Armando Diego Bedoya, MD

• Medical Instructor in the Department of Medicine

https://medicine.duke.edu/faculty/armando-diego-bedoya-md

Importantly antifungal yeast purchase 100 mg diflucan fast delivery, these enzymes are not liver specific anti fungal liquid cheap 100 mg diflucan visa, which means that the clinician must bear in mind other organ origins antifungal medications for nails order diflucan visa. Liver abnormalities in autoimmune diseases consist usually in mild elevations of liver transaminases or cholestasis antifungal horse shampoo safe 150 mg diflucan. The recommended frequency of hepatic monitoring is dependent on the particular pharmacological intervention being used fungus allergy buy discount diflucan 400mg line. However fungal ear drops purchase diflucan on line, a baseline assessment is generally recommended before initiating any of the drugs mentioned above. In addition to drug effects, other conditions that must be ruled out are concomitant viral hepatitis and alcohol abuse. After excluding these common causes of raised liver enzymes, the differentials are between a concomitant specific liver disease and the systemic disease itself with liver involvement. The most important immunemediated diseases that primarily affect the liver are primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis. The most commonly measured markers are serum alkaline phosphatase activity and serum calcium and phosphate concentrations. Severe cases of osteomalacia are associated with hypocalcaemia, hypophosphataemia and increased alkaline phosphatase activity. Parathyroid hormone levels may be high, while vitamin D levels are usually low with this condition. Biochemical markers of cartilage and bone turnover consist of either collagen breakdown products (crosslinked collagen derivatives, pyridinoline, deoxypyridinoline and Ntelopeptides) or noncollagenous matrix proteins and osteoclastspecific enzymes, respectively. Other biochemical tests Patients with chronic inflammatory diseases such as rheumatoid arthritis and lupus are predisposed to atherosclerosis independently of other risk factors. These patients should be screened for modifiable conditions such as diabetes, and dyslipidemia, which may confer increased atherosclerotic risk. Renal function Abnormal renal function may be a component of a rheumatic disease or a consequence of treatment. Non steroidal antiinflammatory drugs are often implicated in renal dysfunction and may necessitate discontinuation of therapy. Dose reduction of renally excreted immune suppressants such as methotrexate may be required in the presence of renal impairment. Similarly, a dose reduction in allopurinol, a uratelowering drug used in the management of gout, is required in the presence of renal impairment. Measurement of plasma creatinine concentration is widely used as a test of renal function. However, it is not sensitive and requires a substantial loss of glomerular function before beginning to rise. The blood urea concentration is also an insensitive marker of renal function and is influenced by factors that include the rate of protein metabolism, adsorption of blood from the enteric tract, fluid balance and steroid use. Patients with glomerulonephritis accompanying autoimmune rheumatic diseases will have active urinary sediment with protein and/or blood on dipstick testing and red cells and granular or cellular casts on light microscopy. Twentyfour hour urine collection, once thought to be the gold standard for quantification of proteinuria and to assess creatinine clearance, is now being replaced by a spot urine protein:creatinine ratio test, given its reliability and ease of determination. Serial estimations of urinary protein excretion are helpful to monitor treatment in rheumatological patients with renal involvement. Immunological tests Autoantibodies Autoantibodies are immunoglobulins that bind to self antigens. Virtually every molecule in the body can be an antigen and drive an autoimmune response, if the normal mechanisms of selftolerance fail. Low concentrations of autoantibodies are present in the plasma of many normal individuals and have a higher prevalence in the normal elderly population. Autoantibodies may in some healthy people be anticipatory, that is, they may be found in the serum for months or years before the relevant disease manifests clinically. These antibodies are overexpressed in autoimmune conditions, and can also be involved in pathogenic mechanisms. Relatives of patients with rheumatic diseases may show positivity for autoantibodies, reflecting a genetic tendency to autoimmunity; these antibodies are usually not organ specific. A titre of greater than 1:80 is usually considered positive, although autoimmune disease is generally associated with higher titres (>1:320). It occurs at significant titre in approximately 5% of the healthy population, and at low titre in up to 20% (more common in women and the elderly). In infectious diseases, the test tends to be positive only transiently, but in the right clinical context, a positive test is strongly suggestive of an autoimmune rheumatic disease. The pattern of immunofluorescence varies according to which nuclear or cytoplasmic antigens are recognized (Table 25. These antibodies are monitored in lupus patients, as they may reflect disease activity, and a rising titre may be predictive of a flare, especially if associated with a falling C3 level. These antibodies are predominantly of the IgM subtype and are rarely associated with a lupuslike syndrome. They were initially detected by counterimmunoelectrophoresis, a technique in which serum is tested against a saline extract of mammalian nuclei and compared with reference sera to determine a line of precipitation. Thus, falsepositive results for syphilis can occur in the presence of antiphospholipid antibodies. This test is of limited diagnostic value for the detection of antiphospholipid antibodies. Apart from thrombotic phenomena (both arterial and venous), this syndrome is characterized by recurrent fetal loss, thrombocytopenia and various neurological disorders. One of the subtypes in particular (IgG4) is associated with a specific disease pattern (IgG4related disease). Although the lupus anticoagulant is associated with thrombotic episodes in vivo, paradoxically the in vitro test relies on prolongation of the activated partial thromboplastin time. This is thought to be due to the interaction with the phospholipid portion of the prothrombin activator complex of the clotting cascade. When normal plasma is added to patient plasma, clotting factors are replenished and a clotting factor deficiencyrelated clotting prolongation will be corrected. However, if antiphospholipid antibodies are the cause of an abnormal test result, the clotting time will not correct. An excess of phospholipids may be added in the form of platelets, which should then correct the clotting prolongation. Microbiology the differential diagnosis in any acute monoarthropathy must include septic arthritis. This is easily excluded by joint aspiration, with culture of synovial fluid and blood. It is necessary to inform the laboratory if tuberculosis or gonococcal infections are suspected, as specific culture media and techniques are required. Acute rheumatic fever, which is rare in the Western world, is associated with streptococcal infection. The seronegative spondyloarthropathies may be related temporally to a diarrhoeal illness or to urethritis. Organisms often implicated in these diseases include Salmonella, Yersinia, Campylobacter and Chlamydia. Parvovirus B19 has been associated with a selflimiting polyarthritis similar to rheumatoid arthritis. Other viruses such as rubella and human Tlymphotropic virus may present with an arthralgia. Lyme disease is associated with a rash and polyarthropathy and the diagnosis depends on demonstration of antibodies to the spirochaete Borrelia burgdorferi. Complement Proteins of the complement cascade play a central role in cell lysis, opsonization of bacteria and clearance of immune complexes. Genetic associations Most rheumatic disorders are polygenic, and analysis of genetic markers is of limited value. A thorough clinical assessment with appropriate haematological, biochemical, immunological and radiological investigations should lead to a definitive diagnosis. It is relatively safe and provides information on a broad range of different conditions affecting bones and joints. Osteoarthritis is an extremely common degenerative disorder of the joints, and is a major cause of morbidity worldwide. Its incidence increases with age, but is also influenced by a number of genetic, metabolic and occupational factors. Eventually, bone remodelling and attrition result in flattening or deformities of the articular bone surfaces. Radioopaque loose bodies may also be seen and are a relatively common finding on plain radiographs of the knee. They represent fragments of cartilage or bone which have broken free within the