White Piedra

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).

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

(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

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

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 discharge diagnosis estimated the mortality from candidemia to be age- related, – 15% to 25% for adults and –ESCMID10% to 15% for Online children. Lecture Library Estimated incidences of candidemia: population-based studies in Europe, USA and Canada

Kett DH Crit Care Med 2011;39:665-70 © by author

Pfaller & Diekema Clin Microbiol Rev 2007; 20:133-63

ESCMID Online Lecture Library Severity of invasive candidiasis

Pathogen causing BSI Non ICU crude ICU crude mortality, mortality, % % Coag (-) staph. 13.8 25.7 S. aureus 18.9 34.4 Enterococci 24 43 Candida spp. 29 47.1 Pseudomonas 27.6 47.9 aeruginosa Acinetobacter 16.3 43.4 baumanii © by author

Second First ESCMIDFrom Wisplinghoff Online et al. Clin LectureInfect Dis 2004;39:309- Library317 Attributable mortality (Ma) of nosocomial candidemia Iowa University - O. Gudlaugsson et al. 2003 CID

 Type of study: case-control study performed between 1997-2001. Cases = at least one blood culture positive for Candida spp. in a patient with signs and symptoms of BSI>48 h after hospital admission. Matched controls selected from all categories of critical patients admitted in the same tertiary care hospital (813 beds, 40,000 admissions/year)

 Comparison with Ma ascertained in the same hospital 1983-1986, Ma= 38%

 Attributable mortality of nosocomial candidemia = crude mortality rate in cases - crude mortality rate in controls (matched 1:1, age, gender, lenth of stay, Charlson comorbidity index, without knowledge of outcome for either cases or controls). Comorbidity index for cases vs controls 3,4 vs. 3,3 (p = 0,6)

 108 cases of nosocomial candidemia, the fourth cause of systemic infections  Incidence of nosocomial candidemia = 5.3 episods (1983-1986) /10,000 admissions vs. 8.5 episods /10,000 admissions (1997-2001)  Timing of candidemia = 13-20 days after admission.

 Candida albicans 63%>, C. glabrata 17%, C. parapsilosis 12%>C tropicalis 10%> C. lusitaniae 2%> C. krusei 2%, susceptible to fluconazole excepting C. glabrata şi C. krusei

 Crude Mortality rate (CMRcases)=© Deaths by author among cases 66/108= 61%  Crude Mortality rate (CMRcontrols)= Deaths among controls 13/108= 12%  Ma = CMRcases - CMRcontrols= 49% (CL=38-60%)

 Ma = 40-75% found in other tertiary care hospitals in USA

ESCMID Online Lecture Library Invasive aspergillosis

 Unlike invasive candidiasis, – the incidence rate of invasive aspergillosis per 100,000 US population declined from 3.4 in 1996 to 2.2 in 2003, – the incidence rate from 3 to 2 per 10,000 hospital discharges (Pfaller& Diekema. Clin Microbiol Rev 2007; 20:133-63).  in severely immunocompromised patients (HSCT recipients), invasive aspergillosis remains the most important cause of infection-related mortality.  In a large prospective registry of 234 HSCT recipients with invasive fungal infection, aspergillosis accounted for 59% of all invasive fungal infections and was associated with a 6-week mortality rate of 22% [Neofytos D, et al. Epidemiology and outcome of invasive fungal infection in adult hematopoietic stem cell transplant recipients: analysis of Multicenter Prospective Antifungal Therapy (PATH) Alliance registry. Clin Infect Dis 2009;48(3):265–73]. © by author  This mortality rate is lower than previously reported rates and may be related to the increasing use of nonmyeloablative HSCT, early diagnosis, and use of broad-spectrum antifungals (voriconazole).  The average length of stay for a hospitalization related to Aspergillus infection was 17 days.ESCMID Online Lecture Library

The most frequent invasive fungal© by infections author: Candida and Aspergillus spp.– Germen university hospital - 200 in vivo and autopsic documented invasive fungal infections reported to 11,000 autopsies performed during the study period (statistically significant increase p<0.001) associated with invasive Aspergillus infections (p< 0.001, incidence = number autopsies performed dividedESCMID by the number Onlineof cases diagnosed Lecture that increased Library from 6% in 1983- 1987 to 11% in 1988-1992).

