idsa antifungal guideline ver 2
Post on 14-Apr-2017
120 Views
Preview:
TRANSCRIPT
Clinical Practice Guideline for the Management of Candidiasis
IDSA 2016 updated Presenter: Yu Tian Hsieh
Preceptor : Pinzy Chen 15th, April
Outline
Part I • Brief review of antifungal agent (spectrum, PK-PD) • Candidemia in non-neutropenic & neutropenic
– Medication choice in C. parapsilosis – CVC removal
• Empirical /prophylaxis in ICU • Intra-abdominal candidiasis • In disseminated(hepatosplenic) candidiasis Part II • Management of Candidiasis in other places
2
±
Elizabeth S. Dodds Ashley et al. Clin Infect Dis. 2006;43:S28-S39
mold
yeast
±
3
Co
mm
on
p
atho
gen
C. glabrata : SDD- R (SDD: susceptible dose dependent ) C. parasilosis: S –R , but R uncommon C. krusei : R to fluconazole, SDD –R to itraconazole, I-R to flucytosine
AmB: S─I to C. glabrata, C. krusei
Comparative pharmacokinetics of the antifungal agents.
Elizabeth S. Dodds Ashley et al. Clin Infect Dis. 2006;43:S28-
S39
CYP 3A4 , 2C19, 2C9 substrate/inhibitors
Renal dose adjustment only in fluconazole, flucytosine
Only few data of dose in hepatic disease • Voriconazole(mild-moderate cirrhosis) • Caspofungin(svere liver disease
child-pugh score)
4
CANDIDEMIA, PROPHYLAXIS, EMPIRIC IN ICU DISSEMINATED CANDIDIASIS INTRA-ABDOMINAL
Part I.
5
Therapy
Candidmia Primary alternative Comment
Non-neutropenic
Echinocandin • Caspofungin LD 70 mg; 50 mg • Micafungin 100 mg QD • Anidulafungin LD: 200 mg,
then 100 mg QD Fluconzaole 800 mg (12 mg/kg), then 400 mg (6 mg/kg) in stable, seem S to flu-
AmB d LF AmB (3-5 mg/kg daily)
• Transition to fluconazole after 5-7 days if Susceptible, clinical stable, culture (-)
• Ophthalmological examination 1 week after dx
• Duration of therapy 14 days after clearance of blood stream and symptom resolved
• f/u blood culture qd/qod* • Suggest azole susceptibility test
for all bloodstream Candida isolate
• Test for Echinocandin if previously echinocandin use, C. glabrtata , C. parapsilosis
• early catheter, CVC removal (individualized) esp.C.parasilosis
Species
C. glabrata • Echinocandin
Transition to 1. Higher dose of
fluconazole (800 mg) 2. Voriconazle
if susceptible (3-4 mg/kg)
C. krusei as above
• Voriconazole (6 mg/kg 2 dose, then 3 mg/kg BID) as step-down therapy
C. Parapsilosis • Fluconazole
• No difference btw candin and flu-[176]
6
• Isavuconazole ≈ vori/posa[ref. ]??
• Espcially , C. parasilo
Therapy
candidemia Initial alternatives Comment
Neutropenic Echinocandin • LF AmB (less attractive) • Fluconazole [207]
• Voriconazole if mold coverage is desired, susceptible to voriconazole [weak, low]
• Step down to flu-/ voriconazole in clinical stable
• catheter, CVC removal (individualized) • Ophthalmological examination(after
neutropenic resolved) • Duration of therapy 14 days after clearance
of blood stream+ neutropenia+ symptom resolved
• Granulocyte transfusions in persistent candidemia with anticipated protracted neutropenia [weak, low]
Species Treatment
C. parapsilosis
• Fluconazole . LF AmB is prefered
• No clinical study superior to fluconazole
• Systemic review includes 17 trials, randomized 342 neutropenic patient with invasive candidiasis show:
• Favors non-polyenes > polyenes [205]
問 Extensively prophylaxis in hematology patients cause lack meaningful prospective data, and diminished therapeutic role, except maintenance or step-down 去確認
7
• New observative data from Spain (n=200) show no difference of outcome [176]
9
Study design prospective, multicenter(29 Spanish hospitals), population-based surveillance program on Candida BSI
Inclusion criteria Incident episode ─first positive blood culture C. parapsilosis complex. (peripheral vein) ; Of 752 episodes, 200 (26.6%) episodes
Exclusion criteria • simultaneously non–C. parapsilosis (mixed candidemia) • Patients who died within the first 72 hours
Management initial antifungal in first 72 hrs, Antifungal agent : azole, echinocadin, AmB, combination
1st endpoint (1) all-cause mortality between days 3 - 30 from the initial blood culture(+) or (2) persistent C. parapsilosis BSI for ≥72 hours after the initiation therapy
2nd endpoint 30-day all-cause mortality
The Prospective Population Study on Candidemia in Spain (CANDIPOP) ─ C. Parapsilosis related candidemia
Clin Infect Dis 2014; 58:1413–21.
