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PCL 301 – Introduction to infectionsWhat is an infectious disease?Infectious diseases are caused by microorganisms such as viruses,?bacteria, fungi or parasites. Microorganisms that cause diseases are collectively called pathogens. Pathogens cause disease either by disrupting the bodies normal processes and/or stimulating the immune system to produce a defensive response, resulting in high fever, inflammation and other symptoms.Infectious diseases can be spread from one person to another, for example through contact with bodily fluids,?by aerosols (through coughing and sneezing), or via a vector, for example a mosquito.Infection can be defined as the injurious colonization of a host organism, by a foreign species. In such a case, the foreign species, which can also be called the infecting organism, starts utilizing the resources of the host. The result is that the normal functioning of the host is adversely affected. In human beings, the negative effects might manifest themselves in the form of chronic wounds, loss of an infected limb, gangrene and, in some cases, even death. The foreign species usually comprise of microscopic organisms, like bacteria, viruses, parasites, fungi and protozoans. In an infection, the infecting organism seeks to utilize the host's resources to multiply, usually at the expense of the host. The infecting organism, or pathogen, interferes with the normal functioning of the host and can lead to chronic wounds, gangrene, loss of an infected limb, and even death. The host's response to infection is inflammation. Colloquially, a pathogen is usually considered a microscopic organism though the definition is broader, including parasites, fungi, viruses, prions, and viroids. A symbiosis between parasite and host, whereby the relationship is beneficial for the former but detrimental to the latter, is characterised as parasitism. The branch of medicine that focuses on infections and pathogens is infectious disease. When infection attacks the body, anti-infective drugs can help turn the tide of battle. Four types of anti-infective drugs exist: antibacterial, antiviral, antitubercular and antifungalMany individuals develop a variety of infections but quickly overcome them. However, some individuals are unfortunate and develop chronic or persistent infections. In the majority of cases, persistent infections are caused by viruses and not bacteria. The common viruses that can cause chronic infection include measles, hepatitis, various viruses that affect the brain (mad cow) , herpes, infectious mononucleosis and Cytomegalovirus (CMV). Bacteria can also cause chronic infections in individuals with diabetes, those with compromised immunity and in individuals who smoke.Determining Colonization Versus InfectionInfection refers to the presence of bacteria that are causing disease (e.g. the organisms are found in normally sterile anatomic sites or in nonsterile sites with signs/symptoms of infection). Colonization refers to the presence of bacteria that are not causing disease. Only bacteria that cause diseases should be targeted with antimicrobial therapy and non-disease producing colonizing bacteria should be left intact. It is important to differentiate infection from colonization because antimicrobial therapy targeting bacterial colonization is inappropriate and may lead to the development of resistant bacteria.Infection and DiseasePeople should understand that infection and disease is not the same thing. Infection occurs when an organism enters the body and starts to grow. However, disease only occurs if the organism starts to multiply and produce symptoms. Our bodies have tremendous capacity to fight off organisms. Diseases result when these protective mechanism fail or are compromised.Moreover, not all infectious agents are likely to cause disease. For example, the polio virus infects many people, but in less than 5% of individuals does it actually cause disease. On the other hand, some organisms are not contagious but very virulent. The mad cow virus kills almost everyone who is infected. The most dangerous organisms are those that are both very virulent and contagious. All organisms must enter the body in order to cause disease. The organism must stick or adhere to a specific cell, invade, colonize and inflict some type of damage to the host. This chain of events is the same for all organisms.The Infection CycleThere are various parts to the infection cycle and include:EntranceEntrance to the host generally occurs through the normal openings like the oral cavity, nose, eyes, genitalia, anus, or open wounds. While a few organisms can grow at the initial site of entry, many invade and start to grow in different organs where they are hard to detect. Some organisms grow within the host cells whereas others grow freely in blood. Microorganisms can cause tissue damage by releasing a variety of toxins or