joint. Chondrocalcinosis is the radiological finding of calcific deposits within cartilage, usually in older patients. However, it can also be an incidental finding and is not necessarily of clinical significance. If not adequately treated, it can be highly erosive and lead to significant joint damage and deformity. Ankylosis (fusion) of the joints may occur, most characteristically at the carpal bones. The degenerative changes are most marked in the interphalangeal joints, first metacarpophalangeal and scaphotrapezoid joints. The most common patterns are radial deviation of the hand at the carpometacarpal joints and ulnar deviation of the fingers at the metacarpophalangeal joints. Patients with suspected rheumatoid arthritis should undergo plain radiographs of both hands and both feet. The films of the feet are essential, even in patients who do not complain of foot symptoms. This is because the earliest erosive changes often occur in the joints of the feet (most commonly at the fifth metatarsophalangeal joint) and early inflammation may be subclinical. It is likely that there will continue to be a small number of patients in whom this cannot be avoided, due to severe disease phenotype or medications being either contraindicated or poorly tolerated. The radiographic features of psoriatic arthritis are similar to those of rheumatoid arthritis, and in some cases the two diseases can be difficult to distinguish. Arthritis mutilans is a rare but highly destructive small joint arthropathy which can occur in either rheumatoid or psoriatic arthritis. The most classic site for these changes is the first metatarsophalangeal joint (usually in patients who have suffered recurrent episodes of podagra) but gout can occur in any peripheral joint. Plain radiography is also useful in the diagnosis of axial spondylarthropathy (ankylosing spondylitis and related disorders). Axial inflammation often (but not always) starts at the base of the spine and progressively ascends. For this reason, patients are usually assessed initially via plain radiographs of the Box 26. Vertebral squaring is seen on lateral views of the spine and is the earliest abnormality, caused by erosions at the corners of the vertebral bodies. In more advanced disease, there is ossification of the longitudinal ligaments and the outer fibres of the intervertebral discs, resulting in the formation of syndesmophytes. Eventually, this process of progressive fusion (ankylosis) spreads to involve the entire spine. It is not suitable for areas obscured by bone, such as the spine or the full articular surface of a joint. This has been shown to correlate with disease activity and the future risk of bone damage and flare of symptoms. Ultrasound is also highly useful in confirming common entheseal lesions, which may be primary mechanical disorders in their own right or may represent manifestation of an underlying inflammatory disorder, typically a spondylarthropathy such as psoriatic arthritis. There are Romanus lesions (arrows), particularly notable in the first and second lumbar vertebrae. There is grossly thickened synovium (S), which is seen distending the joint capsule (white arrows). Magnetic resonance imaging remains relatively expensive, and imaging times are long compared with other modalities. It is also contraindicated in some patients, including those with pacemakers or metallic implants. Computed tomography Computed tomography scanning is not used frequently in rheumatology practice. For example, angiography of the coeliac axis may demonstrate microaneurysm formation in polyarteritis nodosa. Bone scintigraphy Bone scintigraphy (isotope bone scanning) is a nuclear medicine investigation in which a radioactive tracer (usually technetium99 m) is injected intravenously and taken up by any bone tissue with excessive metabolic activity. The main limitation of bone scintigraphy is that tracer uptake is nonspecific and thus not usually diagnostic. Another important limitation of bone scintigraphy is that it does not detect the lytic bony lesions of multiple myeloma; for this condition, a skeletal survey (systematic series of plain radiographs of the entire axial skeleton and long bones) is used. Increased tracer uptake is detected in tissues with excessive metabolic activity; again, this is most commonly due to inflammation, infection or malignancy. These highly metabolically active tissues demonstrate high levels of tracer uptake in all subjects. This includes females aged over 65, those with a history of lowtrauma fracture and those receiving glucocorticoid therapy. The assessment and management of osteoporosis are discussed in greater detail in Chapter 11.

Duodenal atresia is most common (50%) anti fungal wash for dogs purchase 400 mg diflucan with mastercard, followed by jejunoileal (45%) and colonic (5%) atresias antifungal gel for nose cheap diflucan 50 mg on line. Hirschsprung disease is due to absence of ganglion cells and typically affects the rectosigmoid colon antifungal iv drugs discount diflucan 150 mg fast delivery. Asymptomatic malrotation: diagnosis and surgical management: an American Pediatric Surgical Association outcomes and evidence based practice committee systematic review fungus gnats root rot buy diflucan online pills. Factors determining the need for operative reduction in children with intussusception: a populationbased study antifungal over the counter pill cheap diflucan 50mg. Rectal biopsies for Hirschsprung disease: patient characteristics by diagnosis and attending specialty antifungal antibacterial dog shampoo discount diflucan 200mg with amex. Anorectal malformation is a term used to designate a series of congenital defects characterized by the absence of an anal opening. However, most of the time, the rectum is abnormally connected to the perineum or to the urogenital tract. Actually, only 5% of all cases suffer from a real blind rectum and half of that particular group suffers from Down syndrome. Fifty percent of the cases have a urologic abnormality, 30% a vertebral one, 25% a spinal cord anomaly, 10% a cardiac condition that requires treatment, and 8% esophageal atresia. On the good side of the spectrum are malformations relatively easy to repair, with an excellent functional prognosis. On the bad side of the spectrum, we see complex defects, such as cloacas and cloacal exstrophies, that require a specialized team of surgeons to repair; and the patients suffer from very serious functional sequelae, mainly related to bowel and urinary control as well as sexual and fertility problems. Important prognostic factors include (1) characteristics of the sacrum, (2) presence or absence of tethered cord, and (3) specific type of malformation. What are the external signs that help to suspect and differentiate a malformation with good functional prognosis from a one with bad prognosis What are the diagnostic and therapeutic priorities in the management of a newborn with anorectal malformation Depending on the experience of the surgeon: Colostomy to be done in the majority of malformations. Depending on the experience of the surgeons and the general condition of the patient, the main repair can be done as soon as the patient shows normal growth and development. It consists of approaching the defect through a midsagittal, posterior incision in between both buttocks. To identify the sphincter mechanism with an electrical stimulator, to separate the rectum form the urogenital tract under direct vision, mobilize the rectum, and place it in the center of the sphincter mechanism. In cases of perineal fistula, the procedure follows the same principles but is done with a small incision. An abdominal approach (laparotomy or laparoscopy) is indicated to find and mobilize an extremely highly located rectum in 10% of the male cases and 35% of the patients with cloacas. What are the indications of a laparoscopic approach in cases of anorectal malformations Depending on the experience of the surgeon, some cases of rectoprostatic fistula can also be repaired via laparoscopy. Anorectal malformation is a term used to designate a series of congenital anomalies of the anus and rectum, characterized by the absence of an external anal opening. The rectum is connected to the perineum or to the urogenital tract in 95% of the cases. These malformations present in the form of a spectrum, including benign defects in one extreme and very severe and complex in the other. Ten percent of the male cases and 35% of the cloacas in females need, in addition, a laparotomy or laparoscopy. Patients with anorectal malformations do not die from the anorectal defect, but rather from one of the associated conditions (cardiac and/or urologic). The pathogenesis for the development of esophageal atresia, with and without fistula, is still unknown. Theories include imperfect separation of the tracheoesophageal septum or defective pharyngeal arch development. More than 50% of cases of esophageal atresia with tracheoesophageal atresia are associated