T10_Micoses Oportunistas ★ Flashcards
Quais são os principais agentes etiológicos das micoses oportunistas?
6
Candida spp.
Cryptococcus spp.
Aspergillus spp.
Zygomycetes
Pneumocystis jirovecii
Talaromyces marneffei
Como podemos distinguir os agentes das micoses oportunistas quanto à sua origem?
Humana (comensais)
* Candida spp
Ambiente
* os restantes (Cryptococcus spp., Aspergillus spp., Zygomycetes, Pneumocystis jirovecii, Talaromyces marneffei)
Como podemos distinguir os agentes das micoses oportunistas quanto à sua virulência?
Baixa - a maioria, afetando os:
Imunocomprometidos
Portadores de próteses ou catéteres vasculares
Exceção: Cryptococcus neoformans
* virulência elevada afeta o Indivíduo saudável
Quais são os fatores de risco das micoses oportunistas?
9*
- Transplante de medula óssea
- Transplante de órgão sólido
- Grande cirurgia (principalmente G-I)
- SIDA
- Doença neoplásica (LMA, SMD)
- Terapia imunossupressora
- Idade avançada
- RN prematuro
- Outros (diabetes, linfomas, quebra barreiras mucosas, desequilíbrios flora saprófita)
Caracteriza a Candidíase
It is clear that the most important group of opportunistic fungal pathogens is the Candida species.
Candida spp. are the third most common cause of central line-associated bloodstream infections (BSIs), exceeding that of any individual Gram (-) pathogen. Between 1980 and the present, the frequency of Candida BSIs has risen steadily in hospitals of all sizes and in all age groups.
C. albicans is the species most commonly isolated from clinical material and generally accounts for 90% to 100% of mucosal isolates and 40% to 70% of isolates from BSI, depending on the clinical service and the patient’s underlying disease.
Approximately 95% of all Candida BSIs are accounted for by four species: C. albicans, C. glabrata, C. parapsilosis, and C. tropicalis.
Among these common species, only C. glabrata can be said to be truly “emerging” as a cause of BSI, in part because of its intrinsic and acquired resistance to azoles and other commonly used antifungal agents.
The remaining 5% of Candida BSIs encompasses 12 to 14 different species, including C. krusei, C. lusitaniae, C. dubliniensis, and C. rugosa, among others. Although these species must be considered “rare” causes of candidiasis, several have been observed to occur in nosocomial clusters and/or to exhibit innate or acquired resistance to one or more established antifungal agents.
C. auris is an emerging species of great concern worldwide. Originally described in 2009 in association with otitis externa, this multidrug-resistant and highly pathogenic yeast has simultaneously emerged on three continents as an important nosocomial pathogen with evidence of high levels of interhospital and intrahospital transmission and distinct geographically constrained clonal lineages.
All Candida species exist as oval yeastlike forms (3 to 5 μm) that produce buds or blastoconidia.
Species of Candida other than C. glabrata also produce pseudohyphae and true hyphae. In addition, C. albicans forms germ tubes and terminal, thick-walled chlamydoconidia.
C. glabrata, the second most common species of Candida in many settings, is incapable of forming pseudohyphae, germ tubes, or true hyphae under most conditions.
In histologic sections, all Candida spp. stain poorly with hematoxylin and eosin (H&E) and well with the periodic acid–Schiff (PAS), Gomori methenamine silver (GMS), and Gridley fungus stains.
In culture, most Candida spp. form smooth, white, creamy, domed colonies. C. albicans and other species may also undergo phenotypic switching, in which a single strain of Candida may change reversibly among several different morphotypes, ranging from the typical smooth, white colony composed of predominantly budding yeast-like cells to very “fuzzy” or “hairy” colonies composed primarily of pseudohyphal and hyphal forms.
