Fungus: SICUFungus: SICU

Bradley J. Phillips, M.D.

Burn-Trauma-ICUAdults & Pediatrics

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

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%

Candida

• Most commonly isolated fungus

• yeast form: colonization

• mycelial form : invasive

Blastospores Pseudohyphae

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 %)

Candida albicans

blood 18%

peritoneum 215%

urine 215%

wound 215%

sputum 647%

sputum 6blood 1urine 2peritoneum 2wound 2

Candida glabrata

blood 267%

central line 133%

blood 2central line 1

Candida Tropicalis

wound 1100%

wound 1

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

Diagnosis

• Combination of:– Laboratory findings– Clinical findings– High index of suspicion

Recognizing the risk factors for fungal Recognizing the risk factors for fungal

infections !!!infections !!!

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

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)

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

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

What Does This Mean?

What Is the Practical Value?

How Do We Manage Our Patients?

?

International Conference for the Development of a Consensus on the

Management and Prevention of Severe Candida Infections

Harbor-UCLA Research and Educational InstituteSt. John’s Cardiovascular Research Center

Clinical Infectious Disease1997

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

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

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

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

BMC-SICU Fungal Protocol

Urine - only source without symptoms: change

catheter and repeat urine culture, monitor patient

- symptomatic, more than two sources, or transplant patients: Change foley and Fluconazole 400mg/day

Sputum - only source without symptoms: no treatment,

observe patient - symptomatic, more than two sources: Fluconazole 400mg/day

BMC-SICU Fungal Protocol• 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

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

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

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

Case

• Left chest tube placed in the OR

• Midline exploration performed

Fajitas!

Fajitas!

More fajitas!!!

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

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

Case

• Risk factors:– GI perforation– multiple antibiotics– indwelling catheters– immunosuppression

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.

Question 4

• What is the role of prophylactic antifungal agents in nonneutropenic patients?

Fungal therpay should not be given on a routine basisIf given, Fluconazole is the drug of choice.