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Saudi Journal of Kidney Diseases and Transplantation
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CASE REPORT Table of Contents   
Year : 2010  |  Volume : 21  |  Issue : 5  |  Page : 914-918
Disseminated invasive aspergillosis successfully treated with micafungin in a renal transplant recipient


Internal Medicine Department, Jordan Hospital and Medical Center, Amman, Jordan

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Date of Web Publication31-Aug-2010
 

   Abstract 

Earlier experience with micafungin demonstrated a successful outcome in treating pulmonary aspergillosis in leukemic patients. We report a case of renal transplant recipient (RTR) who developed disseminated invasive aspergillosis. The patient was treated with micafungin with complete clinical and radiological response.

How to cite this article:
Wadi J, Al-kawasmeh SI, Kamel MT, AlJayyousi BB. Disseminated invasive aspergillosis successfully treated with micafungin in a renal transplant recipient. Saudi J Kidney Dis Transpl 2010;21:914-8

How to cite this URL:
Wadi J, Al-kawasmeh SI, Kamel MT, AlJayyousi BB. Disseminated invasive aspergillosis successfully treated with micafungin in a renal transplant recipient. Saudi J Kidney Dis Transpl [serial online] 2010 [cited 2020 Jun 6];21:914-8. Available from: http://www.sjkdt.org/text.asp?2010/21/5/914/68891

   Introduction Top


Aspergillus is a ubiquitous mold, widely abun­dant in nature and its spores spread by air. Humans acquire spores by inhalation. [1] Suscep­tible host may develop invasive aspergillosis in an organ or it disseminates to several organs (DIA). The highest risk groups are bone marrow transplant recipients (BMT) and patients with hematological malignancies receiving chemo­therapy; less commonly, solid organ transplant recipients (SOTR) are infected in different proportions. HIV patients are at increased risk though to less extent.

Commonly IA affects lungs and sinuses; how­ever dissemination to CNS, bone, heart and skin may occur. Mortality associated with IA is high and depends on organ(s) involved; 99% for cerebral, 86% for pulmonary, and 66% for invasive sinus aspergillosis, and ranges from 20-100%, in SOTR close to 95% in BMT recipients. [2],[3],[4],[5],[6]

Efforts have been continuous to develop new agents with improved activity against aspe­rgillus and improved survival with less toxi­city. The "gold standard" has been amphote­ricin B deoxycholate for few decades, or its lipid formulations thus allowing higher doses with relatively less toxicity. [7],[8]

Triazoles with activity against aspergillus show good activity with survival benefit, how­ever their hepatotoxicity and drug interaction profile are of concern especially in patients on immunosuppressive therapy. [9],[10],[11] Recently, Mica­fungin, an Echinocandin, showed excellent in vitro and in vivo activity against aspergillus; it demonstrated clinical activity in salvage and primary therapy groups. [3],[7] Here we report a case of renal transplant recipient who developed DIA. Micafungin was used in 100 mg/day do­sage, the patient showed excellent response with complete resolution of all lesions, inclu­ding those not surgically drained.


   Case Report Top


A 52-year-old man with diabetes mellitus, who received a living non-related renal trans­plant, was admitted in Jordan hospital on July 6, 2006, with a 20-day history of fever that started following transplantation. He was on prednisone, cyclosporine and mycophenolate mofetil. Physical examination disclosed a pale patient with BP: 110/70 mmHg, oral tempera­ture: 38.7ºC, respiratory rate: 24/minute, and pulse rate: 100/minute. Auscultation of the lungs and heart was unremarkable. Abdominal exam was also unremarkable except for a palpable transplanted kidney in the right iliac fossa. La­boratory investigations revealed hemoglobin: 7.7 gm/dL, WBC: 7,900/mm 3 , neutrophiles: 50%, lymphocytes: 47%, platelets: 369,000/mm 3 . Glu­cose: 634 mg/dL. Na + : 122 mmol/L, K + : 7 mmol/L, urea: 245 mg/dL, Creatinine: 2.9 mg/ dL, Ca ++ : 8.5 mg/dL, PO4: 5 mg/dL. SGOT: 39 U/L, SGPT: 23 U/L, alkaline phosphatase: 374 U/L, total protein: 5.5 gm/dL, albumin: 2.6 gm/dL, PT: 16.2 seconds, PTT: 33.9 seconds. Urine culture grew Extended Spectrum B­ lactamases (ESBL) E. coli; blood culture was negative. An echocardiogram was within no­mal limits. The transplanted kidney ultrasound revealed moderate hydronephrosis. A chest computerized tomography (CT) scan showed multiple nodular lesions, and a fine needle as­piration (FNA) of a lesion grew ESBL-E. coli for which the patient was treated with 6 weeks imipenem, and cytology silver, PAS, and acid fast stains were negative. An abdominal CT scan was unremarkable. The patient was dis­charged three weeks later on his immunosup­pressive regimen and parenteral imipenem for three more weeks; his creatinine was 1.9 mg/ dL and Hgb: 9.9 gm/dL.

