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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
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Antibiotic misuse, sometimes called antibiotic abuse or antibiotic overuse, refers to the misuse or overuse of antibiotics, with potentially serious effects on health. It is a contributing factor to the development of antibiotic resistance, including the creation of multidrug-resistant bacteria, informally called "super bugs": relatively harmless bacteria (such as staphylococcus, enterococcus and acinetobacter) can develop resistance to multiple antibiotics and cause life-threatening infections.
Carbapenem-resistant Enterobacteriaceae (CRE) have been defined as carbapenem-nonsusceptible and extended-spectrum cephalosporin-resistant "Escherichia coli, Enterobacter aerogenes, Enterobacter cloacae" complex, "Klebsiella pneumoniae", or "Klebsiella oxytoca". Some exclude ertapenem resistance from the definition.
Vancomycin-resistant "Staphylococcus aureus" are strains of "Staphylococcus aureus" that have become resistant to the glycopeptide antibiotic vancomycin.
Carbapenem-resistant Enterobacteriaceae (CRE) or carbapenemase-producing Enterobacteriaceae (CPE) are Gram-negative bacteria that are resistant to the carbapenem class of antibiotics, considered the drugs of last resort for such infections. They are resistant because they produce an enzyme called a carbapenemase that disables the drug molecule. The resistance can vary from moderate to severe. Enterobacteriaceae are common commensals and infectious agents. Experts fear CRE as the new "superbug". The bacteria can kill up to half of patients who get bloodstream infections. Tom Frieden, former head of the Centers for Disease Control and Prevention has referred to CRE as "nightmare bacteria". Types of CRE are sometimes known as KPC (Klebsiella pneumoniae carbapenemase) and NDM (New Delhi Metallo-beta-lactamase). KPC and NDM are enzymes that break down carbapenems and make them ineffective. Both of these enzymes, as well as the enzyme VIM (Verona Integron-Mediated Metallo-β-lactamase) have also been reported in Pseudomonas.
Strains of hVISA and VISA do not have resistant genes found in "Enterococcus" and the proposed mechanisms of resistance include the sequential mutations resulting in a thicker cell wall and the synthesis of excess amounts of D-ala-D-ala residues. VRSA strain acquired the vancomycin resistance gene cluster "vanA" from VRE.
Antimicrobial resistance (AMR) is the ability of a microbe to resist the effects of medication previously used to treat them. The term includes the more specific "antibiotic resistance", which applies only to bacteria becoming resistant to antibiotics. Resistant microbes are more difficult to treat, requiring alternative medications or higher doses, both of which may be more expensive or more toxic. Microbes resistant to multiple antimicrobials are called multidrug resistant (MDR); or sometimes superbugs.
Resistance arises through one of three mechanisms: natural resistance in certain types of bacteria, genetic mutation, or by one species acquiring resistance from another. All classes of microbes can develop resistance: fungi develop antifungal resistance, viruses develop antiviral resistance, protozoa develop antiprotozoal resistance, and bacteria develop antibiotic resistance. Resistance can appear spontaneously because of random mutations; or more commonly following gradual buildup over time.
Preventive measures include only using antibiotics when needed, thereby stopping misuse of antibiotics or antimicrobials. Narrow-spectrum antibiotics are preferred over broad-spectrum antibiotics when possible, as effectively and accurately targeting specific organisms is less likely to cause resistance. For people who take these medications at home, education about proper use is essential. Health care providers can minimize spread of resistant infections by use of proper sanitation and hygiene, including handwashing and disinfecting between patients, and should encourage the same of the patient, visitors, and family members.
Rising drug resistance is caused mainly by use of antimicrobials in humans and other animals, and spread of resistant strains between the two. Antibiotics increase selective pressure in bacterial populations, causing vulnerable bacteria to die; this increases the percentage of resistant bacteria which continue growing. With resistance to antibiotics becoming more common there is greater need for alternative treatments. Calls for new antibiotic therapies have been issued, but new drug development is becoming rarer.
Antimicrobial resistance is on the rise. Estimates are that 700,000 to several million deaths result per year. Each year in the United States, at least 2 million people become infected with bacteria that are resistant to antibiotics and at least 23,000 people die as a result. There are public calls for global collective action to address the threat include proposals for international treaties on antimicrobial resistance. Worldwide antibiotic resistance is not fully mapped, but poorer countries with weak healthcare systems are more affected.