© by author Solid organ transplant and hematopoietic stem cell transplant (Detroit) - Aspergillus spp. has gradually been on the incline, A. fumigatus was recovered more frequent than the other species.ESCMID Online Lecture Library Increasing trend in the incidence of invasive mycosis United Kingdom 1990 - 1999 Lamagni et al. - PHSL 2001 Incidence rate - per million per year

Men Female

1990 1999 1990 1999

Aspergillosis 0,1 1,9 0,1 1,7

Candidiadis 6,8 13,7 5,1 10,4 © by author Criptococcosis 1,1 0,7 0,0 0,4

ESCMID Online Lecture Library Ecology and epidemiology

 Source of infection – inanimate and animate environment, individuals (exogenous and endogenous infections)  Transmission  Host susceptibility Fungi © by author Host factors

ESCMID Online Lecture Library Environment Candida - Ecology and transmission . Candida spp. . commensals - found on skin, GI tract, sputum, female genital tract, skin of HCW, . recovered from soil, hospital environments, inanimate objects and food, . Infection/colonization of multiple sites is an independent risk factor for invasive infection (site, extent, and duration of colonization have not been clearly defined), . Pittet et al. used semiquantitative measures to demonstrate that the density of colonization is important. The presence of genetically identical Candida species in ≥3 samples from distinct body sites on at least 2 consecutive days was significantly associated with the development of IC. . Candida colonization index (CI- for the frequency) and a corrected Candida colonization index© (CCI by – forauthor the density of colonization) were calculated and if CCI ≥0.4 severe invazive candidiasis occurred. . The lack of colonization at 2 distinct body sites – accurate predictor for the absence of candidal infection. . No correlation between colonization and invazive candidiasis was found in ESCMIDother studies. Online Lecture Library “Candida score” & Candida Colonization Index

 The CS for a cutoff value of 3 (sensitivity 61%, specificity 86%), variables are coded as absent 0 and present 1. CS = total parenteral nutrition (1) + surgery (1) + multifocal Candida colonization (1) + severe sepsis (2).  The colonization index (CI) = ratio of the number of culture-positive surveillance sites to the total number of sites cultured (excluding positive blood cultures). The colonization index was registered if >0.5.  The rate of IC was 2.3% (95% [CI] 1.06 –3.54) among patients with CS <3, with a linear association between increasing values of CS and IC rate (p < 0.001).  The relative risk for developing IC in colonized patients without antifungal treatment was 6.83 (95% CI 3.81–12.45).

 In this cohort of colonized patients© by staying author >7 days, with a CS <3 and not receiving antifungal treatment, the rate of IC was <5%. IC is highly improbable if a Candida-colonized non-neutropenic critically ill patient has a CS <3. (Crit Care Med 2009; 37:1624 –1633).

ESCMID LeonOnline C, Ruiz-Santana Lecture et al: Crit Care Med Library 2006; 34:730– 737 Leon C et al., Crit Care Med 2009;37:51624-33 Candida - Ecology and transmission

. in critically ill patients, the source of candidemia is most likely the intravascular catheters colonized by Candida spp. from the patient’s endogenous microflora or Candida spp. acquired from the health care environment

. the propensity of Candida spp, especially Candida parapsilosis, to cause CRBSIs is likely related to this pathogen’s ability to form biofilms on catheters

 the vast majority of Candida infections are endogenous but exogenous transmission of Candida spp. may occur particularly in neonatal ICUs © by author

 33% of surgical ICU and 29% of neonatal ICU medical personnel had Candida spp. recovered from their hands. ESCMID Online Lecture Library Molds – ecology and transmission

Aspergillus spp. – ubiquitous worldwide (in soil, food, air, decaying vegetation, water supplies), – asexual reproduction through conidia or spores, – conidia (2.5–3.0 µm diameter) are frequently inhaled but invasive pulmonary disease is rare in immunocompetent persons, – Aspergillus fumigatus is the species most often associated with disease (Aspergillus flavus, Aspergillus niger, Aspergillus terreus, Aspergillus nidulans© by, andauthor Aspergillus ustus), – infections are mainly exogenous.  invasive disease caused by Aspergillus spp. and molds generally involves severely immunocompromised patients. ESCMID Online Lecture Library Molds – ecology and transmission

