Dr C Sriruttan Clinical Microbiology & Infectious Disease /11/20161 Principles & Approach

1. Classification scheme 2. Is there a problem? 3. Role of the host & environment 4. Candidiasis 5. Management principles 6. Antifungal agents 7. Other mycoses 6/11/20162

1. Mycological 1. Yeasts 2. Moulds 3. Dimorphic 2. Epidemiological 1. Risk factors & geographical 2. Infective syndrome or clinical presentation. 6/11/20163

 Healthcare-associated (nosocomial)  Almost all HCA fungal infections may be considered opportunistic mycoses, ▪ They are usually non pathogenic and harmless, ▪ In seriously ill and/or immunocompromised patients these harmless fungi can cause life- threatening infections.  Community-acquired  Endemic mycoses e.g. blastomycosis  Common superficial fungal infections e.g. dermatophytoses  Other: related to particular risk factors 6/11/20164

 Has increased dramatically  207% increase  The morbidity and mortality associated with these infections are substantial  ~40% mortality rate  Fungal diseases have emerged as important public health problems  Surveillance is important 6/11/20165

RankIsolatesNumber (%) 1Coagulase-negative staphylococci 3,908(31.9) 2Staphylococcus aureus1,928(15.7) 3Enterococci1.354 (11.1) 4 Candida spp. 934 (7.6) 5Escherichia coli700 (5.7) 6Klebsiella spp.662 (5.4) 7Enterobacter spp.557 (4.5) 8Pseudomonas spp.542 (4.4) 9Serratia spp.177 (1.4) 10Viridans streptococci173 (1.4) 6

 Immunosuppressed or immunocompromised patients (e.g., Cancer, diabetes, AIDS)  Old age with increased prevalence of chronic medical conditions  Use of broad-spectrum antibiotics, cytotoxic chemotherapies  Organ transplant. 6/11/20168

 It is estimated that number of fungal species is now exceeding , with ~ 1500 new species each year,  Most of them are caused by Candida and Aspergillus species.  Emerging fungal pathogens  Yeasts ▪ Malassezia ▪ M. furfur and pachydermatis ▪ Trichosporon beigelii ▪ Rodotorula rubra ▪ Saccharomyces cervisiae  Hyalohyphomycetes ▪ Fusarium spp. ▪ Acremonium ▪ Paecilomyces lilacinus ▪ Pseudallescheria boydii  Phaeohyphomycetes ▪ Alternaria spp. 6/11/20169

10 *Reported in organ transplant recipients. 1.Pfaller MA et al. Diagn Microbiol Infect Dis. 1999;33: Husain S et al. Clin Infect Dis *2*

 Increased frequency of Candida bloodstream isolates  Emergence of non-albicans Candida species  Widespread use of prophylactic and empiric fluconazole  Development of azole resistance  Well defined risk factors  Species-related mortality 6/11/201611

 Candidemia  Catheter related candidemia  Acute disseminated candidiasis  Chronic disseminated candididiasis  Deep organ candidiasis 6/11/201612

 Central venous catheters  Systemic antibiotic exposure ICU >72 hours  Major surgery, especially abdominal  Pancreatitis  Any dialysis  Neutropaenia  Immunosuppressive agents (steroids, etc)  Colonization with Candida spp.  Parenteral nutrition 6/11/201613

1. Problematic 2. Approach 1. Index of suspicion is key 2. Select appropriate tests ▪ Culture & Histology 3. Repeat appropriate tests 4. Empiric therapy 6/11/201614

1. Specimen for MC&S 1. Invasive vs Non-invasive disease 2. Blood & Tissue (commonly) 2. Adjunctive tests 1. Antigen assays e.g. β-D glucan; galactomannan; cryptococcal Ag etc. 6/11/201615

1. Options are limited 2. Broad-spectrum empiric cover is the norm. Know spectrum of antifungal agents available 3. Appropriate dosing is imperative 4. Tailor treatment once pathogen identified 5. Treat for appropriate duration 6. Monitor clinical response 6/11/201616

6/11/2016Dr W Lowman17

 Polyenes  Amphotericin B  Amphotericin B lipid complex  Nystatin in pipeline  Azoles  Ketoconazole  Fluconazole  Itraconazole  Voriconazole  Posaconazole  Echinocandins  Caspofungin  Micofungin  Anidulafungin  Antimetabolites  Flucytosine  Allylamines  Griseofulvin 6/11/201618

 Consider:  Endogenous source as primary reservoir for infection ▪ Major endogenous reservoir is gastrointestinal tract, ▪ Mucosal colonization is an additional risk factor  Exogenous acquisition from environment ▪ To high-risk patients by contaminated infusates, biomedical devices, or the hands of health care workers.  Prevention:  Optimize use of invasive devices, immunosuppressives, & infection control strategies associated with high risk patient groups  Methods to decrease mucosal colonization  Decreased use of broad-spectrum antimicrobials. 6/11/201619

 Opportunistic yeasts and molds  Include the geographically endemic dimorphic fungi  These organisms are typically environmental and share a similar natural history with respect to human infections.  Port of entry;  Inhalation, ingestion, or traumatic inoculation, and a localized infection is initiated in the lung, paranasal sinus, or tissues. 6/11/201620

 The extent of infection depends on:  The infectious dose  Immune status of the host  Specific properties of the infecting organism.  Several of these community acquired mycoses produce serious, life-threatening disease, in immune-compromising condition such as AIDS. 6/11/201621

 Fungal infections are associated with substantial morbidity & mortality  There are an increasing number of fungal infections in hospital and community environment- BE VIGILANT!  Continued epidemiologic and laboratory investigation is needed to better characterize this increase and to improve diagnostic, therapeutic, and preventive strategies. 6/11/201622

6/11/201623