SUCCESSFUL
TREATMENT
OF
MUCORMYCOSIS
ENDOCARDITIS
COMPLICATED BY PULMONARY INVOLVEMENT
Nina Gubarev M.D.1 , Jadranka Šeparović M.D., Ph.D.2, Ivan Jelić M.D., Ph.D.3 ,
Vladimir Gašparović M.D., Ph.D.1
1 Division of Emergency and Intensive Care Medicine, Department of Intarnal Medicine,
University Hospital Rebro, Zagreb
2 Department of Cardiology, University Hospital Rebro, Zagreb
3 Department for Cardiac Surgery, University Hospital Rebro, Zagreb
Running title: Successful treatment of mucormycosis endocarditis
Address for correspondence: Nina Gubarev
Prilaz Gj. Deželića 59
10 000 Zagreb
Croatia
E-mail: ngubarev@inet.hr
Tel: 00385 1 377 18 17
Fax: 00385 1 242 18 89 or 00385 1 370 50 44
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ABSTRACT
This case report describes mucormycosis endocarditis in immunosuppressed
patient with ulcerative colitis on corticosteroid therapy. There was a possibility that he
had also hematogenous spread to the lung. Therefore he was treated with surgery and
high dose of liposomal amphotericin B. In our experience this resulted in clinical
satisfying result with two months control period.
KEYWORDS
Endocarditis, Mucormycosis, High-dose liposomal amphotericin B therapy
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CASE REPORT
A 37-year-old male patient with ulcerative colitis was treated with corticosteroids
and mesalazin for exacerbation of ulcerative colitis that had lasted 2,5 months. Since
there was no improvement after 1,5 months of therapy the patient was admitted to the
hospital. After admission he was treated with long term antibiotic therapy with
ciprofloxacin and metronidazol, corticosteroids, mesalazin and total parenteral nutrition.
Therapy was given by jugular vein catheter.
After 4 weeks of hospitalization and therapy patient become febrile. Jugular
catheter was suspected as a source of infection and was removed. Next day the patient
developed septic shock and was admitted to our intensive care unit (ICU). C-reactive
protein (CRP) 164. Blood cultures were taken. After stabilisation with initial resuscitation
and dopamine we have started antibiotic therapy with tazobactam + piperacilin and
vankomycin. Blood cultures were positive for Enterococcus faecim sensitive to
vankomycin and one was positive also for Candida parapsylosis. After receiving blood
culture results vancomycin 2x1 gr.i.v. was continued and liposomal amphoterycin B
0.5mg/kg was introduced in therapy.
After four days of targeted antibiotic treatment the patient was hemodinamicaly
stabile, but still febrile, CRP 183. Transthoracic and transesophageal echocardiography
showed right atrial intracardial mass 6x1.8cm that could be endocarditis vegetation or
myxoma (Figure 1.). Chest radiography showed right lobe pneumonia.
10- days after the admission to ICU patient underwent cardiac surgery. Tumor
mass was removed completely. Histology revealed micotyc hyphae and spoores –
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showing Mucormycosis (Figure 2.). Microbiology of operative specimen was positive for
Mucor species that grew in large number, but also Enterococcus faecim.
Treatment was continued with vankomycin and liposomal amphotericin B 0.5
mg/kg. 14-days after operation treatment with vankomycin was terminated and with
amphotericin B was continued.
Control chest radiography showed regression of infiltration but there were also
multiple nodal lesions. Thoracic MSCT described nodal lesion few millimeters to 1.4 cm
in diameter, close to the blood vessels, some with central necrosis. CRP level was high
(CRP 126). Bronchoscopy was performed. Bronchoalveolar lavage (BAL) specimen was
negative for mucormycosis.
Although BAL was negative for mucormycosis we suspected possibility of the
hematogenus spread of mucormycosis to the lung and decided to treat the patient with
high dose of liposomal amphotericin B of 5 mg/kg. The goal was to give the total dose of
15000 mg of liposomal amphotericin B.
The patient responded well and clinical improvement was obvious. At that time,
ulcerative colitis was in remission and allowed us to gradually terminate corticosteroid
therapy.
When we reached the dose of 15 000 mg of liposomal amphotericin B CRP level
was still slightly above normal (CRP 32), so we decided to give him another 3000 mg of
liposomal amphotericin B.
