Fungal infection in the immunocompromised patient Dr Kirsty Dodgson
Aims Discuss different types of fungi Overview of types of clinical infections Clinical Manifestations
Fungus Includes Moulds Aspergillus Fusarium Dematiaceaous moulds e.g. Exophiala Mucoraceous moulds e.g. Rhizopus Yeasts Candida Pneumocystis Cryptococcus
Epidemiology Moulds are everywhere We breathe them in constantly Soil, vegetation Warm moist humid environments Neutropenic diet tries to reduce risk Crisps Pepper
Candida albicans Most common species isolated from superficial sites and blood. Most pathogenic species. Sensitive to most antifungal agents.
Non-albicans Candida species Many different species, very heterogeneous. Generally: Increasing frequency- multifactorial explanation. Probably less pathogenic than C. albicans. Often more resistant than C. albicans.
Changing Epidemiology ing aggressive therapy, leads to more susceptible patients. Ageing population more susceptible patients Use of prophylactic fluconazole leads to decrease in susceptible sp (e.g. albicans) and replacement with resistant sp (e.g. glabrata).
Skin and mucosa Asymptomatic colonisation Cutaneous candidiasis Chronic mucocutaneous candidiasis Oesophagitis Onychomycosis Oropharyngeal candidiasis Vulvovaginitis
Oesophagitis
Thrush Assocoiated with decrease in normal flora Watch for recurrent cases If occur perform ID and susceptibilities
Invasive Candidiasis Candidaemia Intravascular Catheters Disseminated candidiasis
Hepatosplenic Candidiasis Within the four overlapping forms of invasive candidiasis, there is a distinct clinical picture that has been given a variety of names: Chronic Disseminated Candidiasis (CDC) Hepatosplenic Candidiasis, Hepatic Candidiasis and Granulomatous Hepatitis. However, the other terms are equally valid.
Interestingly this is a condition that affects almost exclusively patients undergoing remission induction chemotherapy or bone marrow transplantation for acute leukemia HS Candidiasis
HS Candidiasis Another remarkable aspect of this condition is that it manifests only on recovery from prolonged periods of neutropenia. The other near constant finding is one of a group of abdominal symptoms. Right upper quadrant tenderness, hepatomegaly, abdominal distension, nausea, vomiting and diarrhoea occur with variable frequency.
HS Candidiasis Liver Function Tests. One of the most consistent biochemical findings in hepatosplenic candidiasis is a marked elevation on serum alkaline phosphatase. White Blood Count. Another commonly reported finding among patients with CDC is rebound leukocytosis Unfortunately, these laboratory changes are very similar to those found in cases of GVHD and sepsisrelated cholestatic liver disease, thus confusing the diagnosis
Deep Organ Candidiasis Abdomen (Peritonitis) Peritoneal Dialysis-related Candida Peritonitis Gut-injury Related Candida Peritonitis Bone & Joint Candidiasis Candida Osteomyelitis Candida Arthritis Brain & Nerves (CNS candidiasis) Neurosurgery-related CNS candidiasis Eye (Endophthalmitis) Gallbladder (Biliary Candidiasis) Heart (Cardiac Candidiasis) Lung (Candida Pneumonia) Kidney & Bladder (Urinary Candidiasis) Fungus Balls in Urinary Tract Asymptomatic Funguria Liver & Spleen (Hepatosplenic Candidiasis) Pancreas (Pancreatic Candidiasis)
Pneumocystis Jiroveci Pneumonia Normal flora in healthy competent individuals Normally seen as a reactivation in immunocompromised patients Traditionally an AIDS defining illness but seen in any immunocompromised pt Haematology, oncology and solid organ transplant pts Previously Pneumocystis carinii (PCP)
PJP Main symptom, exertional dyspnoea Marked desaturation Its actually a fungus Send deep samples for PJP PCR Sputum not ideal but better than nothing BAL is the gold standard
PJP
PJP Rx Treat with Septrin HD Atovaquone suspension - However, oral atovaquone has limited and unpredictable bioavailability Dapsone with trimethoprim - dapsone is given intravenously or occasionally in nebulised form in the treatment of PCP. Clindamycin with primaquine (unlicensed use in the UK) Aerosolised pentamidine isetionate is no longer recommended because it is associated with increased frequency of relapse Must receive 21 days total treatment
Crytococcus Characteristic features: Yeast forms capsule (seen on india ink stain)
Cryptococcus neoformans
Cryptococcus 34 species in the genus C. neoformans only one of real importance though case reports of other sp causing disease. 2 varieties exist: C. neoformans var neoformans and var gattii
Cryptococcus var neoformans found worldwide pigeon droppings soil Serotypes A, D & AD var gattii Tropical and subtropical eucalyptus trees Serotypes B & C
Cryptococcus Disease Organism inhaled-usually no or mild symptoms. pneumonia rare even in immunocompromised Meningitis-strongly neurotropic often subacute onset in immunocompetent Immunocompromised-HIV, transplant
Cryptococcus Diagnosis Microscopy of CSF Culture-CSF, Blood Anitgen-Blood, CSF
Aspergillus Most common mould infection but not all mould infections are aspergillus Diagnostics are poor so clinical diagnosis is key Fungi are angioinvasive so blood/sputum are rarely positive even by PCR Consider B-Glucan and galactomannan based on local policy
Aspergillus
Gram Stain
Sites of Infection Categories Colonization Allergic bronchopulmonary aspergillosis Pulmonary aspergilloma Invasive aspergillosis Sites Involved Sinuses, lungs Sinuses, lungs Pre-existing lung cavity - Pulmonary aspergillosis 1 - CNS aspergillosis - Sinonasal aspergillosis - Osteomyelitis - Endophthalmitis - Endocarditis - Renal abscesses - Cutaneous Others - Cutaneous: burns, post surgical wounds, IV insertion sites, etc. - Otomycosis - Exogenous endophthalmitis - Allergic fungal sinusitis - Urinary tract fungus balls 1This is the most common site of primary invasive aspergillosis.
Aspergilloma Colonise pre-existing cavities May be excised as can erode through and cause haemoptysis
Invasive Apergillosis
Invasive Apergillosis
18 mo girl with leukaemia
Other Moulds Zygomycetes Causes mucormyosis Rhinocerebral mucor, high mortality Fusarium Disseminated infection
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