MYCOLOGY

1. MYCOLOGY OPPORTUNISTIC MYCOSES

2. Opportunistic mycoses (2 hours) • 1. Defines “Opportunistic mycoses ’’ • 1.1. Lists the microorganisms that cause opportunistic mycoses. • 1.2. Lists virulance factors, defines tissue damage mechanisms. • 2. Lists the clinical tables related with opportunistic mycoses and defines pathogenetic mechanisms. • 2.1. Defines the clinical importance of opportunistic mycoses (Candida spp.,Aspergillus spp, Cryptococcus neoformans,Malassezia spp, Trichosporon spp,Rhodotorula spp, Blastoschizomyces capitatus, Scedosporium spp, Acromonium spp, Paecilomyces spp, Trichoderma spp, Scopulariopsis spp, Alternaria spp, Cladosporium spp, Curvularia spp, Bipolaris spp, Exserohilum spp,Pneumocystis jirovecii ) • 2.2. Lists the diagnostic laboratory methods of opportunistic mycoses.

3. Candida • Candida organisms are yeasts—that is, fungi—that exist predominantly in a unicellular form. • They are small (4-6 µm), thin-walled, ovoid cells (blastospores) that reproduce by budding. • They grow well in vented routine blood culture bottles and on agar plates and do not require special fungal media for cultivation. • Yeast forms, pseudohyphae, and hyphae may be found in microscopic examination of clinical specimens; identification of the hyphae and pseudohyphae is facilitated with 10% potassium hydroxide, which clears the epithelial cells, and with fluorescent microscopic examination of calcofluor white–stained smears. • The organism also stains gram-positive. • Candida organisms form smooth, creamy white, glistening colonies that may resemble staphylococcal colonies. • A rapid, presumptive identification of C. albicans can be made by placing the organism in serum and observing germ tube formation—small projections from the cell surface that appear within 90 minutes. • However, both false-negative and false-positive germ tube formation may occur.

4. Chlamydospore formation is also used to identify C. albicans. There are more than 150 species of Candida, but only a small percentage are regarded as frequent pathogens for humans: C. dubliniensis is a relatively newly described species that was formerly included within C. albicans. C. dubliniensis forms germ tubes and chlamydospores and is identified as C. albicans by the most common methods. However, it will not grow at 45° C, is darker green when initially isolated on CHROMagarcandida, C. albicans, C. guilliermondii, C. krusei, C. parapsilosis, C. tropicalis, C. pseudotropicalis, C. lusitaniae, C. dubliniensis, C. glabrata (formerly classified as Torulopsisglabrata).

5. C. albicans organisms have been recovered from soil, animals, hospital environments, inanimate objects, and food. • Nonalbicans species may live in animal or nonanimal environments. • Only rarely are Candida spp. laboratory contaminants. The organisms are normal commensals of humans and are commonly found on There is a relatively high incidence of carriage on the skin of health care workers. Although the vast majority of Candida infections are of endogenous origin, human-to-human transmission is possible: • thrush of the newborn, which may be acquired from the maternal vagina, • balanitis in the uncircumcised man, which may be acquired through contact with a partner having Candidavaginitis. • Candida infection can be acquired from the hospital environment. skin, throughout the entire gastrointestinal (GI) tract, in expectorated sputum, in the female genital tract, and in the urine of patients with indwelling Foley catheters.

6. Clinical Manifestations • MUCOUS MEMBRANE INFECTIONS • Thrush • Oral Candida infections are common • a specific form of oral candidiasis characterized by creamy white, curdlike patches on the tongue and on other oral mucosal surfaces; • the patches are removable by scraping and leave a raw, bleeding, and painful surface. • The patches are actually a pseudomembrane consisting of Candida, desquamated epithelial cells, leukocytes, bacteria, keratin, necrotic tissue, and food debris • The diagnosis can be made by the clinical appearance of the lesion and by scraping, using either a potassium hydroxide smear, Calcofluor white, or Gram stain to show masses of hyphae, pseudohyphae, and yeast forms.

