1. Fungus: SICU Bradley J. Phillips, M.D. Burn-Trauma-ICU Adults & Pediatrics

2. Fungal Infections-History Opportunistic fungal infections rare before the 1960’s –Virulent : Histoplasma, Coccidioides, Blastomyces –Opportunistic : Candida, Cryptococcus, Aspergillus 1968- Kraus demonstrated invasive potential of fungus 1980’s- potential for affecting outcome of the critically ill

3. Fungal Infections-History Candida: increased in rank from 8th to 4th most common nosocomial pathogen isolated in blood Accounts for 8-15% of all hospital acquired positive blood cultures Increased LOS: as much as 30 days Increased mortality: 30-80%

4. Candida Most commonly isolated fungus yeast form: colonization mycelial form : invasive BlastosporesPseudohyphae

5. Candida BU surveillance in SICU –time period: 3 months (Jan-March/2001) –251 patients total –17 isolates 13 Candida albicans (76. 5%) 3 Candida glabrata (17.6%) 1 Candida tropicalis (5.9 %)

6. Candida albicans

7. Candida glabrata

8. Candida Tropicalis

9. Colonization vs. Infection Colonization: presence of organism without evidence of invasive infection –skin, urine, airway Invasive infection: histologic presence of the pathogen in normally sterile tissues –biopsy specimens, foreign bodies Dissemination: –positive blood cultures

10. Diagnosis Combination of: –Laboratory findings –Clinical findings –High index of suspicion Recognizing the risk factors for fungal infections !!! infections !!!

11. Risk for Fungus Case -control study of 88 pairs of patients over 3 years Risk factors: –Antibiotic use (0-2 vs 3-5) OR=12.50 –Hickman catheter OR=7.23 –Dialysis OR 18.13 –Candida :site other than blood OR=10.37 Wey et al. Archives of Internal Medicine, 1989

12. Risk for Fungus Severity of illness : APACHE II >10 Ventilator use > 48 hours broad spectrum antibiotics indwelling access catheters malnutrition immunosuppression burns Dean et al. The American Journal of Surgery, 1996 (review article)

13. Fungus Among Trauma Patients Retrospective case-control study –459 trauma patients reviewed over 3 years –> 4 days in ICU, age > 16 Risk factors studied –steroids –dialysis –burns –GI perforation –glucose > 180mg/dl –colonization –APACHE II –PRBC transfused –TPN –central line –vent Borzotta et al. Archives of Surgery, 1999

14. Results Infection rate of 4.4 % (20/459) 33% colonization- did not relate to infection No difference in mortality with/without infection Only TPN was an independent risk factor Univariate analysis showed significance (P<0.05) in the following: –number of units transfused in the first 24hrs –GI perforation –hemodialysis –TPN

15. What Does This Mean? What Is the Practical Value? How Do We Manage Our Patients? ?

16. International Conference for the Development of a Consensus on the Management and Prevention of Severe Candida Infections Harbor-UCLA Research and Educational Institute St. John’s Cardiovascular Research Center Clinical Infectious Disease 1997

17. Question 1 Should all candidemic patients be treated with an antifungal? –High mortality rates 30-80% –Current methods of risk factor analysis not accurate enough to assign deep-tissue infection 19/20 investigators -affirmative answer inaccuracy in determining which patients need treatment therapeutic options with less toxic effects are available morbidity/long term sequele in untreated patients is high

18. Question 2 What antifungal agents should be used in the management of candidemia? –Study of nonneutropenic patients with candidemia treated with either Ampho B or Fluconazole for 2 weeks after the last positive cultures showed no difference. Stable with no evidence of seeding: 20/20 chose Fluconazole Previous treatment with Fluconazole: 17/20 chose Ampho B

19. Question 3 When should empiric therapy given to nonneutropenic patients? –Consider for critically ill with signs of infection who have not responded to optimal antibiotic therapy with evaluation for bacterial infection 18/20 investigators treated with > 2 risk factors and Candida in sputum or urine 10/20 investigators treated with no Candida isolated

20. BU-SICU Fungal Protocol Blood -fundoscopic exam -repeat cultures -treat with Fluconazole load 800mg, then 400mg/day for 7-14 days - C. Albicans, C. tropicalis, C. parapsilosis, C. lusitania -treat with Amphotericin B 0.5-1.0 mg/kg/day Peritoneal fluid –Fluconazole 800 mg/d load, then 400mg/day for 7-14 days

21. BMC-SICU Fungal Protocol

22. Fungal infection must be considered when the patient fails to improve despite appropriate or broad spectrum antibiotic therapy. Empiric treatment should be started in those patients with two or more of the following risk factors: 1. > 1 week of antibiotic therapy 2. Immunosuppression 3. Long term intravenous catheters 4. Violation of the GI tract 5. Intra-abdominal abscesses 6. Prolonged hospital stay 7. SIRS or Multi-system Organ Failure

23. BMC-SICU Fungal Protocol 1. Send fungal cultures of urine, sputum, blood, other body fluids or foreign bodies and perform a fundoscpic exam 2. Treat with Fluconazole 800mg IV/day as loading dose, then 400mg IV/day for 7-14 days. For renal failure patients: CrCl > 50ml/min 400mg/day 20-50 ml/min 200 mg/day 10-20 ml/min 100 mg/day dialysis pts 400mg after dialysis

24. Fluconazole (Diflucan ® ) Aims at ergosterol of cell membranes Availabe forms: tablets, suspension, IV Excretion: 80% in urine as active form, Half life: 30 hours Adverse effects: nausea, HA, rash hepatic reactions, SJ syndrome Drug interactions: coumadin, CSA, dilantin, oral hypoglycemics, rifampin, seldane

25. Case 24y/o AA male with single GSW to left mid axillary line at the level of the 10th rib. Awake and alert on presentation Taken immediately to the OR for exploration

26. Case Left chest tube placed in the OR Midline exploration performed Fajitas! More fajitas!!!

27. Case Left nephrectomy for a shattered kidney Repair of anterior and posterior gastrotomy Repair of duodenal injury with pyloric exclusion (Jordan procedure) Feeding jejunostomy tube placement

28. Case Pt with persistent fevers and elevated white count despite triple antibiotics. Fever work-up performed Candida albicans grew from sputum, blood and peritoneal cavity

29. Case Risk factors: –GI perforation –multiple antibiotics –indwelling catheters –immunosuppression

30. Case Currently on the floor, decannulated trach site, tolerating PO intake. Barium study shows open pylorus, functioning gastrojejunostomy and no evidence of leak or stricture at duodenum.

31. Question 4 What is the role of prophylactic antifungal agents in nonneutropenic patients? Fungal therpay should not be given on a routine basis If given, Fluconazole is the drug of choice.