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Amanda Chamieh

TREATMENT GUIDELINES : CANDIDA INFECTIOUS DISEASE PGY-IV


DECEMBER 5 2016
WHAT IS CANDIDEMIA
othe presence of Candida species in the blood
onever contaminant ,so always search for the source of infection
oFor many patients, candidemia is a manifestation of disseminated candidiasis,
whereas for others it reflects colonization of an indwelling intravenous catheter
ohalf to two-thirds of all episodes of candidemia occur in an ICU
oattributable mortality rates for invasive candidiasis in ICU are 30%40%
PATHOGENESIS
oThrough the gastrointestinal tract mucosal barrier
oVia an intravascular catheter
oFrom a localized focus of infection, such as pyelonephritis
DIAGNOSIS
ogold standard: positive blood culture; blood cultures should be obtained in all
patients with suspected candidemia, around 50% sensitive
oIf focal findings (eg, skin lesions or parenchymal involvement), biopsy should be
performed for staining, culture, and histopathologic evaluation.
obeta-D-glucan assay because it can be a useful adjunct to blood cultures and biopsy
oT2Candida assay: detects pathogens from a blood specimen in 3-5 hrs.
o The assay breaks yeast cells apart, releasing DNA; copies the target DNA; and detects the amplified
DNA using magnetic resonance technology

oPCR: 80% sensitive for invasive candidiasis, 89% sensitive for deep-seated
candidiasis as compated to B-D-glucan assay
oNo approved commercial test available
EPIDEMIOLOGY
oIn USA, between 2004 and 2008, 54% of 2019 bloodstream isolates represented
non-albicans Candida spp and 46% C. albicans
oC. glabrata 26%, followed by C. parapsilosis 16%, C. tropicalis 8%, C. krusei 3%
oOther studies have shown a similar order of frequency, although the incidence of
each species varies in different patient populations and geographic regions
osusceptibility to antifungal agents varies among the species.
oall isolates of C. krusei are fluconazole resistant
oan increasing proportion of C. glabrata are fluconazole resistant
oSome cases of echinocandin resistant C.glabrata
RISK FACTORS FOR CANDIDEMIA CAUSED BY
FLUCONAZOLE-RESISTANT ISOLATES
omostly due to C. glabrata
o neutropenia
ochronic renal disease
ochronic lung disease
omale gender
oprevious fluconazole or other antifungal exposure
MDR CANDIDA
oIn 2016, CDC and Public Health England issued warnings about the emergence of a
multidrug-resistant Candida species, C. auris
ofirst described in 2009 , invasive healthcare-associated infections, associated with high
mortality rates
oCountries with cases have included Colombia, India, Israel, Japan, Kenya, Kuwait, Pakistan,
South Africa, South Korea, Venezuela, the United Kingdom, and the United States
oMolecular typing suggests that the isolates are highly related within each country or region
but distinct between continents.
oC. auris requires specialized methods for identification, and it could therefore be misidentified
as another yeast (C. haemulonii or Saccharomyces cerevisiae) when using traditional
biochemical methods.
CASE 1
78 yo male, CAD, CHF, DM, COPD, bedridden, frequent admissions for
decompensation of HF by UTI or pneumonia
-admitted to regular floor for pneumonia 20 days ago, received broad spectrum
antibiotics
-develops septic shock due to CAUTI, transferred to ICU
-no clinical improvement, dependent on vasopressors
-central line in place for >7 days

-Blood cultures grow candida albicans, sensitive, from peripheral and central blood
samples
CASE 2
55 yo male with chronic pancreatitis, admitted for severe acute necrotizing
pancreatitis
-no improvement so surgical drainage done
-ongoing sepsis, clinical deterioration, surgical debridement done 2 more times
-develops severeal episodes of fever, with no focus,
-patient is on TPN, has central venous catheter
-blood cultures are negative
RISK FACTORS FOR CANDIDIASIS
1. Candida colonization
2. severity of illness
3. exposure to broad spectrum antibiotics
4. recent major surgery, particularly abdominal surgery
5. recurrent gastrointestinal perforation, anastomotic leaks, acute necrotizing pancreatitis
6. dialysis
7. parenteral nutrition
8. corticosteroids
9. use of CVCs
oIn those patients who have septic shock due to Candida species and who do
not have adequate source control or antifungal therapy begun within 24 hours,
the mortality approaches 100%
oPrompt initiation of appropriate antifungal therapy has been associated with
as much as a 50% reduction in mortality
EMPIRIC TREATMENT FOR SUSPECTED INVASIVE
CANDIDIASIS IN NONNEUTROPENIC PATIENTS IN THE ICU
1. Empiric antifungal therapy should be considered in critically ill patients with risk
factors for invasive candidiasis and no other known cause of fever and should be
based on clinical assessment of risk factors, surrogate markers for invasive
candidiasis, and/or culture data from nonsterile sites.
2. echinocandin:
caspofungin: loading dose 70 mg, then 50 mg daily
micafungin: 100 mg daily
anidulafungin: loading dose 200 mg, then 100 mg daily