The frequency of the switching phenomenon is too high to result from gene mutations and too low to be attributable to mass conversion, in which all cells in the population change their phenotype in response to signals from the environment. It is likely that switching serves as some type of master system in C. albicans, and other species, for rapid response at the level of individual cells to changes in the local microenvironment. It has been postulated that phenotypic switching explains the ability of C. albicans to survive in many different environmental microniches within the human host.
Como descreverias a epidemiologia da Candidíase?
Candida spp. are known colonizers of humans and other warm-blooded animals. As such, they are found in humans and in nature worldwide.
The primary site of colonization is the GI tract from mouth to rectum. They also may be found as commensals in the vagina and urethra, on the skin, and under the fingernails and toenails.
C. albicans, the most common etiologic agent of human disease, has also been found apart from humans and animals in air, water, and soil.
It is estimated that 25% to 50% of healthy persons carry Candida as part of the normal flora of the mouth, with C. albicans accounting for 70% to 80% of isolates.
Oral carriage rates are increased substantially in:
* hospitalized patients;
* those with human immunodeficiency virus (HIV) infection,
* dentures, and diabetes;
* patients receiving antineoplastic chemotherapy;
* those receiving antibiotics;
* and children.
Virtually all humans may carry one or more Candida species throughout their GI tract, and the levels of carriage may increase to that detectable in illness or other circumstances in which the host’s microbial suppression mechanisms become compromised.
The predominant source of infection caused by Candida spp., from superficial mucosal and cutaneous disease to hematogenous dissemination, IS THE PATIENT.
That is, most types of candidiasis represent endogenous infection in which the normally commensal host flora take advantage of the “opportunity” to cause infection. To do so, there must be:
* a lowering of the host’s anti-Candida barrier.
In the cases of Candida BSIs transfer of the organism from the GI mucosa to the bloodstream requires:
* prior overgrowth of the numbers of yeasts in their commensal habitat
* a breach in the integrity of the GI mucosa.
Exogenous transmission of Candida also may account for a proportion of certain types of candidiasis. Examples include:
* the use of contaminated irrigation solutions,
* parenteral nutrition fluids,
* vascular pressure transducers,
* cardiac valves, and corneas.
Transmission of Candida spp. from health care workers to patients and from patient to patient has been well documented, especially in the intensive care unit environment. The hands of health care workers serve as potential reservoirs for nosocomial transmission of Candida spp..
Among the various species of Candida capable of causing human infection, C. albicans predominates in most types of infection. Infections of genital, cutaneous, and oral sites almost always involve C. albicans.
A wider array of Candida spp. is seen causing BSIs and other forms of invasive candidiasis, and although C. albicans usually predominates, the frequency with which this and other species of Candida are isolated from blood varies considerably according to
* the clinical service;
* the age of the patient;
* and the local, regional, or global setting.
Whereas C. albicans and C. parapsilosis (infants less than 1 year old) predominate as causes of BSIs among infants and children, a decrease in C. albicans and C. parapsilosis infections and a prominent increase in C. glabrata infections is seen among older individuals.
Also, although C. glabrata is the second most common species causing BSIs in North America, it is seen at a lower frequency in Latin America, in which C. parapsilosis and C. tropicalis are more common.
The differences in the number and types of Candida spp. causing infections may be influenced by numerous factors, including:
* patient age,
* increased immunosuppression,
* antifungal drug exposure,
* or differences in infection-control practices.
Each one of these factors, alone or in combination, may affect the prevalence of different Candida spp. in each institution. For example, the use of azoles (e.g., fluconazole) for antifungal prophylaxis in hematologic malignancy patients and recipients of stem cell transplantation may increase the likelihood of infections caused by C. glabrata and C. krusei, which are two species with decreased susceptibility to this class of antifungals.
Also, breaks in infection-control precautions and in the proper care of vascular catheters may lead to more infections with C. parapsilosis, which is the predominant species isolated from the hands of health care workers and a frequent cause of catheter-related fungemia.
In the last several years, C. auris has emerged simultaneously on three continents as an important novel cause of nosocomial infections, with geographically restricted clonal lineages and high interhospital and intrahospital transmission rates.
