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Nosocomial fungal infections – epidemiology, prevention and control © by author Assoc. Prof. Amanda Rădulescu MD., PhD. The “Iuliu Hatieganu” University of Medicine and Pharmacy”ESCMID Cluj-Napoca, Online Romania Lecture Library Etiology – epidemiological characteristics of fungi Microrganisms that are normal commensals, parasites or saprophytes classified according to their appearance by microscopy and in culture, and by the method of reproduction (sexual or asexual). © by author ESCMID Online Lecture Library Clinical groupings for fungal infections Allergies resulting from hipersensitivity to fungal antigens e.g., inhaled fungal spores – Stachybotrys chartarum – “outbreak” of asthma in children, 1997- USA, allergic bronchopulmonary aspergillosis Mycotoxicoses resulting from ingestion of fungal toxins in contaminated food or poisonous mushrooms Mycoses – resulting from invasion of living tissue by a fungus Superficial mycoses - skin, mucous membranes, keratinous tissues - Malassezia furfur - tinea versicolor, candidiasis of the skin, nails, or mucous membranes, Dermatophytoses (ringworm) - Trichophyton spp., Trichosporon beigelii - white piedra Subcutaneous– sporotrichosis - Sporothrix schenkii, mycetoma- Madurella mycetomatis, Pseudollasheria boydii Systemic – deep tissue invasion (histo/cytochemistry showing hyphae or yeast cells from a needle aspiration© by with author evidence of associated tissue damage or positive culture obtained from a normally sterile site consistent with infection, excluding urine) or – fungemia (positive blood cultures of fungi, excluding Aspergillus spp. and Penicillium spp. (other than Penicillium marneffei) accompanied by temporally related clinical signs and symptoms compatible with the ESCMIDrelevant organism). Online Lecture Library Invasive fungal infections Endemic fungal infections (systemic or confined to lungs) Histoplasmosis - Histoplasma capsulatum Coccidiodomycosis - Coccidioides immitis Blastomycosis – Blastomices dermatidis Paracoccidiodomycosis - Paracoccidioides brasiliensis Systemic Candidiasis, systemic - Candida spp. Aspergillosis - Aspergillus spp. Cryptococosis – Cryptococcus neoformans Mucormycosis – Rhizopus,© by Mucor, author Rhizomucor, Absidia Hyalohyphomycosis – Penicillium, Scedosporium, Fusarium Phaeohyphomycosis - Cladosporium, Alternaria Uncommon– Trichosporon spp., Malassezia furfur, Fusarium, dematitiaceous fungi (Alternaria, spp, Cladophialophora, ESCMIDScedosporium, Online Curvularia) Lecture Library Pnecumocystis jiroveci pneumonia Emerging opportunistic yeast infections There has been an overall increase in fungal health care–associated infections (HAIs) in the last decades, a consequence of the advances in medical and surgical therapies More aggressive treatments: – hematopoietic stem cell transplantation (HSCT), – solid organ transplantation (SOT), – new chemotherapeutic© by agents, author and – immunomodulatory agents, has increased the population of immunocompromised patients at risk for invasive fungal infection. ESCMID Online Lecture Library Factors predisposing to fungal infections in patients with cancers Mandel, Douglas and Bennett’s Principles & Practice of Infectious Diseases, 7th ed. 2009 Churchill Livingstone Elsevier Host defense Predisposing factors Fungal pathogens Skin Intravenous and percutaneous Aspergillus spp., Candida spp, M. catheters, total parenteral furfur, Trichosporon spp, Rhizopus nutrition species Gastrointestinal Mucositis, nasogastric tubes, Candida spp., Trichosporon spp. gastrointestinal surgery, antibiotic use Neutrophils, Chemotherapy, hyperglycemia Aspergillus spp., Candida spp, granulocytopenia Mucor, Fusarium, Pseudallescheria boydii, Trichosporon spp. Macrophages Chemotherapy, ©hypergl byycemia author Aspergillus spp., Candida spp, Mucoralles, Histoplasma capsulatum Impaired cellular HIV infection, lymphomas H şi Aspergillus spp. Cryptococcus immunity N-H, corticosteroids neoformans, H. capsulatum, C. ESCMID Online Lectureimmitis, Library P. jiroveci Incidence of systemic fungal infections Accurate data regarding the incidence of systemic mycoses and associated mortality are difficult to obtain due to variable reporting requirements, underdiagnosis, misdiagnosis or not being specified The increasing incidence and attributable mortality of fungal infections were obvious since the last decade of the XXth century representing 3% and 6% of sepsis in United States and Europe, respectively. The incidence: in general population - 8 episodes/100,000 person-year Reese et al. [1998] study performed in San Francisco Bay Area hospitals (45) found 1,600 documented invasive mycoses (1992-1993), incidence ratio of 178 episodes/ 1,000,000 /year,© death by-to author-case rate 