Multiple drug resistance (MDR), multidrug resistance or multiresistance is antimicrobial resistance shown by a species of microorganism to multiple antimicrobial drugs. The types most threatening to public health are MDR bacteria that resist multiple antibiotics; other types include MDR viruses, fungi, and parasites (resistant to multiple antifungal, antiviral, and antiparasitic drugs of a wide chemical variety). Recognizing different degrees of MDR, the terms extensively drug resistant (XDR) and pandrug-resistant (PDR) have been introduced. The definitions were published in 2011 in the journal "Clinical Microbiology and Infection" and are openly accessible.
In documented BPF cases, the symptoms include high fever (101.3 degrees F or higher), nausea, vomiting, severe abdominal pain, septic shock, and ultimately death. A history of conjunctivitis 30 days prior to the onset of fever was also present in the documented BPF cases.
The physical presentation of children infected with BPF include purpuric skin lesions affecting mainly the face and extremities, cyanosis, rapid necrosis of soft tissue, particularly the hands, feet, nose, and ears. Analysis of the fatalities due to BPF showed hemorrhage in the skin, lungs, and adrenal glands. Histopathology showed hemorrhage, intravascular microthrombi and necrosis in the upper dermis, renal glomeruli, lungs, and hepatic sinusoids.
The Gonorrhea bacterium Neisseria gonorrhoeae has developed antibiotic resistance to many antibiotics.
The bacteria was first identified in 1879, although some Biblical scholars believe that references to the disease can be found as early as Parshat Metzora of the Old Testament.
In the 1940s effective treatment with penicillin became available, but by the 1970s resistant strains predominated. Resistance to penicillin has developed through two mechanisms: chromasomally mediated resistance (CMRNG) and penicillinase-mediated resistance (PPNG). CMRNG involves step wise mutation of penA, which codes for the penicillin-binding protein (PBP-2); mtr, which encodes an efflux pump that removes penicillin from the cell; and penB, which encodes the bacterial cell wall porins. PPNG involves the acquisition of a plasmid-borne beta-lactamase. "N. gonorrheoea" has a high affinity for horizontal gene transfer, and as a result, the existence of any strain resistant to a given drug could spread easily across strains.
Fluoroquinolones were a useful next-line treatment until resistance was achieved through efflux pumps and mutations to the gyrA gene, which encodes DNA gyrase. Third-generation cephalosporins have been used to treat gonorrhoea since 2007, but resistant strains have emerged. As of 2010, the recommended treatment is a single 250 mg intramuscular injection of ceftriaxone, sometimes in combination with azithromycin or doxycycline. However, certain strains of "N. gonorrhoeae" can be resistant to antibiotics usually that are normally used to treat it. These include: cefixime (an oral cephalosporin), ceftriaxone (an injectable cephalosporin), azithromycin, aminoglycosides, and tetracycline.
Drug resistance is the reduction in effectiveness of a medication such as an antimicrobial or an antineoplastic in curing a disease or condition. The term is used in the context of resistance that pathogens or cancers have "acquired", that is, resistance has evolved. Antimicrobial resistance and antineoplastic resistance challenge clinical care and drive research. When an organism is resistant to more than one drug, it is said to be multidrug-resistant. Even the immune system of an organism is in essence a drug delivery system, albeit endogenous, and faces the same arms race problems as external drug delivery.
The development of antibiotic resistance in particular stems from the drugs targeting only specific bacterial molecules (almost always proteins). Because the drug is "so" specific, any mutation in these molecules will interfere with or negate its destructive effect, resulting in antibiotic resistance. Furthermore there is mounting concern over the abuse of antibiotics in the farming of livestock, which in the European Union alone accounts for three times the volume dispensed to humans – leading to development of super-resistant bacteria.
Bacteria are capable of not only altering the enzyme targeted by antibiotics, but also by the use of enzymes to modify the antibiotic itself and thus neutralise it. Examples of target-altering pathogens are "Staphylococcus aureus", vancomycin-resistant enterococci and macrolide-resistant "Streptococcus", while examples of antibiotic-modifying microbes are "Pseudomonas aeruginosa" and aminoglycoside-resistant "Acinetobacter baumannii".
In short, the lack of concerted effort by governments and the pharmaceutical industry, together with the innate capacity of microbes to develop resistance at a rate that outpaces development of new drugs, suggests that existing strategies for developing viable, long-term anti-microbial therapies are ultimately doomed to failure. Without alternative strategies, the acquisition of drug resistance by pathogenic microorganisms looms as possibly one of the most significant public health threats facing humanity in the 21st century.
Resistance to chemicals is only one aspect of the problem, another being resistance to physical factors such as temperature, pressure, sound, radiation and magnetism, and not discussed in this article, but found at Physical factors affecting microbial life.