destructive enzymes. For example, clostridium tetani releases a toxin which can paralyze muscles, or staphylococcus releases toxins which can produce shock and sepsis.Infectious agentFor an organism to cause disease, there are several factors that must be met before an infection can occur. The organism must be able to grow, multiply, be able to enter the body and have the ability to cause disease. Infectious agents which cause disease in humans include bacteria, viruses, parasites and fungi.ReservoirReservoir is a place where organisms can thrive and multiply. This may be either inside the human body or outside like in an inanimate environment. For example some organisms may thrive in water (mycobacterium tuberculosis), AC units (legionella), furniture (virus) or in a tick (Lyme disease). The reservoir for a disease is the site where the infectious agent survives. Humans are reservoir for the measles virus because this organism does not infect any other mammals. Beside insects, animals also serve as reservoirs for infectious organism. The rabies virus is carried in many small mammals and wild dogs. Portal of exitIn order for microorganisms to survive and repeat the cycle of infection in other humans, it must have a way to exit the reservoir. For example, if the organism was growing in mouldy water in an air conditioning unit it may spread when the unit is switched on. In other cases, the organism may spread from humans to others when an infected individual coughs. Micro-organisms can also be passed from body fluids, faecal material and urine.Mode of transmissionInfectious organisms may be transmitted either by direct or indirect contact. Direct contact occurs when an individual comes into contact with the reservoir. This may mean touching infected bodily fluids or drinking contaminated water or being bitten by the deer tick. Direct contact infections can also result from inhalation of infectious organisms found in aerosol particles emitted by sneezing or coughing. Another common means of direct contact transmission involves sexual activity - oral, vaginal or anal sex.Indirect contact occurs when the organism is able to withstand the harsh environment outside the host for long periods of time and still remain infective when the right opportunity arises. Inanimate objects that are frequently contaminated include toys, furniture, door knobs, tissue wipes or personal care products from an infected individual. Consuming food products and fluid which have been contaminated by contact with an infecting organism is another case of disease transmission by indirect contact. A common method of transmission in under developed countries is faecal oral transmission. In such cases, sewage water is used to wash food or is consumed. This results in food poisoning. Common disorders which are transmitted by the faecal oral route include cholera, giardia, rotavirus, cryptosporidium, ecoli or tape worms All the above modes are examples of horizontal transmission because the infecting organism is transmitted from person to person in the same generation. There are also a variety of infections transmitted vertically - that is from mother to child during the birthing process or fetal development. Common disorders transmitted this way include AIDs, hepatitis, herpes, and cytomegalovirus Portal of entryOrganisms need a point of entry. Some enter via the mucus membrane like the mouth, vagina or nose. Others enter via breaks in the skin, for example a surgical incision or a laceration. Sometimes physicians insert tubes or catheters into the bladder which can cause urinary tract infections. Even an intravenous line can become infected at the site where the needle hole was made on the skin.Susceptibility of hostMost humans are not easily infected. Organisms usually cause infections in people who are weak, sick, malnourished, have cancer, are diabetic or are immuno-suppressed. Individuals who have a suppressed immune system are quickly over powered by the organisms. The majority of chronic or persistent infections occur in individuals who have poor defense mechanism(s).General InfectionsGeneral infections can be divided into two categories, namely systemic infection and local infection. Systemic InfectionThe cause of a systemic infection comprises of bacteria or virus. The main characteristic of such an infection is that it affects the bloodstream of an individual, with the result that the symptoms spread to the whole of the body. In this case, the pathogen is distributed throughout the body, rather than being concentrated in one area. Bacterial toxin is the major reason that leads to systemic infection. The most common examples of a systemic infection are cold, flu, mononucleosis, strep throat, etc. ?Signs and Symptoms of Systemic Infection?Aches: When a person is suffering from systemic infection, he/she experiences ache in areas such as the forehead and back. In extreme cases, the person experiences