Inflammation is not a synonym for infection, even in cases where inflammation is caused by infection. Although infection is caused by a microorganism, inflammation is one of the responses of the organism to the pathogen.
Infections are caused by microorganisms such as viruses, prions, bacteria, and viroids, and larger organisms like parasites and fungi. Hosts can fight infections using their immune system. Therefore, we usually always have an inflammation associated with an infection, but not always we have an infection if there is an inflammation [ 3 ]. This is not just an exercise of semantics, but it is very relevant, particularly for the nuclear medicine point of view. It emerges, as a consequence of what we defined above, that a good radiopharmaceutical for imaging infection should not image inflammation.
This is not always easy, and a certain amount of radiopharmaceutical accumulation in sites of sterile inflammation can often be noticed when seeking for infection. In case of radiolabeled white blood cells WBC and radiolabeled anti-granulocyte monoclonal antibodies, the specificity for infection can be improved by optimizing the image acquisition and interpretation protocols.
Then, images are displayed with the same intensity scale, and any focal increase of activity or size with time should be considered an infection, whereas an accumulation at 3 to 4 h with a decrease at 20 to 24 h is a sign of a sterile inflammation.
As mentioned, it is important that in papers and reviews, we learn to use the correct terminology in order not to create confusion to the readers. The sentence reported in the Abstract by Autio et al. We should clarify that the aim of nuclear medicine in osteomyelitis is to image infection. In IBD and FUO, the situation is much more complicated as we might need to image either the inflammatory events or the sites of pathological granulocyte accumulation abscesses, fistulae, inflammatory stenosis, etc.
Sometimes the immune system of the body becomes more active and starts to harm its tissues. This type of disorder is called an autoimmune disorder. It also leads to inflammation. The pathogen enters the body through contact or other modes and sets at a tissue. The infections are mainly caused by pathogens. These may be viruses, parasites, bacteria, or fungi. The fungal infection is caused by fungi, bacterial by bacteria, viral infections through viruses, etc.
The prevention of these infections is possible by making your body prepared to fight these problems. This means to make your immunity system stringer to fight the incoming pathogens in the body. One should consume a balanced diet consisting of fruits, vegetables, etc.
The treatment of these infections needs to be done at the proper time to stop the reactions and stopping it from spreading to other parts of the body and making the situation worse. The mild infections can be treated at home. But one should consult the doctor if the conditions worsen. Infections are transmittable to other people through cough droplets or by tough. So one should be very careful about it and take necessary precautions. Cyclophosphamide 0. Azathioprine, methotrexate, and leflunomide are effective maintenance therapy drugs.
They may be substituted for cyclophosphamide at 3 months to reduce complications of therapy. Plasmapheresis may be used as an adjunctive therapy in addition to immunosuppression; although its role is far from clear, it is effective in renal vasculitis. This may be tried in rapidly progressive glomerulonephritis or DAH.
It may also improve renal recovery in rapidly progressive glomerulonephritis although offers no survival advantage over immunosuppression. Because of the complications and morbidity associated with steroids and cyclophosphamide, alternative therapies with rituximab and mycophenolate mofetil are equally effective.
Many newer therapies and immunosuppressants are being trialled. IV immunoglobulins in a single dose may be beneficial in Kawasaki disease in children.
The management of these patients in the ICU is supportive in addition to specific immunosuppressive therapy. A few points are worthy of mention:. An endotracheal tube of smaller diameter may be needed and tracheostomy may be required in many. Lung-protective ventilation may reduce lung injury and allow DAH to resolve. Permissive hypercapnea may be beneficial. This will reduce pulmonary oedema and may help in reducing DAH.
This may be temporary, but the majority of patients will require p. Vasculitides are very rare in the ICU and have a high mortality. Some ICUs may never admit such patients as they are usually referred to larger centres. Delays in diagnosis of vasculitides in a previously undiagnosed patient are due to a number of factors, not the least because of the rarity of the condition in UK ICUs.
Nevertheless, prompt diagnosis is important for effective and aggressive therapy to be started. Unusual presentation, a high index of suspicion, detailed history, and clinical examination, along with serology in ANCA-associated vasculitides, will speed the diagnostic process and start of therapy. The reported incidence of severe sepsis in critical care units varies between countries in the developed world. Despite a steady fall in hospital mortality over the past few decades the actual number of deaths has risen, probably as a result of increasing age and the number of comorbidities of patients.
A significant proportion of patients will be admitted because of their infection, whilst others will acquire it during their stay. Respiratory and abdominal infections are the most common cause of severe sepsis, closely followed by urinary tract, soft tissue, and primary bloodstream infection. Surgery is not the only option when considering source control; the benefit of any intervention must be balanced against the inherent risk of performing the procedure itself and any associated complications.