 most cases of invasive aspergillosis are sporadic but several outbreaks of environmental airborne fungal infection within hospital settings have been reported (Aspergillus spp, Zygomycetes spp, Fusarium spp, Scedosporium spp, and Penicillium spp.)  a recent extensive review of nosocomial aspergillosis identified 53 reported outbreaks involving 458 patients – 33 outbreaks involved 299 patients (65% occurred in HSCT recipients or patients with hematologic malignancies and SOT recipients - 10%)  Aspergillosis was associated with mortality greater than 50% in patients with hematologic malignancies, HSCT and SOT recipients, and patients with severe immunodeficiency  The most common site of infection was the lungs in 77% of cases  A. fumigatus and A. flavus were the most commonly identified Aspergillus spp.  Volumetric air sampling performed during the course of epidemiologic investigations in 24 of the© outbreaks by author noted spore counts ranging from 0 to 100 spores per cubic meter. Outbreaks were primarily attributed to airborne infections related to construction or renovation activities in about 50% of cases and to compromised air quality in 17% (Vonberg RP, Gastmeier P. Nosocomial aspergillosis in outbreak settings. J Hosp InfectESCMID 2006;63:246 Online–54). Lecture Library

Molds – ecology and transmission

 The various environmental vehicles implicated in the transmission of Aspergillus spp. and other molds include: – improperly functioning ventilation systems, – poorly maintained air filters, – contamination of false ceilings and insulation material, – construction within and around the hospital, – water leaks, food, and ornamental plants.

. Agents of mucormycosis (Rhizopus, Mucor, Absidia) . ubiquitous, decaying matter, moldy bread, . tongue depressors -© pseudoepidemics by author in neonates, nonsterile adhesive tapes - primary cutaneous mucormycosis, . besides immunocompromised hosts and with diabetes mellitus scattered cases in immunocompetent persons were recently described. ESCMID Online Lecture Library “Vectors of fungal infections”

ESCMID Online Lecture Library Co-morbid conditions and health - care associated factors for candidaemia in hospitalized patients

Co–morbid conditions HC associated factors

 Extremes of age (<1 and >70 years),  Broad-spectrum antimicrobial agents very low birth weight neonates (number and duration)  Malignancy  Steroids (therapy and prophylaxis)  Neutropenia (<500 ⁄mm3)  Chemotherapy  Any renal failure (haemodialysis)  Previous colonization (‡2 sites)  Malnutrition  Gastric acid suppression  Burns  Indwelling catheter (CVC, Hickmann  Pancreatitis catheter)  Diabetes mellitus  Total parenteral nutrition  Severity of disease  Surgery (gastrointestinal) or gastrointestinal damage  Mucositis  Mechanical ventilation  GvHD (acute and chronic) © by author  ICU stay (>10 days), >APACHE II  Stem-cell and organ transplant recipients score  Iron load ESCMID Online Lecture Library Aspergillosis Haematological malignancies / Organ transplant patients

 Leukaemia  Lung, liver, heart, renal  Myelodysplastic syndrome  Acute and chronic rejection  Stem-cell transplant GvHD (acute  Steroids and chronic)  Haemodialysis  Prolonged neutropenia  Tacrolimus, OKT 3  Induction chemotherapy  Renal failure  Fungal colonization  Cytomegalo virus (CMV)  Local epidemiology  Re-transplantation  Steroid prophylaxis  Splenectomy  Neutrophil dysfunction  Alemtuzumab  Cytotoxic drugs  Diabetes mellitus  Infliximab © by author  Skin breakdown  Alemtuzumab

 Diabetic ketoacidosis

 T-cell-depleted stem-cell products  CD34ESCMID-selected stem-cell Online products Lecture Library  Skin breakdown

Prevention of invasive candidiasis

 Guidelines for the prevention of intravascular CRBSIs. 1. education and training of HCWs who insert and maintain catheters, 2. use of maximal sterile-barrier precautions during CVC insertion, 3. use of 2% chlorhexidine for skin antisepsis, 4. avoiding routine replacement of CVCs, and 5. use of antibiotic/antiseptic-impregnated CVCs.