with other anomalies; 10% are found in specific chromosomal or single gene disorders. Describe the three most common anatomic patterns of tracheoesophageal disorders and their relative incidence. The overall incidence of esophageal atresia, with or without tracheoesophageal fistula, is 1:3500 live-born infants. What are the other common anomalies that occur with tracheoesophageal malformations Approximately 70% of affected infants have at least one associated congenital malformation. The most common anomalies include cardiovascular (35%), genitourinary (25%), gastrointestinal (25%), musculoskeletal (15%), and central nervous system (7%). What are additional prognostic factors to consider when evaluating an infant with esophageal atresia with and without tracheoesophageal atresia Infants weighing 2 kg or more without cardiac anomalies have a better prognosis than those weighing <2 kg with heart defects. Infants without major additional anomalies generally undergo early repair with near 100% survival. Severely premature infants or those with life-threatening anomalies may benefit from delayed repair. Describe the clinical presentation, diagnosis, and preoperative management of esophageal atresia with distal tracheoesophageal fistula. The earliest clinical signs of esophageal atresia with distal tracheoesophageal fistula include excessive salivation and pooling of secretions in the pharynx. Respiratory distress develops because of aspiration of secretions or feeds from the proximal pouch. Reflux of gastric acid into the airways and lungs via the distal tracheoesophageal fistula contributes to respiratory distress. An air-filled stomach and normal bowel gas pattern are present because of the anomalous connection of the distal esophagus (fistula) to the airway. The infant is maintained in the semi-upright position with sump catheter drainage of the proximal esophageal pouch to minimize lung contamination. Describe the clinical presentation, diagnosis, and preoperative management of isolated esophageal atresia. Isolated esophageal atresia is associated with excessive secretions, choking, and regurgitation of feeds. The esophagus is either placed on traction (Foker technique) or allowed to grow to reduce gap distance for eventual anastomosis. Describe the clinical presentation, diagnosis, and preoperative management of tracheoesophageal fistula without esophageal atresia. These infants frequently choke or have cyanotic spells with feeds due to reflux from the esophagus into the lungs via the anomalous connection between esophagus and airway. Older infants and children may have recurrent pneumonias or reactive airway disease. Prone pull-back contrast esophagram can be diagnostic; bronchoscopy and esophagoscopy are confirmatory. The surgical goals are separating the pathologic connection of the esophagus to the trachea, eliminating contamination of the airway, and establishing esophageal continuity for feeding. Correction of esophageal atresia with distal tracheoesophageal fistula can be performed open via a thoracotomy or thoracoscopically. The first goal is ligation of the tracheoesophageal fistula followed by an end-to-end esophageal anastomosis when possible. In infants with pure esophageal atresia, an anastomosis between the proximal and distal esophagus is usually attempted after a period of waiting or traction. If the distance between the two ends is too long, the stomach can be used as a conduit to allow for a connection between the proximal esophagus and the bowel. What are the pros and cons of open versus thoracoscopic repairs for tracheoesophageal fistula with esophageal atresia Scoliosis and scapula alata occur more commonly in patients who have undergone open repairs versus thoracoscopic repair. The major advantage of the thoracoscopic approach is avoidance of an open thoracotomy and scar. Thoracoscopic repair is associated with a higher rate of vocal cord paresis/paralysis due to dissection of the esophagus high into the thoracic inlet. It appears that there is no difference between the approaches with regard to anastomotic stricture, leak, or tracheomalacia. Late complications Anastomotic stricture: 25% Gastroesophageal reflux: 50% Esophageal dysmotility: 100% 11. Symptoms include drooling, pooling of secretions, choking, need for prolonged and frequent feeds, and emesis. Most strictures respond to one to three dilations performed in the first 6 months of life. The three most common variants are proximal esophageal atresia with distal tracheoesophageal fistula, isolated esophageal atresia, and tracheoesophageal fistula without esophageal atresia. Surgical treatment includes separation of the pathologic connection between the esophagus and airway and establishment of esophageal continuity. Common complications of repair of tracheoesophageal malformations include leak, stricture, and gastroesophageal reflux. The great debate: open or thoracoscopic repair for oesophageal atresia or diaphragmatic hernia. Hypercapnia and acidosis during the thoracoscopic repair of oesophageal atresia and congenital diaphragmatic hernia. Foker process for the correction of long gap esophageal atresia: primary treatment versus secondary treatment after prior esophageal surgery. Thoracoscopic versus open repair of tracheoesophageal fistulas and rates of vocal cord paresis. Congenital abnormalities of the diaphragm include a posterolateral defect (Bochdalek hernia), an anteromedial defect (Morgagni hernia), or the eventration (central weakening) of the diaphragm. This defect is most common on the left (80%), 20% are right-sided lesions, and <1% are bilateral. At birth or shortly thereafter, the infant can develop severe dyspnea, retractions, and cyanosis. Heart sounds can be heard more easily in the contralateral chest, and the abdomen is scaphoid because of the herniation of abdominal viscera into the chest. The radiograph demonstrates multiple loops of air-filled intestine or stomach in the ipsilateral thorax. If a chest radiograph is obtained before entry of significant amounts of air into the bowel, a confusing pattern of mediastinal shift, cardiac displacement, and opacification of the hemithorax may be observed. If conventional ventilator settings fail to achieve these goals, high-frequency oscillatory ventilation can be used to stabilize the infant. Previously, infants were taken emergently to the operating room for reduction of the intraabdominal contents and repair of the hernia soon after birth. The length of preoperative stabilization is highly variable, ranging from days to weeks. The operation can be performed from either the abdomen (laparotomy or laparoscopy) or the chest (thoracotomy or thoracoscopy). These histologic changes contribute to elevated pulmonary vascular resistance and pulmonary arterial hypertension. This then leads to right-to-left shunting of deoxygenated blood to the systemic circulation through the patent ductus arteriosus and patent foramen ovale then causing hypoxemia, acidosis, and shock. Monitoring: Oximetry or arterial sampling (preductal in the right upper extremity; postductal in the lower extremity) permits early detection of shunting of deoxygenated blood to the systemic circulation. Ventilation: Hypercarbia is corrected by mechanical ventilation with adequate sedation. Oxygenation: Hypoxemia is corrected by adequate ventilation and high concentrations of inspired oxygen (generally, fraction of inspired oxygen = 100%). Resuscitation: Metabolic acidosis is managed by restoring adequate tissue perfusion (intravenous fluids or blood, inotropes, and sodium bicarbonate). The major determinants of survival are the degree of pulmonary hypoplasia, severity of pulmonary hypertension, and associated major congenital anomalies. Late deaths occur in approximately 10% of children, secondary to persistent pulmonary hypertension. However, current research has focused on the role of tracheal occlusion during the fetal period as a means to promote lung growth. The price of success in the management of congenital diaphragmatic hernia: is improved survival accompanied by an increase in long-term morbidity Pulmonary vasodilator therapy in congenital diaphragmatic hernia: acute, late, and chronic pulmonary hypertension. Congenital diaphragmatic hernia: a systematic review and summary of best-evidence practice strategies. Retrospective study of 111 cases of congenital diaphragmatic hernia treated with early highfrequency oscillatory ventilation and presurgical stabilization. Factors influencing survival in newborns with congenital diaphragmatic hernia: the relative role of timing of surgery. Early recurrence of congenital diaphragmatic hernia is higher after thoracoscopic than open repair: a single institutional study. Split abdominal wall muscle flap repair vs patch repair of large congenital diaphragmatic hernias. Fetal tracheal occlusion for severe pulmonary hypoplasia in isolated congenital diaphragmatic hernia: a systematic review and meta-analysis of survival.

