Edward R.M. O'Brien, MD

• Professor of Medicine, Cardiology
• Research Chair, Canadian Institutes of Health Research/Medtronic
• University of Ottawa Heart Institute
• Ottawa, Ontario, Canada

The process has also emerged as a powerful gene silencing technique that is useful in research and development of therapeutics generic pregabalin 75mg online. The most commonly affected sites are the lungs cheap pregabalin 150mg fast delivery, lymphatic system generic pregabalin 150mg online, skin and eyes; the upper respiratory system safe 150mg pregabalin, liver, bone marrow, spleen among other organs can also be affected. See also Sepsis and Sepsis, Severe Seroconversion the development of detectable specific antibodies to a virus or other microorganism in the serum as a result of infection or immunization. Serology A blood test that detects the presence of antibodies to a particular antigen. Serotype the genotype of a unicellular organism that is defined by antisera against antigenic determinants expressed on the surface. It is characterized by fever and coughing or difficulty breathing or hypoxia and can be fatal. Single-Blind A research testing parameter in which patients do not know which of several treatments they are receiving, thus preventing personal bias from influencing their reactions and study results. Depending on their cytokine profile, they are divided into Th0, Th1, Th2 and Th3 subsets. Th0 Cells A T helper cell population from which Th1, Th2 and Th3 subsets are thought to develop. These cells are effective against intracellular pathogens such as viruses, bacteria and parasites. These cytokines enhance humoral responses by helping B cells in the production of different classes of immunoglobulins (Igs). Th2 cells are important in eliciting both antibody-mediated cytotoxicity against extracellular parasites and antibody responses against viral proteins. These cells may be partly responsible for the activity attributed to T suppressor (Ts) cells. Thrombocytopenia A condition characterized by a decrease in the number of platelets in the blood. It is an interferon-induced peptide expressed in hematopoietic cells and it regulates actin cytoskeleton by preventing G-actin polymerization. It is cleaved into seraspenide which inhibits the entry of hematopoietic pluripotent stem cells into the S-phase. An acquired drug tolerance is a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. They are the key recognition structures of the innate immune system that recognize molecules shared by pathogens but distinct from host molecules. Trachea the air passage responsible for conveying air to and from the lungs that extends from the larynx into the thorax, where it branches into the right and left main bronchi. The resulting transgenic animal expresses the protein(s) that the new gene(s) encodes. Activated factors induce the transcription of antiapoptotic, proliferative, immunomodulatory and inflammatory genes. It is also used to describe events that occur early on within sequential reactions. See also Downstream V Vaccine Any preparation intended for active immunological prophylaxis or therapy. Viral Envelope Proteins Layers of protein which surround the capsid in animal viruses with tubular nucleocapsids. The envelope consists of an inner layer of lipids and virus-specific proteins also called membrane or matrix proteins. The outer layer consists of one or more types of morphological subunits called peplomers which are glycoproteins and project from the viral envelope. Viral Shedding the expelling of virus particles from the body, one route for which is through the respiratory tract. Virus shedding is an important means of transmission, although evidence of virus shedding does not necessarily equate trasmmissibility. Virus A small infectious particle between 10 and 300 nm in diameter, not visible with a light microscope. Viruses have no cell structure and thus differ from other infectious agents or cells. They are obligate parasites and need to enter a plant or animal cell in order to reproduce. Also the parent strain of a virus, bacteria, mouse, or other laboratory organism that are found in the wild. It is an estimate of the average years a person would have lived if he or she had not died prematurely and therefore can it indicate the impact of various diseases and other lethal factors on a population. Responding to the epidemic of severe acute respiratory syndrome 2003 348(20):1967 Identification of a novel coronavirus in patients with severe acute respiratory syndrome 77 2003 348(20):1995 Identification of severe acute respiratory syndrome in Canada Poutanen, S. By supporting data-driven decisions, Cortellis helps pharmaceutical companies, biotech and medical device/diagnostic firms accelerate innovation. Republication or redistribution of Clarivate Analytics content, including