A wide variety of deep-seated infections in addition to candidemia have been reported, and this multidrug-resistant (intrinsically resistant to fluconazole with reported resistances to amphotericin B, the echinocandins, and 5-FC) species has been shown to persist in hospital environments and cause long-term colonization of patients in high-intensity care settings, leading to specific guidelines for the management of patients infected or colonized with this organism.
The consequences of a Candida BSI in the hospitalized patient are severe.
Hospitalized patients with candidemia have been shown to be at a twofold greater risk of death in hospital than those with noncandidal BSIs.
Among all patients with nosocomial (hospital-acquired) BSIs, candidemia was found to be an independent predictor of death in hospital. Although estimates of mortality may be confounded by the serious nature of the underlying diseases in many of these patients, matched cohort studies have confirmed that the mortality directly attributable to the fungal infection is quite high. Notably, the excess or attributable mortality resulting from candidemia has not decreased from that observed in the mid-1980s to that observed in the present day, despite the introduction of new antifungal agents with good activity against most species of Candida.
Clearly, more is known about the epidemiology of nosocomial candidemia than any other fungal infection. The accumulated evidence allows one to propose a general view of nosocomial candidemia. Certain hospitalized individuals are clearly at increased risk of acquiring candidemia during hospitalization because of their underlying medical condition:
* patients with hematologic malignancies and/or neutropenia,
* those undergoing GI surgery,
* premature infants,
* and patients older than 70 years.
Compared with control subjects without the specific risk factors or exposures, the likelihood of these already high-risk patients contracting candidemia in hospital is approximately:
* 2 times greater for each class of antibiotics they receive,
* 7 times greater if they have a central venous catheter,
* 10 times greater if Candida has been found to be colonizing other anatomic sites,
* and 18 times greater if the patient has undergone acute hemodialysis.
Hospitalization in the intensive care unit setting provides the opportunity for transmission of Candida among patients and has been shown to be an additional independent risk factor.
The available epidemiologic data indicate that between 20 and 40 of every 1000 high-risk patients exposed to the previously mentioned risk factors will contract a BSI caused by Candida spp. (8% to 10% of all nosocomial BSIs).
Approximately 49% of these patients will die as a result of their infection, 12% will die of their underlying disease, and 39% will survive hospitalization (see Fig. 65.4).
This picture has not changed, and may even be worse, from that seen in the mid-1980s. The outcome for almost half of those patients with candidemia could be improved by more effective means of prevention, diagnosis, and therapy.
Clearly the most desirable of these is prevention, which is best approached by rigorous control of the exposures, especially limiting the use of broad-spectrum antibiotics, improving catheter care, and adhering to infection-control practices.
Quais são as espécies de Candida mais prevalentes no trasplante de células estaminais? Qual é a razão?
C. glabrata e C. krusei
Uma das terapêuticas anti-fúngicas profiláticas usadas no transplante de MO é o flucanozole. Estas 2 espécies têm uma resistência aumentada para os azóis, levando a que haja uma maior prevalência das mesmas neste tipo de doentes.
A Candida spp. dá o quê? Descreve a clínica deste agente
Given the right setting, Candida spp. can cause clinically apparent infection of virtually any organ system.
Infections range from superficial mucosal and cutaneous candidiasis to widespread hematogenous dissemination involving target organs, such as the liver, spleen, kidney, heart, and brain. In the latter situation, the mortality directly attributable to the infectious process approaches 50%.
Mucosal infections caused by Candida spp. (known as “thrush”) may be limited to the oropharynx or extend to the esophagus and the entire GI tract.
In women, the vaginal mucosa also is a common site of infection. These infections are generally seen in individuals with local or generalized immunosuppression or in those settings in which candidal overgrowth is favored. These infections usually present as white “cottage cheese”–like patches on the mucosal surface.