body ache too.Chills: Systemic infection triggers chills, which make a person shiver even after wearing layers of woolen clothes.Fever: Fever is a telltale sign of systemic infection. Depending upon the severity of the infection, the person might suffer from low to high fever.Nausea: Systemic infection triggers a feeling of nausea. The person reacts to certain smells by vomiting.Vomiting: Vomiting is one of the major symptoms of systemic infection. The person would have the tendency of puking, even after consuming regular food.Weakness: Overall weakness in the body is another symptom of systemic infection. Local InfectionA local infection can be explained as that infection, which does not affect the whole body of an individual. Rather, it is limited to a specific portion of the body. It does not attack the bloodstream and is limited to the outer surface of the body. Some of the most common examples of a local infection include an infected wound, an infected cut, etc. Symptoms of a local infection are indicative to the site and includeSigns and Symptoms of Local Infection?Fever: Fever is the only systemic symptom that can be caused by a local infection. Foul Odor Discharge: A foul odor discharge from the affected area is a telltale sign that the person has incurred a problem of local infection.Heat at the Site: In some cases, local infection might cause swelling in the affected area, which would in turn cause heat at the site. Pain: Pain in the area, which has been infected, is a very visible sign of local infection.Pus: One can figure out whether a wound is infected or not, by observing the amount of pus released from there.Redness and Swelling: Local infection might cause redness and swelling in the affected area.The only systemic symptom a local infection can cause is fever. Paracetamol, ibuprofen or aspirin help for fever and pain. For local infections, keep site clean, warm moist compresses may be applied.What causes an infectious disease?BacteriaThese one-cell organisms are responsible for illnesses such as strep throat, urinary tract infections and tuberculosis.Bacteria are single-celled microorganisms.They come in many shapes?including ball-, rod- and spiral-shaped.Most bacteria are not harmful and some are actually beneficial. Less than one per cent of bacteria will actually make people ill.Infectious bacteria can grow, divide and spread in the body, leading to infectious disease.Some infectious bacteria give off toxins which can make some diseases more severe.Bacteria are spread in many ways including: Spread by aerosols (through coughing and sneezing). For example, Streptococcus.Spread by surface and skin contact. For example, Staphylococcus aureus, including MRSA.Spread through body fluids, such as blood and saliva. For example, meningococcal disease (meningitis).Antibiotics are usually given to treat severe bacterial infections.Antibiotic resistance in bacteria is a significant problem.Bacterial Infection Symptoms: Vary according to the type of bacterial infections. Bacterial infections are caused by certain typical bacteria that are harmful to the human body and health. There are numerous bacteria that are present in our surroundings. Amongst them, not all bacteria are harmful. Human body is inhabited by millions of bacteria (microscopic organisms), most of whom are totally harmless. In fact, many of them are important for proper functioning of the body. Causes of Bacterial InfectionBacterial infections are undoubtedly caused by different types of bacteria that inhibit our body for a longer period of time, making the existing bacteria to lose their balance. Some of the bacteria that mainly cause bacterial infections are:Haemophilus Influenzae: One of the most common bacteria that affects the body and causes bacterial infections. Bacterial infection symptoms include infections of the respiratory tract, types of meningitis and ear infections. There are several drugs that can treat infections caused by this bacterium. Infants and children are immunized against this organismStaphylococcus: Also known as staph, this bacterium is also one of the most common bacteria that inhabits the human body. Bacterial infection symptoms include skin infection, boil, rash, abscess, eczema, impetigo, furuncle, etc. Staph can also lead to inflammation of breasts often called as mastitis, that releases bacteria to the mother's milk and creates complications for the health of the infant.Methicillin-resistant Staphylococcus Aureus: This is a type of staph that has developed as an antibiotic-resistant bacteria. Symptoms of bacterial infection include sepsis, necrotic pneumonia, toxic shock syndrome, etc.Streptococcus: This is also one of the common bacteria that can result into several infections like strep throat, respiratory infections, pneumonia, rheumatic fever, scarlet fever. The symptoms of strep throat include painful sore throat, swollen lymph nodes in the neck, fever