Prevention is better than cure—the following not exhaustive should always be considered:. These are usually incorporated into local policy. Some are common sense, some have strong evidence, and some do not. Any infective process may fuel an inflammatory response and may result in severe sepsis and multiorgan failure.
The source may be an abscess, necrotic tissue, contamination secondary to a perforated viscus, or an infected foreign body, e. In broad terms, source management may involve:. Recent advances in imaging and interventional techniques frequently make percutaneous management an option with a better risk—benefit profile. The early use of appropriate antibiotics, i. This approach is associated with improved survival irrespective of whether infection is suspected or confirmed the Surviving Sepsis Campaign guidelines.
It also helps with source control. Knowledge of the local ecology and resistance patterns is essential in antibiotic choice; a good working relationship with the microbiology department is vital. Protocols may be in place but these need to evolve to fit the local ecology.
If non-stock antibiotics are needed, then mechanisms to allow them to be rapidly dispensed from the pharmacy will minimize delays in administration.
An abscess is a liquid-filled collection containing a variety of cells walled off from surrounding healthy tissue. It may drain spontaneously, to form a sinus or fistula, or as a result of surgical or radiological intervention. Imaging by ultrasound and CT are now both accurate and easy, and, in competent hands, can be combined with percutaneous drainage.
This reduces the risk of contamination, avoids the need for an operation, and hence the complications associated with a surgical wound, e.
The site of the collection and severity of illness of the patient will have some bearing on the method of control, e. More invasive radiological or surgical intervention will require transfer of the patient to another department with the additional risks that this entails.
It is important to consider unusual sources of infection, including sinus and dental collections. Source control is secondary to appropriate resuscitation measures, but may have to occur concurrently and, indeed, may on occasion assist resuscitation. In dire circumstances where surgical drainage is necessary, the use of a temporary percutaneous drain could allow time for adequate resuscitation prior to definitive surgery.
The source of infection may be from a perforated viscus. This is likely to be identified clinically but is aided by imaging. Management will be influenced by the severity of illness of the patient, the available surgical expertise, and the site of the perforation.
Options include:. The Surviving Sepsis Campaign guidelines and Guidelines for the Provision of Intensive Care Services recommend surgical source control within 12 h of identification, although a prospective study on patients with gastrointestinal perforation in suggested that source control within 6 h has a positive impact on day outcome. The intervention chosen should be that which is deemed most effective with the least physiological insult, and may require multidisciplinary input.
Dead tissue is an ideal medium to support the growth of microorganisms. Debridement, if possible, is the optimal management, and timing is critical; however, there are also a variety of potential approaches in different circumstances:. Typical radiological signs of necrosis are not always evident and, in these circumstances, particularly when the patient is critically ill, surgery is the only safe option.
In most circumstances, debridement is not required immediately and therefore there will be time to resuscitate and stabilize the patient prior to surgery, e.
There are some situations where delay is beneficial and is associated with better outcome, e. It is for this reason that delayed pancreatic necrosectomy is associated with a better outcome. The use of continuous peritoneal lavage may remove contaminated tissue and reduce the risk of recurrent infection.
This avoids the risks associated with raised intra-abdominal pressure but can expose the patient to further infection and is labour-intensive to manage. It makes sense to remove an infected object but this may not always be possible, e. When an in-dwelling vascular catheter is suspected as a source of infection, blood for culture should be taken via the line and peripheral venepuncture.
If there is any suggestion that a line has been inserted in a non-sterile way it should be replaced within 24 h. A different site should be chosen but, if the risks outweigh the benefits, e. Tunnelled lines are less likely to become infected, and soft-tissue infection can be managed with appropriate antibiotics.
There is debate as to when lines should be changed. Venous catheters should be reviewed daily and changed when there is evidence of local or systemic infection and removed as soon as they are no longer required. Local guidelines should be followed.
Source identification:. Seek advice from radiologist. May require contrast studies. Source control:. The protocol comprises a combination of administering hygiene measures, oropharyngeal, and enteral non-absorbable antimicrobials e. Selective oropharyngeal decontamination consists of SDD without the enteral suspension and without IV antibiotics. Once a patient has been successfully decolonized, the unaffected anaerobic flora offer prevention against new colonization with PPMs, a principle called colonization resistance.
Nosocomial infection in the ICU carries a significant morbidity burden. During critical illness, alteration of the normal gut flora and colonization of the oropharynx by enteric bacteria increase the susceptibility of acquiring nosocomial infection. Regular microbiological screening e.
Critical illness importantly impacts the body flora, promoting a shift from normal to abnormal carriage and from low-grade carriage to high-grade carriage, i.