Other presentations include:
* the pseudomembranous type, which reveals a raw bleeding surface when scraped;
* the erythematous type, which has flat, red, and occasionally sore areas;
* candidal leukoplakia,which has nonremovable white thickening of epithelium caused by Candida spp.;
* and angular cheilitis, which has sore fissures at the corners of the mouth.
Candida spp. may cause localized skin infection in areas in which the skin surface is occluded and moist (e.g., groin, axillae, toe webs, breast folds). These infections present as a pruritic rash with erythematous vesiculopustular lesions. Onychomycosis and paronychia may occur in the setting of a mixed microbial flora, including Candida. The species most commonly involved are C. albicans, C. parapsilosis, and C. guilliermondii.
Skin lesions may also appear during the course of hematogenous dissemination. These lesions are of major diagnostic importance; they can be directly biopsied and thus provide an etiologic diagnosis of a systemic process.
Chronic mucocutaneous candidiasis is a rare condition marked by a deficiency in T-lymphocyte responsiveness to Candida spp. These patients suffer from severe, unremitting mucocutaneous Candida lesions, including extensive nail involvement and vaginitis. The lesions may become quite large, with a disfiguring granulomatous appearance.
Urinary tract involvement with Candida spp. ranges from asymptomatic bladder colonization to renal abscesses secondary to hematogenous seeding.
Bladder colonization with Candida spp. is essentially not seen, unless:
* a patient requires an indwelling bladder catheter,
* has diabetes,
* suffers from urinary obstruction,
* or has had prior urinary procedures.
Benign colonization of the bladder is most common in these settings, but urethritis and/or cystitis may occur.
Hematogenous seeding of the kidney may result in:
* renal abscess,
* papillary necrosis,
* or “fungus ball” of the ureter or renal pelvis.
Intraabdominal candidiasis in patients who have had recent abdominal surgery or intraabdominal events refers to a heterogeneous group of infections that includes:
* peritonitis,
* abdominal abscess,
* and purulent or necrotic infection at sites of GI perforation or anastomotic leak.
Candida peritonitis may be seen in the setting of chronic ambulatory peritoneal dialysis or after GI surgery, anastomotic leak, or intestinal perforation.
These infections may:
* remain localized to the abdomen,
* involve adjacent organs,
* or lead to hematogenous candidiasis.
Up to 40% of patients with secondary or tertiary peritonitis, as defined by a multinational consensus panel, may develop intraabdominal candidiasis with a high mortality rate.
A subset of postsurgical patients, particularly those with recurrent gastroduodenal perforation, anastomotic leaks, or acute necrotizing pancreatitis, are at uniquely high risk for invasive candidiasis.
In other settings, such as perforated appendicitis, invasive candidiasis appears to be a rare complication. Infections are often polymicrobial, with yeast noted in as high as 20% of all cases and 40% in patients with a recent gastroduodenal perforation.
Diagnosis is hampered by the lack of specific clinical signs and symptoms.
Blood cultures are often negative.
A laboratory report of yeast isolated from an abdominal specimen must be evaluated to distinguish between contamination, colonization, and invasive infection.
Hematogenous candidiasis may be acute or chronic and usually results in seeding of deep tissues, including the:
* abdominal viscera,
* heart,
* eyes,
* bones and joints,
* and brain.
Chronic hepatosplenic candidiasis may occur after overt or occult fungemia and presents as an indolent process marked by fever, elevated alkaline phosphatase, and multiple lesions in the liver and spleen.
Central nervous system (CNS) candidiasis may occur secondary to hematogenous disease or be associated with neurosurgical procedures and ventriculoperitoneal shunts.
This process may mimic bacterial meningitis, or the course may be indolent or chronic.
Most cardiac involvement with Candida spp. is the result of hematogenous seeding of a prosthetic or damaged heart valve, the myocardium, or pericardial space.
