-causing bacteria have flexible respiration. Being facultative anaerobes, they are the most versatile type of bacteria and can live either with or without oxygen. Sepsis-causing bacteria grow and proliferate in a certain range of respiratory activity. Bacteria better tolerate suppression of respiration than acceleration of respiration; moreover, inhibition of respiration may increase bacterial survival and tolerance to toxic agents whereas acceleration of respiration increases vulnerability of bacteria to detrimental factors.
Growth inhibition from bacteriostatic antibiotics is associated with suppressed cellular respiration whereas cell death from most bactericidal antibiotics is associated with accelerated respiration [ ].
In case of simultaneous action of bactericidal and bacteriostatic antibiotics, respiration deceleration provides bacterial survival. Suppression of cellular respiration by the bacteriostatic antibiotic is the dominant effect that blocks pathogen killing [ ]. Inhibition of cellular respiration by knockout of the cytochrome oxidases is sufficient to attenuate bactericidal lethality whereas acceleration of basal respiration by genetically uncoupling ATP synthesis from electron transport resulted in potentiation of the killing effect of bactericidal antibiotics.
Bactericidal activity can be arrested by attenuated respiration and potentiated by accelerated respiration [ ]. Bacteriostatic— bactericidal combination treatments result in attenuation of bactericidal activity [ , ]. Clinically, this effect can have negative consequences in high morbidity infections like meningitis [ ], or positive effects by inhibiting lysis and exotoxin release in toxin-mediated syndromes [ ].
The predominant cellular process targeted by bacteriostatic antibiotics is translation, which accounts for a major portion of the energy consumption in the cell at steady state [ , ].
Disruption of this process may cause significant changes in cellular energy dynamics [ ]. The response to bacteriostatic antibiotics may involve downregulation of major metabolic pathways [ ], potentially suggesting a reduction in metabolic rates. In comparison with the bacteriostatic response, bactericidal agents may increase cellular metabolic rates and bactericidal antibiotic efficacy may be related directly to metabolic state [ ].
The transcriptional response to bactericidal antibiotics involves upregulation of genes involved in central metabolism and respiration [ , ].
At present selective accelerators and decelerators of bacterial respiration are not available and developing such agents remain a perspective field for future research. Bacterial resistance to carbapenems [ ] and colistin [ ] indicate that the post-antibiotic era has arrived and common infections will not be treatable with the current arsenal of antibiotics.
As a result new options should be developed for treating sepsis. It includes the use of bacteriophage, Bdellovibrio like organisms and Saccharomyces therapy. The use of bacteriophages as a replacement for antibiotics in sepsis is an attractive option. Bacteriophages may be useful in the treatment of sepsis caused by antibiotic resistant bacterial infections. They have some advantages over antibiotics being more effective in treating certain infections in humans [ — ].
Phage therapy is safe and can be given intravenously in systemic infections. Bacterial isolates from septicemia patients spontaneously secrete phages active against other isolates of the same bacterial strain, but not to the strain causing the disease [ ].
Such phages were also detected in the initial blood cultures, indicating that phages are circulating in the blood at the onset of sepsis. The fact that most of the septicemic bacterial isolates carry functional prophages suggests an active role of phages in bacterial infections [ ]. Prophages present in sepsis-causing bacterial clones play a role in clonal selection during bacterial invasion [ ].
The major problem of bacteriophage usage is their exquisite specificity; bacteriophages are much more specific than antibiotics. They attack only specific for them strains of bacteria, thereby precluding their use as empiric therapy in sepsis.
Phage therapy is possible after identification of sepsis causing bacterium and selection of appropriate phage from existing stocks. Stocking a hospital laboratory with a complete library of phage for every conceivable bacterial pathogen is a major challenge [ ]. Bdellovibrio and like organisms prey on other bacteria.
They can be used as medical microbiological settings [ , ]. Bdellovibrio bacteriovorus attacks a wide range of pathogens: Escherichia coli , Salmonella enteric , Pseudomonas aeruginosa , S.
It invades and grows within the periplasm. Bdellovibrio bacteriovorus is highly motile, flagellated, Gram-negative and measures 0. It uses a single polar flagellum to stalk other bacteria; it burrows through the surface of its prey by secreting enzymes and consumes its host from the inside out [ , ]. Bdellovibrio bacteriovorus has dual probiotic and antibiotic nature [ , ] and it is perspective to try it in the therapy of sepsis.
Saccharomyces boulardii SB is a non-pathogenic yeast used in the prevention or the treatment of diarrheas [ , ]. SB directly inhibits the growth of Candida albicans , E. SB exerts direct anti-toxin effects and inhibits the growth of pathogens. SB also produces a phosphatase that dephosphorylates endotoxins such as lipopolysaccharide of E. SB maintains epithelial barrier integrity during bacterial infection [ ]. SB affects the immune response of host cells and stimulates the secretion of secretory immunoglobulin A [ ].