A positive BPF diagnosis includes the clinical symptoms (mainly the fever, purpuric lesions, and rapid progression of the disease), isolation of "Haemophilus Influenzae" Biogroup aegyptius from blood, and negative laboratory tests for "Neisseria meningitidis".
The negative tests for "Neisseria meningitidis" rules out the possibility of the symptoms being caused by meningitis, since the clinical presentations of the two diseases are similar.
The WHO defines antimicrobial resistance as a microorganism's resistance to an antimicrobial drug that was once able to treat an infection by that microorganism.
A person cannot become resistant to antibiotics. Resistance is a property of the microbe, not a person or other organism infected by a microbe.
A group A streptococcal infection is an infection with group A streptococcus (GAS). "Streptococcus pyogenes" comprises the vast majority of the Lancefield group A streptococci, and is often used as a synonym for GAS. However, "S. dysgalactiae" can also be group A. "S. pyogenes" is a beta-hemolytic species of Gram positive bacteria that is responsible for a wide range of both invasive and noninvasive infections.
Infection of GAS may spread through direct contact with mucus or sores on the skin. GAS infections can cause >500,000 deaths per year. Despite the emergence of antibiotics as a treatment for group A β-hemolytic streptococcus, infection of GAS is an increasing problem, particularly on the continent of Africa.
There are many other types of streptococci (species of "Streptococcus"), including group B streptococcus ("Streptococcus agalactiae") and "Streptococcus pneumoniae", which cause other types of infections and should not be confused with group A strep. Several virulence factors contribute to the pathogenesis of GAS, such as M protein, hemolysins, and extracellular enzymes.
Bacteremia (also bacteraemia) is the presence of bacteria in the blood. Blood is normally a sterile environment, so the detection of bacteria in the blood (most commonly accomplished by blood cultures) is always abnormal. It is distinct from sepsis, which is the host response to the bacteria.
Bacteria can enter the bloodstream as a severe complication of infections (like pneumonia or meningitis), during surgery (especially when involving mucous membranes such as the gastrointestinal tract), or due to catheters and other foreign bodies entering the arteries or veins (including during intravenous drug abuse). Transient bacteremia can result after dental procedures or brushing of teeth.
Bacteremia can have several important health consequences. The immune response to the bacteria can cause sepsis and septic shock, which has a high mortality rate. Bacteria can also spread via the blood to other parts of the body (which is called hematogenous spread), causing infections away from the original site of infection, such as endocarditis or osteomyelitis. Treatment for bacteremia is with antibiotics, and prevention with antibiotic prophylaxis can be given in high risk situations.
Antibiotics can cause severe reactions and add significantly to the cost of care. In the United States, antibiotics and anti-infectives are the leading cause of adverse effect from drugs. In a study of 32 States in 2011, antibiotics and anti-infectives accounted for nearly 24 percent of ADEs that were present on admission, and 28 percent of those that occurred during a hospital stay.
Prescribing by an infectious disease specialist compared with prescribing by a non-infectious disease specialist decreases antibiotic consumption and reduces costs.
Group A β-hemolytic streptococcus can cause infections of the throat and skin. These may vary from very mild conditions to severe, life-threatening diseases. Although it is not completely clear what causes different people to develop different diseases as a result of infection with the same pathogenic bacteria, it is suspected that host phenotypic and epigenetic factors are the source of such variation. Indeed, the many virulence factors of GAS can influence the epigenetics of the host. Furthermore, persons with suppressed or compromised immune systems may be more susceptible to certain diseases caused by GAS than other persons with intact immune systems.
Humans may also carry the GAS either on the skin or in the throat and show no symptoms. These carriers are less contagious than symptomatic carriers of the bacteria.
The non-invasive infections caused by GAS tend to be less severe and more common. They occur when the bacteria colonizes the throat area, where it recognizes epithelial cells. The two most prominent infections of GAS are both non-invasive: strep throat (pharyngitis) where it causes 15- 30% of the childhood cases and 10% of adult cases, and impetigo. These may be effectively treated with antibiotics. Scarlet fever is also a non-invasive infection caused by GAS, although much less common.
The invasive infections caused by Group A β-hemolytic streptococcus tend to be more severe and less common. These occurs when the bacterium is able to infect areas where bacteria are not usually found, such as blood and organs. The diseases that may be caused as a result of this include streptococcal toxic shock syndrome (STSS), necrotizing fasciitis (NF), pneumonia, and bacteremia.