Implantation of heart valves contaminated with C. parapsilosis has been reported. The clinical presentation resembles bacterial endocarditis, with fever and a new or changing heart murmur. The vegetations are classically large and friable, and
*embolic events are more common with endocarditis caused by Candida spp. than with bacterial endocarditis.
The eye is frequently involved in patients with hematogenous candidiasis, presenting as chorioretinitis and endophthalmitis. For this reason, all patients at risk for candidemia should receive careful and frequent ophthalmologic examinations. Traumatic keratitis also may be seen.
Bone and joint infections caused by Candida spp. are almost always sequelae of candidemia. Often, these infections will present several months after successful treatment of candidemia. Similarly occult or “transient” candidemia may result in seeding of a skeletal focus that becomes clinically apparent at a later time.
Vertebral osteomyelitis is a frequent presentation, with local pain and low-grade fever.
Although hematogenous candidiasis is most often an endogenous infection arising from the GI or genitourinary tract, it may also result from the contamination of an indwelling catheter. Organisms transferred to the hub or lumen of the catheter may form a biofilm within the lumen of the catheter and subsequently spread into the circulation.
Although such infections are no less serious than those arising from an endogenous source, they may be dealt with somewhat more successfully because removal of the catheter essentially removes the nidus of infection. Of course, if the infected catheter resulted in the seeding of distant organs, the consequences and problems in treating the infection would be the same as those arising from an endogenous source.
Fala da candidúria e a sua abordagem
Factores risco para candidúria
* Catéter vesical (algaliação)
* Obstrução urinária
* Procedimentos urinários
* Diabetes mellitus
* AB largo espectro
Candidúria sintomática
* Tratar sempre
Candidúria assintomática
* Tratar nos doentes com > risco disseminação:
- Neutropénico
- Obstrução do tracto urinário
- Doentes que vão sofrer procedimento urológico
Urinary tract involvement with Candida spp. ranges from asymptomatic bladder colonization to renal abscesses secondary to hematogenous seeding.
Bladder colonization with Candida spp. is essentially not seen, unless:
* a patient requires an indwelling bladder catheter,
* has diabetes,
* suffers from urinary obstruction,
* or has had prior urinary procedures.
Benign colonization of the bladder is most common in these settings, but urethritis and/or cystitis may occur.
Hematogenous seeding of the kidney may result in:
* renal abscess,
* papillary necrosis,
* or “fungus ball” of the ureter or renal pelvis.
Fala da candidémia e a sua abordagem
Fatores predisponentes - 8
É muito importante saber quais são os fatores de risco que um doente tem, para poder antecipar as infeções que se podem desenvolver.
Factores predisponentes
* Cirurgia abdominal
* UCI
* Transplante de MO e órgão sólido
* Colonização
* AB prolongado
* Hemodiálise
* Imunossupressão
* Idades extremas
A maior parte dos doentes com candidémia (Candida em circulação, que é tradução da doença sistémica) são doentes que foram submetidos a uma grande cirurgia abdominal, com perfuração de órgão oco e que estão há vários dias na UCI em situação grave.
Isto porque, como já foi referido, a Candida coloniza o trato GI e, portanto, se há uma cirurgia desta gravidade num doente instável, com perfuração de víscera oca e extravasamento de conteúdo fecal, a Candida pode colonizar e invadir outros locais que, de outra forma, seriam inatingíveis.
Uma candidémia traduz maior probabilidade de haver doença disseminada.
Peritonite e Candida spp.? Há relação?
Fatores predisponentes - 5
Factores predisponentes
* Perfuração G-I
* Cirurgia abdominal
* Pancreatite
* “leaks” de anastomoses
* DPCA (Diálise Peritoneal Contínua Ambulatória)
Intraabdominal candidiasis in patients who have had recent abdominal surgery or intraabdominal events refers to a heterogeneous group of infections that includes:
* peritonitis,
* abdominal abscess,
* and purulent or necrotic infection at sites of GI perforation or anastomotic leak.