Probably, the antimicrobial and antifungal products, produced by SB may be studied as a possible therapeutic option in sepsis. Bacteria removal from the bloodstream by technical devices has a good perspective: it is effective in case of all bacterial species and does not need bacteria identification before the procedure. Plaktonic bacteria and biofilm fragments may be easily removed from the bloodstream whereas encapsulated bacteria, pathogens inside erythrocytes and bacterial L-forms may escape removal.
The technical devices should be used as soon as sepsis is suspected and it should be done before empiric use of antibiotics because the latter may cause bacterial encapsulation and formation of L-forms.
On the other hand, the devices provide removal and accumulation of removed bacteria in devices facilitating precise identification of pathogens. Bacteria were removed by matrix of micro-encapsulated albumin activated charcoal ACAC. The bacteria adhered to the ACAC, but the charcoal was not bactericidal. It includes hollow fiber that removes lipopolysaccharides LPS and lipoteichoic acids LTA from blood or plasma in an extracorporeal perfusion system.
Some years ago, for bacteria and endotoxin removing from the blood magnetic nanoparticles MNPs modified with bis-Zn-DPA, a synthetic ligand that binds to bacteria, was used [ ]. Recently an external device that mimics the structure of a spleen and cleanses the blood in acute sepsis has been tested [ ].
In this device the blood is mixed with magnetic nanobeads coated with an engineered human opsonin—mannose-binding lectin MBL. Magnets pull the opsonin-bound pathogens and toxins from the blood then the cleansed blood is returned back to the individual. Mechanical devices can remove from the bloodstream not only bacteria, but also toxins and cytokines.
For example, a mechanical devices has been developed to remove a variety of cytokines, lipopolysaccharide, or C5a from plasma [ ].
A cytokine adsorption device CAD filled with porous polymer beads efficiently depletes middle-molecular weight cytokines from a circulating solution [ ]. At present mechanical removal of pathogens and their toxins from the bloodstream by mechanical devices is the most promising clinical application that rapidly may be seen in the near future. It is most effective in case of planktonic bacteria and less effective in the removing of encapsulated bacteria and bacterial L-forms.
Antimicrobial actions needed for increasing the effectiveness of antibacterial therapy in sepsis are summarized in Table 3. In sepsis planktonic bacteria cause abundant release of oxygen from erythrocytes [ 22 , 23 ]. Oxygen oxidizes and inactivates plasma hormones and other biologically active substances. As a result, a severe endocrine dysregulation occurs in septic patients and so the replacement of hormones, peptides and other active substances in sepsis is indispensable.
Corticosteroids were the first drugs tested in randomized controlled trials [ — ], then catecholamines, anti-diuretic hormone, thyroxin, insulin, adrenocorticotropin, growth hormone, estrogens, androgens, etc. The results of separate and combined use of hormones are controversial and the positive effect is not convincing.
Hormonal replacement therapy protocol should include simultaneous use of a combination of hormones that takes into account their synergism and antagonism, anabolic and catabolic properties, half-life, resistance to oxidation, pharmacokinetics, pharmacodynamics, etc.
The profile and proportions of most important hormones and regulatory substances for support of vital functions should be established and the replacement of all indispensable hormonal and other regulatory components should be performed. Injected components may be oxidized and inactivated so constant control of their concentrations is necessary.
Central venous catheters CVC are an integral part in medical management of sepsis, particularly, they are indispensable for antibiotic therapy. In sepsis catheters can be placed in veins in the neck internal jugular vein , chest subclavian vein or axillary vein , groin femoral vein , or through veins in the arms a PICC line, or peripherally inserted central catheters.
Three anatomical sites the subclavian, jugular, or femoral vein are commonly used to insert central venous catheters, but insertion at each site has the potential for major complications.
Subclavian-vein catheterization is associated with a lower risk of bloodstream infection and symptomatic thrombosis and a higher risk of pneumothorax than jugular-vein or femoral-vein catheterization [ ]. Subclavian and internal jugular CVC have similar risks for catheter-related complications in long-term catheterization.
Subclavian CVC is preferable to femoral CVC in short-term catheterization because of lower risks of catheter colonization and thrombotic complications. In short-term catheterization, femoral and internal jugular CVA routes have similar risks for catheter-related complications; internal jugular CVA routes are associated with higher risks of mechanical complications [ ].
In sepsis pathogens circulate in the bloodstream. Catheters themselves can introduce bacteria into the bloodstream. Catheter-related bloodstream infections CRBSIs may deteriorate the condition of patients with sepsis. Although earlier studies showed a lower risk of catheter-related bloodstream infections when the internal jugular was compared to the femoral site, recent studies show no difference in the rate of catheter-related bloodstream infections between the sites [ ].