Therapy 152 Episodes Detail
Azoles –based 73 (42.0%) Fluconazole 70
Voriconazole 3
Echinocandin 43 (24.7) Caspofungin 23
Anidulafungin 12
Micafungin 8
Amphotericin B 33 (19.0%),
combination 25 (14.4%)
Results
10
Initially echinocandin in C. parapsilosis candidemia doesn’t affect outcome
11
Primary
Secondary
No difference of C. parapsilosis BSI btw Azole & echinocandin
CVC REMOVAL DURING ANTIFUNGAL THERAPY IN CANDIDEMIA
A recently study
12
Clin Infect Dis.-2012-Andes-1110-22
Inclusion criteria : 1. Review 7 RCT, compare antifungal therapy for candidemia , IC 2. Available data on mortality & treatment success with each
Candida species (individual patient-level data) Primary outcome: 30 day all cause mortality Secondary outcome:
• clinical and microbiologic success (symptom resolution and negative cultures at the end of therapy, typically 14 days)
14
CVC removal & APACH II score
15 12 24 36 47
P= 0.05 P= 0.01 P= 0.002 P= 0.41
CVC removal during treatment can applied to different severity of disease (Individualized)
Clin Infect Dis.-2012-Andes-1110-22
III. Empiric treatment for suspected invasive candidiasis in non-neutropenic patients in ICU
• Who : critically ill patients, who has risk factors, unknown fever, culture from non-sterile site
• When: as early as possible if risk factors and sign of septic shock
• Why:high prevalence and mortality in ICU
• What: as candidemia in non-neutropenic
• How long/ when to stop
– 2 weeks after improve ( same as treatment)
– if no clinical response x 4-5 day, no subsequent evidence of invasive candidiasis / non-culture based diagnosis( high sensitivity ) consider stop antifungal
17
Risk factors: candida colonization, severity of illness, number/ duration of using broadspectrum abx, previous surgery , dialysis, CVC, TPN, length of ICU stay…
if no timely source control, antifungal < 24 hr approches 100 % mortality in septic shock with candidemia [14]
Prophylaxis antifungal be use in ICU patients? Solid organ transplant, neutropenia with chemotherapy, stem cell transplant Who : high-risk patients in adult ICU with high rate (>5%) of candidiasis [260-262]
What -dose same as previously
• Fluconazole [263]
• Echinocandin as alternatives [249]
Others
• Daily bathing with Chlorhexidine decrease bloodstream infection, includes candidemia in a 2012 meta-analysis [weak, moderate] [274]
18
2014, multicenter placebo-controlled, blinded trial of caspofungin prophylaxis in ICU for high risk of invasive candidiasis (NOT achieve significant difference, n =102, 84 )
Intra-abdominal Candidiasis 1. Infection usually polymicrobial, yeast 20 % in all cases,
40 % in gastroduodenal perforation 2. 40% of patient with 2nd /3rd peritonitis, developed with
high mortality rate, except for appendicitis 3. Blood culture often (-), hard to distinguish with
contaminated, colonized • Treatment
– Source control, appropriate drainage, and / or debridement – Empiric antifungal for recently IAI, significant risk factors,
abdominal surgery, anastomotic leaks, necrotizing pancreatitis
• Choice of medication: same as treatment / empiric therapy in non-neutropenic
IAI: intra-abdominal infection 19
Treatment of disseminated ( hepatosplenic ) candidiasis
• Uncommon syndrome, except for hematologic malignancy • Presentation: fever, upper quadrant discomfort, nausea,
elevation of LFTs, occur following return of neutrophils and persist for month unless treatment
• Pathogen : C. albican most common, others also seen • Antifungal : initially fluconazole, AmB-d, LF AmB OR