and headache while symptoms of bacterial pneumonia are fever, chills, coughs, difficulty breathing, chest and abdominal pain, loss of appetiteEscherichia coli: This bacterium colonizes the gastrointestinal region of the body and can cause several dysfunctions of gastrointestinal region including diarrhoea. These bacteria can also cause food poisoning if they are transmitted through various contaminated food items. Symptoms are abdominal cramps, bloody diarrhoea, nausea, vomiting, fever, kidney failure.Helicobacter Pylori: These are the main culprits responsible for stomach ulcers. These are also found in colonies in the gastrointestinal region. Bacterial infection symptoms include stomach pain, inflammation of the stomach, cell walls, etc. Salmonella: This pathogen can cause salmonella food poisoning or salmonellosis. Causes of salmonella infection are often contaminated poultry products like raw eggs and symptoms include stomach cramps, nausea, vomiting, diarrhoea and fever.Clostridium causes botulism or food poisoning. This disease affects the nervous system and causes muscle paralysis, difficulty breathing and swallowing, dry mouth, double vision, nausea, vomiting, abdominal cramps, constipation, sore throat, dizziness, diarrhoea. Neisseria meningitidis causes meningitis. The symptoms are fever, vomiting, diarrhoea, severe headache, neck stiffness, joint or muscle pain, stomach cramps, sensitivity to bright light, drowsiness, confusion or disorientation, possible rash.VirusesSmaller than bacteria, viruses cause a multitude of diseases — ranging from the common cold to AIDS.Viruses are tiny infectious agents that replicate only in the living cells of other organisms.Viruses have a very simple?structure consisting of genetic material in the form of?DNA or?RNA within a protein capsule.They can infect all types of life forms, from animals to plants and?bacteria to amoebae.Viruses can be spread in many ways including: ?From plant to plant by insects that feed on plant sap. For example, Potato virus Y which is spread by aphids.From animal to animal by blood-sucking insects. For example, Dengue virus which is spread by mosquitos.Spread by aerosols (through coughing and sneezing). For example, influenza virus.Spread by not washing hands after going to the toilet. For example, norovirus or rotavirus.Spread by sexual contact. For example, HIV and Human Papillomavirus (HPV).Spread by exposure to infected blood. For example, Hepatitis B.Viruses can often be prevented through vaccines.Bacterial vs. Viral InfectionsBacterial and viral infections can both cause symptoms such as malaise, fever, and chills. It can be difficult to distinguish which is the cause of a specific infection. It is important to distinguish, because viral infections cannot be cured by antibiotics. Comparison of viral and bacterial infectionCharacteristicViralBacterialTypical symptomsIn general, viral infections are systemic. This means they involve many different parts of the body or more than one body system at the same time; i.e. a runny nose, sinus congestion, cough, body aches etc. They can be local at times as in viral conjunctivitis or "pink eye" and herpes. Only a few viral infections are painful, like herpes. The pain of viral infections is often described as itchy or burning. The classic symptoms of a bacterial infection are localized redness, heat, swelling and pain. One of the hallmarks of a bacterial infection is local pain, pain that is in a specific part of the body. For example, if a cut occurs and it is infected with bacteria, pain will occur at the site of the infection. Bacterial throat pain is often characterised by more pain on one side of the throat. An ear infection is more likely to be bacterial if the pain occurs in only one ear. An infection that produces pus is not always bacterial. CausePathogenic virusesPathogenic bacteriaFungiMany skin diseases, such as ringworm and athlete's foot, are caused by fungi. Other types of fungi can infect the lungs or nervous system.Fungi are microorganisms characterized by cell walls made from a substance called chitin.Most fungi are harmless to humans and some are edible.Other fungi?can be infectious and may lead to life-threatening diseases.Fungi reproduce by releasing spores that can be picked up by direct contact or even inhaled.Fungal infections often affect the lungs, skin or nails. Some infections may also penetrate the body to affect organs and cause whole-body infections.Examples of fungal infections include: Athlete’s foot:?itching, scaling or cracking of the skinRingworm:?reddish, itchy, scaly rash usually on the skin and scalpThrush:?caused by the fungus?Candida albicans?which can infect the?mouth, vagina, stomach and urinary tract.Fig. 1: Normal flora and concentrations of bacteria (organisms per millilitre)ParasitesParasites are organisms that live in or on another organism and benefit by getting nutrients at the expense of their