A case of invasive A case of invasive aspergillosis aspergillosis

in a lung transplant patientin a lung transplant patient

Dr. Dino Dr. Dino SgarabottoSgarabotto

Transplant ID UnitTransplant ID Unit

Padova General Padova General HospitalHospital

ItalyItaly

Cystic fibrosis Pancreatic insufficiencyInsulin-dependent diabetes mellitus Bilateral lung transplant (2008)

>> cyclosporine and steroids

HypertensionMild renal impairment

AC, 35 years oldAC, 35 years old

20092009: Invasive aspergillosis involving:

brain, lung and mitral valve,Treated with Caspofungin and Voriconazole for 60 days Voriconazole 200 mg bid for 16 months No surgery Sensitivity testing not done

Clinical HistoryClinical History

[>> Urine culture grew Aspergillus sp., so he received a longer treatment with caspofungin]

September 2010September 2010:Pneumocystis carinii pneumonia: ICU admission

The patient suffered from fever and urine retention.Treated unsuccessfully with ciprofloxacin. Persistence of 39°C intermittent fever every 3 days: new hospitalization

December 2010December 2010

Blood and urine culture: negativeBlood and urine culture: negative

WBC: normal; anemiaWBC: normal; anemia

CRP: 128 mg/dLCRP: 128 mg/dL

PSA: normalPSA: normal

Creatinine: 132 mmol/LCreatinine: 132 mmol/L

Chest X-Ray: negativeChest X-Ray: negative

December 2010December 2010

Transrectal US: small prostatic abscesssmall prostatic abscess

Cultures from post-prostatic massage fluid: Aspergillus sppAspergillus spp..

Abdomen US: 4.5 cm mass on the left upper 4.5 cm mass on the left upper kidneykidney

Chest CT scan, echocardiography and cerebral MRI : Chest CT scan, echocardiography and cerebral MRI : unremarkable. unremarkable.

Abdomen MRIAbdomen MRI

Abdomen MRIAbdomen MRI

DiagnosisDiagnosis

AspergillusAspergillus prostatic prostatic abscessabscess

…plus….

1.1. PTLDPTLD

2.2. Renal cancerRenal cancer

3.3. AspergillomaAspergilloma

PET-CT scanPET-CT scan

The patient was restarted on voriconazole/caspofungin

3 weeks later

fever unchanged, CRP 110 mg/dL and voriconazole trough level 3.2 ug/dL

Patient treatment Patient treatment hystoryhystory

Therapy was switched to Liposomal Amphotericin B 3mg/Kg/daily

quick (1 day) disappearance of fever,CRP normalization,

new culture of post-prostatic massage fluid: negative

Clinical case: March 2011… no fever, Clinical case: March 2011… no fever, but…but…

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crea

tin

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ol/

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surgical enucleation

CultureCultures:s:

Surgical enucleationSurgical enucleation

Hystology: Hystology: aspergillomaaspergilloma

Follow up: May-July 2011Follow up: May-July 2011

US scan: no recrudescenceUS scan: no recrudescence No feverNo fever

…but..

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crea

tin

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/dL

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CR

P m

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STOPSTOPLAmb 3 mg/kg/die

LAmb 3 mg/kg/die

Lung transplant recipients are at high risk of invasive Aspergillosis.

However, isolated urinary involvement of invasive aspergillosis is uncommon and its

treatment is very controversial.

Conclusions (1)Conclusions (1)

• We observed the development of microbiological resistance to Voriconazole and pharmacokinetic/clinical inefficacy of Caspofungin.

•Voriconazole-resistant Aspergillus is a new problem

• Efficacy of LAmB… …but hard management because nefrotoxicity

and concomitant use of Cyclosporine

Conclusions (2)Conclusions (2)

• In invasive aspergillosis: LAmB effectiveness only if combined to surgery?• Is there a genetic predisposition for invasive aspergillosis or are there other still unknown risk factors?• How can we manage antifungal secondary prophylaxis in this patient?• Secondary prophylaxis with iv Ambisome is not yet defined:

•3 mg/kg/daily 2 weeks a month? •5 mk/Kg twice a week?•10 mg/Kg/weekly? How long???

Further questions Further questions