echinocandin for several weeks, then PO fluconazole if not resistance (as neutropenic tx)
• Duration : months after return of neutrophils, f/u by CT • Others: Short term steroid (tapering dose) or NSAID can
achieve afebrile, improve LFTs [WEAK, LOW] 20
Part II. outline Candida isolated • respiratory tract not recommended (not change) Candidiasis • Intravascular infections
(endocarditis & implantable cardiac devices & pericarditis/myocarditis)
• Osteomyelitis & septic arthritis • UTI • Endophthalmitis • CNS • Oropharyngeal & Esophageal (not change) • Vulvovaginal (not change) • Neonate
21
Management of osteomyelitis, septic arthritis
22
Osteoarticular Primary Alternatives comment
Osteomyelitis • Fluconazole, (6 mg/kg) daily, for 6–12 mons OR
• echinocandin for at least 2 wks followed by fluconazole, for 6–12 mons
• AmB d
LF AmB(less attractive) ,3–5 mg/kg daily, for at least 2 wks followed by fluconazole, 6 mg/kg daily, for 6–12 months
• Mech. Hematogenous dissemination or contiguous spread
• Surgical debridement is recommended [strong, low]
Septic Arthritis • Fluconazole, (6 mg/kg) daily, for 6 wks OR
• echinocandin for at least 2 wks followed by fluconazole, for 4 wks (at least)
• AmB d
LF AmB(less attractive) ,3–5 mg/kg daily, for at least 2 wks followed by fluconazole, 6 mg/kg daily, for 4 wks (at least)
[strong, moderate] • Surgical drainage in all
cases • Prosthetic device
removal [strong, low] • Chronic suppression
with fluconazole, if susceptible
Treatment of Asymptomatic Candiduria
• Not recommend treatment
• Elimination of predisposing factors, such as indwelling bladder catheter is recommended, whenever feasible
• Except for high risk of dissemination:
– Neutropenia, infant < 1500 g treat as candidemia
– Urologic procedure oral fluconazole 6 mg/kg_ , AmB deoxycholate, 0.3-0.6 mg/kg daily for several days BEFORE, AFTER procedures. [strong, low]
23
Symptomatic candiduria ─ cystitis /pyelonephritis • Susceptibility & urine penetration is the key
24
UTI Primary Alternatives comment
Cystitis Fluconazole 3 mg/kg PO QD for 2 weeks
Fluconazole resistance C. glabrata • AmB deoxycholate 0.3–0.6 mg/kg for 1–7 days; • OR flucytosine 25 mg/kg qid for 7–10 days C. Krusei • AmB deoxycholate 0.3–0.6 mg/kg for 1–7 days; Both can consider AmB deoxycholate irrigation 50 mg/L sterile water daily for 5 days, but highly recurrent rate in several weeks [weak, low]
Removal of indwelling device, if feasible
Pyelonephritis Fluconazole 3- 6 mg/kg PO QD for 2 weeks
Fluconazole resistance C. glabrata • AmB deoxycholate 0.3–0.6 mg/kg for 1–7 days ± flucytosine 25 mg/kg qid for 1-7 days • Monotherapy of flucytosine x 2 weeks [weak,low] C. Krusei • AmB deoxycholate 0.3–0.6 mg/kg for 1–7 days Adjunct irrigation with AmB-d (conc. As above)
Removal of indwelling device, if feasible Elimination of urinary tract obstruction
Fungus ball 1. Surgical intervention in adult 2. antifungal as above(both) 3. irrigation thru nephrostomy
Management of Candidia Chorioretinitis ± vitritis
• Consult ophthalmologist (dilated retinal examination) • Vitrectomy considered in macular/vitritis involvement [strong, low]
Fluconazole / voriconazole- susceptible isolates – Fluconazole LD: 12 mg/kg, then 6-12 mg/kg daily – Voriconazole 6 mg/kg BID, then 4 mg/kg BID (IV/PO)
Fluconazole / voriconazole- resistance- isolates – Liposomal AmB 3-5 mg/kg IV ± flucytosine 25 mg/g QID – Chandin, AmB d
With macular or vitritis involvement – PLUS intravitreal injection of AmB deoxycholate 5-10 μ g or
Voriconazole 100 μg in 0.1 ml sterile water
• Duration:at least 4-6 weeks with resolution of lesion 25