host.Parasites can be found in many different body sites, for example?in the blood, liver, digestive system, brain and even the eyes.Malaria is caused by a tiny parasite that is transmitted by a mosquito bite. Other parasites may be transmitted to humans from animal faecesThere are several groups of parasites that infect humans: Roundworms: these are nematode worms that can get into humans by ingestion, directly penetrating the skin?or through insect bites. Examples: whipworm (ingested),?hookworms (directly penetrate?the skin), Wuchereria bancrofti (transmitted by mosquitos)Protozoa:? these are single-celled parasites. Many are delivered by biting insects or are ingested with contaminated water or food.? They invade or eat host cells, or swim around the bloodstream and quickly reproduce by copying themselves. Examples: Giardia (ingested), Plasmodium falciparum (causes malaria and is transmitted by mosquitos), Trichomonas (sexually transmitted)Tapeworms: these are flatworms whose heads hook on to the intestinal wall of their host. Their larvae migrate to other parts of the body. They can live in the host for decades. Example: Pork tapewormFlukes: blood flukes are flatworms that are caught through contact with contaminated?water. Blood fluke larvae are released from infected snails into freshwater.? Liver flukes can be found in raw or undercooked fish or water plants and can live in the body of the host for decades. Example: Schistosomes (blood flukes).How are infectious diseases contracted?Direct contactAn easy way to catch most infectious diseases is by coming in contact with a person or animal who has the infection. Three ways infectious diseases can be spread through direct contact are:Person to person. A common way for infectious diseases to spread is through the direct transfer of bacteria, viruses or other germs from one person to another. This can occur when an individual with the bacterium or virus touches, kisses, or coughs or sneezes on someone who isn't infected.These germs can also spread through the exchange of body fluids from sexual contact. The person who passes the germ may have no symptoms of the disease, but may simply be a carrier.Animal to person. Being bitten or scratched by an infected animal — even a pet — can make you sick and, in extreme circumstances, can be fatal. Handling animal waste can be hazardous, too. For example, you can acquire a toxoplasmosis infection by scooping your cat's litter box.Mother to unborn child. A pregnant woman may pass germs that cause infectious diseases to her unborn baby. Some germs can pass through the placenta. Germs in the vagina can be transmitted to the baby during birth.Indirect contactDisease-causing organisms also can be passed by indirect contact. Many germs can linger on an inanimate object, such as a tabletop, doorknob or faucet handle.When you touch a doorknob handled by someone ill with the flu or a cold, for example, you can pick up the germs he or she left behind. If you then touch your eyes, mouth or nose before washing your hands, you may become infected.Insect bitesSome germs rely on insect carriers — such as mosquitoes, fleas, lice or ticks — to move from host to host. These carriers are known as vectors. Mosquitoes can carry the malaria parasite or West Nile virus, and deer ticks may carry the bacterium that causes Lyme disease.Food contaminationAnother way disease-causing germs can infect you is through contaminated food and water. This mechanism of transmission allows germs to be spread to many people through a single source. E. coli, for example, is a bacterium present in or on certain foods — such as undercooked hamburger or unpasteurized fruit juice.Risk factorsWhile anyone can catch infectious diseases, some people are more likely to get sick if their immune system is not working properly. This may occur if:One is taking steroids or other medications that suppress the immune system, such as anti-rejection drugs for a transplanted organOne has HIV or AIDSOne has certain types of cancer or other disorders that affect the immune systemIn addition, certain other medical conditions may predispose one to infection, including implanted medical devices, malnutrition and extremes of age, among plicationsMost infectious diseases have only minor complications. But some infections — such as pneumonia, AIDS and meningitis — can become life-threatening. A few types of infections have been linked to a long-term increased risk of cancer:Human papillomavirus is linked to cervical cancerHelicobacter pylori is linked to stomach cancer and peptic ulcersHepatitis B and C have been linked to liver cancerIn addition, some infectious diseases may become silent, only to appear again in the future — sometimes even decades later. For example, someone who has had a chickenpox infection may develop shingles much later in life.Clinical Presentation and Diagnosis of Patients with InfectionClinical Presentation is necessary