7. Clinical Manifestations • other manifestations include • (1) acute atrophic candidiasis, a nonspecific atrophy of the tongue that is thought to be a sequela of acute pseudomembranouscandidiasis; • (2) chronic atrophic candidiasis or “denture sore mouth,” which is a chronic inflammatory reaction and epithelial thinning under the dental plates; • (3) angular cheilitis, an inflammatory reaction at the corners of the mouth (not due exclusively to Candida) • (4) Candidaleukoplakia, which are firm, white plaques affecting the cheek, lips, and tongue that have a protracted course (and, in rare instances, may be precancerous). • Since the introduction of inhaled steroids for the treatment of asthma, especially in children, oral thrush has been reported extensively in patients treated with these agents. • Other patients with a high incidence of thrush are cancer patients and those with AIDS. Patients with thrush for no obvious reason should be evaluated for AIDS. Because of the introduction of potent antiretroviral therapy, the incidence of thrush has declined in patients with AIDS.

8. Clinical Manifestations • CandidaEsophagitis • Although there have been a small number of reports of Candidaesophagitis occurring in patients with no known underlying illness, it is more commonly associated with treatment of malignancy of the hematopoietic or lymphatic systems and in AIDS patients. • Esophageal disease was believed to occur by direct spread from oral disease (thrush), • but reviews have shown that Candidaesophagitis may occur frequently without thrush. • The most common symptoms of Candidaesophagitis include painful swallowing, a feeling of obstruction on swallowing, and substernal chest pain. Nausea and vomiting may also occur. • It is important to recognize that Candidaesophagitis can occur simultaneously with herpes simplex virus or cytomegalovirus infection in severely immunocompromised patients.

9. Clinical Manifestations • Nonesophageal Gastrointestinal Candidiasis • The most common clinical setting for GI-tract candidiasis is in patients with neoplastic disease. The esophagus is the most common site, followed by the stomach. The most frequent lesions are single or multiple ulcerations containing Candida deep in the ulcer beds. In addition, but with lesser frequency, chronic gastric ulcer, gastric perforation, and malignant gastric ulcer with concomitant Candida infection are seen. Small bowel and large bowel infection occur also. Ulceration is the most common lesion. • CandidaVaginitis • This common infection is most frequently seen in a setting of diabetes mellitus, antibiotic therapy, and pregnancy .In addition, the use of birth control pills may be a predisposing factor, although this association is controversial. However, estimates are that 75% of women have an episode of candidalvaginitis during their lifetime; many have no recognizable underlying predisposing factor. Candida has assumed the role of the most common cause of vaginitis with higher frequency rates than those of Trichomonas or bacterial vaginosis. The widespread use of antibiotic therapy may be the most important factor responsible for the emergence of Candida-induced vaginitis. Reviews of the current trends in the epidemiology and pathogenesis of vaginal candidiasis are now available. In these reviews the rising incidence of non-albicansCandida species is emphasized. • Although Candida-induced vaginitis may be accompanied by a thick, curdlike discharge, scanty discharge may instead characterize the infection. Edema and intense pruritus of the vulva are almost always present. The discharge consists of epithelial cells and masses of hyphae and pseudohyphae; a polymorphonuclear leukocyte response is not a component of the inflammatory reaction. The vagina and labia are usually erythematous, and extension onto skin of the perineum can occur. In addition, endometritis due to Candida has been reported, and the urethra may become secondarily infected.

10. Clinical Manifestations • CUTANEOUS CANDIDIASIS SYNDROMES • Generalized CutaneousCandidiasis • This condition is an unusual form of cutaneouscandidiasis and is characterized by widespread eruptions over the trunk, thorax, and extremities, with increased severity in the genitocrural folds, anal region, axillae, hands, and feet . The process begins as individual lesions that spread into large confluent areas. It occurs in both adults and children. • ErosioInterdigitalisBlastomycetica • This term applies to Candida infection occurring between the fingers or toes . It has a red base, may extend onto the sides of the digits, is painful, and is predisposed to by maceration. • Perianalcandidiasis • with pruritusani either alone or in combination, Candida is a frequent cause. The perianal skin develops marked erythema and progresses to maceration . Intense pruritus results. Complications include involvement of the anal canal and extensive spread over the perineum.