3. Fluconazole, 800-mg (12 mg/kg) loading dose, then 400 mg (6 mg/kg)


daily, is an acceptable alternative for patients who have had no recent
azole exposure and are not colonized with azole-resistant Candida species
EMPIRIC TREATMENT FOR SUSPECTED INVASIVE
CANDIDIASIS IN NONNEUTROPENIC PATIENTS IN THE
ICU
4. Lipid formulation AmB, 35 mg/kg daily, is an alternative if there is intolerance to
other antifungal agents
5. Recommended duration of empiric therapy for suspected invasive candidiasis in
those patients who improve is 2 weeks, the same as for treatment of documented
candidemia
6. For patients who have no clinical response to empiric antifungal therapy at 45
days and who do not have subsequent evidence of invasive candidiasis after the
start of empiric therapy or have a negative non-culture-based diagnostic assay
with a high negative predictive value, consideration should be given to stopping
antifungal therapy
SHOULD PROPHYLAXIS BE USED TO PREVENT INVASIVE
CANDIDIASIS IN THE ICU SETTING?WEAK RECOMMENDATIONS
1. Fluconazole, 800-mg (12 mg/kg) loading dose, then 400 mg (6 mg/kg) daily,
could be used in high-risk patients in adult ICUs with a high rate (>5%) of invasive
candidiasis
2. Echinocandin:
caspofungin: loading dose 70 mg, then 50 mg daily
micafungin: 100 mg daily
anidulafungin: loading dose 200 mg, then 100 mg daily

3. Daily bathing of ICU patients with chlorhexidine, which has been shown to
decrease the incidence of bloodstream infections including candidemia, could be
considered
WHAT IS THE TREATMENT FOR CANDIDA
SUPPURATIVE THROMBOPHLEBITIS?
1. Catheter removal and incision and drainage or resection of the vein, if feasible, is
recommended
2. Lipid formulation AmB, 35 mg/kg daily, OR fluconazole, 400800 mg (612
mg/kg) daily, OR an echinocandin (caspofungin 150 mg daily, micafungin 150 mg
daily, or anidulafungin 200 mg daily) for at least 2 weeks after candidemia (if
present) has cleared is recommended
3. Step-down therapy to fluconazole, 400800 mg (612 mg/kg) daily, should be
considered for patients who have initially responded to AmB or an echinocandin,
are clinically stable, and have a fluconazole-susceptible isolate.
4. Resolution of the thrombus can be used as evidence to discontinue antifungal
therapy if clinical and culture data are supportive
CASE 3
65 yo male, sigmoid ca, s/p partial colectomy with anastomosis, complicated by
enterocutaneous fistula
-NPO, started on TPN by central venous access
-after 18 days, develops fever
-abdominal CT scan is not significant
-blood cultures grow candida albicans sensitive
-source?
CASE 4
70 yo male with myasthenia gravis, on corticosteroids and azathioprine, admitted for
closure of colostomy due to SBO 1y ptp, d4 post-op develops mesenteric ischemia, so
colectomy done
-pt with short bowel syndrome, ileostomy in place, central venous catheter for TPN
-fever around d10 postop; peritoneal collection
-CT guided drainged of peritoneal fluid that grows candida glabrata sensitive
INTRA-ABDOMINAL CANDIDIASIS
1. Empiric antifungal therapy should be considered for patients with clinical evidence
of intra-abdominal infection and significant risk factors for candidiasis, including
recent abdominal surgery, anastomotic leaks, or necrotizing pancreatitis
2. Treatment of intra-abdominal candidiasis should include source control, with
appropriate drainage and/or debridement
3. The choice of antifungal therapy is the same as for the treatment of candidemia
or empiric therapy for nonneutropenic patients in the ICU
4. The duration of therapy should be determined by adequacy of source control and
clinical response
CASE 4 CONTINUED
Why did our patient develop candidemia 1 month later?
CANDIDEMIA: NEUTROPENIC AND
NONNEUTROPENIC PATIENTS
1. Echinocandin:
caspofungin: loading dose 70 mg, then 50 mg daily
micafungin: 100 mg daily
anidulafungin: loading dose 200 mg, then 100 mg daily