by framing or similar means, is prohibited without the prior written consent of Clarivate Analytics. Cortellis and its logo, as well as all other trademarks used herein are trademarks of their respective owners and used under license. Lung Development Jamie Havrilak, PhD Postdoctoral Research Associate Layden Lab October 28th, 2015 hDp://depts. Nicholas Hartsoeker 1694 Homunculus Each of the germ layers gives rise to many different cell types Developmental Biology, 9e, Figure 1. Gene regulatory network governing respiratory specificaon Rankin and Zorn, 2015, J. Published by the Company of Biologists Ltd Go through many different stages before it can become a lung cell Rankin and Zorn, 2015, J. Lung Morphogenesis and Differenaon 40 Cell Types Need to Orchestrate Proper: Place Time Cell Types Cell Numbers Size Funcon Repair Regulaon of Processes: Commitment Specificaon Restricon Differenaon Proliferaon Maturaon PaDerning How do we make a lung in a dish? MaB Kofron Mike MunEfering Kyle McCracken (Wells Lab) Kristen Melton (Flk-1mut mice). The source of the fluid varies, as does the treatment (dependent on the etiology). Edema, as always, is favored by an increased capillary hydrostatic pressure, a decreased capillary oncotic pressure, or an increased vascular permeability. Hemodynamic Pulmonary Edema = "Forcing Fluid Out" Dependent on an increased hydrostatic pressure (most commonly Left Sided heart Failure) Basal Regions develop edema first (dependent edema) b/c pressure greatest in dependent areas Alveolar Macrophages have hemosiderin in them, called siderophages or heart failure cells Fibrosis and thickening of the affected areas results in a gross brown and firm appearance, called brown induration. This is the type of edema we talked about in cardiovascular block 1 O w l C l u b R e v i e w S h e e t s Pathology Pulmonary Microvascular Injury Pulmonary Edema = "Leaky Capillaries" Dependent on an increased capillary permeability; the second most common form of edema Increased capillary permeability is a result of microvascular injury o Most commonly associated with pneumonia (localized edema) o Also caused by inhaled gases (O2, Smoke) Liquid Aspiration (neardrowning) or Trauma o Remember pharm link to Bleomycin and Amphoterecin B. Edema begins in the vascular endothelium then moves into the alveoli When local, the underlying cause overshadows the edema; when diffuse it is life threatening Acute Respiratory Distress Syndrome the extreme case of microvascular injury pulmonary edema. It is a serious, lifethreatening disorder that correlates to an extreme microvascular injury that is both diffuse and abundant. Anything that causes microvascular injury pulmonary edema can lead to this pathological state. He has a barrelchest, is pink (normal), breathing through pursed lips, and has wheezing. These symptoms are usually associated with widespread but variable bronchoconstriction and airflow limitation that is at least partly reversible, either spontaneously or with treatment. This predisposes to infection because eosinophilia (which destroy the wall there is no mucociliary escalator themselves) Cystic Fibrosis Morphology o Gross Lower Lobes Bilaterally (dependent regions) unless caused by a focal obstruction (tumor or foreign body aspiration) in which case there are focal lesions Airways are dilated sometimes up to 4x normal size which can be traced to the pleural surface, where, on dissection, they look like cysts filled with pus o Histo Acute = inflammatory exudate associated with desquamination of the epithelium or even ulcerations Chronic = pseudostratification and sqaumous metaplasia, almost always with fibrosis Organisms can be cultured at any phase, often H. Case 1: 4 month old African American infant with a low grade fever and wheezing for 2 days (thinking upper respiratory tract infection). It had a term birth without perinatal problems and all the immunizations are covered. Its vitals look scary (160 bpm for the heart rate, 60 on the respiratory rate) but since this baby is the side of your forearm, the vitals are only a little fast (normal 120 hr, 30 rr). The chest Xray reveals hyperinflation without focal infiltrates and the diagnosis of bronchiolitis, a viral infection of small airways, is made. Bronchiolitis Epidemiology o Effects children less than 2 years of age usually occurring in colder months (OctMar) o Spread by large particle/selfinoculation ­ wash your hands! This indicates air trapping Blood Vessel Alveoli Airway is full of cellular debris with inflammatory exudate Reminder: Causes of Hypoxemia are listed on slide 11. Pathogenesis o There is a general lack of alveoli or decreased surfactant that results in collapsed peripheral airspaces. Surface tension increases, making it harder to expand the alveoli with each breath No black = No air = Uhoh!