11. Clinical Manifestations • Candida Folliculitis • Infection at the hair follicles with Candida can occur . Rarely, the condition may become extensive. It must be distinguished from folliculitis caused by the dermatophytes and tineaversicolor. This folliculitis has been described in immunocompromised hosts and intravenous drug abusers. As expected, its incidence is increased in obesity. • CandidaBalanitis • This process begins as vesicles on the penis that develop into patches resembling thrush and are accompanied by severe itching and burning. It may spread to the thighs, gluteal folds, buttocks, and scrotum. It can be acquired through sexual intercourse with a partner having vaginal candidiasis. Candida is one of the more common causes of balanitis • Cutaneous Lesions of Disseminated Candidiasis • Four distinct types of lesions associated with disseminated candidiasis have been described. The macronodular lesions are 0.5 to 1 cm in diameter, pink to red, and may either be single or occur widely distributed over the entire body. The most accurate method of making a specific diagnosis is by punch biopsy and demonstration of organisms on histologic section. Most patients with these lesions are neutropenic, and all have disseminated candidiasis, not local inoculation. Additionally, lesions resembling ecthymagangrenosum,purpurafulminans and leukocytoclasticvasculitis have been described. Chronic lesions of pyodermagangrenosa may become superinfected with Candida and delay their definitive diagnosis.

12. Clinical Manifestations • Intertrigo • This common skin condition affects any site in which skin surfaces are in close proximity and provide a warm, moist environment. It begins as vesicopustules, which enlarge and rupture, causing maceration and fissuring. • Paronychia and Onychomycosis • Candida is one of the most common causes of paronychia. Species other than albicans may be causative. Many skin bacteria, as well as Candida, can usually be recovered by culture of the infected area. • Unless the disease process is stopped, secondary thickening, ridging, and discoloration occur, and nail loss may result. • Candidaparonychia occurs in association with frequent immersion of the hands in water. People who may contract paronychia include dishwashers, laundry workers, and parents of young children. • There is also a higher incidence of paronychia among diabetic patients than in the nondiabetic population. • Diaper Rash • Candida is a common cause of diaper rash in infants. The condition generally starts in the perianal area and spreads over the perineum in the region of diaper contact . The process is facilitated by maceration caused by wet diapers. The probable origin is the GI tract. Diagnosis is made by scraping the area and demonstrating the organisms on potassium hydroxide preparation.

13. Clinical Manifestations • Chronic MucocutaneousCandidiasis • The term chronic mucocutaneouscandidiasis (CMC) is used to describe a heterogeneous group of Candida infections of the skin, mucous membranes, hair, and nails that have a protracted and persistent course despite what is usually adequate therapy. • Although most patients with CMC survive for a prolonged period with their disease, patients may succumb if the cutaneous condition and immunodeficiencies are severe enough. Disseminated candidiasis has been a rare complication of this disease; the most common cause of death is bacterial sepsis. The topic of Candida skin infection in general has been reviewed extensively. • Most forms of CMC begin in infancy or within the first 2 decades; rarely, the onset may be after the age of 30 years. The first manifestation is usually oral thrush followed by nail infections and then skin involvement

14. Clinical Manifestations • Central Nervous System Candidiasis • Candida infects both parenchymal brain tissue and the meninges, usually as a complication of hematogenously disseminated candidiasis. Approximately 50% of patients with Candida meningitis have had disseminated disease in other organs. • When infection occurs in brain parenchyma, it generally forms multiple microabscesses and small macroabscesses scattered throughout the tissue. Rarely, larger abscesses have occurred and may be visualized by MRI. • The clinical manifestations of central nervous system involvement with diffuse microabscesses may be variable. If the patient is comatose or noncommunicative, detection of abnormalities may be exceptionally difficult. When meningitis is present, the signs of meningeal irritation (headache, stiff neck, irritability), typical of any meningeal infection, are frequently present. In the newborn, particularly the very low birth weight neonate, diagnosis is often difficult and delayed, leading to permanent neurologic sequelae. Lumbar puncture should be considered when the blood culture of such infants contains Candida. • In addition to occurring as a complication of disseminated candidiasis, Candida meningitis may result from infection of a ventricular shunt or may be introduced by lumbar puncture, trauma, or neurosurgery. The signs and symptoms are nonspecific, with typically an indolent onset. Untreated, the mortality rate is very high; it is reduced substantially with antifungal therapy. Hydrocephalus is a reasonably frequently occurring complication of the infection. An increase in the number of cases of Candida meningitis reported in neonates is occurring. AIDS is considered a predisposing factor for Candida meningitis.

