1 Patient Patient’ s headache is s headache is our headache our headache Princess Margaret Hospital Princess Margaret Hospital Dr. Lo Man Wai / Dr. Tang Hon Dr. Lo Man Wai / Dr. Tang Hon Lok Lok 8 th th Nov 2006 Nov 2006 History History n SM Leung, F/66 SM Leung, F/66 n DM nephropathy, HT DM nephropathy, HT n ESRF with pre ESRF with pre-emptive emptive cadaveric cadaveric renal renal transplant done on 19 transplant done on 19 th th Dec 2003 in mainland Dec 2003 in mainland China China n Post op no AR, baseline Post op no AR, baseline creatinine creatinine around around 130 130µmol/L mol/L n Initial Initial immunosuppression immunosuppression: : tacrolimus tacrolimus 3mg 3mg bd bd, , MMF 250mg MMF 250mg bd bd, , prednisolone prednisolone 10mg daily 10mg daily n Changed to Changed to neoral neoral 125mg 125mg bd bd at post transplant at post transplant 6 months 6 months 6 6 months post transplant (Jun 04) months post transplant (Jun 04) n Complained of headache for 2 months in Complained of headache for 2 months in clinic clinic n No vomiting No vomiting n No focal neurological deficit No focal neurological deficit n No fever No fever n Relieved by Relieved by paracetamol paracetamol CT brain CT brain MRI brain MRI brain Radiological diagnosis Radiological diagnosis n CT brain CT brain - 0.5 x 1 x 1.8cm convex shape extra 0.5 x 1 x 1.8cm convex shape extra- axial enhancing lesion over L frontal region with axial enhancing lesion over L frontal region with mild mild perifocal perifocal edema, edema, ddx ddx meningioma meningioma or or abscess abscess n MRI brain (6 weeks later) MRI brain (6 weeks later) – n Multilocular Multilocular extra extra-axial collection (maximum axial collection (maximum dimensions of about 3.5 x 3.5 x 2cm) dimensions of about 3.5 x 3.5 x 2cm) demonstrated in the L frontal lobe compatible demonstrated in the L frontal lobe compatible with with subdural subdural empyema empyema n An underlying rim enhancing cystic nodule An underlying rim enhancing cystic nodule around 1cm in diameter compatible with a brain around 1cm in diameter compatible with a brain abscess abscess
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PatientPatient’’s headache is s headache is our headacheour headache
Princess Margaret HospitalPrincess Margaret HospitalDr. Lo Man Wai / Dr. Tang Hon Dr. Lo Man Wai / Dr. Tang Hon LokLok
88thth Nov 2006Nov 2006
HistoryHistorynn SM Leung, F/66SM Leung, F/66nn DM nephropathy, HTDM nephropathy, HTnn ESRF with preESRF with pre--emptive emptive cadavericcadaveric renal renal
transplant done on 19transplant done on 19thth Dec 2003 in mainland Dec 2003 in mainland ChinaChina
nn Post op no AR, baseline Post op no AR, baseline creatininecreatinine around around 130130µµmol/Lmol/L
nn Changed to Changed to neoralneoral 125mg 125mg bdbd at post transplant at post transplant 6 months6 months
6 6 months post transplant (Jun 04)months post transplant (Jun 04)
nn Complained of headache for 2 months in Complained of headache for 2 months in clinicclinic
nn No vomitingNo vomitingnn No focal neurological deficitNo focal neurological deficitnn No feverNo fevernn Relieved by Relieved by paracetamolparacetamol
CT brainCT brain
MRI brainMRI brain Radiological diagnosisRadiological diagnosisnn CT brain CT brain -- 0.5 x 1 x 1.8cm convex shape extra0.5 x 1 x 1.8cm convex shape extra--
axial enhancing lesion over L frontal region with axial enhancing lesion over L frontal region with mild mild perifocalperifocal edema, edema, ddxddx meningiomameningioma or or abscessabscess
dimensions of about 3.5 x 3.5 x 2cm) dimensions of about 3.5 x 3.5 x 2cm) demonstrated in the L frontal lobe compatible demonstrated in the L frontal lobe compatible with with subduralsubdural empyemaempyema
nn An underlying rim enhancing cystic nodule An underlying rim enhancing cystic nodule around 1cm in diameter compatible with a brain around 1cm in diameter compatible with a brain abscessabscess
titretitre = 8, = 8, aspergillusaspergillus fumigatusfumigatus antibody, antibody, toxoplasmatoxoplasma antibody and antibody and histoplasmahistoplasmacapsulatumcapsulatum antibody negativeantibody negative
TreatmentTreatmentnn MMF was stoppedMMF was stoppednn Given a course of Given a course of ceftriaxoneceftriaxone and and
metronidazolemetronidazole, headache subsided, headache subsidednn Remained Remained afebrileafebrile all along, CRP all along, CRP
