A case of invasive aspergillosis

1. A case of invasive aspergillosis A case of invasive aspergillosis
in a lung transplant patientin a lung transplant patient
Dr. Dino SgarabottoDr. Dino Sgarabotto
Transplant ID UnitTransplant ID Unit
Padova General HospitalPadova General Hospital
ItalyItaly

2. Cystic fibrosis
Pancreatic insufficiency
Insulin-dependent diabetes mellitus
Bilateral lung transplant (2008)
>> cyclosporine and steroids
Hypertension
Mild renal impairment
AC, 35 years oldAC, 35 years old

3. 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

4. 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

5. 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 kidney4.5 cm mass on the left upper kidney
Chest CT scan, echocardiography and cerebral MRI : Chest CT scan, echocardiography and cerebral MRI :
unremarkable. unremarkable.

6. Abdomen MRIAbdomen MRI

7. Abdomen MRIAbdomen MRI

8. DiagnosisDiagnosis
AspergillusAspergillus prostatic abscess prostatic abscess
…plus….
1.1.PTLDPTLD
2.2.Renal cancerRenal cancer
3.3.AspergillomaAspergilloma

9. PET-CT scanPET-CT scan

10. 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 hystoryPatient treatment hystory
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

11. Clinical case: March 2011… no fever, but…Clinical case: March 2011… no fever, but…
0
50
100
150
200
250
300
350
days
creatinine mmol/L
surgical
enucleation

12. Cultures:Cultures:
Surgical enucleationSurgical enucleation
Hystology: Hystology:
aspergillomaaspergilloma

13. Follow up: May-July 2011Follow up: May-July 2011
US scan: no recrudescenceUS scan: no recrudescence No feverNo fever
…but..
100
150
200
250
300
350
05 /05 /2 011
09 -m ag 12 -m ag 16 -m ag 19 -m ag 23 -m ag 26 -m ag 30 -m ag
02 -gi u 06 -gi u 09 -gi u 13 -gi u 16 -gi u 20 -gi u 23 -gi u 30 -gi u
creatinine mg/dL
0
10
20
30
40
50
60
CRP mg/dL
STOPSTOP
LAmb 3 mg/kg/dieLAmb 3 mg/kg/die

14. 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)

15. • 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)

16. • 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