15. Clinical Manifestations • Respiratory Tract Candidiasis • In general, Candida pneumonia occurs in two forms: either local or diffuse bronchopneumonia originating from endobronchial inoculation of the lung, a very rare event, or as a hematogenously seeded, finely nodular, diffuse infiltrate, which in its early stages may be difficult to distinguish from congestive heart failure or Pneumocystis pneumonia • Cardiac Candidiasis • In addition to causing endocarditis, Candida infects both the pericardium and the myocardium. Candidamyocarditis occurs as diffuse microabscesses scattered throughout the myocardium with normal intervening myocardial tissue. Of interest has been the emergence of Candida organisms as a cause of pericarditis. A review of purulent pericarditis spanning the years 1960 to 1974 revealed that Candida organisms were either the single cause or combined with Aspergillus in 15% of the 26 cases. The association of Candidapericarditis with either cardiac surgery or burns has been emphasized. • CandidaEndocarditis • This manifestation of Candida was once a distinctly rare phenomenon, but its true incidence has increased simultaneously with the generalized increase in Candida infections. Of all the forms of fungal endocarditis, Candida is by far the most common • The pathogenic mechanisms for fungal endocarditis are not fully understood, but patients who undergo cardiac surgery are at risk for candidemia by being exposed to multiple antibiotics, prolonged intravenous fluid administration, and intravenous plastic catheters. Both the damaged endocardium and prosthetic material apparently serve as foci for the localization of Candida organisms.

16. Clinical Manifestations • Urinary Tract Candidiasis • Urethral candidiasis can occur in both men and women. • In men, it usually results from sexual contact with women with Candidavaginitis. In women, it is generally thought to be acquired from extension of Candidavaginitis. Candida prostatic infection has also been reported. • A history of previous antibiotic use has been frequent in most patients. • The presence of Candida in the urine is common and usually does not indicate renal tract infection. • Antibiotics and Foley catheters have been associated with the acquisition of candiduria. Visualization (cystoscopy) or biopsy proof of either fungus balls or tissue invasion is requisite for linking candiduria to infection. • Hematogenous dissemination from the urinary tract may occur, usually with instrumention. • Candida cystitis is most commonly a complication of an indwelling Foley catheter. In the absence of bladder instrumentation, Candida cystitis has been associated most often with diabetes mellitus. • Candida infection of the upper urinary tract has been classified into two distinct forms: • primary, presumably from an ascending route • secondary, from hematogenous spread. • Papillary necrosis, calyceal invasion, fungus ball formation, and perinephric abscess can result from ascending infection, particularly in the presence of urinary tract obstruction, renal stones, or diabetes mellitus. • Percutaneousnephrostomy can introduce Candida into the renal pelvis. The hematogenous form of the disease is by far the most common. The pathologic changes are those of multiple microabscesses, especially in the cortical areas. • Emphysematous pyelonephritis may occur.

17. Clinical Manifestations • Candida Arthritis, Osteomyelitis, Costochondritis, and Myositis • These manifestations of Candida infections were once extremely rare, but their true incidence has increased • Candida arthritis occurs most frequently as a complication of disseminated candidiasis. It can also occur from trauma, surgery, and intra-articular injections of steroids, and as a complication of heroin injection, rheumatoid arthritis, and AIDS. • In Candida arthritis occurring unassociated with disseminated candidiasis, non-albicans species have been the most common. Although the majority of cases of Candida arthritis have been acute, chronic Candida arthritis has been reported, especially in leukemic patients. • Candida Infection of Peritoneum, Liver, Spleen, and Gallbladder • Candida infection of the peritoneum is a complication of peritoneal dialysis, GI surgery, and perforation of an abdominal viscus. • Prior antibiotic administration has been an important predisposing factor. • Low-birth-weight neonates disseminate more frequently from intra-abdominal sites, such as complications of surgical correction of intestinal or renal congenital abnormalities. Other GI organs infected with Candida that have been reported include the gallbladder,liver and spleen, spleen alone, and pancreas. • Hepatospleniccandidiasis has emerged as an important clinical problem in immunocompromised hosts and is particularly difficult to treat successfully. • Fungus balls may form in the gallbladder and bile ducts.