If a central line infection is suspected in a person, blood cultures are taken from both the catheter and a vein elsewhere in the body. Quantative blood culture is more accurate, but it is not widely available [ ]. To prevent infection, stringent cleaning of the catheter insertion site is advised. Povidone-iodine solution is often used for such cleaning, but chlorhexidine is twice as effective as iodine [ ].
Routine replacement of lines makes no difference in preventing infection [ ]. Recommendations regarding risk reduction for infection of CVCs, include antibiotic lock therapy - a method for sterilizing the catheter lumen that involves instilling high concentrations of antibiotics into the catheter lumen for extended periods of time.
Results from in vitro studies demonstrate stability of antibiotics while maintaining high concentrations for prolonged periods of time. In vivo studies show antibiotic lock technique as an effective and safe option for both prevention and treatment of CRBSIs [ ]. Recently, non-antibiotic antimicrobial catheter lock solutions also are used [ ].
Sepsis starts when infection enters the bloodstream and overcomes the host mechanisms of blood clearing from bacteria. The most common primary sites of infection include the lungs, urinary tract, abdominal organs, and pelvis.
Early source identification is important if sepsis is to be treated adequately. Before giving antibiotics, blood cultures should be taken. Blood culture provides information regarding the infection and bacteria sensitivity to antibiotics.
Revealing the source of infection is necessary for targeting of antibiotics. The primary site of infection may be the source of constant bacteremia during the course of sepsis. The blood culture may help to choose appropriate antibiotics and de-escalate from broad spectrum to narrow spectrum antimicrobials.
Although blood cultures are the gold standard in identifying infections, other interventions may be also needed. Current guidelines recommend starting antibiotic therapy in sepsis as early as possible and within one hour of identification of septic shock [ 7 ].
Updated versions were published in [ ], [ 11 ] and most recently in [ ] and [ ]. Applying the sepsis bundle simplifies the complex processes of the care of patients with sepsis. Updates to clinical management guidelines precede the updates to the sepsis bundles. The Hour-1 bundle should be viewed as a quality improvement opportunity moving toward an ideal state. For critically ill patients with sepsis or septic shock, time is of the essence.
Fact Sheets. In a typical year: At least 1. Nearly , Americans die as a result of sepsis. Top of Page. Adults 65 or older. People with weakened immune systems.
People with recent severe illness or hospitalization. Sepsis survivors. Children younger than one. High heart rate or low blood pressure. Confusion or disorientation.
Extreme pain or discomfort. When diagnosed very early, septicemia can be treated effectively with antibiotics. Research efforts are focused on finding out better ways to diagnose the condition earlier.
This is especially true for people with preexisting conditions that affect their immune systems. There have been many medical developments in diagnosis, treatment, monitoring, and training for septicemia. This has helped reduce mortality rates. According to a study published in Critical Care Medicine , hospital mortality rate from severe sepsis has decreased from 47 percent between and to 29 percent between and If you develop the symptoms of septicemia or sepsis after surgery or an infection, be sure to seek medical care right away.
Cellulitis is a common bacterial skin infection. Learn more about its symptoms, how it's treated, and how you can prevent it in the first place. Blood poisoning is a serious infection. It occurs when bacteria are in the bloodstream.
Despite its name, the infection has nothing to do with poison…. Meningitis occurs when the membranes that cover the brain and spinal cord become inflamed. This is normally caused by infection but can also have…. Septic shock is a complication of sepsis. It can become life threatening if left untreated. Learn the signs and symptoms. Endometritis is an inflammatory condition of the lining of the uterus, usually due to an infection.
We'll explain what puts you at risk and what to do. Acute respiratory distress syndrome is a severe condition that occurs when fluid fills up the air sacs in the lungs. It can prevent your organs from…. A gallbladder rupture is a medical condition where the gallbladder leaks or bursts.
Ruptures are commonly caused by inflammation of the gallbladder. Pseudomonas infections are diseases caused by a bacterium from the genus Pseudomonas.
This bacterium does not usually cause infections in healthy…. Septic shock is a severe and systemic infection. Progression to septic shock increases the risk of death.
Signs of progression to septic shock include:. Most often, sepsis occurs in people who are hospitalized or who have recently been hospitalized. People in an intensive care unit are more likely to develop infections that can then lead to sepsis. Any infection, however, could lead to sepsis. See your doctor about an infection or wound that hasn't responded to treatment. Signs or symptoms, such as confusion or rapid breathing, require emergency care.
While any type of infection — bacterial, viral or fungal — can lead to sepsis, infections that more commonly result in sepsis include infections of:.
As sepsis worsens, blood flow to vital organs, such as your brain, heart and kidneys, becomes impaired. Sepsis may cause abnormal blood clotting that results in small clots or burst blood vessels that damage or destroy tissues.
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