to classify the infection and guide therapy. Review of symptoms must be consistent with an infectious aetiology. Signs and symptoms may be nonspecific (e.g. fever) or specific. Diagnosis of infections is necessary to select the best treatment for the episode.Physical Examination (PE).Findings on physical examination, along with the clinical presentation, can help to provide the anatomic location of an infection. Once the anatomic site is identified, the most probable pathogens associated with disease can be determined based on likely endogenous or exogenous flora.Patient HistoryHistory of present illnessComorbiditiesCurrent medications,Allergies,Previous antibiotic exposure (may provide clues as to colonization or infection with new specific pathogens or pathogens that may be resistant to certain antimicrobials)Previous hospitalization or healthcare utilization (also a key determinant in selecting therapy because the patient may be at risk for specific pathogens and/or resistant pathogen)Travel historySocial historyPet/animal exposureOccupational exposureEnvironmental exposurePhysical findingsFindings consistent with an infectious etiology will help identify the infection. Fever often accompanies infection and is defined as a rise in body temperature above the normal 37oC. Fever is a host response to bacterial toxins but may be caused by other factors such as fungal or viral infection, medications, trauma or other medical conditions.Vital signsBody system abnormalities (e.g. rales, altered mental status, localized inflammation, erythema, warmth, edema, pain and pus)Diagnostic imagingImaging studies also may help to identify anatomic localization of the infection. Performed along with other tests to establish or rule out the presence of an infectionRadiographs (x-rays)CT scans – type of x-ray that produces a three dimensional image of the combination of soft tissue, bone and blood vesselsMRI – use electromagnetic radio waves to produce two- or three-dimensional images of soft tissues and blood vessels with less detail of bony structures. MRI produce more detailed images of soft tissues and organs than CT scans whereas CT scans produce more detailed images of bones.Labeled leukocyte scansLaboratory studies Data from laboratory and diagnostic tests and procedures provide information regarding the response to drug therapy, ability of patients to metabolize and eliminate specific therapeutic agents, diagnosis of specific disease, and progression and regression of disease. Laboratory and diagnostic tests are considered either invasive or non-invasive. Invasive tests such as collection of blood (venipuncture) for determining a drug serum concentration and insertion of a central venous catheter for measuring cardiac output and pulmonary artery occlusion pressure involve penetration of the skin or use of instruments that pose some risk to the patient. The degree of risk varies from relatively minor risks such as pain, bleeding, and bruising (associated with venipuncture) to death (associated with more invasive procedures such as coronary angiography). Noninvasive tests such as the taking of chest x-ray films and collection of spontaneously voided urine are associated with minimal risk. The selection of specific tests and procedures depends on the patient’s underlying condition and the need for the information. For example, venipuncture may be considered too invasive and therefore unnecessary for patients with chronic, stable disease but an essential risk when initiating drug treatment in a patient with unstable disease. For a clinically oriented pharmacist to be able to follow the reasoning of the therapy directed at the patient, he must be conversant with laboratory tests, their values and interpretations. The ability to interpret and apply clinical laboratory data to drug therapy has become relevant with the new role of pharmacists. Laboratory investigations are monitored by pharmacists to assess the need for additional or alternative drug therapy, to assess the therapeutic and adverse effect of drugs, to prevent misinterpretation of tests as a result of drug interference, and determine the proper drug dose. The results of laboratory investigations fall within a predetermined range of values, which are referred, to as “normal.”Non-microbiologic laboratory studiesIn most cases, WBC count is elevated in response to infection, but it may be decreased owing to overwhelming or long-standing infection. The differential is the percentage of each type of WBCWhite blood cell count (WBC) with differentialErythrocyte sedimentation rate (ESR)C-reactive proteinType of CellNormal values (%)FunctionAbnormalitiesNeutrophilSegs 40-60Bands 3-5PhagocyticLeukocytosis Bacterial infectionsFungal infectionsPhysiologic stressTissue injuryMedications e.g. corticosteroidsLeukopaeniaLong standing infectionCancerMedications e.g. chemotherapyLymphocyte20 – 40T cells (cell mediated immunity)B cells (humoral antibody response)LymphocytosisViral infections e.g. mononucleosisTuberculosisFungal infections LymphopeniaHIVMonocyte2 – 8PhagocyticPrecursor to macrophagesMonocytosisTuberculosisProtozoal infectionsLeukemiaEosinophil1 – 4Antigen-antibody reactionsEosinophiliaHypersensitivity reactions, including medicationsParasitic infectionsBasophilLess than 1Hypersensitivity reactionsMicrobiologic studiesMicrobiologic studies that allow for direct examination of a specimen (e.g. sputum, blood, or urine) also may aid in a presumptive diagnosis and give an indication of the characteristics of the infecting organism. Generally, microbial cultures are obtained with a Gram stain of the cultured material. A poor specimen can give misleading information regarding the underlying pathogen and is a waste of laboratory personnel time and patient cost.Culture and susceptibility testing (MCS) Gram stainGeneral Approach to TreatmentWhile selection of antimicrobial therapy may be a major consideration in treating infectious diseases, it may not be the only therapeutic intervention. Other important therapies may include adequate hydration, ventilator support, and other supportive medications. In addition, antimicrobials are unlikely to be effective if the process or source that leads to the infection is not controlled. Source control refers to this process and may involve removal of prosthetic materials such as catheters and infected tissue or drainage of an abscess. Source control considerations should be a fundamental component of any infectious diseases treatment. It is also important to recognize that there may be many different antimicrobial regimens that may cure the patient. Factors to consider when selecting antimicrobial regimens can be broadly divided into two groups:Antimicrobial Considerations in Selecting TherapySpectrum of activity and Effects on non-targeted floraDosingSingle versus combination therapyAntimicrobial dosePharmacokinetic properties; Pharmacodynamic properties;Adverse-effect potentialDrug-interaction potential; CostPatient Considerations in Antimicrobial SelectionAnatomic location of infectionAntimicrobial historyDrug allergy historyRenal and hepatic functionConcomitant medicationsPregnancy or lactationCompliance potentialOrgan dysfunction that may affect drug clearance, immunosuppression, compliance and severity of illnessFailure of Antimicrobial TherapyWhile many infections respond readily to antimicrobials, some infections do not. A relatively common question when a patients’ condition fails to improve relates to whether the antimicrobial therapy has failed. Changing antimicrobials generally is one of the easiest interventions relative to other options. However, it is important to remember that antimicrobial therapy comprises only a portion of the overall disease treatment, and there may be many factors that contribute to a lack of improvement. In general, inadequate diagnosis resulting in poor initial antimicrobial or other drug selection, poor source control, or the development of a new infection with a resistant organism are relatively common causes of antimicrobial failure. An infection-related diagnosis may be difficult to establish and generally has two componentsDifferentiating infection from non-infection-related disease and Providing adequate empirical spectrum if the cause is infectiousFailure of improvement in a patients’ condition should warrant broadening the differential diagnosis to include non-infection-related causes as well as considering other potential infectious sources and/or pathogenic organisms. Another common cause of failure is poor source control. Less common but still frequent causes of failure include the development of secondary infections. In this case, the patient generally improves, but then develops a new infection caused by an antimicrobial resistant pathogen and relapses. The emergence of resistance to a targeted pathogen while on antimicrobial therapy can be associated with therapeutic failure but is usually limited to tuberculosis, pseudomonads or other gram negative enteric agents.PreventionKnowing the chain of infection is important for prevention. For examples techniques like hand washing, gowning and wearing face masks can help prevent infections from the surgeon to the patient or vice versa. Frequent hand washing remains the most important factors in preventing spread of non-wanted organisms. Nutrition has to be improved and changes in life style are indicated for some infectious agents - like avoiding overcrowding, use of illicit drugs, using a condom and entering an exercise program.Cooking foods well and avoiding eating foods which have been left outside for a long time is also important. Do not take antibiotics for longer than needed. Long term use of antibiotics leads to resistance and chances of developing opportunistic infections like clostridium difficile colitis. Prevention practices1. Get plenty of rest.Lack of sleep can weaken your immune system, making you more vulnerable to infections. A good night's sleep is between?six?to nine hours?a night. 