Candida peritonitis may be seen in the setting of chronic ambulatory peritoneal dialysis or after GI surgery, anastomotic leak, or intestinal perforation.
These infections may:
* remain localized to the abdomen,
* involve adjacent organs,
* or lead to hematogenous candidiasis.
Up to 40% of patients with secondary or tertiary peritonitis, as defined by a multinational consensus panel, may develop intraabdominal candidiasis with a high mortality rate.
A subset of postsurgical patients, particularly those with recurrent gastroduodenal perforation, anastomotic leaks, or acute necrotizing pancreatitis, are at uniquely high risk for invasive candidiasis.
In other settings, such as perforated appendicitis, invasive candidiasis appears to be a rare complication. Infections are often polymicrobial, with yeast noted in as high as 20% of all cases and 40% in patients with a recent gastroduodenal perforation.
Diagnosis is hampered by the lack of specific clinical signs and symptoms.
Blood cultures are often negative.
A laboratory report of yeast isolated from an abdominal specimen must be evaluated to distinguish between contamination, colonization, and invasive infection.
A que é que associas a Candidíase mucocutânea crónica?
Chronic mucocutaneous candidiasis is a rare condition marked by a deficiency in T-lymphocyte responsiveness to Candida spp. These patients suffer from severe, unremitting mucocutaneous Candida lesions, including extensive nail involvement and vaginitis. The lesions may become quite large, with a disfiguring granulomatous appearance.
Quais são os fatores predisponentes para a Candidíase no SNC?
Factores predisponentes - 3
- Infeção hematogénea
- Shunt ventriculo-peritoneal
- Cirurgia SNC ou ocular
Central nervous system (CNS) candidiasis may occur secondary to hematogenous disease or be associated with neurosurgical procedures and ventriculoperitoneal shunts.
This process may mimic bacterial meningitis, or the course may be indolent or chronic.
O que é isto?
Gram urina (objectiva 100x, Candida albicans)
Tens um doente internado com pneumonia. A infeção por Candida spp. pode ser um possível diagnóstico? Justifica
Ainda hoje se discute se a Candida, ou se os fungos do género Candida, podem ser responsabilizados por pneumonias.
À partida, um indivíduo que esteja hospitalizado por mais de uma semana, estará colonizado por Candida, sendo muito frequente encontrarmos esses fungos nos exames culturais das amostras respiratórias.
No entanto, não podemos considerar que existe uma pneumonia por Candida, uma vez que, qualquer individuo hospitalizado há mais de uma semana, terá Candida nas amostras respiratórias, logo não é um critério.
Quando a patologia pressupõe que pode haver uma infeção respiratória oportunista que inclui a Candida, o diagnóstico da situação tem de ser feito por biópsia (única forma de fazer o diagnóstico é encontrar as leveduras no interior do tecido).
O exame cultural da expetoração não serve, visto que a amostra que vai ser colhida vai passar pela orofaringe e pela boca, arrastando sempre leveduras (quando se encontram leveduras numa amostra respiratória, é
considerado como um dado negativo).
Caracteriza o diagnóstico cultural da Candidíase
O diagnóstico da candidíase faz-se por exame cultural e por exame microscópico, através da colheita da amostra no local da lesão.
* Se a amostra for fluída, podemos realizar um exame a fresco. As leveduras são facilmente observáveis no exame direto dado serem de grandes dimensões e produzirem umas estruturas filamentosas fáceis de identificar. Também coram bem com a coloração Gram (Gram+).
* O exame cultural é feito no meio de Sabouraud. As colónias crescem ao fim de 24h a 48h, são brancas e têm um odor característico a fermento de padeiro (“cheiro a massa de pizza”).
A partir da cultura, podemos identificar os microrganismos dessas colónias ao microscópio (observam-se estruturas de grandes dimensões e redondas, tipo leveduriformes).
Poderíamos então realizar uma prova de filamentação precoce (prova que se fazia antigamente), que permite distinguir a espécie C.albicans das outras espécies.