Syndromes

• Family history of the disease
• Pregnancy (hormonal changes increase the sensitivity of the gums)
• Natural supplements
• Rash or hives
• Thrombotic thromocytic purpura (TTP)
• Kidney damage from the dye

Massage parotid gland for 30 seconds and then swab parotid (Stensen) duct using a viral culture transport swab cheap pregabalin 150 mg fast delivery. Acute rubella infection can be serologically confirmed by documenting seroconversion to IgM and/or IgG positivity or a 4-fold rise in antirubella IgG titers between acute and convalescent serum specimens discount 150mg pregabalin. As with measles and mumps serologic assays buy pregabalin 75 mg fast delivery, however purchase pregabalin 150mg otc, assays providing quantitative titers for antibodies to rubella are not commonly offered at local or reference laboratories. Only approximately 50% of patients are positive for IgM antibodies to rubella at the time of rash onset, which emphasizes the importance of collecting a convalescent sample. Acute phase serum should be collected upon patient presentation and again 14­21 days (minimum of 7) days later. Due to the rarity of rubella in the United States and thus the low pretest probability of infection, serologic evaluation should only be performed in patients with appropriate exposure risks and a clinical presentation highly suggestive of acute rubella; in patients not meeting these criteria, positive rubella IgM results should be interpreted with caution as they may be falsely positive. Congenital rubella syndrome can be diagnosed by the presence of IgM-class antibodies to rubella in a neonate, alongside symptoms consistent with congenital rubella syndrome, appropriate exposure history of the mother, and lack of maternal protective immunity. Therefore, if used as a screening test, only high levels (ie, above a laboratory-established threshold that correlates with disease) should be considered significant. Though viral isolation is possible during this timeframe, it is not routinely performed in clinical laboratories [278]. However, such infection in developed countries may be encountered in return travelers (acute hepatitis E) or organ transplant recipients (acute or chronic) [280]. In acute infection, its appearance predates clinical symptoms by 4 weeks and it remains detectable for 1­6 weeks. The tests for detecting hepatitis B and D disease are primarily serologic and molecular (Table 62). Antibody may not be detectable until 6­10 weeks after the onset of clinical illness. Signal-to-cutoff ratios (calculated by dividing the optical density value of the sample tested by the optical density value of the assay cutoff for that run) are an alternative to supplemental testing. Plasma or serum is useful for diagnosis of sepsis syndrome in a newborn due to enterovirus, but testing is less reliable beyond the newborn period. Serologic evaluation for enteroviruses requires assessment of acute and convalescent titers, due to the high seroprevalence in the population. Therefore, serology is typically not useful in clinical practice, with the exception of determining whether a patient with myocarditis has had exposure to enteroviruses (eg, Coxsackie B virus). Respiratory Syncytial Virus Rapid diagnosis of influenza virus infection (48 hours following the onset of symptoms) is needed to facilitate early administration of antiviral therapy. During seasons of low prevalence of influenza, false-positive tests are more likely to occur when using rapid antigen tests. Influenza virus can be recovered in routine viral cell culture, but confirmation is needed, typically through the use of hemadsorption and/or hemagglutination techniques. Serologic testing is not useful for the routine diagnosis of influenza due to high rates of vaccination and/or prior exposure. Viral culture, while possible, is insensitive and not routinely offered at local or reference laboratories. Adenovirus In otherwise healthy individuals, adenoviruses may cause mild, self-limiting respiratory illness or conjunctivitis, with most cases being diagnosed on clinical grounds. Occasionally, adenovirus infections in immunocompetent hosts can result in death, especially in children with asthma. In immunocompromised patients, adenoviruses may cause pneumonia, disseminated infection, gastroenteritis, hemorrhagic cystitis, meningoencephalitis, or hepatitis. Viral culture has a long turnaround time (~5 to 7 days), but this can be reduced by using shell vial technology. Postmortem histopathology of brain biopsies in patients with rabies are notable for mononuclear infiltration, perivascular cuffing of lymphocytes, lymphocytic foci, and Negri bodies. Serologic testing may be used to document postvaccination seroconversion, if there is significant deviation from a prophylaxis schedule. In children, the viruses