The other important bacterial stain is the acid-fast stain that is retained only by a few bacteria that have a characteristic lipid-rich cell wall antifungal topical purchase diflucan 100 mg amex. This group is further subdivided by how difficult it is to remove the acid-fast stain (the stain is named because an acid solution removes the stain from most other bacteria) antifungal topical order diflucan 400mg on line. Finally antifungal yard treatment order diflucan overnight, there are groups of organisms that do not stain with these procedures so they are separated by other features antifungal hiv generic diflucan 150mg without a prescription, such as shape (spiral-shaped bacteria) or their need to grow inside a host cell fungus gnats stuck to buds buy diflucan cheap. As can be seen antifungal washing detergent cheap 100 mg diflucan with visa, the line separating these two groups is not as well defined as that separating these organisms from the bacteria or viruses, but the classification is still well recognized. Bacteria are prokaryotic organisms; that is, simple unicellular organisms with no nuclear membrane, mitochondria, Golgi bodies, or endoplasmic reticulum and they reproduce by asexual division. Molds are complex organisms with the cells organized into threadlike tubular structures (hyphae) and specialized asexual reproductive forms (conidia). The molds are then further subdivided by the structure of the hyphae (pigmented or nonpigmented, separated into individual cells [septated molds] or not) and the arrangement of the conidia. Parasites Parasites are also subdivided into single-celled organisms (protozoa) or multi-celled organisms (worms and bugs). Members of the family Protozoa are then further divided into amebae, flagellates (think of them as hairy protozoa), and coccidia (some are sphericalshaped but many are not). The worms (technically called helminthes) are nicely classified by their shape: roundworms, flatworms, and tapeworms. Pretty simple, although many have very complex lifecycles that unfortunately are important for understanding how they cause disease. They are important because they are vectors of a number of viruses and bacteria (not fungi) that are responsible for diseases. Other bugs obviously exist (such as spiders), but these generally are not vectors for other pathogenic microbes. If these organisms are maintained in their proper balance, then health can be maintained. Infectious diseases are also initiated when the members of the microbiome are introduced into normally sterile sites. This is referred to as an endogenous infection or an infection caused by the normal microbial population. Finally, infections can be caused by exogenous organisms; that is, those introduced from outside. Only a few of the microbes that we encounter from our environment are pathogens, but some of the most serious infections are caused by these exogenous pathogens. So the important lesson is that most microbes are good and not associated with disease. A subset of our endogenous organisms can cause disease when introduced into normally sterile areas, but most endogenous organisms do not have the virulent properties to cause disease. Likewise, most of the exogenous organisms we are exposed to cause no problems at all, but some can cause quite significant disease. It is important to understand which organisms have the necessary properties (virulence) to cause disease and under what circumstances this will occur. It is also important to understand which organisms to ignore because they are not associated with disease. We have coined the derogatory term germs, and great efforts are made to eliminate our exposure to these organisms. The surfaces of the skin, nose, mouth, gut, and genitourinary tract are covered with bacteria, as well as some fungi and parasites. This is further simplified if we separate the pathogens from nonpathogens and then understand the conditions under which the pathogens produce disease. The following chapters are designed to develop these themes for the individual groups of organisms. I certainly do not expect the student to master these details before he or she moves on to the rest of the bacteriology chapters. Then, as each subsequent chapter is digested, this chapter can provide a framework for linking each of the bacteriology chapters. This is a useful exercise that can provide some order to an otherwise confusing list of organisms. The following tables are not comprehensive; rather, these are a listing of the most commonly isolated or clinically important bacteria. They are unicellular and have no nuclear membrane, mitochondria, Golgi bodies, or endoplasmic reticulum, and they reproduce by asexual division. The bacterial cell wall is complex, consisting of one of two basic forms defined by their staining ability with the Gram stain: a gram-positive cell wall with a thick peptidoglycan layer, and a gram-negative cell wall with a thin peptidoglycan layer and an overlying outer membrane. Some bacteria lack this cell wall structure and compensate by surviving only inside host cells in a hypertonic environment. The human body is inhabited by thousands of different bacterial species (called the "microbiome"), some living transiently, others in a permanent synergistic relationship. Likewise, the environment that surrounds us, including the air we breathe, water we drink, and food we eat is populated with bacteria, many of which are relatively harmless and some of which are capable of causing life-threatening disease. The clinical management of infections is predicted by the ability to develop an accurate differential diagnosis defined by the most common organisms associated with the clinical picture, selection of the appropriate diagnostic tests, and initiation of effective empirical therapy. Once the diagnosis is confirmed, empirical therapy can be modified to provide narrow-spectrum, directed therapy. The following is a list of the most common organisms associated with specific clinical syndromes. Common Organisms and Their Associated Clinical Syndromes Disease Sepsis Most Common Pathogens General sepsis Catheter-related sepsis Septic thrombophlebitis Cardiovascular Infections Staphylococcus aureus, coagulase-negative Staphylococcus, Escherichia coli, Klebsiella pneumoniae Coagulase-negative Staphylococcus S. Additionally, in the following chapters, the recommended therapies for individual organisms are listed. Staphylococcus, Streptococcus, and Enterococcus Genus Staphylococcus Historical Derivation Staphyle, bunch of grapes; coccus, grain or berry; round, berrylike bacterial cells arranged in grapelike clusters Streptus, pliant; coccus, grain or berry; refers to the appearance of long, flexible chains of cocci Enteron, intestine; coccus, berry; intestinal coccus Streptococcus Enterococcus the staphylococci, streptococci, and enterococci are gram-positive cocci, typically arranged in clusters (Staphylococcus), chains (Streptococcus), or pairs (S. The structure of the thick, cross-linked cell wall allows these bacteria to survive on dry surfaces, such as hospital linens, tables, and door knobs. Virulence is determined by the ability to avoid the host immune system, adhere to and invade host cells, and produce toxins and hydrolytic enzymes. Particularly noteworthy are a group of toxins: staphylococcal enterotoxins, exfoliative toxins, and toxic shock syndrome toxin, as well as S. These toxins are termed "superantigens" because they stimulate a massive release of cytokines by the patient with resulting pathology. Although staphylococci, streptococci, and enterococci are among the most common bacteria implicated in disease, it is important to remember that these are also common residents on the human body. Disease is found in specific populations of patients and under well-defined conditions, so it is important to understand this epidemiology. Likewise, diagnosis of infections caused by streptococci and enterococci is not difficult; however, because many of these bacteria are part of the normal microbial population in the body, care must be used to collect uncontaminated specimens. Most streptococcal infections can be treated with penicillins, cephalosporins, or macrolides, although resistance is observed with S. Serious enterococcal infections are difficult to manage because antibiotic resistance is common. Pregnant women are screened for vaginal carriage with this organism shortly before delivery, and colonized women are treated with antibiotic prophylaxis. Other species, commonly referred to as coagulase-negative staphylococci, are primarily opportunistic pathogens, but three species are noteworthy: Staphylococcus epidermidis, Staphylococcus saprophyticus, and Staph ylococcus lugdunensis. The streptococci can be divided into two groups: (1) -hemolytic (complete hemolysis on blood agar) species that are subclassified by serologic properties (grouped from A to W); and (2) the viridans streptococci group that consists of -hemolytic (cause partial hemolysis of blood) and -hemolytic (no hemolysis) species. Some species of viridans streptococci such as members of the Streptococcus anginosus group (with three species) are classified in both the -hemolytic group and the viridans group because they are biochemically the same but have different hemolytic patterns. The following are the most important representatives of the -hemolytic and viridans group streptococci. Two species of enterococci are particularly important because they cause similar diseases and are frequently resistant to most antibiotics. There is a very high mortality rate associated with this disease unless antibiotics are promptly administered and the local infection managed. The patient was treated with oxacillin for 6 weeks with resolution of the endocarditis and the