18. Clinical Manifestations • Candida Infection of Vasculature • The incidence of Candida intravascular infection has increased significantly, probably due to the increased number of susceptible patients and the widespread increased use of indwelling intravascular devices for advanced life support. Both peripheral and deep vascular structures have been involved, as well as both the venous and the arterial sides of the circulation and implanted prosthetic vascular materials. Although the exact pathogenesis is not known, presumably the damaged endothelium becomes susceptible to Candida invasion. Candida adherence to catheters may also play a role. Complications have included superior cava obstruction, mural endocarditis of the right atrium, tricuspid endocarditis, and pulmonary venous thrombosis. Of importance is that in patients with peripheral septic thrombophlebitis, there may be minimal symptoms and the extent of the disease may be greater than is apparent on initial clinical assessment. These patients require aggressive surgical exploration to determine the extent of the disease process. Culture of the blood and involved veins is frequently positive. • Ocular Candidiasis • Candida can infect the eye by either hematogenous spread or direct inoculation, especially during eye surgery. Candida can infect virtually any eye structure, including conjunctiva, cornea, lens, ciliary body, vitreous humor, and the entire uveal tract. Once endophthalmitis occurs, therapy is difficult, and the incidence of permanent intraocular damage is high.

19. Clinical Manifestations • Through the 1970s there was increased reporting of hematogenousCandidaendophthalmitis and an actual increase in incidence of this complication of candidemia. Previous estimates of the incidence of the lesions in candidemic patients ranged as high as 28%. Recent studies report a lower incidence. An increased use of empiric and prophylactic antifungals may be an explanation for this possible decrease in incidence. A high association of retinopathy of prematurity with candidemia in very low birth weight neonates has been described. Case reports include Candidaendophthalmitis as a complication of tatooing, childbirth, abortion, therapy for HIV infection, and intravenous administration of contaminated dextrose infusion solution for minor ailments in a rural setting. • The lesions are important because they can cause permanent blindness, and they may indicate underlying disseminated candidiasis. Chorioretinal lesions are single or multiple, white, round, and initially sharply defined. As a lesion progresses over several days, the overlying vitreous humor becomes hazy, making the lesion margins indistinct. Eventually, Candida and neutrophils form white, cotton ball–like abscesses in a densely clouded vitreous. Use of the indirect ophthalmoscope facilitates visualization of their three-dimensional characteristics. Neutropenia inhibits the formation of ocular lesions in the experimental rabbit model and may be associated with a lack of formation of easily seen lesions in some neutropenic patients. Diagnosis can be made by the characteristic fundoscopic picture, plus, in half the cases, an episode of known candidemia. Aspiration of the anterior chamber is rarely diagnostic. However, elective pars planavitrectomy may be helpful both diagnostically and therapeutically in patients with vitreous abscesses.Centrifuged sediment of vitrectomy fluid should be examined by smear and culture, Diagnosis may be facilitated with Candida specific polymerase chain reaction (PCR) of vitrectomy fluid or vitreous aspirate. Symptoms include visual blurring, floating scotomas, and, with extension to the anterior chamber, bulbar pain. Importantly, many patients in intensive care units are too ill to complain of symptoms. Although C. albicans has been the most frequent species causing endophthalmitis, other species have been reported with increasing frequency.