have also caused exacerbation of asthma and otitis media. Human Coronavirus Parainfluenza viruses are a major cause of croup (laryngotracheobronchitis), bronchiolitis, and pneumonia as well as upper respiratory tract infections. Of the 4 antigenically distinct types, types 1 and 2 are most commonly associated with croup syndrome, while type 3 is associated most commonly with bronchiolitis and pneumonia. Parainfluenza virus infections account for up to 11% of all hospitalizations in children <5 years old [285]. Human Metapneumovirus the coronaviruses are host specific and can infect a variety of animals as well as humans. Four distinct genera have been described with human pathogens belonging to the genera Table 68. The virus has been associated with cases of bronchiolitis in infants as well as pneumonia, exacerbations of asthma and croup, and upper respiratory infections with concomitant otitis media in children. Some parasitic infections are associated with high morbidity and mortality (eg, malaria, amebic encephalitis), whereas others cause only mild or asymptomatic disease (eg, filariasis due to Mansonella spp, toxoplasmosis in immunocompetent adults). As expected, the most commonly submitted specimens for laboratory identification of these parasites are whole blood, tissue aspirates/biopsies, and serum for serologic studies. Microscopy remains the cornerstone of laboratory testing for the identification of most blood parasites and many tissue parasites [289­291]. Expert microscopic examination of Giemsastained thick and thin peripheral blood films is used for detection and identification of the protozoan blood parasites Plasmodium, Babesia, and Trypanosoma, and the filarial nematodes Brugia, Table 71. Although requiring a minimal amount of reagents and equipment, the accuracy of microscopic methods requires well-trained and experienced technologists. Even in the best hands, diagnosis may be hampered by sparseness of organisms on the slide and the subjective nature of differentiating similar-appearing organisms (Plasmodium vs Babesia; various microfilariae) or in identifying the species of Plasmodium present. The laboratory can enhance the sensitivity of these methods by employing a number of concentration procedures such as buffy coat examination, centrifugation, and filtration. In all of these procedures, samples must be properly obtained, transported to the laboratory as quickly as possible, and processed in a timely fashion to preserve organism viability and/or morphology. Organism viability and morphology may be adversely affected by a number of different factors including temperature, humidity, and exposure to fixatives or anticoagulants. Transportation requirements are described for each organism in the corresponding sections below. Serologic assays for detection of antibodies are available as adjunctive methods for the diagnosis of a number of blood and tissue parasite infections. Unfortunately, none are sensitive or specific enough to be used to establish the diagnosis on their own. In particular, assays for infection with one helminth will often cross-react with antibodies to a different helminth [290]. When available, antibody titers may be used to determine the strength of the immune response or detect a trend in antibody levels over time. Thus, clinicians will not be able to determine if a positive result was a very strong positive or a very weak one without calling the laboratory for more information. This can have important implications for interpretation of results that are not entirely consistent with the clinical picture. Laboratory methods that detect parasite antigens and/or nucleic acid provide an attractive alternative to traditional morphologic and serologic techniques. Clinicians should consult their microbiology laboratory to determine if their reference laboratory or other entity offers the desired testing. Molecular assays may be of particular use in patients with very low parasitemias or in specifically identifying organisms that cannot be differentiated microscopically. In addition, the current restriction to the reference laboratory setting means that the time from specimen collection to receipt of result may be longer than desired for optimal patient care. In situations where infection is potentially life-threatening, initial testing should be performed locally and empiric treatment should be considered while awaiting results from the outside laboratory. Key points for the laboratory diagnosis of blood and tissue parasites: · Microscopy is the cornerstone of laboratory identification but is highly subjective and dependent on technologist experience and training. Table 72 presents an inclusive overview of the approach to the diagnosis of blood and tissue parasitic infections based on published recommendations [288­290].