pulmonary abscesses. One month earlier the patient, who had previously been in good health, was seen at an urgent care clinic because of a red, hard, painful lump that had developed on her right lower leg 3 days earlier. The lesion was excised and drained, and she was treated with a 10-day course of cephalexin and trimethoprim-sulfamethoxazole. Upon arrival in the emergency department, the patient was agitated, had a temperature of 39. She rapidly deteriorated and was transferred to the intensive care unit where she was managed for septic shock. Despite clinical efforts, her hypoxemia, hypercardia, acidosis, and hypotension worsened and she died less than 12 hours after arrival at the hospital. A 15-year-old girl was admitted to the hospital with a 2-day history of pharyngitis and vaginitis associated with vomiting and watery diarrhea. She was febrile and hypotensive on admission, with a diffuse erythematous rash over her entire body. Laboratory tests were consistent with acidosis, oliguria, and disseminated intravascular coagulation with severe thrombocytopenia. She was admitted to the hospital intensive care unit where she was stabilized and she improved gradually over a 17-day period. On the 3rd day fine desquamation started on her face, trunk, and extremities and progressed to peeling of the palms and soles by the 14th day. This case illustrates the initial presentation of toxic shock syndrome, the multiorgan toxicity, and the protracted period of recovery. A total of 18 persons attending a retirement party became ill approximately 3 to 4 hours after eating. A food preparer had cooked the ham at home, transported it to her workplace, sliced it while it was still hot, and then refrigerated the ham in a large plastic container covered with foil. The delays involved in refrigerating the ham and the fact it was stored in a single container allowed the organism to proliferate and produce enterotoxin. The rapid onset and short duration of nausea, vomiting, and diarrhea is typical of this disease. Care must be used to avoid contamination of salted meats such as ham because reheating the food at a later time will not inactivate the heat-stable toxin. Suppurative diseases range from pharyngitis to localized skin and soft-tissue infections to necrotizing fasciitis ("flesh eating" bacterial infection) and streptococcal toxic shock syndrome. Nonsuppurative diseases are an autoimmune complication following streptococcal pharyngitis (rheumatic fever, acute glomerulonephritis) and pyodermal infections (only acute glomerulonephritis). Antibodies directed against specific M proteins cross-react with host tissues in nonsuppurative diseases. Two days before admission to the hospital he noticed a lesion on the dorsum of his right hand and thought it was an insect bite. That evening his mother found him obtunded, vomiting, and incontinent and he was rushed to the emergency department. The right hand was mottled and swollen, with a 1-cm black eschar on the dorsum, and swelling up his forearm. A radiograph of the hand revealed prominent soft-tissue swelling and chest radiograph showed findings consistent with interstitial edema. A diagnosis of severe sepsis was made and intravenous vancomycin and clindamycin were administered. The patient was taken to surgery 4 hours after arrival in the hospital and complete debridement of the skin and fascia up to the elbow of the right arm was required. Pathologic examination of the tissues revealed liquefactive necrosis involving the fascial planes and superficial fat. Small blood vessel intraluminal thrombi and infiltration of mononuclear cells and neutrophils was also observed in the tissues, as well as abundant gram-positive cocci subsequently identified as group A streptococci. The patient was aggressively treated with penicillin G, clindamycin, vancomycin, and cefepime, and slowly improved until his discharge 16 days after hospitalization. This case illustrates the rapid progression of disease from a relatively innocuous superficial skin lesion to necrotizing fasciitis, septic shock, and multiorgan involvement. Mortality with necrotizing fasciitis and toxic shock syndrome approaches 50%, and is only successfully managed with aggressive surgical debridement and antibiotic therapy. Casey and colleagues 6 described a 28-year-old woman who presented with a history of joint pain and swelling, initially in her right foot and ankle that resolved after a few days and then pain and swelling in other joints. Upon physical examination, diffuse tenderness of the joints was noted on palpation but no swelling or erythema. Cardiovascular examination was notable for tachycardia, but no murmurs were detected. The diagnosis of a "viral infection" was made and she was discharged with a course of nonsteroidal antiinflammatory drugs. After 5 days, the patient returned with progressive shortness of breath and persistent pain in her knee. Physical examination revealed a low-grade temperature, tachycardia, and a new heart murmur with mitral valve regurgitation. The left knee was warm to the touch, the range of motion was limited, and it was painful on flexion. The diagnosis of bacterial endocarditis was considered but all blood cultures were negative. Medical history revealed that as a child she became short of breath easily and was unable to play with other children. Recent evidence of infection with group A Streptococcus is required to confirm the diagnosis, but throat culture is insensitive because symptoms of acute rheumatic fever appear 2 to 3 weeks after the infection. Physical examinations of the infant were normal during the first week of life; however, the child started feeding irregularly during the second week.

The most compelling results have come from studies of highintensity immunosuppression and autologous peripheral stem cell rescue fungus yellow foam buy discount diflucan on-line. A number of other approaches are being evaluated in clinical trials antifungal remedies purchase diflucan 50 mg amex, such as highdose immunosuppression with autologous peripheral stem cell rescue fungus like protists diflucan 100 mg mastercard. Treatment depends on the level of symptoms african violet fungus gnats order genuine diflucan on-line, defined mainly by the degree of dyspnoea antifungal kit order diflucan 400 mg on line. These agents have improved symptoms and are associated with improved longterm outcome antifungal extracts 400 mg diflucan for sale. This represents the current gold standard for detecting parenchymal lung disease and allows the extent and pattern to be ascertained. Studies suggest that extensive disease, defined as more than 20% involvement of the total lung volume, is associated with a high risk of progression and these cases should be actively treated. The cornerstone of treatment is immunosuppression and this is underpinned by supportive evidence from two placebocontrolled trials. Our practice is to add lowdose prednisolone, 10 mg daily, and other agents such as Nacetylcysteine may be useful. There is emerging evidence that rituximab may be used as a rescue treatment for cases that are refractory to treatment with other agents. The major problem is one of recognition, and education of both patients and physicians is important. Patients should be admitted for blood pressure control and monitoring of renal function. There may be significant recovery in renal function for up to 2 years after renal crisis, and decisions regarding transplantation should be delayed until that time. Up to 90% of patients demonstrate oesophageal dysmotility with reflux, and the proton pump inhibitors have dramatically improved symptomatic disease. Midgut disease with bacterial overgrowth may respond to broad spectrum antibiotics, although maintenance treatment may be required. Paradoxically, colonic involvement may lead to severe constipation, and anorectal incontinence is prevalent. This may relate to altered expression of the antigen in tumours, especially breast or ovarian tumours. Conclusion Scleroderma remains an important disease with high morbidity and mortality but one for which a number of treatments are now available and others are likely to be developed soon. It is a common and troublesome disorder that needs appropriate investigation and assessment. Further randomized controlled trials are needed to improve the therapeutics of this difficult condition. It has often been confused and compared with causalgia, a different condition with similar clinical symptoms. Generally speaking, the more words used in the description of a condition, the less we understand that condition. This change in nomenclature has done little to reassure the nonspecialist that our understanding of the condition has substantially improved. Although diagnostic criteria have been proposed, these have not been validated and are complicated by the fact that not all features may be present at the same time and may vary in their intensity. Usually one limb is affected, but it can become bilateral, or affect another limb. However, a recent prospective study suggested that 21% of patients fulfilled diagnostic criteria 1 month after operation, falling to 12. These receptors become expressed on nocioceptors in some cases of soft tissue and nerve injury. Some patients demonstrate supersensitivity to catecholamines, consistent with increased adrenoceptor responsiveness. Patients exhibit normal thresholds for the detection of cold and heat, but reduced thresholds for coldpain and heatpain, suggesting a central nervous disturbance. The latter occur in the absence of pain, suggesting an uncoupling of the mechanisms that under pin the pain and sensory symptoms from the autonomic features. Tests on normal volunteers that create conflict between motor sensory central nervous processing can lead to pain