In addition, infection of GAS may lead to further complications and health conditions, namely acute rheumatic fever and poststreptococcal glomerulonephritis.
Most Common:
- impetigo, cellulitis, and erysipelas – infections of the skin which can be complicated by necrotizing fasciitis – skin, fascia and muscle
- strep throat AKA strep pharyngitis – pharynx
Less Common:
- Bacteremia can be associated with these infections, but is not typical.
- septic arthritis – joints
- osteomyelitis – bones
- vaginitis – vagina (more common in pre-pubescent girls)
- meningitis* – meninges
- sinusitis* – sinuses
- pneumonia* – pulmonary alveolus
It resembles bacterial sepsis and can occur after initiation of antibacterials, such as mild silver protein, penicillin or tetracycline, for the treatment of louse-borne relapsing fever (80–90% of patients) and in tick-borne relapsing fever (30–40%). It usually manifests within a few hours of the first dose of antibiotic as fever, chills, rigor, hypotension, headache, tachycardia, hyperventilation, vasodilation with flushing, myalgia (muscle pain), exacerbation of skin lesions and anxiety. The intensity of the reaction indicates the severity of inflammation. Reaction commonly occurs within two hours of drug administration, but is usually self-limiting. It is observed in 50% of patients with primary syphilis and about 90% of patients with secondary syphilis.
Bacteremia is the presence of bacteria in the bloodstream that are alive and capable of reproducing. It is a type of bloodstream infection. Bacteremia is defined as either a primary or secondary process. In primary bacteremia, bacteria have been directly introduced into the bloodstream. Injection drug use may lead to primary bacteremia. In the hospital setting, use of blood vessel catheters contaminated with bacteria may also lead to primary bacteremia. Secondary bacteremia occurs when bacteria have entered the body at another site, such as the cuts in the skin, or the mucous membranes of the lungs (respiratory tract), mouth or intestines (gastrointestinal tract), bladder (urinary tract), or genitals. Bacteria that have infected the body at these sites may then spread into the lymphatic system and gain access to the bloodstream, where further spread can occur.
Bacteremia may also be defined by the timing of bacteria presence in the bloodstream: transient, intermittent, or persistent. In transient bacteremia, bacteria are present in the bloodstream for minutes to a few hours before being cleared from the body, and the result is typically harmless in healthy people. This can occur after manipulation of parts of the body normally colonized by bacteria, such as the mucosal surfaces of the mouth during teeth brushing, flossing, or dental procedures, or instrumentation of the bladder or colon. Intermittent bacteremia is characterized by periodic seeding of the same bacteria into the bloodstream by an existing infection elsewhere in the body, such as an abscess, pneumonia, or bone infection, followed by clearing of that bacteria from the bloodstream. This cycle will often repeat until the existing infection is successfully treated. Persistent bacteremia is characterized by the continuous presence of bacteria in the bloodstream. It is usually the result of an infected heart valve, a central line-associated bloodstream infection (CLABSI), an infected blood clot (suppurative thrombophlebitis), or an infected blood vessel graft. Persistent bacteremia can also occur as part of the infection process of typhoid fever, brucellosis, and bacterial meningitis. Left untreated, conditions causing persistent bacteremia can be potentially fatal.
Bacteremia is clinically distinct from sepsis, which is a condition where the blood stream infection is associated with an inflammatory response from the body, often causing abnormalities in body temperature, heart rate, breathing rate, blood pressure, and white blood cell count.
Common multidrug-resistant organisms are usually bacteria:
- Vancomycin-Resistant Enterococci (VRE)
- Methicillin-Resistant "Staphylococcus" "aureus" (MRSA)
- Extended-spectrum β-lactamase (ESBLs) producing Gram-negative bacteria
- "Klebsiella" "pneumoniae" carbapenemase (KPC) producing Gram-negatives
- Multidrug-Resistant gram negative rods (MDR GNR) MDRGN bacteria such as "Enterobacter species", "E.coli", "Klebsiella pneumoniae", "Acinetobacter baumannii", "Pseudomonas aeruginosa"
A group of gram-positive and gram-negative bacteria of particular recent importance have been dubbed as the ESKAPE group ("Enterococcus faecium", "Staphylococcus aureus", "Klebsiella pneumoniae", "Acinetobacter baumannii", "Pseudomonas aeruginosa" and Enterobacter species).
- Multi-drug-resistant tuberculosis
The Jarisch–Herxheimer reaction is traditionally associated with antimicrobial treatment of syphilis. The reaction is also seen in the other diseases caused by spirochetes: Lyme disease, relapsing fever, and leptospirosis. There have been case reports of the Jarisch-Herxheimer reaction accompanying treatment of other infections, including Q fever, bartonellosis, brucellosis, trichinellosis, and African trypanosomiasis.