normalizednormalizednn FU CT brain showed resolved L frontal FU CT brain showed resolved L frontal
lobe epidural collection and nonlobe epidural collection and non--specific wall thickening of sphenoid specific wall thickening of sphenoid sinussinus
nn Seen by ENT Seen by ENT –– no signs of nasal / no signs of nasal / aural infectionaural infection
nn MMF was resumed at 250mg MMF was resumed at 250mg bdbd 1 1 months after dischargemonths after discharge
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4 4 months after dischargemonths after discharge……
Recurrence of headacheRecurrence of headache
nn Admitted for headache for 1 weekAdmitted for headache for 1 weeknn Associate with low grade fever and Associate with low grade fever and
deliriumdeliriumnn No focal neurological deficitNo focal neurological deficitnn Local inflammation over previous scalp Local inflammation over previous scalp
woundwound
Recurrence of Recurrence of empyemaempyema
nn CT brain CT brain –– L frontal L frontal subduralsubduralempyemaempyema around 1.3cm widtharound 1.3cm width
nn Treated conservative with iv Treated conservative with iv ampicillinampicillin, , metronidazolemetronidazole and and cefotaximecefotaxime
nn Increase in drowsinessIncrease in drowsinessnn Pus discharge from old scalp Pus discharge from old scalp
woundwoundnn CT brain CT brain –– enlargement of enlargement of
subduralsubdural empyemaempyema over L over L frontal region frontal region
nn Craniotomy done Craniotomy done nn Multiple pockets of Multiple pockets of subduralsubdural
empyemaempyema and brain abscess and brain abscess identified and drainedidentified and drained
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Real culprit revealedReal culprit revealednn Histology showed broad fungal Histology showed broad fungal hyphaehyphae with with
dichotomous branchingdichotomous branchingnn Fungal culture showed Fungal culture showed AspergillusAspergillus fumigatusfumigatusnn Serum Serum galactomannangalactomannan negativenegativenn CefotaximeCefotaxime and and metronidazolemetronidazole stopped stopped nn AmphotericinAmphotericin B given for 1 week (0.8mg/kg/day)B given for 1 week (0.8mg/kg/day)nn Changed to iv Changed to iv voriconazolevoriconazole (200mg then (200mg then
stepped up to 400mg stepped up to 400mg bdbd because of concomitant because of concomitant dilantindilantin therapy) after discussion with infectious therapy) after discussion with infectious disease teamdisease team
Stormy clinical courseStormy clinical course
nn Complicated by pneumonia, UTI with Complicated by pneumonia, UTI with septicaemiasepticaemia, DVT required IVC filter , DVT required IVC filter insertion, cardiac arrest successfully insertion, cardiac arrest successfully resuscitated, infected pressure soreresuscitated, infected pressure sore
nn Relatives insisted to continue Relatives insisted to continue immunosuppressantimmunosuppressant
nn CyclosporinCyclosporin A stepped down to 25mg A stepped down to 25mg bdbdand and prednisoloneprednisolone 7.5mg daily7.5mg daily
nn No deterioration in renal functionNo deterioration in renal function
After 12 weeksAfter 12 weeksnn FU CT brain showed no residual FU CT brain showed no residual
collectioncollectionnn WCC and CRP WCC and CRP normalisednormalisednn AfebrileAfebrilenn GCS gradually improved to GCS gradually improved to
15/1515/15nn Cyclosporine A stepped up to Cyclosporine A stepped up to
100mg/day and 100mg/day and prednisoloneprednisolonestepped down to 5mg daily (C0 stepped down to 5mg daily (C0 level 30, AUC 705)level 30, AUC 705)
nn VoriconazoleVoriconazole stoppedstopped
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Just as everything Just as everything seems going wellseems going well……
3 3 weeks after stopping antifungal weeks after stopping antifungal therapytherapy
nn Small scalp mass developed Small scalp mass developed just next to previous just next to previous craniotomy sitecraniotomy site
nn Bedside aspiration performed Bedside aspiration performed ––fungal culture grew fungal culture grew AspergillusAspergillusfumigatusfumigatus
nn CT brain CT brain –– lentiformlentiform epidural epidural fluid collection (1.9cm) at L fluid collection (1.9cm) at L frontal regionfrontal region
What will you do next?What will you do next?
