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 follow-

up 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

2005; 366:1013-25

2. Ribes JA, Vanover-Sams CL and Baker DJ. Zygomyces in human disease. Clin.

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.