Gut overgrowth i. Most ICU infections are primary endogenous infections, followed by secondary endogenous and exogenous infections. Pathogens have been divided into normal and abnormal PPMs. These include aerobic Gram-negative bacteria, methicillin-susceptible S. See Table Table IV antibiotics, e. Enteral antimicrobials, e. High level of hygiene, e.
Prevent exogenous infections, especially lower airway. SDD has amongst the greatest bases of evidence for any practice in intensive care, comprising over 50 randomized controlled studies and over 10 meta-analyses investigating its use since Proponents cite that many of these trials point toward benefit, for instance:.
Significant reduction in carriage and infection due to aerobic Gram-negative bacilli and yeasts. Reduction in Gram-positive lower airway infections odds ratio [OR] 0.
No significant reduction in carriage due to Gram-positive bacteria. No increase in Gram-positive bloodstream infections OR 1. Does not significantly reduce fungaemia OR 0. Research has not adequately addressed concerns about antibiotic resistance and SDD, and consequently,. SDD may increase antibiotic resistance, particularly in areas with pre-existing high prevalence of drug resistance.
SDD may increase rates of C. While recent reviews and meta-analyses conclude that there is no relationship between the use of SDD or selective oropharyngeal decontamination and the development of antimicrobial resistance in pathogens in patients in the ICU, there is still widespread concern that long-term ICU-level changes in resistance rates have not been adequately assessed.
These concerns are being addressed with ongoing research studies. The diagnosis of infection is often difficult. Infection triggers a host inflammatory response, and changes in heart rate, respiratory rate, blood pressure, temperature, and leukocyte count may simply reflect non-infectious systemic inflammation. These changes are neither specific nor sensitive for infection in critical illness. Sepsis, the most serious clinical manifestation of infection, is caused by the dysregulated host response to infection.
In clinical practice sepsis is a syndrome defined by non-specific alterations in physiology. Consensus definitions such as Sepsis-3 and the systemic inflammatory response syndrome SIRS attempt to improve the consistency, sensitivity, and specificity of sepsis diagnosis, but these definitions lack specificity to discriminate infection.
Confirmation of infection is still largely dependent on the isolation and culture of infectious organisms. This takes time and lacks sensitivity. The absence of sepsis-specific biomarkers compounds the diagnostic challenges and contributes to delays in the administration of appropriate antimicrobials and the use of unnecessary antimicrobial agents. The ideal marker of infection should accurately diagnose infection, differentiating between infectious and non-infectious causes of inflammation.
It should be inexpensive, technically straightforward to use, shorten the time to diagnosis, differentiate between viral, bacterial, and fungal infection, provide prognostic information, and reflect the effectiveness of treatments such as source control and antimicrobial treatment. None of the sepsis biomarkers currently in use fulfil these criteria, with many best described as markers of the host inflammatory response. Some have good negative predictive value e.
CRP, procalcitonin [PCT], and endotoxin , with low levels effectively excluding infection, but all have limited specificity in distinguishing infective from non-infective causes of inflammation. It is likely that diagnostic accuracy of individual markers is improved using a multimarker approach.
Gene expression profiling transcriptomics , the study of proteins produced by the genome proteomics , and cellular metabolites metabolomics will allow greater characterization of the host response to infection in the future and will facilitate rapid non-culture-based identification of microorganisms.
These techniques are not yet established in routine clinical practice. While the source of fever is often due to infection, it may be non-infectious e. Infection commonly causes a rise in total white cell count WCC; leukocytosis. It is also seen in chronic intracellular bacterial infection e. It is an indirect measure of the concentration of prosedimentation factors in the acute phase response, most notably fibrinogen.
ESR is a non-specific marker and is raised in most causes of local and systemic inflammation, infection, tissue injury, malignancy, and trauma. The lack of specificity for infection coupled with a slower response time than other markers e. CRP limit its utility in critical care. CRP is an acute phase plasma protein, synthesized and released by the liver in response to proinflammatory cytokines, notably interleukin IL Part of the innate immune response, CRP has a number of roles, including complement activation, pathogen opsonization, and p.
CRP rises rapidly 6—8 h in response to infection, inflammation, and trauma, peaking at 48 h. As a sensitive but non-specific marker of inflammation, CRP is frequently used as a screening test for infection and, with serial measurements, to monitor the resolution of inflammation following treatment.
Questions remain regarding the predictive value of CRP as a biomarker of infection in critical care. CRP concentration at ICU admission appears to correlate with severity of illness organ dysfunction, ICU length of stay, and mortality , and several studies have shown higher levels in patients with proven infection compared to non-infected patients.
There is no clear threshold for diagnosing infection. PCT is the precursor of the hormone calcitonin. Following bacterial infection, non-neuroendocrine tissue expression of PCT increases significantly and serum levels increase rapidly 3—6 h.