Although it accounts for less than 5 per cent of skin malignancy order pregabalin 75 mg amex, it is responsible for over 75 per cent of deaths caused by skin malignancy discount pregabalin 75 mg overnight delivery. A Infection (ventriculitis) B Blockage of the proximal catheter C Breakage of the distal catheter D Intraventricular haemorrhage E Seizures pregabalin 75mg on line. A Seizures B Focal neurological deficits C Endocrine dysfunction D Intracranial bleeds E Visual loss buy discount pregabalin 150mg on line. A Memory dysfunction B Contralateral superior quadrantanopia C Ipsilateral hemiparesis D Dysphasia E Blindness in the ipsilateral eye. A Gradual onset of severe headache B Neck pain and stiffness C Third nerve palsy D Photophobia E Purpuric rash 23. D the 10-year recurrence rate after complete resection is approximately 10 per cent. C the risk of rebleeding is greater if aneurysms are present on the feeding vessels. B It can be caused by vascular compression of the 5th cranial nerve near its root entry zone. D Patients often wake with pain and paraesthesiae in the thumb, index and middle fingers. A, C, D Intracranial pressure in a normal adult varies between 5 and 15 mmHg at rest. A, B, C, D Cerebral oedema is an increase in brain water and can be cytotoxic or vasogenic. A, D the brain is dependent on glucose and oxygen for its energy and does not have large stores of either. The brain cannot switch to anaerobic metabolism and brain function will cease if brain blood flow falls below 20 per cent of normal. After 48 h of starvation, the brain can switch to using ketone bodies as an energy source. The 6th nerve has a long intracranial course and is prone to stretch with brain shifts or hydrocephalus. In infants, the presenting features may be increasing head circumference, bulging fontanelle, sunsetting eyes, irritability, vomiting and failure to thrive. A, B, C, E Cerebrospinal fluid is made by the choroid plexus of the lateral, third and fourth ventricles and by diffusion of extracellular fluid from the brain. Obstructive hydrocephalus is caused by, for example, tumours blocking the foramen of Monro, cerebral aqueduct or fourth ventricle. Meningitis often causes adhesions at the base of the brain in the basal cisterns and therefore causes communicating hydrocephalus. Encephalitis is an infection or inflammation of the brain and is not usually a cause of hydrocephalus. The proximal catheter which lies in the ventricle is the commonest site of shunt blockage. There is a 1 per cent risk of causing intraventricular haemorrhage during shunt insertion. The shunt valve can stop working or become blocked with debris or red blood cells. A, B, C, D, E Cerebral abscesses can be caused by direct spread from an infected sinus (frontal or mastoid) or by blood-borne spread. Severe tooth decay or gum disease can also be a source of organisms in the bloodstream. Patients with left-to-right shunts in the heart are at increased risk, as blood will bypass the lungs which mop up a lot of organisms. It appears to have spread from cows infected with bovine spongiform encephalitis which then entered the food chain. Some tumours have a propensity to bleed and may present as a life-threatening intracerebral bleed. Visual loss can be caused by the tumour itself or present secondary to raised pressure and papilloedema. Dominant parietal lobe lesions cause left­right disorientation, finger agnosia, acalculia and agraphia. The foot part of the motor cortex is in the posterior frontal cortex on the upper medial side next to