The document discusses treatment options for a 74-year-old male patient admitted with fever, chills, and rigors who was diagnosed with urosepsis and ketoacidosis. Initial treatment with cefepime and fluconazole provided marginal benefit. Blood and urine cultures grew Candida albicans, Candida glabrata, and E. coli. The document reviews antifungal treatment options and their pros and cons, considering the patient's renal insufficiency and isolated fungal species. It recommends systemic antifungal treatment along with nephrostomy tube placement and local antifungal infusion to remove the fungal obstruction.

1. Update on New Antifungals Grand Rounds Jack D. Sobel, M.D. Professor of Medicine Wayne State University School of Medicine Detroit, MI

2. A 74-year-old male is admitted with a one day history of fever, chills and rigors. He also reports nausea, vomiting but denies any urinary or respiratory symptoms. He is a Type I, severe diabetic on a moderately high dose of insulin, whose control has been poor. Past medical history is positive for two episodes of myocardial infarction, coronary angioplasty ~2002, moderate intermittent claudication and a mixed sensory-motor peripheral neuropathy. Hypertension for approximately 20 years.

3. In the E.M. Department, he was found to be moderately dehydrated, temperature 103.2°F, pulse 128/m, BP 110/60, but was lucid and fully orientated. JVP not elevated, lungs clear to auscultation and CVS examination revealed a summation gallop and grade 2/6 ESM at left parasternal border. Abdominal exam was normal. Rectal exam showed mild BPH and a symmetrical peripheral neuropathy was evident. No pulses detectable below popliteal region.

6. A presumptive diagnosis of urosepsis with ketoacidosis and dehydration was made and in the E.R. patient was given Cefepime, rehydration and insulin and transferred to MICU.

14. Fluconazole - How Good?

25. What about the echinocandins??

26. Echinocandins Fungal Cell Wall 1 Non-competitive Inhibition by : Lipopeptide Class of Antifungals (Enchinocandins, Pnuemocandins, Papulacandins) 2 GTP UDP glucose Catalytic subunit Regulatory Subunit (GTPase) Continuous fibrils of Glucan Fibrous (  1,3) Glucan Plasma Membrane (phospholipid bilayer) Surface-Layer Mannoprotein  1-6 Tail  1-6 Branched Glucan Entrapped Mannoprotein Chitin Plasma Membrane Glycosyl Phosphatidylinositol “(GPI) Anchor” (to mannoproteins)  1,3) Glucan Sythase Enzyme Complex 1 Adapted from: Kurtz, MB. ASM News . Jan 1998;64(1):31-9. 2 Chiou CC et al. Oncologist , 2000;5:120-35. Ergosterol Chitin Synthase Candida, Aspergillus

29. Caspofungin versus Amphotericin B for Invasive Candidiasis 0 20 40 60 80 100 Successful outcomes (%) 73% 62% 81% 65% Analysis of all patients (non-stratified) Successful outcome = symptom resolution and microbiological clearance Modified ITT Evaluable patients Mora-Duarte J et al. N Engl J Med . 2002;347(25):2020-9. Caspofungin Amphotericin B