Esta identificação é importante pois, ao reconhecer qual é a espécie, sabemos qual o antifúngico adequado. Esta prova tinha uma duração de apenas 3h, o que significava que podíamos fazer a identificação da C.albicans no próprio dia em que tínhamos a colónia (as identificações por provas bioquímicas demoravam 24h).
Prova de filamentação precoce: As colónias são incubadas com um soro (humano ou bovino fetal) durante 3h. Ao fim desse tempo, só a C.albicans é que tem a capacidade de formar um filamento a partir da levedura.
- Obtenção correta da amostra
- Exame direto
- Cultura
- Meio cromogénico ou provas bioquímicas/MALDI-TOF para a identificação da espécie
Lesões cutâneas - descamação, recolhe-se uma dessas “escasmas” e colocamos Hidróxido de Potássio (KOH 10%-20%), permitindo detetar as pseudohifas.
Exame cultural procede-se da seguinte forma:
* Meios típicos para isolamento de fungos (estes crescem na maioria dos meios mas pode ser um processo demorado, daí ser mais rápido usar meios mais nutritivos. Os “típicos” são o BHI - Brain Heart Infusion agar - para fungos fastidiosos, ou, o SABHI - Sabouraud dextrose and BHI agar - para a maioria)
* Meio cromogénico para crescimento específico, como o CHROMagar Candida
Fica azul - Candida albicans
Fica verda - Candida tropicalis
Comentário importantes:
* A cultura será sempre necessária para o diagnóstico, a não ser que seja possível a obtenção do tecido infetado, para observação direta (muitas vezes é demasiado difícil por ser necessária a biópsia)
* Sempre que possível fazemos uma biópsia de lesão cutânea, corando com o GMS (ou outra coloração fúngica)
* A observação de das leveduras características (grandes e redondas) e as pseudohifas é suficiente para o Dx de Candidíase
The laboratory diagnosis of candidiasis involves the procurement of appropriate clinical material followed by direct microscopic examination and culture.
Scrapings of mucosal or cutaneous lesions may be examined directly after treatment with 10% to 20% potassium hydroxide (KOH) containing calcofluor white. The budding yeastlike forms and pseudohyphae are easily detected on examination with a fluorescence microscope (see Fig. 60.1).
Culture on standard mycologic medium will allow the isolation of the organism for subsequent identification to species. Increasingly, such specimens are plated directly on a selective chromogenic medium such as CHROMagar Candida, which allows the detection of mixed species of Candida within the specimen and the rapid identification of C. albicans (green colonies) and C. tropicalis (blue colonies) based on their morphologic appearance (Fig. 65.5).
All other types of infection require culture for diagnosis unless tissue can be obtained for histopathologic examination.
Whenever possible, skin lesions should be biopsied and histologic sections stained with GMS or another fungal-specific stain.
Visualization of characteristic budding yeasts and pseudohyphae is sufficient for the diagnosis of candidiasis (Fig. 65.6).
Cultures of blood, tissue, and normally sterile body fluids also should be performed.
Identification of Candida isolates to species level is important, given the differences in response to the various antifungal agents. This can be accomplished as described in Chapter 60, using:
* the germ-tube test (C. albicans),
* various chromogenic media/tests (see Fig. 65.5),
* peptide nucleic acid–fluorescence in situ hybridization (PNA-FISH),
* and commercially available sugar assimilation panels.
Alternatively the use of nucleic acid sequence–based methods or proteomics provides a rapid, accurate, and cost-effective means of species identification.
Immunologic, biochemical, and molecular markers for the diagnosis of candidiasis are described in Chapter 60. Although these methods are not widely available at the present time, recent breakthroughs in direct detection technology hold great promise for the rapid diagnosis of invasive candidiasis.
Como distinguir uma prova de filamentação precoce verdadeira de uma prova falsa?
Existem outras espécies de Candida que conseguem produzir hifas (túbulos germinativos), mas tratam-se de hifas falsas (a albicans produz hifas verdadeiras).