 The effectiveness of the strategy was examined in 103 ICUs in Michigan. The median rate© of CRBSIsby author during the 18 months after implementation declined 66% from 2.7 to 0 per 1000 catheter-days [Pronovost P, et al. An intervention to decrease catheter-related bloodstream infections in the ICU. N Engl J Med 2006;355(26ESCMID):2725– 32].Online Lecture Library Fungal control

Water, air, food (food for fungi- cardboard, wallpaper glue, soap and body oil, carpet fibers……)

 Construction, ventilation systems, areas of special protection, moisture absorbtion systems, air conditioning vs. de- humidifying  Fungicides/fungistatics (Na hypochlorite, phenols, quaternary ammonium compounds, acids, Copper 8 quinolinate)  Review existing ventilation, distances  Take air quality baseline samples  Determine methods to monitor air quality  Identify potential contaminants  Check integrity of air filters  Determine shut-down times  Decide need for duct cleaning/treatment  Define post-construction clean-up  Decontamination of negative pressure respirators  Removal of containment materials and© filters by author  Cleaning contaminated area during construction  Hand hygiene. ESCMID Online Lecture Library Requirements of protective environment rooms

Protective environment - Central or point-of-use high-efficiency particulate air (HEPA) filters with 99.97% efficiency for removing particles 0.3 mm or larger

- Directed airflow, air intake occurs at 1 side and air exhaust occurs at the opposite side of the room

- Positive air pressure differential between room and corridor (2.5 Pa)

- Well sealed patient rooms.

MMWR Recommendations 2003;52(RR–10):1–42. ESCMID Online Lecture Library Infection control risk assessement

 potential effect of construction within an HCF on the environment and exposure of at-risk patients to infectious agents, particularly fungal spores.

ICRA process before start of any construction activity: 1. Categorize the type of construction activity (types A–D) based on the degree of dust generated. Type A activities are those that produce no dust (eg, electrical trim work), and type D activities are major demolition or construction.

2. Identify the patients who will be affected by the construction activity and determine the level of infection risk: low risk (eg, office areas), medium risk, high risk and highest risk (eg, immunocompromised patient areas). © by author

3. Match the patient risk group with the type of construction activity and determine the class of infection control precautions necessary. The classes of infection control precautions range from class 1 (minimal precautions)ESCMID to class 4Online (major precautions, Lecture including Library barriers and safe air handling). Recommendations for chemoprophylaxis

1. The use of prophylactic AFs can decrease the incidence of fungal infections in select high-risk groups of patients.

2. Widespread use of prophylactic AF agents in all ICU patients is not warranted and may lead to an increase in resistance and adverse events.

1. Prophylactic AFs are indicated in patients with recurrent intestinalESCMID perforations Online and/or Lecture anastomotic Library leaks. Prophylaxis of Candida infection/colonization

 Selective digestive decontamination regimens that include nystatin significantly reduce fungal carriage and overall fungal infections, but without impact on fungemia (administered 6 times daily and initiated at admission to the ICU).

 Fluconazole - 400 mg/daily, starting as soon as possible after ICU admission.

 Ketoconazole or nonabsorbable antifungal agents. Gubbinis PG. Fungal infections in Vincent Textbook of Critical Care 2011: 1050-60, ESCMID Online6th ed. Lecture Saunders Elsevier Library  Aspergillosis prophylaxis – Posaconazole 200 mg q 8 h in patients with GVHD or neutropenic with AML or MDS – Itraconazole 200 mg q 12 h iv 2 days then 200 mg q 24 iv or 200 mg q 12 h po or micafungin© 50 by mg/day. author

Gubbinis PG. Fungal infections in Vincent Textbook of Critical Care 2011: 1050-60, ESCMID Online6th ed. Lecture Saunders Elsevier Library

Evolution in predisposing factors

 Increasing number of susceptible hosts,  Greater laboratory expertise in the detection and identification of fungi,  Use of new transplantation modalities for hematopoietic stem cell transplantation,  Evolution in organ transplantation practices (fewer units of blood, biliary anastomosis without stents etc),  Use of corticosteroid-sparing regimens,  Use of novel immunosuppressive© by author agents,  Prevention policies (construction, ventilation, protective environment)  Use of antimicrobial prophylactic practices (fluconazole- antifungalESCMID prophylaxis, Online ganciclovir-CMV Lecture prophylaxis, Library quinolones for gram-negative bacterial prophylaxis). Final comments

 The incidence of fungal infections is increasing presenting an enormous challenge to healthcare professionals,

 Noteworthy the increasing incidence of infections with Candida spp. and mycelial fungi,

 Critical need for better and earlier diagnosis, more effective antifungal agents and studies to assess the risk of developing IFI and the efficacy of© combination by author of antifungal agents for the management of invazive fungal infections.

ESCMID Online Lecture Library