Antifungal and surgeryAntifungal and surgery
nn Iv Iv voriconazolevoriconazole 400mg q12h restarted400mg q12h restartednn CyclosporinCyclosporin A stepped down to 25mg dailyA stepped down to 25mg dailynn Increase in mental dullness and fever Increase in mental dullness and fever
despite treatmentdespite treatmentnn Second craniotomy performed with Second craniotomy performed with
excision of fungal brain abscess and excision of fungal brain abscess and necrotic tissue donenecrotic tissue done
nn CT brain 3 weeks after CT brain 3 weeks after operation showed 2.5cm fluid operation showed 2.5cm fluid attenuation in L frontal lobe attenuation in L frontal lobe compatible with abscesscompatible with abscess What will you do next?What will you do next?
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More antifungalMore antifungal
nn CaspofunginCaspofungin 70mg daily added 70mg daily added but stopped after 8 weeks but stopped after 8 weeks because of profuse because of profuse diarrhoeadiarrhoea
nn CT brain showed resolved CT brain showed resolved abscess 2 weeks before abscess 2 weeks before stopping the drugstopping the drug
nn CRP and WCC CRP and WCC normalisednormalisednn AfebrileAfebrilenn VoriconazoleVoriconazole was continuedwas continued
ENT lesionENT lesionnn FU CT brain also showed FU CT brain also showed
collection with calcification in L collection with calcification in L sphenoid sinussphenoid sinus
nn Seen by ENT and suggested L Seen by ENT and suggested L functional functional endoscopicendoscopic sinus sinus surgery under GA to drain surgery under GA to drain abscess abscess
nn Surgery was performed in YCH Surgery was performed in YCH uneventfully in Dec 05uneventfully in Dec 05’’ and and muddy material was drainedmuddy material was drained
End of story?End of story?
3 3 months after stopping months after stopping caspofungincaspofungin
nn Noticed to have swelling over the Noticed to have swelling over the scalp with fluctuationscalp with fluctuation
nn Tapping done and culture showed Tapping done and culture showed recurrence of recurrence of AspergillusAspergillus
nn CT brain showed a 4cm rimCT brain showed a 4cm rim--enhancing lesion compatible with enhancing lesion compatible with empyemaempyema
What can we do next?What can we do next?
Treatment failureTreatment failurenn Seen by neurosurgical Seen by neurosurgical –– suggest suggest
conservative managementconservative managementnn PatientPatient’’s relatives insist to continue the s relatives insist to continue the
immunosuppressantimmunosuppressantnn VoriconazoleVoriconazole stopped and stopped and amphotericinamphotericin
B triedB triednn FU CT brain showed mild increase in FU CT brain showed mild increase in
size of the size of the subduralsubdural empyemaempyemann Clinically treatment failure, Clinically treatment failure,
amphotericinamphotericin B stopped after the 4 B stopped after the 4 week courseweek course
nn Patient was discharged Patient was discharged
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Just as everything Just as everything seems getting worseseems getting worse……
And they live happily togetherAnd they live happily together……
nn PatientPatient’’s conscious state did not s conscious state did not deteriorate after dischargedeteriorate after discharge
nn Pus discharge from scalp wound, Pus discharge from scalp wound, on daily dressing (still positive on daily dressing (still positive for for AspergillusAspergillus))
nn Latest CT brain in July 06Latest CT brain in July 06’’showed mild interval resolution showed mild interval resolution of the of the parasagittalparasagittal frontal frontal subduralsubdural empyemaempyema
……with a stable renal functionwith a stable renal function
nn Last seen in clinic on 18th Oct 2006 (7 Last seen in clinic on 18th Oct 2006 (7 months after declared treatment failure)months after declared treatment failure)
nn Renal function stable (serum Renal function stable (serum creatininecreatinine4949µµmol/L), on mol/L), on CsACsA 75mg daily and 75mg daily and prednisoloneprednisolone 10mg daily10mg daily
Relationship between immunosuppressant Relationship between immunosuppressant and and antifungalsantifungals
0
100
200
300
400
1. 9.0 4
1 .1 0 .0 4