the falx. A, B, D the temporal lobe structures are very involved in memory, speech and hearing. The temporal lobe is closely applied to the posterior frontal lobe at the Sylvian fissure, which carries the middle cerebral artery. Part of the optic radiation passes around the temporal lobe and can be affected by temporal lobe lesions. Temporal lobe lesions would not cause blindness in the ipsilateral eye or an ipsilateral hemiparesis ­ the motor cortex is in the posterior frontal lobe but supplies the contralateral limbs. Nonsecreting tumours tend to be larger at presentation and often present with visual failure. Pressure on the normal pituitary gland will cause loss of normal secretion and hypopituitarism. A pituitary tumour will grow out of the pituitary fossa and compress the optic nerve or chiasm from below. Other types of glioma include oligodendroglioma (cell of origin is the oligodendrocyte) and ependymoma. These tumours are diffuse infiltrative tumours and it is difficult to completely excise them. They are radiosensitive tumours but complete excision is often possible in the posterior fossa and is the treatment of choice. A, B, D, E Meningiomas are usually benign tumours; 80 per cent are found supratentorially. They can cause vasogenic brain oedema and seizures as well as focal neurological deficits. They are often slow-growing but a small proportion show atypical features on microscopy. If a meningioma is completely excised, the recurrence rate is approximately 10 per cent unless a wide margin of associated dura can also be excised. A, B, C, D, E the commonest primary tumour that gives rise to cerebral metastases is bronchogenic carcinoma, closely followed by breast cancer. Risk factors are hypertension, cocaine abuse and fibromuscular dysplasia, which leads to weakness of blood vessel walls and predisposes to aneurysm formation. B, C, D the presenting features are typically severe, sudden, headache associated with nausea and vomiting, neck stiffness and photophobia. The features need to be distinguished from meningitis (headache comes on more slowly, with rash and fever often present). A posterior communicating aneurysm may present with a painful third nerve palsy with the pupil being affected before eye movements. This is due to rapid expansion of the aneurysm, causing it to press on the third cranial nerve. They can be treated by surgery, endovascular techniques or stereotactic radiotherapy. Focal abnormalities such as cortical dysplasias and low-grade tumours can be good surgical targets. It can be caused by multiple sclerosis but in many cases a vascular loop can be seen in contact with the 5th nerve, close to its root entry zone. A, C, D, E Carpal tunnel syndrome is caused by compression of the median nerve at the wrist. Patients typically wake at night with pain and paraesthesia in the thumb, index and middle fingers. How should a recent-onset suspected basal cell carcinoma of the eyelid skin be treated? A Photograph and clinical follow-up B Liquid nitrogen cryotherapy C Curettage D Excision biopsy E Radiotherapy. A Through the nasolacrimal duct B Through the lacrimal duct C Through the 10­15 lacrimal gland ducts D Through the meibomian orifices E Through the ducts of Moll. What is a potential route of spread of infection from the eyelid skin to the intracranial cavity? A Orbital lymphatics B Ophthalmic veins C Subperiosteal potential spaces D Facial artery E Perineura of branches of the trigeminal nerve. What is the typical cause of acute infection of the tear sac (acute dacryocystitis)?