and sensory disturbances, such as using mirrors during congruent and incongruent limb movements. It has been proposed that central processing of persistent sensory motor conflict may lead to chronic pain in some vulnerable individuals. Neuropetides may also be released in response to impaired blood flow, oxygen deficiency and an increase in protons and skin lactate levels. Signs of inflammation predominate in early disease, with redness, increased skin temperature due to inhibition of cutaneous vasoconstrictor neurons, with subsequent loss of function and pain. Early in the disease, the sympathetic nervous system plays a role, but when central sensitization takes over, with changes at the dorsal root ganglion level, the pain becomes independent of sympathetic nerves. There is competition between the continued inhibition of vasoconstriction and supersensitivity of the peripheral vessels to circulating adrenaline. Late intractable disease can be characterized by a cold, painful limb with poor or no function, with disuse leading to immobility and contractures. Sex Age Genetics Personality traits Psychological Some patients can have motor weakness and factors movement disorders relieved by placebo, nerve blocks or infusions Table 20. A crucial question that has not been satisfactorily answered is: Why do the majority of patients who suffer the potential triggers listed in Table 20. A number of theories have been propounded, but revolve around peripheral mechanisms, central mechanisms and neurogenic inflammation with microvascular dysfunction. Continuing pain, allodynia or hyperalgesia, in which the pain is disproportionate to any inciting event 3. Evidence at some time of oedema, changes in skin blood flow or abnormal sudomotor activity in the region of the pain 4. In the late intractable disease, when the limb becomes cold, chronic arterial insufficiency needs to be considered. Routine investigations, such as a full blood count and erythrocyte sedimentation rate should be normal, and if not an explanation should be sought. On bone scanning there is increased uptake in early disease and reduced uptake in late disease. Patients with markedly increased uptake may have a better prognosis, possibly reflecting the fact that they have not yet progressed to latestage disease. Thermography detects asymmetry in limb surface temperature, but is not widely available. Early mobilization following predisposing conditions is important, and graded physiotherapy may be very helpful. Although many experts and committees have recommended physiotherapy, occupational therapy, vocational rehabilitation and behavioural therapy, the evidence base for these is weak or lacking. One study compared physiotherapy and occupational therapy with social work intervention as the control, and showed no differences in the three groups for pain at 12 months, with only small improvements in temperature and global impairment for the intervention arms of the trial. Because pain can be the main ratelimiting factor in rehabilitation, medical and psychological therapies often have to run side by side (Table 20. The mainstay of drug interventions is analgesics and non steroidal antiinflammatories. Lowdose antidepressants and anticonvulsants are commonly used, but the evidence base is sparse. A systematic review of therapies concluded that the only trial data that consistently demonstrated analgesia was with oral corticosteroids. However, many clinicians have understandable concerns about using steroids for disease that has the potential to become chronic, and where the evidence base for ongoing inflammation driving the disease is limited. A controlled trial of alendronate showed improved bone mineral content of the affected limb, but only small benefits to pain management. By contrast, a trial of intravenous clodronate showed substantial improvements in pain management at 6 months, with highly significant pain reduction compared with placebo. However, a systematic review found this treatment to be ineffective, so its use may decline in future. Continuous blockade of the brachial or lumbar plexus has been advocated with drugs such as morphine, so that whenever the catheter is in place, the patient can take advantage of the pain relief to maximize their rehabilitation. Intrathecal baclofen proved to be effective for the upper limb dystonias in six out of seven patients, but did not improve pain. Spinal cord stimulation has been shown to be effective in relieving pain in controlled trials. The procedure is, however, not without risk, as it involves placing an electrode on the dorsal aspect of the spinal cord, and an electric current produces paraesthesias that block the pain in the affected area. However, the average improvement in pain is sustained but not substantial, and functional and qualityoflife benefits have not been demonstrated. This leaves the dilemma of whether invasive and costly interventions that provide modest pain relief are justified. Clearly, these concerns and the risks involved mean that patients have to be carefully selected. Complex regional pain syndrome: practical diagnostic and treatment guidelines, 4th edn. Treatment of complex regional pain syndrome in adults: a systematic review of randomized controlled trials published from June 2000 to February 2012. From a management perspective, it is important not only to recognize and treat potentially aggressive disease, but also to avoid overtreatment in patients where either the diagnosis is unclear or the disease has a potentially benign course. Autoantibody profile in diagnosis Antinuclear antibodies are a hallmark of systemic autoimmune rheumatic diseases and can be found in a variety of clinical settings. Serology is of particular value in situations where clinical expression of the autoimmune rheumatic disease is incomplete, where the presence of a particular antinuclear antibody profile may be diagnostic. It is therefore imperative that requests for antinuclear antibody tests and the interpretation of the results be done in the light of clinical findings. In systemic lupus erythematosus and scleroderma, antinuclear antibodies can be detected in 95% or more of untreated patients with active disease by this method. In patients suspected of having an autoimmune rheumatic disease, the indirect immunoflourescence test is enough as a screening test for antinuclear antibodies. The individual antinuclear antibody fluorescent patterns are of limited diagnostic utility but may provide guidance to more specific immunological tests. In such cases, the clinical picture dictates that specific autoantibody assays should be undertaken. Having detected antinuclear antibodies with the screening test, it is important to determine their specificity. This is part of the standard Systemic autoimmune rheumatic diseases, also commonly referred to as connective tissue diseases, are immunemediated inflammatory disorders associated with autoantibodies. The diagnosis of these disorders, such as systemic lupus erythematosus and scleroderma, can be challenging because many of the presenting clinical features are nonspecific and this often results in delayed diagnosis. Classification criteria for the major systemic autoimmune rheumatic diseases (see Chapters 12 and 18) have been developed primarily as a means of standardizing patient populations for clinical research rather than for diagnosis in routine clinical practice. These classification criteria are extremely limited for the early diagnosis of these disorders as they were designed to be highly specific and therefore lack diagnostic sensitivity. Specific antinuclear antibody tests are often helpful in stratifying patients into clinical subsets, which may be useful in the further management of specific clinical manifestations and prognostication (Table 21. These autoantibodies are usually present from the beginning of the clinical presentation and are detectable throughout the course of the disease. Some studies have shown that autoantibodies may be present for many years prior to clinical presentation. Many serology laboratories use commercial kits to detect specific autoantibodies and there is a move to using bead based multiplex immunoassays. Although the newer tests are less labour intensive, they vary in sensitivity and sometimes produce falsepositive results. Although the clinical presentation in the early stages can be similar between the systemic autoimmune rheumatic diseases, the evolution of typical clinical features over weeks or months usually distinguishes the characteristic patterns associated with the different diseases. Early diagnosis is aided by recognition of distinctive serological profiles that are generally present with the earliest clinical manifestations. Diagnosis can also be facilitated by typical laboratory abnormalities and histological changes in the tissues involved. Diagnosis is often complicated if lupus is part of an overlap syndrome and the patient fulfils classification criteria for more than one systemic autoimmune rheumatic disease. Sometimes the overlap features are evident at initial presentation; at other times, the picture evolves sequentially. These patients are usually diagnosed as having rheumatoid arthritis initially because of typical rheumatoid features Is It an Autoimmune Rheumatic Disease However, there is much controversy as to whether this is a distinct systemic rheumatic disease, with critics and protagonists. It refers to patients who present with symptoms and laboratory features of systemic autoimmune disease but who do not fulfil criteria for any specific systemic autoimmune rheumatic disorder. Only a minority of these patients, about 30% in the larger studies, evolve clinically to fulfil classification criteria of a defined autoimmune rheumatic disease.