1 .1 1. 04
1. 12. 0
4
1 .1 . 05
1 .2 . 05
1. 3.0 5
1. 4.0 5
1. 5. 0 5
Amphotericin B
CsA/day
Prednisolone/day
Antifungal
Voriconazole
200 mg BD
Voriconazole400mg bd
10mg
125mg 150mg 125mg 75mg
7mg
50mg
10mg
MMF 250mg bd
Craniectomy Craniotomy
Relationship between immunosuppressant Relationship between immunosuppressant and and antifungalsantifungals
0
100
200
300
400
1. 6.0 5
1 . 7.05
1. 8.0 5
1 . 9.05
1 .1 0 .0 5
1. 11 . 05
1 .1 2 .0 5
1 .1 . 06
1. 2. 0 6
1 .3 . 06
Amphotericin B
CsA/day
Prednisolone/day
Antifungal Voriconazole 400 mg BD
Voriconazole400mg bd
5mg
100mg
10mg
25mg
Nil Nil
Caspofungin
Craniotomy
50mg
SummarySummary
nn F/66 post F/66 post cadavericcadaveric renal transplant presented renal transplant presented with with aspergillusaspergillus brain abscess 6 months post brain abscess 6 months post transplanttransplant
nn Treated with Treated with amphotericinamphotericin B, B, voriconazolevoriconazole, , voriconazolevoriconazole and and caspofungincaspofungin combination combination therapy with adjuvant surgical interventiontherapy with adjuvant surgical intervention
nn Recurrence of brain abscess despite treatmentRecurrence of brain abscess despite treatmentnn Preserved allograft function with minimal Preserved allograft function with minimal
immunosuppressionimmunosuppression
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Literature review on Literature review on AspergillusAspergillus infectioninfection
Mycology of Mycology of AspergillusAspergillus
nn Exist only as mold; not Exist only as mold; not dimorphicdimorphic
nn SeptateSeptate hyphaehyphae that that form form dichotomusdichotomusbraches (V shaped)braches (V shaped)
nn The conidia form The conidia form radiating chainsradiating chains
Transmission and pathogenesisTransmission and pathogenesis
nn Ubiquitous in natureUbiquitous in naturenn Transmission is by airborne conidiaTransmission is by airborne conidiann Colonize and later invade abraded skin, Colonize and later invade abraded skin,
wound, burns, cornea, external ear and wound, burns, cornea, external ear and paranasalparanasal sinusessinuses
nn In In immunocompromisedimmunocompromised host, they will host, they will further invade into lung and other organsfurther invade into lung and other organs
Epidemiology Epidemiology
nn Prevalence of invasive Prevalence of invasive aspergillosisaspergillosisestimated to be 0.7% among kidney estimated to be 0.7% among kidney transplant recipientstransplant recipients
nn Most occur within the first 6 months of Most occur within the first 6 months of transplantationtransplantation
Singh N. Program and Abstracts, Focus on Fungal infections 8,March 4-6, 1998, Orlando, Florida
Clinical features of fungal brain Clinical features of fungal brain abscessabscess
nn Fever (76%)Fever (76%)nn Altered mental status (65%)Altered mental status (65%)nn HemiplegiaHemiplegia or or hemiparesishemiparesis (35%)(35%)nn Cranial nerves abnormalities (29%)Cranial nerves abnormalities (29%)nn Seizures, nausea and vomiting, headache Seizures, nausea and vomiting, headache
(10(10--20%)20%)
Baddley et al. Clin Transplant 2002: 16: 419-424
Treatment of Treatment of aspergillusaspergillus brain brain abscessabscess
nn Reversal of Reversal of immunosuppressionimmunosuppressionnn AntiAnti--fungal therapyfungal therapynn Surgery to Surgery to debridedebride necrotic tissue and to necrotic tissue and to
remove infected tissueremove infected tissue
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AmphotericinAmphotericin BBnn A A macrolidmacrolid antibiotic of complex structureantibiotic of complex structurenn It acts by binding to fungal cell membranes It acts by binding to fungal cell membranes
preferentially and interfere with its permeability preferentially and interfere with its permeability and transport functionand transport function
nn Lipid formulation is the preferred over the Lipid formulation is the preferred over the conventional because it can deliver higher dose conventional because it can deliver higher dose with fewer toxic effectswith fewer toxic effects