2. Eat healthy foods.Your body has a better chance of fighting harmful bacteria if you eat regular meals of healthy foods, such as whole wheat breads, vegetables and fruits. 3. Wash your hands frequently.Washing your hands?removes bacteria. Clean thoroughly between the fingers and around the nails. 4. Brush your teeth and gums.Brushing your teeth and gums at least twice a day helps removes bacteria. Floss daily to remove the bacteria from between your teeth. Overview of Anti-Infective AgentsAntibacterial agents: These are used to treat infections with bacteria. They include:Aminoglycosides e.g. gentamycin, amikacin and streptomycinCarbapenems e.g. imipenem, ertapenem and meropenemCephalosporins e.g. cephalexin, cefuroxime and ceftazidimeErythromycins e.g. erythromycin ethylsuccinate, azithromycin and clarithromycinPenicillins e.g. Natural penicillins (penicillin G, Penicillin V), cloxacillin, amoxicillin and carbenicillinSulfonamides e.g. sulfadiazine, sulfamethoxazole and sulfisoxazoleTetracyclines e.g. Doxycycline, Minocycline and oxytetracyclineFluoroquinolones e.g. ciprofloxacin, levofloxacin and sparfloxacinUrinary tract antiseptics e.g. Cinoxacin, fosfomycin, nitrofurantoin and nalidixic acidMiscellaneous antibacterials e.g. atovaquone, clindamycin, mupirocin and trimethoprimBefore Starting Therapy with antibacterial agentsViral infections should not be treated with antibacterialsSamples should be taken for culture and sensitivity testing (MCS) as blind antibacterial therapy can lead to further difficulty in establishing the diagnosisKnowledge of prevalent organisms and their current sensitivity is of great help in choosing an antibacterial before bacteriological confirmation is availableThe dose of an antibacterial varies according to a number of factors including age, weight, renal function, and severity of infectionThe route of administration is often dependent on the severity of the infection. Life threatening infection requires intravenous therapyDuration of therapy depends on the nature of the infection and the response to treatment. Courses should not be unduly prolonged as this encourages resistance, may lead to side effects and are costlyAntifungal agents: Antifungal agents are broadly subdivided into two groups:Systemic agents: Used to treat systemic and local fungal (mycotic) agents. Most of these diseases resist treatment with antibacterial drugs.Examples are: Griseofulvin, nystatin, imidazoles, amphotericin B and caspofunginTopical agents: For topical use for fungal infectionsExamples are: Amphotericin B, nystatin, ketoconazole, butenafine, terbinafine and gentian violetAntiprotozoal agents: These drugs fall into two main categories: Antimalarial agents: Used to treat malaria infection and include chloroquine and hydroxychloroquine, primaquine, pyrimethamine, quinine and mefloquine;Amoebicides and trichomonacides: Used to treat amoebic and trichomonal infections. These include Diloxanide, emetine iodoquinolol, metronidazole, paromomycin and quinacrineAntitubercular agents: Drugs used to treat tuberculosis suppress or kill the slow growing mycobacteria that cause this disease. Antitubercular agents fall into two main categories – primary agents (including rifampicin, ethambutol, isoniazid and streptomycin) and retreatment agents (such as aminosalicylic acid, capreomycin, cycloserine, ethionamide and kanamycin). Because the causative organisms tend to develop resistance to any single drug, combination drug therapy is the standard in treating TB.Antiviral agents: These drugs treat viral infections by influencing viral replication. Because viruses lack independent metabolic activity and can replicate only within living host cells, antiviral agents tend to injure host as well as viral cells. Unlike antibacterial agents, few antiviral drugs have been introduced over the years; most are active against only one virus, either DNA or RNA viruses. Examples of antiviral active DNA viruses include acyclovir, amantadine, ribavirin, foscarnet and valganciclovir. Antiviral agents active against RNA viruses include: reverse transcriptase inhibitors (RTIs) Nucleoside RTIs - abacavir, stavudine, zidovudine, lamivudine; Non-nucleoside RTIs - efavirenz, delarvidine, nevirapine; Nucleotide RTIs - tenofovirprotease inhibitors - amprenavir, indinavir ritonavir and saquinavirfusion inhibitors - enfurvitideAnthelminthic agents: These drugs are used to rid the body of worms (helminths). These agents may act locally to rid the GI tract of worms or work systematically to eradicate worms that are invading organs or tissues. Examples of anthelminthics are mebendazole, albendazole diethylcarbamazine citrate, pyrantel, piperazine, oxaminiquine, quinacrine and praziquantel ................
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