Use mainly for isolation of fungi discount 150 mg pregabalin visa, Mycobacterium discount 75mg pregabalin with visa, or other fastidious aerobes and for elimination of antibiotics from cultured blood in which organisms are concentrated by centrifugation purchase pregabalin 75mg. Stool Stool for routine culture; stool for Salmonella generic 150 mg pregabalin otc, Shigella, and Campylobacter Stool for Yersinia, Escherichia coli O157 Stool for Aeromonas and Plesiomonas Rectal swab or (preferably) fresh, randomly collected stool Fresh, randomly collected stool Fresh, randomly collected stool 1 g of stool or 2 rectal swabs Plastic-coated cardboard cup or plastic cup with tightfitting lid. Plastic-coated cardboard cup or plastic cup with tight-fitting lid Plastic-coated cardboard cup or plastic cup with tight-fitting lid If Vibrio spp. Limitations: Stool should not be cultured for these organisms unless also cultured for other enteric pathogens. Specimen may be left in syringe used for collection if the syringe is capped before transport. Biopsy and aspirated materials Wounds Tissue removed at surgery, bone, anticoagulated bone marrow, biopsy samples, or other specimens from normally sterile areas Purulent material or abscess contents obtained from wound or abscess without contamination by normal microflora 1 mL of fluid or a 1-g piece of tissue 2 swabs or 0. Culturette swab or similar transport system or sterile tube with tight-fitting screw cap. For simultaneous anaerobic cultures, send specimen in anaerobic transport device or closed syringe. Enough tissue should be collected for both microbiologic and histopathologic evaluations. Collection: Abscess contents or other fluids should be collected in a syringe (rather than with a swab) when possible to provide an adequate sample volume and an anaerobic environment. Special Recommendations 417 Fungi Mycobacterium (acid-fast bacilli) Specimen types listed above may be used. When urine or sputum is cultured for fungi, a first morning specimen is usually preferred. Sputum, tissue, urine, body fluids 1 mL or as specified above for individual listing of specimens. Sterile, leak-proof container with tight-fitting cap Sterile container with tightfitting cap Collection: Specimen should be transported to microbiology laboratory within 1 h of collection. Contamination with normal flora from skin, rectum, vaginal tract, or other body surfaces should be avoided. Smears and cultures of pleural, peritoneal, and pericardial fluids often have low yields. Aspirated specimens from abscesses or body fluids Respiratory secretions, wash aspirates from respiratory tract, nasal swabs, blood samples (including buffy coats), vaginal and rectal swabs, swab specimens from suspicious skin lesions, stool samples (in some cases) Type of Culture (Synonyms) Legionella Minimum Volume 1 mL of fluid; any size tissue sample, although a 0. Plasma samples and buffy coats in sterile collection tubes should be kept at 4­8°C. If specimens are to be shipped or kept for a long time, freezing at ­80°C is usually adequate. Virusesf Specimens cultured for obligate anaerobes should be cultured for facultative bacteria as well. Most samples for culture are transported in holding medium containing antibiotics to prevent bacterial overgrowth and viral inactivation. Many specimens should be kept cool but not frozen, provided they are transported promptly to the laboratory. Procedures and transport media vary with the agent to be cultured and the duration of transport. This informa- tion determines the selection of culture media and the length of culture time. For children, from whom only limited volumes of blood can be obtained, only an aerobic culture should be done unless there is specific concern about anaerobic sepsis. Special considerations: There is no more important clinical microbiology test than the detection of blood-borne pathogens. Bacteria may be present in blood either continuously (as in endocarditis, overwhelming sepsis, and the early stages of salmonellosis and brucellosis) or intermittently (as in most other bacterial infections, in which bacteria are shed into the blood on a sporadic basis). Most blood culture systems employ two separate bottles containing broth medium: one that is vented in the laboratory for the growth of facultative and aerobic organisms and a second that is maintained under anaerobic conditions. In cases of suspected continuous bacteremia/fungemia, two or three samples should be drawn before the start of therapy, with additional sets obtained if fastidious organisms are thought to be involved. For intermittent bacteremia, two or three samples should be obtained at least 1 h apart during the first 24 h. Aerobic culture of the