nn 3 formulations currently marketed: ABLC 3 formulations currently marketed: ABLC ((amphotericinamphotericin B lipid complex), B lipid complex), AmiBisomeAmiBisome((liposomalliposomal amphotericinamphotericin) and ABCD ) and ABCD ((amphotericinamphotericin B colloidal dispersion)B colloidal dispersion)
AmphotericinAmphotericin B B –– side effectsside effects
nn Suggested dosage Suggested dosage ––nn ABLC / ABLC / amibisomeamibisome 5mg/kg/day for 3 to 6 5mg/kg/day for 3 to 6
months, in critically ill patients months, in critically ill patients 10mg/kg/day up to 15mg/kg/day10mg/kg/day up to 15mg/kg/day
AmphotericinAmphotericin B B –– precautions for precautions for renal physicianrenal physician
nn Renal impairment: total daily dose Renal impairment: total daily dose decrease 50% or given on alternate daysdecrease 50% or given on alternate days
nn Important drug interactions:Important drug interactions:nn Increase Increase nephrotoxicitynephrotoxicity with cyclosporine with cyclosporine
or or aminoglycosideaminoglycosidenn PotentiationPotentiation of of hypokalaemiahypokalaemia with with
corticosteroidscorticosteroids
VoriconazoleVoriconazole
nn New New azoleazole groupgroupnn Action by inhibit the fungal P450 enzymes Action by inhibit the fungal P450 enzymes
for the synthesis of the main sterol in cell for the synthesis of the main sterol in cell membrane, thus inhibit fungal cell membrane, thus inhibit fungal cell membrane formationmembrane formation
nn FungistaticFungistatic against all fungi including against all fungi including resistant strains, and is fungicidal against resistant strains, and is fungicidal against aspergillusaspergillus
VoriconazoleVoriconazole –– side effectsside effectsnn Visual changesVisual changesnn PhotophobiaPhotophobiann ColourColour changeschangesnn Change in visual acuityChange in visual acuity
nn Suggested dosage:Suggested dosage:nn Loading dose 6mg/kg every 12 hours for 2 Loading dose 6mg/kg every 12 hours for 2
doses; followed by maintenance dose of 4mg/kg doses; followed by maintenance dose of 4mg/kg every 12 hoursevery 12 hours
nn Renal impairment Renal impairment –– no need to reduce the dose no need to reduce the dose but maintenance dose should be in oral formbut maintenance dose should be in oral form
VoriconazoleVoriconazole –– precautions to renal precautions to renal physiciansphysicians
nn VoriconazoleVoriconazole increases the serum levels increases the serum levels and effects of cyclosporine, dosage of and effects of cyclosporine, dosage of cyclosporine should be reduced by half cyclosporine should be reduced by half and level monitored closelyand level monitored closely
nn VoriconazoleVoriconazole will also increase the serum will also increase the serum levels of levels of sirolimussirolimus and and tacrolimustacrolimus
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CaspofunginCaspofungin
nn An An echinocandinsechinocandins derivativederivativenn Action on signal transduction essential for fungal Action on signal transduction essential for fungal
cell wall assemblycell wall assembly
nn Suggested dosage:Suggested dosage:nn 70mg on day 1 then 50mg/day subsequently70mg on day 1 then 50mg/day subsequentlynn Duration of treatment determined by patient Duration of treatment determined by patient
status and clinical response (suggested to stop status and clinical response (suggested to stop drug 2 weeks after culture negative)drug 2 weeks after culture negative)
CaspofunginCaspofungin –– side effectsside effects
nn Well toleratedWell toleratednn Elevation in ALP and Elevation in ALP and transaminasestransaminasesnn Fever, chills, headacheFever, chills, headachenn Nausea, vomiting, abdominal pain and Nausea, vomiting, abdominal pain and
diarrhoeadiarrhoea
CaspofunginCaspofungin –– precautions for precautions for renal physiciansrenal physicians
nn Concomitant use with cyclosporine may Concomitant use with cyclosporine may increase increase caspofungincaspofungin concentration and concentration and cause elevation in hepatic cause elevation in hepatic transaminasetransaminase
nn CaspofunginCaspofungin may decrease blood may decrease blood concentration of concentration of tacrolimustacrolimus
nn No specific dosage modification is required No specific dosage modification is required for renal impairmentfor renal impairment
Which one is better?Which one is better?