A diferença entre as hifas verdadeiras e as hifas falsas é que a falsa hifa tem uma constrição na zona de ligação à levedura e a hifa verdadeira não. Atualmente, este método já não é muito utilizado, sendo mais comum fazer a identificação mediante provas bioquímicas ou MALDI-TOF.
Caracteriza o diagnóstico serológico da Candidíase. Começa por indicar as situações em que é feito.
CANDIDÍASE INVASIVA
Nas doenças graves, o diagnóstico da candidíase ou da candidémia por exame cultural, é um diagnóstico tardio, ou seja, as amostras são positivas quando o doente já apresenta sintomas há alguns dias.
Portanto, basear o diagnóstico no exame cultural, nestes casos graves, é atrasar muito a terapêutica, sendo que estas situações têm uma mortalidade muito elevada.
Tornou-se então necessário encontrar formas de fazer o diagnóstico destas patologias que fossem mais precoces, isto é, antes do doente estar tão gravemente doente. Procuraram-se então marcadores de doença, moléculas, que fossem libertadas de forma sistémica e que fossem a tradução da presença da Candida nos doentes (chamam-se as estas moléculas biomarcadores).
Para a candidíase invasiva, um dos marcadores que existe é o antigénio Mannan (e o respetivo anticorpo, o anti-mannan). Estes marcadores, quando utilizados nos doentes gravemente doentes, poderiam identificar os indivíduos que estariam a desenvolver doença ainda de uma forma silenciosa, contudo, hoje em dia, são pouco utilizados
O 1,3-ß-D-glucan é outro marcador. É uma molécula que está presente em vários fungos (não exclusivo da Candida). Por essa razão, trata-se de um marcador pan-fúngico, porque vai estar positivo em infeções sistémicas causadas por muitos fungos (Candida, Aspergillus, Pneumocystis jirovecii…). Porém, existem fungos que, caracteristicamente, não têm este marcador.
Portanto, a positividade deste teste não é exclusiva da Candida mas, numa suspeita de candidémia, um teste positivo destes pode ajudar no diagnóstico.
Como caracterizarias um Tratamento baseado num teste laboratorial?
Refere-se a uma terapêutica antecipada. O
doente ainda não tem sintoma nenhum, mas suspeita-se de infeção (nomeadamente pela presença de fatores de risco). Face a uma pesquisa de biomarcadores, se estes forem positivos supõe-se que está a desenvolver uma candidíase e podemos tratar o doente precocemente, antes ainda de ter sintomas.
Quais são os marcadores da Candidíase invasiva? Caracteriza a sua utilidade geral
- Antigénio de Mannan
- 1,3-ß-D-glucan
Já não são tão utilizados dada as novas tecnologias mais rápidas, contudo, em situações emergentes podem ser utilizados de forma a acelerar o processo.
O que é o 1,3-ß-D-glucan? Em que situações se usa? Tem limitações?
Qual é a única espécie de Aspergillus que tem uma morfologia tecidual diferente?
The important species Aspergillus terreus can be identified in tissue by its spheric or oval aleurioconidia that develop from the lateral walls of the mycelium; otherwise, the hyphae of pathogenic Aspergillus spp. are morphologically indistinguishable from one another in tissue.
Quais são os dois sinais radiológicos que podemos ver num doente com Aspergilose?
Sinal do “halo” – sugestivo de Aspergilose
Também ocorre com outros fungos e bactérias:
* Zygomycetes
* Scedosporium
* Pseudomonas aeruginosa
* Nocardia
Sinal do “guizo” – sugestivo de Aspergilose
* Observado numa cavidade
* Corresponde a uma zona de ar que rodeia
uma zona densa
* O fungo coloniza uma cavidade, invade a vasculatura com consequente hemorragia, trombose e enfarte; posteriormente há retração da zona central. O ar ocupa espaço entre o centro e a periferia.