Five weeks later he was readmitted with right hip pain and limitation of movement of two weeks duration. He looked in distress, afebrile with B.P: 130/80 mmHg, pulse rate: 82/min, and respiratory rate: 14/min. There was no change from previous physical examination. His labo­ratory investigations revealed Hgb: 10.9 gm/ dL, WBC: 7,900/mm 3 , urea: 164 mg/dL, Crea­tinine: 2 mg/dL. Magnetic resonance imaging (MRI) of the patient's lumbosacral spine and hips showed a collection in the right psoas muscle and right Iliacus posterior to the trans­planted kidney, another collection appeared anterior to right common iliac artery. The iliop­soas collection was drained under CT scan guidance, with subsidence of hip pain, later; pus culture grew aspergillus and ESBL- E. coli. Two days later his chest CT scan showed mul­tiple nodular opacities in the lungs fields, and abdomen and pelvis CT scans showed that the iliopsos abscess was completely drained, while the collection anterior to the common iliac ar­tery was still present. The surgical opinion was against drainage of this collection due to its proximity to the great vessels. CT guided lung nodule was sampled by FNA; it also grew aspergillus species. Micafungin 100 mg intra­venously once daily was started, two weeks later chest CT scan was repeated and showed questionable increase in the size of lung no­dules, the abdominal and pelvic CT scan showed that the anterior to iliac vessels abscess did not change in size. The patient was switched to oral voriconazole and discharged home.

Less than a month later, he was readmitted with one week history of lethargy, generalized weakness, and anorexia. He looked severely jaundiced, dehydrated with shortness of breath, he had harsh breathing sounds, faint heart sounds, weak peripheral pulses, distended and tender right upper abdominal quadrant with ac­tive bowel sounds. His labs revealed Hgb: 13.7 gm/dL, WBC: 14000/mm 3 , platelets: 469000/ mm 3 , PT: 15.9, PTT: 26.7, Glucose: 392 mg/ dL, urea: 251 mg/dL, Creatinine: 3.36 mg/dL, Na + : 128 mmol/L, K + : 9.6 mmo/L, SGOT: 39 U/L, SGPT: 58 U/L, Albumin: 2.7 gm/dL, total bilirubin: 6.8 mg/dL, direct bilirubin: 5.79 mg/ dL, alkaline phosphatase: 1071 U/L. Chest CT scan showed a decrease in the left parame­diastinal mass, the parahilar round mass lesion did not change in size but it disclosed a slight cavitation, and collapsed consolidation was noted in both basal lung regions more on the right. He received an urgent hemodialysis and 2 days later abdominal and pelvic CT scans re­vealed enlarged liver with scattered well-defined hypodense lesions mainly in the right lobe. The right psoas muscle contained a large collec­tion. In comparison to the previous CT scans, these lesions increased in number and size. Micafungin was restarted in 100 mg I.V. once daily, since the diagnosis was voriconazole hepatotoxicity with disease progression. On the next day the psoas collection was drainage under CT guidance. Pus culture showed heavy growth of ESBL-E. coli and aspergillus [Figure 1]. Three weeks after the resumption of mica­fungin, a chest CT scan showed that the left parahilar nodule, the anterior segment of right upper lobe nodule, the paramediastinal lesion, and the left apical cavitating lesions had dis­appeared. An abdominal CT scan showed that the psoas collection located anterior to the pelvic vessels had completely resolved without evidence of residue. Then he was discharged with hemoglobin: 10.4 gm/dL, PT: 15 seconds, PTT: 24.5 seconds, normal electrolytes, Crea­tinine: 1.1 mg/dL, albumin: 2.7, total bilirubin: 1.14 mg/dL and alkaline phosphatase: 140 U/L.
Figure 1 :Aspergillus surgically drained from the iliopsoas collection.

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The patient was discharged on five more days of parenteral micafungin completing 10 weeks of therapy, and repeated chest and abdominal CT scans just before discharge demonstrated a complete resolution of all his lesions in the lungs, liver, iliopsaos and on bifurcation of the great pelvic vessels [Figure 2]. Follow-up after one year disclosed a stable condition.
Figure 2 :A) An intra abdominal collection resides close to the great vessels B) After treatment, complete
resolution of the intra abdominal collection C) Pulmonary aspergillosis in the left hilar and apical regions D) Complete resolution of the left hilar and apical regions infection


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   Discussion Top


Micafungin mechanism of action includes dis­ruption of growth of fungi by arresting the synthesis of 1, 3- B-D glucan, a highly required component for fungal cell wall. [12]

Studies on micafungin established its indica­tion in esophageal candidiasis, and in candida prophylaxis in hematopoietic stem cell trans­plant recipients (HSCT). [12] Its place in the treat­ment of aspergillus is evolving, where some previous case reports showed good activity and primary studies demonstrated safety of the drug. [13],[14],[15] Denning et al conducted a multina­tional, non-comparative open-label trial to exa­mine the efficacy of micafungin in proven or probable pulmonary aspergillosis in adult and pediatric patient populations; including HSCT, GvHD and patients who received chemothe­rapy for hematologic malignancy. Those trea­ted primarily with micafungin alone showed up to 50% favorable responses, and the sal­vage therapy group showed 40.9% response. Though the numbers were small, the study demonstrated the efficacy of micafungin in invasive pulmonary aspergillosis whether pri­mary or salvage. [3]