The kinetics of the response of PCT to infection appear more favourable than those of CRP, with a more rapid rise and constant half-life approximately 24 h once infection is controlled. The magnitude of rise in PCT appears related to severity of illness and the likelihood of bacteraemia, with low levels predicting the absence of bacteraemia. The increase in PCT with fungaemia is less consistent, therefore limiting the diagnostic value of PCT in fungal infection.
Although less likely than CRP to be elevated in patients with non-infectious systemic inflammation, PCT is increased in a number of non-infectious disorders e. In pneumonia, PCT levels correlate with severity of illness and differentiate between bacterial and viral infection and the risk of bacteraemia. Treatment algorithms incorporating PCT-based thresholds for treatment of respiratory tract infection reduce antibiotic use with no apparent increase in mortality.
The role of PCT in antibiotic stewardship in critical care is supported by systematic review and meta-analyses but requires further validation. With current trends toward shorter duration antimicrobial courses, the added benefit of PCT-guided discontinuation of antibiotic therapy remains unclear. Microbial pathogen-associated molecular patterns, such as endotoxin and peptidoglycan, activate the host immune response by binding to cell membrane toll-like receptors and cytoplasmic pattern recognition receptors.
Levels of proinflammatory cytokines rise within 1 h of infection and have some value in the assessment of the inflammatory response, but this response also occurs following a number of non-infectious proinflammatory stimuli and is not specific to infection. IL-6 is reliably measurable in plasma and has received most attention as a biomarker in sepsis. Although lacking specificity as a diagnostic biomarker, IL-6 appears to have some prognostic value in sepsis, with levels correlating with increasing mortality.
Proinflammatory cytokines upregulate the expression of a number of proteins by neutrophils, macrophages, and monocytes. A number of these proteins, either on the cell surface or in soluble form, have been investigated as biomarkers of sepsis, including cluster of differentiation 64 CD64 , triggering receptor expressed on myeloid cells 1 TREM-1 , receptor for advanced glycation end products RAGE , CD11b, CD14, and heparin-binding protein.
CD64 is a high-affinity receptor for the Fc portion of immunoglobulin. Neutrophil expression of CD64 increases significantly following infection. Initial studies in critically ill adults suggest that CD64 levels correlate with severity of illness in sepsis and have greater specificity for discriminating infection than PCT. TREM-1 is a member of the immunoglobulin superfamily expressed on the surface of myeloid cells. TREM-1 amplifies the toll-like receptor-initiated response to microbial infection and potentiates the release of proinflammatory cytokines.
The released form, soluble TREM-1 sTREM-1 , has been recognized as a potential surrogate marker of infection in sepsis with serum levels rising rapidly following bacterial or fungal infection and correlating with illness severity.
However, more recent studies have demonstrated increased sTREM-1 expression in a number of non-infectious inflammatory disorders such as pancreatitis, postcardiac arrest, and following cardiac and abdominal surgery.
Meta-analyses suggest sTREM-1 has at least moderate diagnostic accuracy as a marker of infection in patients with systemic inflammation. Pleural sTREM-1 has been shown in a number of studies to discriminate infected from non-infected pleural effusions, and increases in CSF sTREM-1 have been shown to discriminate bacterial from viral meningitis.
Alveolar sTREM-1 is increased in bacterial and fungal pulmonary infection, and several studies suggest it performs better than other clinical or laboratory tests including CRP and PCT in discriminating pulmonary infection.
Other studies suggest lower discriminatory value. RAGE is a transmembrane multiligand receptor that binds a variety of damage-associated molecular patterns such as high-mobility group box 1 HMGB1 and other proteins released from necrotic cells. Serum levels of the soluble isoform of the receptor sRAGE are elevated within 24 h of the onset of sepsis in adult patients, with levels correlating with p.
What remains unclear is whether sRAGE is a specific biomarker for infection in the context of sepsis or whether it might more accurately be considered a biomarker of lung injury. In a retrospective study of adult patients with severe sepsis, sRAGE was able to discriminate those patients who developed ARDS from those who did not. Endotoxins are lipopolysaccharides LPSs that form an essential component of the cell membrane of Gram-negative bacteria. Endotoxin is a pathogen-associated molecular pattern and a principal trigger of innate immunity and the host response in Gram-negative sepsis.
Reliable measurement of endotoxin is challenging and the utility of endotoxin as a biomarker of infection is limited. Endotoxaemia is common in critical illness, occurring in more than half of patients. Endotoxin activity level does appear to correlate with likelihood of developing sepsis, illness severity, and risk of Gram-negative infection, but only a small proportion of patients with elevated endotoxin levels have microbiologically proven infection, limiting the specificity of endotoxin as a marker of infection.
Endotoxin does appear to have strong negative predictive value, with infection unlikely in the absence of elevated endotoxin levels.
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