throat ("routine") includes screening for and identification of -hemolytic Streptococcus spp. Although considered components of the normal microflora, organisms such as Staphylococcus aureus, Haemophilus influenzae, and Streptococcus pneumoniae will be identified by most laboratories, if requested. When Neisseria gonorrhoeae or Corynebacterium diphtheriae is suspected, a special culture request is recommended. Neither indwelling catheter tips nor urine from the bag of a catheterized pt should be cultured. Contamination of specimens with normal microflora from the skin, rectum, vaginal vault, or another body site should be avoided. Collection containers for aerobic culture (such as dry swabs) and inappropriate specimens (such as refrigerated samples; expectorated sputum; stool; gastric aspirates; and vaginal, throat, nose, and rectal swabs) should be rejected as unsuitable. Feces should be collected in a clean cardboard container, with the time of collection recorded. Fecal samples should be collected before the ingestion of barium or other contrast agents and before treatment with antidiarrheal agents or antacids; these substances alter fecal consistency and interfere with microscopic detection of parasites. The collection of three samples on alternate days is recommended because of the cyclic shedding of most parasites in the feces. Microscopic examination is not complete until direct wet mounts have been evaluated and concentration techniques as well as permanent stains applied. Sampling of duodenal contents may be needed to detect Giardia lamblia, Cryptosporidium, and Strongyloides larvae. The laboratory procedures for detection of parasites in other body fluids are similar to those used in the examination of feces. The parasites most commonly detected in Giemsa-stained blood smears are the plasmodia, microfilariae, and African trypanosomes; however, wet mounts may be more sensitive for microfilariae and African trypanosomes. Diagnosis of malaria and distinctions among Plasmodium species are made by microscopic examination of thick and thin blood films. Bacterial autolysins (cell-wall recycling enzymes) contribute to cell lysis in the presence of these agents. Aminoglycosides Macrolides (erythromycin, clarithromycin, azithromycin), ketolides (telithromycin), and lincosamides (clindamycin) Streptogramins [quinupristin/dalfopristin (Synercid)] Oxazolidinone (linezolid) Tetracyclines (tetracycline, doxycycline, minocycline) and glycylcyclines (tigecycline) · Inhibition of bacterial metabolism: Drugs interfere with bacterial folic acid synthesis. The major mechanisms of resistance used by bacteria are drug inactivation, alteration or overproduction of the antibacterial target, acquisition of a new drug-insensitive target, decreased permeability to the agent, failure to convert an inactive prodrug to its active derivative, and active efflux of the agent. The mode of excretion is important in adjusting dosage if elimination is impaired. Although combination chemotherapy usually is not indicated, it is used for certain purposes: To prevent emergence of resistance For synergistic or additive activity For therapy directed against multiple potential pathogens · Choose a therapeutic agent on the basis of: Pharmacologic data Adverse reaction profile Site of infection. Evidence-based practice guidelines for most infections are available from the Infectious Diseases Society of America ( The most clinically relevant adverse reactions to common antibacterial drugs are listed below. Nonallergic skin reactions: Ampicillin "rash" is common among pts with Epstein-Barr virus infection. The rates are consistent with those reported by the National Nosocomial Infections Surveillance System (Am J Infect Control 32:470, 2004). Efforts to lower infection risks have been challenged by the growing numbers of immunocompromised pts, antibiotic-resistant bacteria, fungal and viral superinfections, and invasive procedures and devices. Hospital infection-control programs focus primarily on infections associated with the greatest morbidity or the highest costs. Other measures include identifying and eradicating reservoirs of infection and minimizing use of invasive procedures and catheters. Standard precautions are used for all pts when there is a potential for contact with blood, other body fluids, nonintact skin, or mucous membranes. Hand hygiene and use of gloves are central components of standard precautions; in certain cases, masks, eye protection, and gowns are used as well. Transmission-based guidelines: Airborne precautions, droplet precautions, and contact precautions are used to prevent transmission of disease from infected pts.

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