TDM : 2- 5 μ g/ml
CNS candidiasis
• Presentation: as meningitis (fever, neck stiff, headache, others)
• Initial : liposomal AmB, 5 mg/kg daily ± oral flucytosine, 25 mg/kg QID
• Step down : – fluconazole (6-12 mg/kg) daily , Voriconazole in rare case of C. glabrtata,
or C. krusei meningitis (but no report of voriconazole use in CNS candidisis)
• Duration: until all S&S, CSF, radiological resolved (longer for abscess)
• Remove implantable devices, include drain, shunt, wafers…, If can’t remove devices intraventricular AmB-d into (0.01-0.5 / 2 ml D5W) ; toxicity : headache, N&V
26 S& S : sign and symptom
Oropharyngeal & esophageal candidiasis
• Who: commonly occur in immunocompromised patients, like HIV infection, malignancies, steroid use, leukemia…
• Presentation: Dysphagia, odynophagia
27
Oropharyngeal candidiasis • Mild : Clotrimazole troche or miconazole mucoadhesive buccal,
alternative nystatin suspension 4-6 ml 4 times daily OR nystatin pastilles
• Moderate to severe*: PO fluconazole 100-200 mg(≤ 3mg/kg)daily,
• Fluconazole refractory: – Itraconazole solution 200 mg QD / Posaconazole suspension 400 mg(10 c.c)
BID for 3 days, then 400 mg QD, up to 28 days (effectious in 75 %)
– alternative: voriconazole IV/PO 200 mg BID or AmB-d oral suspension, 100 mg/cc QID [strong. weak] IV echinocandin or IV AmB-d (0.3 mg/kg) [weak, moderate]
• Duration: 7-14 days
• Suppressive therapy is not recommended (resistance ↑)
• Denture-related disinfection of the denture + antifungal 28
Esophageal candidiasis
• Diagnostic trial of antifungal before endoscopic examination Systemic antifungal 1. PO Fluconazole (3-6 mg/kg) daily for 14-21 days 2. IV fluconazole (6 mg/kg), echinocandin# if can’t tolerte oral
therapy( mica-150 mg , anidula-200 mg daily, caspo- usual daily) [strong, high]
• Alternative : AmB deoxycholate* 0.3-0.7 mg/kg daily [strong, MODERATE]
• De-escalating to oral fluconazole if stable to tolerate oral intake Fluconazole refractory • itraconazole solution(80%), voriconazole IV/PO(~fluconazole效果),
Echinocandin # 14-21 days, AmB deoxycholate * for 21 days [strong, high] • Posaconazole suspension 400 mg BID, ER-table 300 mg QD [weak, low]
29
Recurrent infections: • Long term prophylaxis of fluconazole: 100-200 mg 3 times
/week in AIDS with CD4 cell count(< 50 cell/𝜇g) • Anti-retroviral therapy in HIV-infected • GM-CSF / InF- 𝛾 can be used as adjunctive
Summary –1 Treatment
• Non-neutropenic : higher dose of fluconzole, voriconazle for C. glabrata; suggest susceptibility of azole, echinocandin( prior exposure)
• Neutropenic:LF AmB (less attractive); granulocyte in prolong neutropenic
• Down-grade to fluconazole/ voriconazole if susceptible, stable
• CVC removal may be individualized
• Initial echinocandin doesn’t affect outcome in treating with C. parapsilosis candidemia
Empiric
• non-neutropenic : As early as possible , stop if no responses after 4-5 days
• intra-abdominal : high risk patient should considered Prophylaxis in ICU
• Echinocandin consider as alternatives
• Bath chlorhexidine can be considered 30
Summary –2
• AmB-d become less attractive, except for eye, CNS(LF AmB 5 mg/kg) , UTI (pyelonephritis: 0.3–0.6 mg/kg ) , oropharyngeal & esophageal
• Echinocandin move ahead, except eye involved
• High risk with asymptomatic candiduria, treat as candidemia (neutropenic) ; higher dose of fluconazole (urologic procedure)
• Medication choice : susceptibility, penetration to tissue, dosage, route , toxicity should be considerate to make appropriate treatment
31
THANK YOU FOR YOUR ATTENTION !!!
32
top related