Our patient had DIA; he was initially treated solely as ESBL-E. coli septicemia for 6 weeks with imipenem after obtaining the same pa­thogen from lungs, he had initial partial res­ponse, denoting a possible co-infection. On his second presentation, aspergillus grew from several sites. Micafungin was started with ob­served clinical improvement, but due to the questionable radiological lack of improvement he was switched to voriconazole, which later was discontinued due to hepatitis. Micafungin was resumed as intravenous 100 mg/day injec­tions after less than a month of interruption. The repeat chest, abdominal, and pelvic CT scans just before discharge showed complete resolutions of all organs involved in DIA.

Our patient was different from others in being RTR and developed not only invasive pulmonary aspergillosis but furthermore it disse­minated to the liver, pelvic space and muscles, and with micafungin treatment he had com­plete clinical and radiological responses and survival more than a year after treatment. [14],[15]

 
   References Top

1.Benet T, Nicolle MC, Thiebaut A, et al. Re­duction of invasive aspergillosis incidence among immunocompromised patients after control of environmental exposure. Clin Infect Dis 2007;45:682-6.  Back to cited text no. 1      
2.Pegues CF, Daar ES, Murthy AR. The epi­demiology of invasive pulmonary aspergillosis at a large teaching hospital. Infect Control Hosp Epidemiol 2001;22(6):1-5.  Back to cited text no. 2      
3.Denning DW, Marr KA, Lau WM, et al. Mica­fungin (FK463), alone or in combination with other systemic antifungal agents, for the treat­ment of acute invasive aspergillosis. J Infect 2006;53:337-49.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]  
4.Lodge BA, Ashley ED, Steele MP, Perfect JR. Aspergillus fumigatus empyema, arthritis, and calcaneal osteomyelitis in a lung transplant patient successfully treated with posaconazole. J Clin Microbiol 2004;42(3):1376-8.  Back to cited text no. 4      
5.Pierrotti LC, Baddour LM. Fungal endocarp­ditis, 1995-2000. Chest 2002;122(1):302-10.  Back to cited text no. 5      
6.Denning DW. Therapeutic outcome in invasive aspergillosis. Clin Infect Dis 1996;23(3):608-15.  Back to cited text no. 6      
7.Clinical Practice Guidelines of the Infectious Diseases Society of America. Treatment of Aspergillosis. Clin Infect Dis 2008;46:327-60.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]  
8.Marr KA, Boeckh M, Carter RA, Kim HW, Corey L. Combination antifungal therapy for invasive aspergillosis. Clin Infect Dis 2004;39: 797-802.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]  
9.Herbrecht R, Denning DW, Patterson TF, et al. Voriconazol versus amphotericin B for pri­mary therapy of invasive aspergillosis. N Engl J Med 2002;347:408-15.  Back to cited text no. 9  [PUBMED]  [FULLTEXT]  
10.Ashley ES, Lewis R, Lewis JS, Martin C, Andes D. Pharmacology of systemic antifungal agents. Clin Infect Dis 2006;43:S28-39.  Back to cited text no. 10      
11.Groll AH, Kolve H, Ehlert K, Paulussen M, Vormoor J. Pharmacokinetic interaction between voriconazole and ciclosporin A follo­wing allogeneic bone marrow transplantation. J Antimicrob Chemother 2004;53:113-4.  Back to cited text no. 11  [PUBMED]  [FULLTEXT]  
12.Chandrasekar PH, Sobel JD Micafungin: A new echinocandin. Clin Infect Dis 2006;42: 1171-8.  Back to cited text no. 12      
13.Ota S, Tanaka J, Kahata K, et al. Successful micafungin treatment of invasive pulmonary aspergillosis in a patient with acute lympho­blastic leukemia in a phase II Study. Int J Hematol 2004;79:390-3.  Back to cited text no. 13  [PUBMED]    
14.Singer MS, Seibel NL, Vezina G, Choi SS, Dinndorf PA. Successful treatment of invasive aspergillosis in two patients with acute myelogenous leukemia. J Pediatr Hematol Oncol 2003;25(3):252-6.  Back to cited text no. 14      
15.Yokote T, Akioka T, Oka S, et al. Successful treatment with micafungin of invasive pul­monary aspergillosis in acute myeloid leuke­mia, with renal failure due to amphotericin B therapy. Ann Hematol 2004;83(1):64-6.  Back to cited text no. 15      

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Correspondence Address:
Jamal Wadi
Chairman of the Infection Control Committee, Chairman of the Pharmacy and Therapeutic Committee, Consultant Infectious Disease, Office 11, 3rd Floor, The Medical Center, Jordan Hospital & Medical Center, Queen Noor Street, P.O. Box 143589, Amman 11814
Jordan
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