22% (90% had serious underlying medical conditions, almost 50% being HIV infected) ICU – 5-10 episodes/1,000 admissions. ESCMID The IVth cause Online of nosocomial Lecture systemic Library infections. Incidence of systemic fungal infections . Fungal infection accounted for 12.3% of all episodes of surgical infection (Raymond et al. Ann Surg 2001) . Fungi accounted for approximately 12.1% of all microbial isolates in their study of severe sepsis among adult admissions to ICUs in Australia and New Zealand (Finfer et al. Intensive Care Med 2006) . the large pan-European Sepsis Occurrence in Acutely Ill Patients (SOAP) study reported fungal infection in 17% of all septic patients in European ICUs (Vincent et al. Crit Care Med 2006) © by author . In a prospective study in ten university surgical ICUs – China, 28.3% of patients with severe sepsis were identified as having IFI with a predominance of 58% Candida albicans) (Guo-Hao XieESCMID et al. Critical CareOnline 2008). Lecture Library Rates of Infectious Complications in Cancer Patients in Studies Published after 2000 – in Mandel, Douglas and Bennett’s Principles & Practice of Infectious Diseases, 7th ed. 2009 Churchill Livingstone Elsevier Episodes/1000 Days at Risk Patient Type of Disease Any Type of Infection or Febrile Bactere Invasive Population Episode mia Mycosis Adults Hematologic malignancies 19.2 4.7 0.7 Children Malignancies 13.3 2.8 0.49 Children Hematologic malignancies, 18.1 5.7 0.27 Children ALL, aggressive treatment — 1.9 0.3 ALL, less aggressive treatment — 0.9 0.1 AnLL, aggressive treatment — 2.7 0.5 Children Solid tumors aggressively treated — 1.1 0.1 Solid tumors less aggressively treated — 0.2 0 Children Aggressive treatment for neuroblastoma — 1.7 0.1 Autologous HSCT for neuroblastoma — 4.3 0 Children Neutropenic AL/NHL, aggressive 31.1 5.1 2.1 treatment © by author Neutropenic AL/NHL, not aggressive 12.8 1.1 0 treatment Neutropenic ST, aggressive treatment 24.7 1.5 0.1 Neutropenic ST, not aggressive 14.7 0.9 0.6 treatmentESCMID Online Lecture Library Neutropenic autologous HSCT 37.8 5.1 0.7 Frequency & Predictors of Mortality in Sepsis Patients. By univariate analysis, Staphylococcus, Pseudomonas species, and C. albicans were © associatedby author with a higher mortality. Jean-Louis Vincent et al. Sepsis in European intensive care units: Results of the SOAP ESCMID OnlineStudy. Lecture Crit Care Med Library 2006 Vol. 34, No. 2 Trends in nosocomial bloodstream infections - USA The study detected 24,179 cases of nosocomial BSI in 49 US hospitals over a 7-year period from March 1995 through September 2002 (60 cases per 10,000 hospital admissions). Gram-positive organisms caused 65% of these BSIs, gram-negative organisms caused 25%, and fungi caused 9.5% (Candida species- 9%). The crude mortality rate was 27%. In neutropenic patients, infections with Candida species, enterococci, and viridans © bygroup author streptococci were significantly more common. Martin GS et al. The epidemiology of sepsis in the United States from 1979 through Wisplinghoff H et al. Clin Infect Dis 2004;39(3):309–17. 2000. N Engl JESCMID Med. 2003; 348: Online1546-54. Lecture Library Trends of IFI - 1991 -2003 in USA © by author (http://www.cdc.gov/nchs/) From Pfaller& ESCMIDDiekema. Clin Microbiol Online Rev 2007; Lecture Library 20:133-63 Incidence rates and distribution of pathogens most commonly isolated from monomicrobial nosocomial bloodstream infections (BSIs) and associated crude mortality rates © by author ESCMIDFrom Online Wisplinghoff Lecture et al. Clin Infect Library Dis 2004;39:309- 317 Time interval between hospital admission and onset of infection for the most frequently isolated pathogens in a series of 24,179 cases of nosocomial bloodstream infection - USA © by author ESCMIDFrom Online Wisplinghoff Lecture et al. Clin Infect Library Dis 2004;39:309- 317 Invasive candidiasis Candida spp. are the most common fungal pathogens causing serious HAIs, especially in patients admitted to intensive care units (ICUs). the incidence rate of invasive candidiasis increased from 23 per 100,000 US population in 1996 to 29 per 100,000 in 2003 (A National Hospital Discharge Survey) Among invasive candidiasis, candidemia is estimated to account for 2 to 8 infections per 10,000 hospital discharges in recent studies from the United States and Europe The true incidence of health care–associated candidemia is likely to be higher because of the relatively poor diagnostic yield (~50%) of positive blood culture results in patients with disseminated candidiasis with implicit candidemia. Matched cohort and case-control studies in various hospitalized patient populations, report attributable© by mortality author rates for candidemia ranging from 5% to 71%. Recent case-control studies based on hospital