2. Fluconazole, IV or PO, 800-mg (12 mg/kg) loading dose, then 400 mg (6 mg/kg)
daily if not critically ill or considered unlikely to have a fluconazole-resistant
Candida Species
3. Transition from an echinocandin to fluconazole (usually within 57 days) if
clinically stable, susceptible to fluconazole (eg, C. albicans), and have negative
repeat blood cultures
CANDIDEMIA: NEUTROPENIC AND
NONNEUTROPENIC PATIENTS
4. For infection due to C. glabrata, transition to higher-dose fluconazole 800 mg (12 mg/kg)
daily or voriconazole 200300 (34 mg/kg) twice daily only if susceptible
5. Lipid formulation amphotericin B (AmB) (35 mg/kg daily) if there is intolerance, limited
availability, or resistance to other antifungal agents
6. Voriconazole 400 mg (6 mg/kg) twice daily for 2 doses, then 200 mg (3 mg/kg) twice daily is
effective for candidemia, but offers little advantage over fluconazole as initial therapy (strong
recommendation; moderate-quality evidence). Voriconazole is recommended as step-down oral
therapy for selected cases of candidemia due to C. krusei
7. Follow-up blood cultures should be performed every day or every other day to establish the
time point at which candidemia has been cleared
8. Recommended duration of therapy for candidemia without obvious metastatic complications is
for 2 weeks after documented clearance of Candida species from the bloodstream and
resolution of symptoms attributable to candidemia
CASE 5
75 yo male, CAD, DM, hx of non-hodgkinds lymphoma treated with chemotherapy
and radiotherapy, off treatment since 1 yr, BPH, admitted for UTI with negative urine
culture that has recurred over the past 2 months ptp
-2 consecutive urine cultures grow candida glabrata
-cystoscopy done suggestive of fungal cystitis?
CASE 6
37 yo female previously healthy
admitted for recurrent vaginal
candidiasis that has become
refractory to fluconazole
-culture grew candida albicans
resistant to fluconazole,
voriconazole
CANDIDA UTIS
ASYMPTOMATIC CANDIDURIA
1. Elimination of predisposing factors, such as indwelling bladder catheters, is recommended
whenever feasible
2. Treatment with antifungal agents is NOT recommended unless the patient belongs to a
group at high risk for dissemination;
3. Neutropenic patients and very lowbirth-weight infants should be treated as
recommended for candidemia
4. Patients undergoing urologic procedures should be treated with oral fluconazole, 400 mg
(6 mg/kg) daily, OR AmB deoxycholate, 0.30.6 mg/kg daily, for several days before
and after the procedure
CANDIDA UTIS
SYMPTOMATIC CANDIDA CYSTITIS
1. For fluconazole-susceptible organisms, oral fluconazole, 200 mg (3 mg/kg) daily
for 2 weeks is recommended
2. For fluconazole-resistant C. glabrata, AmB deoxycholate, 0.30.6 mg/kg daily
for 17 daysOR oral flucytosine, 25 mg/kg 4 times daily for 710 days is
recommended
3. For C. krusei, AmB deoxycholate, 0.30.6 mg/kg daily, for 17 days is
recommended
4. Removal of an indwelling bladder catheter, if feasible, is strongly recommended
5. AmB deoxycholate bladder irrigation, 50 mg/L sterile water daily for 5 days,
may be useful for treatment of cystitis due to fluconazole-resistant species, such as
C. glabrata and C. krusei
CANDIDA UTIS
SYMPTOMATIC ASCENDING CANDIDA PYELONEPHRITIS
1. For fluconazole-susceptible organisms, oral fluconazole, 200400 mg (36 mg/kg) daily
for 2 weeks is recommended
2. For fluconazole-resistant C. glabrata, AmB deoxycholate, 0.30.6 mg/kg daily for 17
days with or without oral flucytosine, 25 mg/kg 4 times daily, is recommended
3. For fluconazole-resistant C. glabrata, monotherapy with oral flucytosine, 25 mg/kg 4 times
daily for 2 weeks, could be considered
4. For C. krusei, AmB deoxycholate, 0.30.6 mg/kg daily, for17 days is recommended
5. Elimination of urinary tract obstruction is strongly recommended
6. For patients who have nephrostomy tubes or stents in place, consider removal or
replacement, if feasible
THANK YOU Amanda Chamieh
INFECTIOUS DISEASE PGY-IV
DECEMBER 5 2016