After total of 18 200 mg of liposomal amphotericin B patient’s CRP level was in
the normal limit. Thoracic MSCT scan showed improvement but not total regression. He
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was afebrile, feeling well. At that time we decided to discontinue liposomal
amphotericine B therapy.
One month later a CT scan is unchanged. BAL and transbronchal biopsy of lung
lesion revealed no evidence of mucormycosis. We will keep patient in long term followup but at this time we think no therapy is needed.
DISCUSSION
In general all invasive fungal infections are rare but life-threatening infections.
Mucormycosis (or zygomycosis) is an uncommon infection caused by fungi in the
Zygomycetes class 1,2. Zygomycetous are ubiquitous in the nature, and almost all humane
infections occur in immunocompromised subjects. The hyphae of zygomycetos fungi are
broad, irregularly branched, and have rare septations. Mucormycosis is characterized by
infarction and necrosis of host tissues that results from invasion of the vasculature by
hyphae. Typical
clinical presentations are rhinocerebral infection, pulmonary
mucormycosis due to inhalation and gastrointestinal mucormycosis due to ingestion.
Cardiac mucormycosis has been reported but rarely and majority of these cases
was diagnosed at autopsy 3. Recently there are some reports of successful treatments of
cardiovascular mucormycosis 4, 5.
Preferred therapy for mucormycosis is early surgery intervention 1. Of all known
antifungal therapy mucormycosis is sensitive only to amphotericin B 1. Amphotericin B
however has been limited by its toxicity- both acute as well as chronic. Walsh has done a
study in neutropenic patients comparing conventional amphotericin B with liposomal
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amphotericin B that showed that liposomal amphotericin B is as effective as conventional
amphotericin B for empirical antifungal therapy in patients with fever and neutropenia
and is associated with fewer breakthrough fungal infections, less infusion-related toxicity,
and less nephrotoxicity 6. Treatment with high-dose of liposomal amphotericin B has
been reported 7. However there is still neither recommendations of precise daily dose nor
the maximum tolerated dose of liposomal amphotericin B.
In this report we show immunosuppressed patient on corticosteroid therapy and
long term broad spectrum antibiotics with sepsis and mucormycosis endocarditis. The
treatment of choice was surgery and high-dose liposomal amphotericin B which enabled
aggressive antifungal therapy. We published our experience that surgical incision
combined with 18000mg of total liposomal amphotericin B therapy resulted in clinical
satisfactory results after two months of follow-up period without therapy. The fact that
patient underlying disease (ulcerative colitis) was in remission enabled us to remove
corticosteroid treatment and recover patient’s immune system to normal was helpful in
treating the patient.
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REFERENCES
1. Patterson T F. Advances and challenges in management of invasive mycoses. Lancet
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Microbiol. Rev. 2001;13:236-301.
3. Virmani R, Connor DH, Mc Allister HA. Cardiac mucormycosis: a report of five
patients and a review of 14 previously reported cases. Am J Clin Pathol 1982; 78:42-7
4. Chen L, Xiao Y, Wang X. Successful treatment of mucormycosis in the pulmonary
artery after cardiac surgery. J Card Surg. 2005 Mar-Apr;20(2):186-8.
5. Mehta NN, Romanelli J, Sutton MG. Native aortic valve endocarditis with
Cunninghamella. Eur J Echocardiogr. 2004. Mar;5(2):156-8
6. Walsh TJ, Finberg RW, Arndt C, et all. Liposomal amphoericin B for empirical
therapy in patients with persistent fever and neutropenia. N Engl J Med. 1999 Mar 11,
340 (10): 764-771
7. Michelle AB, Lay M, Madinger NE. Surgery and Treatment with High-Dose
Liposomal Amphotericin b for Eradication of Craniofacial Zygomycosis in Patient with
Hodgkin’s Disease Who Had Undergone Allogenic Hematopoetic Stem Cell
Transplantation. J Clin Microbiol. 2005 April; 43(4):2012-2014
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Figure 1. Echocardiographic image of the giant right atrial mass (vegetation) protruding
across the tricuspid valve during diastole into the right ventricle. A) transthoracic apical
four chamber view B) transesophageal four chamber view. (RA: right atrium, RV: right
ventricle, TV:tricuspid valve, LA:left atrium, LV:left ventricle)
Figure 2. Patohystology of atrial endocardial vegetation showing hyphae of
mucormycosis, painted with Hemalaun-eozin, x400
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1.A
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1.B
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2.