20. Clinical Manifestations • Syndrome of Disseminated Candidiasis and Candidemia • The problems of management of candidemia and detection of underlying disseminated candidiasis present major enigmas for clinicians dealing with patients who are predisposed to the disseminated form of this disease. The problem is compounded by the absence of positive blood cultures in many patients with disseminated disease. The interpretation of the significance of recovery of increased numbers of Candida from sites such as sputum, urine, feces, and skin is difficult because the organisms can frequently be recovered from these sites without causing infection. • The clinical setting associated with disseminated candidiasis has been previously described. As expected, the populations of patients most commonly affected are those with neoplastic disease, patients who have had complicated postoperative courses, burn patients, patients who have received organ transplants, and low-birth-weight neonates. In the neoplastic group, the most common association has been with the acute leukemic population. In the postoperative group, the patients who have had organ transplantations, heart surgery, or GI-tract surgery are at greatest risk. • When Candida disseminates, multiple organs are usually involved, with the kidney, brain, myocardium, and eye the most common. In cancer patients receiving extensive immunosuppressive therapy, recognition of liver and spleen involvement increased substantially, but the incidence of this complication has been in a downward trajectory. Other organs less frequently infected include the lungs, GI tract, skin, and endocrine glands. The hallmarks of the pathologic changes are diffuse microabscesses with a combined acute suppurative and granulomatous reaction and small macroabscesses. Macroabscesses more than a centimeter in diameter may also form, especially in the liver and spleen.

21. Clinical Manifestations • The rate of premortem diagnosis of disseminated candidiasis has been very low; only approximately 15% to 40% of cases have been diagnosed early enough for appropriate therapy. As an aid to earlier diagnosis, considerable attention has been focused on the detection of serum antibodies to Candida and the detection of Candida antigen. Despite the appearance of a very large number of publications on the serologic diagnosis of disseminated candidiasis, spanning at least three decades, controversies remain regarding the value of various serodiagnostic procedures. Problems with the older diagnostic tests have been reviewed in detail. Currently, there is no validated serodiagnostic test that is widely used. Data are accumulating with the β-glucan assay on serum, but the place of the test in clinical management remains uncertain. • The premortem diagnosis of disseminated candidiasis, therefore, remains a clinical diagnosis. Definitive diagnosis is made by histopathologic demonstration of the organism invading tissues. Of greatest importance in facilitating the diagnosis is awareness of, and persistent evaluation for, the variety of manifestations of disseminated candidiasis that serve as diagnostic clues. Candidemia is detected in about 24 hours with automated blood cultures and once detected, should prompt repeat blood culture, intravenous catheter change, and administration of an antifungal. Some retrospective studies have correlated rapid institution of antifungal therapy with improved outcome in candidemia. The logical extension of this conclusion would be empirical therapy in patients at high risk of having candidemia. Selection of patients for empirical therapy remains incompletely defined, as discussed following. • Miscellaneous Candida Infections • Candida infections that have been described but are beyond the scope of this discussion include ear infections, nasal ulcers, lymphadenitis (in patients with leukemia), laryngeal infection, diarrhea, and the “drunken disease” syndrome described in Japan (thought to be due to Candida fermentation of carbohydrate in the GI tract). Also, Candida infections of numerous types have been reported with increasing frequency in antenates, neonates, and older children. Additionally, the emergence of C. glabrata and C. krusei, and C. tropicalis should be noted. The isolation of unusual Candida species continues to increase in frequency. A partial list is represented in the following descriptions.

22. ASPERGILLOSIS • Invasive aspergillosis • a major cause of morbidity and mortality in immunosuppressed patients. • caused by Aspergillus, • a hyaline mold responsible not only for invasive aspergillosis, a variety of noninvasive or semi-invasive conditions. • These syndromes : • colonization with the organism, such as fungus ball due to aspergillus (also known as aspergilloma); • allergic responses to Aspergillus, including allergic bronchopulmonaryaspergillosis (ABPA); • semi-invasive or invasive infections, (chronic necrotizing pneumonia to invasive pulmonary aspergillosis) and other syndromes of tissue invasion.