Most of the opportunistic fungi are filamentous molds commonly found in the environment and produce disease in humans following inhalation of spores or following trauma (exogenous infections) antifungal therapy generic 200mg diflucan mastercard. In general antifungal tea buy 400mg diflucan mastercard, infections are primarily restricted to individuals with a compromised immune system or some other underlying disease antifungal washing detergent proven 200 mg diflucan. There are three important exceptions to the rule that opportunistic fungi are molds fungus zombie discount diflucan online master card. Cryptococcus is a yeast that exists in nature and is acquired by inhalation of the yeast cells and not spores zeasorb antifungal treatment powder buy diflucan 400mg online. Candida is a yeast that colonizes humans and produces endogenous infections; that is antifungal liver cheap diflucan master card, the yeast moves from normally colonized mucosal surfaces to the blood or other normally sterile sites. Pneumocystis, formerly classified as a parasite, is another yeastlike fungus that colonizes humans but produces disease in immunocompromised patients. The three genera of fungi that will be the focus of this chapter are Candida, Cryptococcus, and Aspergillus. Diagnosis is generally not a problem because these yeasts will grow in 1 to 3 days in culture and identification can be easily accomplished for the most common species. One potential diagnostic problem is relatively few yeasts circulate in the blood of patients with disseminated infections, so documentation of fungemia may be difficult. The following is a summary for Candida species: 145 Candida albicans in blood culture. Infection with both species is acquired by inhalation of the yeast cells followed by an initial mild or asymptomatic process in the lungs. The fungi have a predisposition to disseminate to the central nervous system in susceptible patients. Indeed, Cryptococcus is the most common fungal pathogen responsible for meningitis. The incidence of cryptococcosis has decreased in recent years with the use of prophylactic antifungal agents. Diagnosis of disease is generally made by observation of encapsulated yeast in spinal fluid or detection of the capsular polysaccharide by a specific antigen test (positive for both cryptococcal species). Occasionally yeasts are detected in the blood of infected patients, but blood culture alone is an unreliable diagnostic test because relatively few organisms may be circulating in the blood and culture will require 3 to 7 days before growth is detected. Severe chorioamnionitis was diagnosed, placental and fetal tissues were cultured, and blood cultures and vaginal swabs were obtained. On the basis of fluconazole minimal inhibitory concentrations, which indicated that the organism was susceptible, the patient was placed on fluconazole. Four weeks later, she experienced complete resolution of her symptoms, with eradication of the fungus from her bloodstream. Antifungal treatment was discontinued, and the patient was sent home where she did well. Six months later she was readmitted to the hospital with fever, chills, and fatigue. After 1 month of amphotericin B treatment, blood cultures were sterile, and she was discharged from the hospital. This was an unusual case in that the patient was not immunocompromised yet experienced recurrent candidemia with C. The use of fluconazole as initial therapy, although apparently successful, induced up-regulation of drug efflux pumps in the organism and allowed later isolates to become resistant to fluconazole and other azoles. Note the clusters of individual cells separated by clear spaces occupied by the unstained surrounding envelope. The patient was on chronic immunosuppressive therapy with cyclosporine, azathioprine, and prednisone and was admitted for intravenous antibiotics. Despite 5 days of intravenous nafcillin, the patient failed to improve, and a skin biopsy of the cellulitic area was obtained for histopathologic studies and culture. Unfortunately the patient suffered progressive mental status decline despite aggressive management of intracranial pressure and maximal doses of antifungals. He experienced slow, progressive decline, leading to death 13 days after initiation of antifungal therapy. The patient in this case was highly immunocompromised and presented with cellulitis and headache. Given the high mortality associated with cryptococcal infection, rapid and accurate diagnosis is important. Unfortunately, despite these efforts and the use of aggressive therapy, many such patients succumb to infection. A large number of species has been described, but the number of species associated with human disease is relatively limited, with A. Aspergilli are environment fungi whose spores are inhaled, producing a wide range of diseases including allergic hypersensitivity reactions, primary pulmonary disease, or highly aggressive disseminated disease. A preliminary diagnosis of infection is made by observation of the fungus in tissue (typical appearance is branching, septate [divided into compartments], nonpigmented [hyaline] hyphae) and confirmed by growth of the mold in 2 to 5 days in culture. Identification of the individual species is by the morphologic appearance of the mold growing in culture (color of the colonies, arrangement of spores on the fruiting structures attached to the hyphae). The patient was a 34-year-old woman who presented with 2-day history of weakness, dizziness, left calf pain, and black tarry stools. Her past medical history was significant for diabetes leading to renal failure, for which she received a cadaveric renal transplant in 2002. She was placed on an immunosuppressive regimen of alemtuzumab, tacrolimus, sirolimus, and prednisone. Physical examination revealed a tender venous cord palpable in the popliteal fossa. The patient was given four units of packed red blood cells, and empirical treatment with gatifloxacin. On hospital day 6, vesicular rash developed on the buttocks and left calf, cultures of which were positive for herpes simplex virus, and she was placed on acyclovir. On hospital day 12, the patient exhibited decreased responsiveness, became obtunded, and was intubated for respiratory distress. Culture of bronchoalveolar lavage fluid was positive for Aspergillus species, and viral inclusion bodies suggestive of cytomegalovirus were seen. Multiple acute infarcts in the frontal lobe and cerebellum were seen on a magnetic resonance imaging scan of the brain. This case serves as an extreme example of disseminated aspergillosis in an immunocompromised host. He was placed on broad-spectrum antibacterial agents but remained febrile for 96 hours. To combat a potential fungal infection, voriconazole was added to the therapeutic regimen. After 1 week of treatment, the patient was still febrile and neutropenic, and his antifungal therapy was changed to caspofungin. Initially the rash developed on the upper extremities and consisted of papular, erythematous, plaquelike lesions with centers that became necrotic. Blood cultures and skin biopsy specimens were sent to the laboratory for analysis. The laboratory report indicated that the blood cultures were positive for "yeast", based on the presence of budding cells and pseudohyphae. Despite the antifungal therapy, the lesions increased in number over the next 2 weeks and spread throughout the extremities, trunk, and face. The neutropenia and fever persisted, and he died approximately 3 weeks after the initial diagnosis. The combination of skin lesions and positive blood cultures are typical findings in fusariosis. Although "yeast" was reported from the blood cultures, closer examination revealed the microconidia and hyphae of Fusarium. Likewise, the appearance of septate hyphae in the skin biopsy could represent a number of different hyaline molds, including Fusarium. All parasites are classified as eukaryotic, some are unicellular and others are multicellular, some are as small as 4 to 5 m in diameter and others are up to 10 meters in length, and some are amorphous with minimal features whereas others have characteristic structures, such as a head, body, and legs. The epidemiology of these diseases is equally challenging, with some parasites spread from person to person while others require a complex series of hosts for development into infectious forms. The difficulties confronting students are not only an understanding of the spectrum of diseases caused by parasites but also an appreciation of the epidemiology of these