In most cases AIT is characterized by onset of pain, firmness, tenderness, redness or swelling in the anterior aspect of the neck. Patients will also present with a sudden fever, dysphagia and dysphonia. Symptoms may be present from 1 to 180 days, with most symptoms lasting an average of about 18 days. The main issue associated with the diagnosis of AIT is differentiating it from other more commonly seen forms of thyroid conditions. Pain, fever and swelling are often much more severe and continue to get worse in patients who have AIT compared to those with other thyroid conditions. Patients who are suspected of having AIT often undergo tests to detect for elevated levels of white blood cells as well as an ultrasound to reveal unilobular swelling. Depending on the age and immune status of the patient more invasive procedures may be performed such as fine needle aspiration of the neck mass to facilitate a diagnosis.
In cases where the infection is thought to be associated with a sinus fistula it is often necessary to confirm the presence of the fistula through surgery or laryngoscopic examination. While invasive procedures can often tell definitively whether or not a fistula is present, new studies are working on the use of computed tomography as a useful method to visualize and detect the presence of a sinus fistula.
Community-acquired pneumonia (CAP) refers to pneumonia (any of several lung diseases) contracted by a person with little contact with the healthcare system. The chief difference between hospital-acquired pneumonia (HAP) and CAP is that patients with HAP live in long-term care facilities or have recently visited a hospital. CAP is common, affecting people of all ages, and its symptoms occur as a result of oxygen-absorbing areas of the lung (alveoli) filling with fluid. This inhibits lung function, causing dyspnea, fever, chest pains and cough.
CAP, the most common type of pneumonia, is a leading cause of illness and death worldwide. Its causes include bacteria, viruses, fungi and parasites. CAP is diagnosed by assessing symptoms, making a physical examination and on x-ray. Other tests, such as sputum examination, supplement chest x-rays. Patients with CAP sometimes require hospitalization, and it is treated primarily with antibiotics, antipyretics and cough medicine. Some forms of CAP can be prevented by vaccination and by abstaining from tobacco products.
Over 100 microorganisms can cause CAP, with most cases caused by "Streptococcus pneumoniae". Certain groups of people are more susceptible to CAP-causing pathogens; for example, infants, adults with chronic conditions (such as chronic obstructive pulmonary disease), senior citizens, alcoholics and others with compromised immune systems are more likely to develop CAP from "Haemophilus influenzae" or "Pneumocystis carinii". A definitive cause is identified in only half the cases.
Chronic bacterial prostatitis is a relatively rare condition that usually presents with an intermittent UTI-type picture. It is defined as recurrent urinary tract infections in men originating from a chronic infection in the prostate. Symptoms may be completely absent until there is also bladder infection, and the most troublesome problem is usually recurrent cystitis.
Chronic bacterial prostatitis occurs in less than 5% of patients with prostate-related non-BPH lower urinary tract symptoms (LUTS).
Dr. Weidner, Professor of Medicine, Department of Urology, University of Gießen, has stated: "In studies of 656 men, we seldom found chronic bacterial prostatitis. It is truly a rare disease. Most of those were E-coli."
Despite the thyroid gland being extremely resistant to infection, it is still susceptible to infection by various bacteria. The cause can be almost any bacterium. "Staphylococcus aureus", "Streptococcus pyogenes", "Staphylococcus epidermidis", and "Streptococcus pneumoniae" in descending order are the organisms most commonly isolated from acute thyroiditis cases in children. Other aerobic organisms are "Klebsiella sp", "Haemophilus influenza", "Streptococcus viridans", "Eikenella corrodens", "Enterobacteriaceae", and "salmonella sp".
Occurrences of AIT are most common in patients with prior thyroid disease such as Hashimoto's thyroiditis or thyroid cancer. The most common cause of infection in children is a congenital abnormality such as pyriform sinus fistula. In most cases, the infection originates in the piriform sinus and spreads to the thyroid via the fistula. In many reported cases of AIT the infection occurs following an upper respiratory tract infection. One study found that of the reported cases of AIT, 66% occurred after an acute illness involving the upper respiratory tract. Although the rates of infection are still very low, cases of AIT have been on the rise in recent years due to the higher occurrence of immune-compromised patients.
Other causes of AIT are commonly due to contamination from an outside source and are included below.
- Repeated fine needle aspirates
- Perforation of esophagus
- Regional infection