23. easily cultured • grow rapidly (within 24-72 hours) at a broad range of temperatures on a variety of media. • Blood cultures are still uncommonly positive and often reflect contamination rather than invasive disease. • A distinguishing characteristic of pathogenic Aspergillus species is their ability to grow at 37° C. • In addition, strains of A. fumigatus are able to grow at temperatures of 50° C, a feature that, in addition to morphology, can also be used to identify this species. • Most species initially appear as small, fluffy white colonies on culture plates within 48 hours. • Presumptive identification of an Aspergillus species is usually readily accomplished by appearance of the fungus on gross and microscopic inspection of the colony growing on medium, which provides typical sporulation.

24. Aspergillusfumigatus • most pathogenic species • most common species in invasive infection, • Colonies of A. fumigatus are typically gray-green with a wooly to cottony texture . • hyphae are hyaline (lightly pigmented), • have septa, • usually branched at acute (typically 45 degrees) angles. • The conidial head is columnar with conidiophores that are smooth walled and uncolored, or darkened in the upper portion near the vesicle. • Like other Aspergillus spp., it is widespread in nature—found in soil, on decaying vegetation, in the air, and, more recently, in water supplies.

26. Aspergillusflavus • common isolate in sinusitis as well as in skin and invasive infections. • produces an aflatoxin, is found in soil and decaying vegetation. • Colonies are olive to lime green and grow at a rapid rate .

28. Aspergillusterreus • common soil-related isolate that has been increasingly reported in invasive infection in immunocompromised hosts. • conidia are small (2.0-2.5 µm), and the colony color and fruiting structures are characteristic for this species. • A distinguishing feature : the presence of globose accessory conidia that are produced on hyphae. • resistance to many antifungals, including amphotericin B

30. Aspergillusniger • found in soil, on plants, and even in food and condiments (such as pepper). • Colonies are initially white but quickly become black with the production of the pigmented fruiting structures. • It grows rapidly with a pale yellow reverse. • The role of A. niger in invasive infection is less well established, with its decreased pathogenicity perhaps due in part to the fact that its larger conidia do not readily reach deep into lung tissues. • common colonizing isolate and can cause superficial infection, such as otitisexterna. • Other species of Aspergillus are less common in invasive infection; • Aspergillusnidulans, • Aspergilluscalidoustus • Ustus

32. Diagnosis and Susceptibility Testing • A proven diagnosis of invasive aspergillosis requires a tissue biopsy showing invasion with hyphae and a positive culture for Aspergillus. • The diagnosis can also be established with positive cultures from a normally sterile site such as a needle biopsy or cerebrospinal fluid (CSF), although blood cultures are rarely positive. • not distinguishable from a number of other opportunistic molds, including Fusarium, Scedosporium (Pseudallescheria), and others so that a positive culture is needed to confirm the diagnosis. • Cultures for Aspergillus in respiratory samples in high-risk patients, particularly if obtained via bronchial alveolar lavage, can support the diagnosis of probable invasive aspergillosis. • Aspergillus is also cultured from patients in whom no clinical illness is apparent so that positive cultures in patients with a low risk for invasive aspergillosis should be interpreted with caution.

33. Radiographic findings can also be used in the diagnosis and management of invasive pulmonary aspergillosis. • Nonculture methods have been used to establish a rapid diagnosis of invasive aspergillosis. • Antibody detection is of limited utility because immunosuppressed hosts fail to mount an antibody response even with invasive infection. • Detection of galactomannan by EIA has contributed substantially to the diagnosis of invasive aspergillosis. • False-positive results have been reported, including in some neonates, which may be due to dietary intake or the presence of cross-reacting antigens with bacteria such as Bifidobacterium, and in patients receiving therapy with piperacillin/tazobactam and other antibiotics • Although the method has been used for other body fluids such as CSF and in bronchial alveolar lavage (BAL) fluid, these samples have been less extensively evaluated compared with

34. Other potential markers also include nonspecific fungal marker β-glucan using a variation of the limulus assay to detect endotoxin. • Molecular diagnostics including polymerase chain reaction (PCR) have also been developed for Aspergillus. • Several reports demonstrate the potential for using PCR as an early diagnostic marker, which appears more sensitive than other methods including galactomannan. • These assays are not standardized and remain investigational, although this approach is very promising for improving the diagnosis of invasive aspergillosis.