nn VoriconazoleVoriconazole is drug of choice for treatment of is drug of choice for treatment of invasive invasive aspergillosusaspergillosus
nn In a randomized open label of 277 patients with In a randomized open label of 277 patients with confirmed or probable confirmed or probable aspergillosisaspergillosis
nn Underlying Underlying allogenicallogenic haematopoietichaematopoietic cell cell transplantation, acute transplantation, acute leukaemialeukaemia or other or other haematologichaematologic diseasesdiseases
nn 144 treated with 144 treated with voriconazolevoriconazole and 133 treated and 133 treated with with amphotericinamphotericin B B
Herbrecht et al: NEJM 2002; 347: 408-415
Which one is better?Which one is better?nn VoriconazoleVoriconazole 6mg/kg 6mg/kg bdbd on day 1 then 4mg/kg on day 1 then 4mg/kg bdbd
for 1 week then oral 200mg for 1 week then oral 200mg bdbdnn AmphotericinAmphotericin B B deoxycholatedeoxycholate (conventional) 1 to (conventional) 1 to
1.5mg/kg1.5mg/kgnn At 12 weeks, At 12 weeks, voriconazolevoriconazole group group vsvs amphotericinamphotericin
B group: B group: nn Successful outcome: 52.8% Successful outcome: 52.8% vsvs 31.6% (95% CI 31.6% (95% CI
difference 10.4 to 34.9)difference 10.4 to 34.9)nn Survival rate: 70.8% Survival rate: 70.8% vsvs 57.9% (95% CI hazard 57.9% (95% CI hazard
ratio 0.40 to 0.88)ratio 0.40 to 0.88)
Herbrecht et al: NEJM 2002; 347: 408-415
Which one is better?Which one is better?
nn CaspofunginCaspofungin should not be used for should not be used for primary therapy because of lack of dataprimary therapy because of lack of data
nn It can be used for those who cannot It can be used for those who cannot tolerate or refractory to primary therapytolerate or refractory to primary therapy
nn It can also be used in combination therapyIt can also be used in combination therapy
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Combination therapyCombination therapy
nn The role of combination antifungal therapy The role of combination antifungal therapy as either initial or salvage therapy is as either initial or salvage therapy is unproved since the benefit must be unproved since the benefit must be weighed against the increase in toxicityweighed against the increase in toxicity
nn There are retrospective studies showing a There are retrospective studies showing a marginal benefits of addition of marginal benefits of addition of caspofungincaspofungin on top of on top of amphotericinamphotericin B B therapytherapy
Aliff et al. Cancer 2003; 97: 1563
Kontoyiannis et al. Cancer 2003; 98:292
Combination therapyCombination therapy
nn Data on combination of Data on combination of voriconazolevoriconazole and and caspofungincaspofungin seems more promisingseems more promising
nn In one retrospective study of 47 patients In one retrospective study of 47 patients with progressive with progressive aspergillosisaspergillosis despite despite amphotericinamphotericin B therapyB therapy
nn 31 received 31 received voriconazolevoriconazole only and 16 only and 16 received received voriconazolevoriconazole + + caspofungincaspofungin
nn A significant lower rate of mortality (odds A significant lower rate of mortality (odds ratio 0.28) was found at 3 monthsratio 0.28) was found at 3 months
Marr et al. Clin Infect Dis 2004; 39: 797
Combination therapyCombination therapynn Another Another prosepectiveprosepective study involving 87 patients study involving 87 patients
with SOT suffering from invasive with SOT suffering from invasive aspergillosisaspergillosisnn 47 patients received lipid formulation of 47 patients received lipid formulation of
amphotericinamphotericin B compared with 40 patients B compared with 40 patients received received caspofungincaspofungin and and voriconazolevoriconazole as as primary therapyprimary therapy
nn Survival rate at 90 days was better for those Survival rate at 90 days was better for those who received combination therapy (67.5% who received combination therapy (67.5% vsvs51%)51%)
Singh et al. Transplantation 2006; 81-230
Current recommendationCurrent recommendation
nn Decrease the degree of Decrease the degree of immunosuppressionimmunosuppression whenever possiblewhenever possible
nn VoriconazoleVoriconazole as initial therapyas initial therapynn Combination therapy for those who do not Combination therapy for those who do not
respond to initial therapyrespond to initial therapynn Duration of therapy is dependent upon the Duration of therapy is dependent upon the
patientpatient’’s underlying disease and respond s underlying disease and respond to therapyto therapy
Drug bill Drug bill –– only counting antifungalonly counting antifungal
nn VoriconazoleVoriconazole 400mg 400mg bdbd = $1366= $1366nn Total 9 months = $368,820Total 9 months = $368,820
nn CaspofunginCaspofungin 70mg $412070mg $4120nn Total 8 weeks = $230,720Total 8 weeks = $230,720
nn Grand total = $599,540 (HKD)Grand total = $599,540 (HKD)
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