infections, which is vital for developing a differential diagnosis and an approach to the control and prevention of parasitic infections. With literally hundreds of parasites associated with human disease, the student needs some help in organizing the most relevant information. In this article and subsequent ones, I will concentrate on only the most common parasites associated with human disease, recognizing that avirulent parasites, particularly those classified in the kingdom Protozoa, can colonize humans and create confusion when detected in clinical specimens. In this chapter, I first provide a classification structure for the parasites and then a view of the parasites from the perspective of the diseases they cause. I also provide an overview of the antiparasitic agents that can be used to treat these infections. In the subsequent chapters, I provide a more detailed view of the biology, epidemiology, clinical disease, diagnosis, and treatment of these organisms. The last kingdom, Animalia, includes all eukaryotic organisms that are not Protozoa, Stramenopila, or Fungi. Enterobius vermicularis Trichuris trichiura Ascaris lumbricoides Strongyloides stercoralis Necator americanus Ancylostoma duodenale Brugia malayi Wuchereria bancrofti Loa loa Onchocerca volvulus Trichinella spiralis Toxocara canis Ancylostoma braziliense Trematodes (flatworms) Fasciolopsis buski Fasciola hepatica Opisthorchis sinensis (also known as Clonorchis sinensis) Paragonimus westermani Schistosoma spp. The goal of this section and subsequent chapters is to give the physician the tools to develop this differential diagnosis. Because both parasites and humans are eukaryotic, many antiparasitic agents also act on human metabolic pathways; that is, these agents can pose a risk of toxicity. Differential toxicity is achieved by preferential uptake, metabolic alteration of the drug by the parasite, or differences in susceptibility between host and parasite. The following is a summary of the major antiparasitic agents and clinical indications. Clinical Indications Trypanosomiasis, leishmaniasis Malaria prophylaxis and therapy pathways that are unique for the rapidly proliferating parasites. In contrast, agents used for treatment of the helminth infections target unique metabolic pathways in the nonproliferating adult worms. Because the student may not be familiar with the antiparasitic Drug Class Antiprotozoal Agents Heavy metals Examples Melarsoprol, sodium stibogluconate, meglumine antimoniate Aminoquinoline analogs Chloroquine, mefloquine, quinine, primaquine, halofantrine, lumefantrine Folic acid antagonists Sulfonamides, pyrimethamine, trimethoprim Inhibitors of protein synthesis Clindamycin, spiramycin, paromomycin, tetracycline, doxycycline Diamidines Pentamidine Nitromidazoles Metronidazole, benznidazole, tinidazole Nitrofurans Phosphocholine analog Sulfated naphthylamine Thiazolides Antihelminth Agents Benzimidazoles Tetrahydropyrimidine Piperazine Avermectins Prazinoisoquinoline Phenol Quinolone Organophosphate Sulfated naphthylamidine Nifurtimox Miltefosine Suramin Nitazoxanide Mebendazole, thiabendazole, albendazole Pyrantel pamoate Piperazine, diethylcarbamazine Ivermectin Praziquantel Niclosamide Bithionol, oxamniquine Metrifonate Suramin Toxoplasmosis, malaria, cyclosporiasis Malaria, babesiosis, amebiasis, cryptosporidiosis, leishmaniasis Leishmaniasis, trypanosomiasis Amebiasis, giardiasis, trichomoniasis, trypanosomiasis Trypanosomiasis Leishmaniasis Trypanosomiasis Cryptosporidiosis, giardiasis Broad-spectrum antihelminthic for nematodes and cestodes Ascariasis, pinworm, hookworm Ascaris and pinworm infections Filarial infections, strongyloidiasis, ascariasis, scabies Broad-spectrum antihelminthic for cestodes and trematodes Infesting tapeworm Paragonimiasis, schistosomiasis Schistosomiasis Onchocerciasis the following table is a list of primary and secondary treatments for the most common parasites. Cystoisospora belli Cyclospora cayetanensis Giardia duodenalis note that for many of the groups of parasites, the same antiparasitic agents are used for treatment. Primary Antiparasitic Agents Metronidazole Miltefosine Miltefosine; amphotericin B Chloroquine; refer to current Centers for Disease Control and Prevention recommendations Clindamycin + quinine; atovaquone + azithromycin Pyrimethamine + sulfadiazine Sodium stibogluconate; meglumine anti- Pentamidine; amphotericin B monite; miltefosine Suramin; pentamidine; malarsoprol (for central nervous system disease) Benznidazole; nifurtimox Albendazole Mebendazole Albendazole; mebendazole; pyrantel pamoate Albendazole; mebendazole; pyrantel pamoate Ivermectin Albendazole; mebendazole Diethylcarbamazine Diethylcarbamazine Diethylcarbamazine Ivermectin Mebendazole (adult worms only) Praziquantel Triclabendazole Praziquantel Praziquantel Praziquantel Praziquantel Praziquantel Niclosamide Bithionol Albendazole Triclabendazole Oxamniquine Mebendazole; pyrantel pamoate Albendazole; pyrantel pamoate Secondary Antiparasitic Agents 157 Babesia microti Toxoplasma gondii Leishmania spp. Classification of protozoa is complex but the easiest way to organize these parasites Group Intestinal amoeba Coccidia Parasite Entamoeba histolytica Cyclospora cayetanensis Cryptosporidium spp. Reservoir Humans Humans Humans Humans Humans, beavers, muskrats Humans Environment Environment Humans Rodents Cat Rodents, dogs Domestic animals, humans, cattle, sheep, wild game Wild animals Vector - - - - - - Flagellates Free-living amoeba Blood and Tissue Protozoa Mosquito Tick - Sandfly Tsetse fly Reduviid bug the protozoa listed in this chapter are certainly not a comprehensive list of all protozoa or even all protozoa associated with human disease; however, the most important species are included in this chapter. Although not common in the United States, infections can be acquired when traveling to countries with poor hygienic standards. The patient initially presented with intermittent fever followed by right upper quadrant pain and diarrhea. On admission to the hospital, he was afebrile with an elevated white blood cell count and abnormal liver function tests. He underwent colonoscopy, and multiple discrete ulcers were detected in the rectum and colon. The diagnosis of amebic colitis was confirmed by the demonstration of numerous trophozoites on histopathologic examination of colon biopsy specimens. Ultrasound examination of the abdomen revealed a large heterogeneous mass within the liver, consistent with an abscess. Percutaneous drainage of the abscess obtained chocolate-like pus, and examination of a biopsy from the margin of the abscess revealed only a necrotic material, without evidence of amebae. The patient was treated with metronidazole followed by iodoquinol to eradicate the luminal amebae. Subsequent history revealed he traveled to Thailand 2 months before the onset of the present illness. The patient improved rapidly on antiamebic therapy and was discharged on antiretroviral therapy. Cyclospora infections in the United States are typically associated with food-related outbreaks such as with raw fruits or vegetables shipped from countries with poor hygienic conditions. Cryptosporidium in particular is associated with large outbreaks when drinking water or recreational waters are contaminated. Many species of Cryptosporidium infect a variety of animals, but Cryptosporidium hominis and Cryptosporidium parvum are most commonly associated with human infections. In the fall of 1998 an outbreak of gastroenteritis among university students was reported to the Department of Health. Preliminary findings suggested that the illness was associated with eating at one of the campus cafeterias; four employees of this cafeteria had a similar illness. In a case control study of 88 case patients and 67 control patients, eating in 1 or 2 cafeterias was associated with diarrheal illness. One ill food handler with laboratory-confirmed cryptosporidiosis 163 prepared raw produce on the days surrounding the outbreak. This outbreak illustrates the potential for cryptosporidiosis to cause food-borne illness. Epidemiologic and molecular evidence indicate that an ill food handler was the likely outbreak source. Wild animals are an important reservoir for this parasite and their feces can contaminate many streams and lakes as well as drinking water such as from wells. The patient was unsuccessfully treated five times with metronidazole and albendazole without improvement of diarrhea or cyst shedding.

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