35. CRYPTOCOCCOSIS • a chronic, subacute to acute pulmonary, systemic or meningitic disease, initiated by the inhalation of basidiospores and/or desiccated yeast cells of Cryptococcus neoformans • affects immunocompromised hosts predominantly • the commonest cause of fungal meningitis; worldwide, 7-10% of patients with AIDS are affected. • Meningitis is the predominant clinical presentation with fever and headache as the most common symptoms. • Secondary cutaneous infections occur in up to 15% of patients with disseminated cryptococcosis and often indicate a poor prognosis. • Lesions usually begin as small papules that subsequently ulcerate, but may also present as abscesses, erythematous nodules, or cellulitis.

37. ZYGOMYCOSIS Mucorales, causing subcutaneous and systemic zygomycosis (Mucormycosis) : • Rhizopus, • Mycocladus (Absidia), • Rhizomucor, • Mucor, • Cunninghamella, • Saksenaea, • Apophysomyces, • Cokeromyces • Mortierella

38. in the debilitated patient,the most acute and fulminate fungal infection known. • typically involves the rhino-facial-cranial area, lungs, gastrointestinal tract, skin, or less commonly other organ systems. • often associated with acidotic diabetes, starvation, severe burns, intravenous drug abuse, and other diseases such as leukemia and lymphoma, immunosuppressive therapy, or the use of cytotoxins and corticosteroids, therapy with desferrioxamine (an iron chelating agent for the treatment of iron overload) and other major trauma. • The infecting fungi have a predilection for invading vessels of the arterial system, causing embolization and subsequent necrosis of surrounding tissue. • A rapid diagnosis is extremely important if management and therapy are to be successful.

39. Rhinocerebral zygomycosis: • Infections usually begin in the paranasal sinuses following the inhalation of sporangiospores and may involve the orbit, palate, face, nose or brain. • Pulmonary zygomycosis: • leading to pulmonary infraction and necrosis with cavitation. • Gastrointestinal zygomycosis: • A rare entity, usually associated with severe malnutrition, particularly in children, and gastrointestinal diseases which disrupt the integrity of the mucosa. • Disseminated zygomycosis: • especially in severely debilitated patients with haematological malignancies, burns, diabetes or uraemia. • Central Nervous System alone: • Intravenous drug abuse. Traumatic implantation leading to brain abscess

41. OTHER MYCOSES DUE TO YEASTLIKE FUNGI • Malassezia spp. • usually catheter related • tend to occur in premature infants • other patients receiving lipid infusions • Trichosporon spp. • catheter-associated fungemia • also via the respiratory or gastrointestinal tract • most common cause of noncandidial yeast infection in patients with hematologic malignancies, mortality with excess of 80%

42. Rhodotorula spp. • carotenoid pigments (pink to red colonies) • variably encapsulated, budding yeast cells • immuncompromised patients and those with indwelling devices • central venous catheter infection, fungemia • ocular infections • peritonitis • meningitis

43. Blastoschizomyces capitatus • Hematologic malignancies • Part of normal skin flora • Similar diseases like Trichosporon • Blood cultures usually positive

44. MYCOSES DUE TO OTHER HYALINE MOLDS (Hyalohyphomycosis) • Hyaline (nonpigmented) • septate, • Branching • Filamentous fungi(may be indistinguishable from Aspergillus) • Fusarium • Fungal keratitis (contact lenses) • 75% of patients with positive blood cultures • Macroconidia,microconidia

46. Scedosporium • Antifungal resistant opportunistic pathogen • Disseminated or located infections (corneal ulcers, endophtalmitis, sinusitis, pneumonia, endocarditis, meningitis, arthritis, osteomyelitis)

48. Acremonium • Similar Fusarium • Positive blood cultures • Disseminated skin lesions • Commonly found in soil, decating vegetation

50. Paecilomyces • uncommon • invasive disease in organ and hematopoietic stem cell recipients • individuals with AIDS • other immunocompromised patients • through skin or intravascular catheters • Trichoderma • previously non pathogenic • immuncompromised patients • peritoneal dialysis • fatal disseminated disease