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Case Report

Wound infection due to Absidia corymbifera and Candida

albicans with fatal outcome

R. HORRE*, B. JOVANIC*, S. HERFF*, G. MARKLEIN*, H. ZHOU$, I. HEINZE%, G. S. DE HOOG, R. RUCHEL &

K. P. SCHAAL*

Institutes for*Medical Microbiology and Immunology, $Pathology, %Department of Anaesthesiology, University of Bonn, Bonn,

Department of Bacteriology, University Hospital, Gottingen, Germany andCentraalbureau voor Schimmelcultures,

Utrecht, The Netherlands

A case of a mixed infection due to Candida albicans and the zygomycete Absidia

corymbifera in a 38-year-old, previously healthy, Caucasian male is presented. The

infection developed following serial rib fractures, and ruptures of kidney, liver and

biliary tract as well as a pancreatic contusion resulting from a traffic accident.

During intensive care treatment the patient underwent several surgical procedures

but subsequently experienced multi-organ failure and sepsis. Some weeks later,

fungal growth was observed macroscopically on the patients skin and wounds.

From wound swabs C. albicans and A. corymbifera were grown. Histopathology of

abdominal tissue yielded pseudohyphae and coenocytic hyphae. Although surgical

debridement and antifungal treatment with amphotericin B and 5-flucytosine were

started immediately, the patient died in therapy-refractory septic multi-organ

failure.

Keywords Absidia corymbifera, Candida albicans, zygomycosis

IntroductionDuring the past 10 years, fungal infections have gained

considerable medical importance, particularly in pa-

tients with severe underlying diseases. While Candida

species were previously the predominant causative

agents of invasive mycoses, in recent years opportunis-

tic moulds, such as Aspergillus species or other

hyphomycetes, and zygomycetes, have increasingly

been implicated in human infection. In contrast to

the yeasts, several of these moulds show a high degree

of resistance to most antifungal drugs [1].

The yeast Candida albicans occurs worldwide as a

common colonizer of mucosal sites in humans andwarm blooded animals. With severe underlying illness it

may affect any organ by continuous or haematogenous

spread. Clinical symptoms are usually non-specific [2].Absidia corymbifera is a member of the class Zygomy-

cetes, order Mucorales. It can be isolated from soil,

plants, and air. Rhinocerebral mycosis due to this

mould is the most common clinical manifestation, but

gastrointestinal, pulmonary, cutaneous, and dissemi-

nated infections have also been reported [2]. These

infections are characterized by vascular invasion,

thrombosis, and tissue necrosis [3/6]. The disease is

usually fulminant and has a high mortality rate [7].

Complete debridement of the afflicted tissue forms the

basis of an effective treatment of zygomycosis [8/10].

Case history

A 38-year-old, previously healthy, Caucasian man

suffered from multiple traumata after a bike accident.

He was hospitalized in an intensive care unit of a

peripheral hospital because of scapula and serial rib

fractures, right-sided kidney, liver and biliary tract

ruptures, and pancreatic contusion as a consequence

Correspondence: Regine Horre, Federal Institute for Drugs and

Medical Devices, Kurt-Georg-Kiesinger Allee 3, D-53175 Bonn,

Germany. Tel: '/49 228 207 3267; E-mail: [email protected]

Received 1 June 2003; Accepted 4 August 2003

2004 ISHAM DOI: 10.1080/1369378032000141426

Medical Mycology August 2004, 42, 373/378

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of blunt abdominal and thoracic injury. No wounds

could be observed on the patients head, neck or

extremities. The patient rapidly developed haema-

tothorax and was subjected to abdominal and thoracic

surgery, including right-sided nephrectomy. One week

later, he was transported to the Department of

Anaesthesiology, University of Bonn, Germany, be-cause of suspected abdominal bleeding, signs of multi-

organ failure and sepsis. The patient was intubated, put

on catecholamines and treated for pain. Intravenous

antibiotic therapy was started with ciprofloxacin (0.4 g/

day) and piperacillin/combactam (4.0/1.0 g/day). Bleed-

ing of the liver ceased, but 8 days after accident, the

patient developed an intra-abdominal compartment

syndrome and a leakage of his biliary tract. Repeated

abdominal surgery followed, whereby the abdomen had

to be kept open because of elevated intra-abdominal

pressure due to retroperitoneal haematoma and swel-

ling of the intra-abdominal organs. Therefore, daily

surgical wound revision followed, after which thewound was covered with sterile organic foil (Sterile

Vi-Drape Isolation Bag; Medical Concepts Develop-

ment, Woodbury, USA) and rinsed daily with sterile

physiological NaCl. From abdominal wound swabs as

well as from tracheal secretions Escherichia coli and an

Enterococcus species were isolated first, but 10 days

after the accident, C. albicans was cultured from a

tracheal secretion; 2 days later (12 days after the

accident), C. albicans and A. corymbifera were grown

from an abdominal swab. Amphotericin B in liquid

glucose solution (40 mg/500 ml) was then used for

rinsing twice daily. On day 16 after the accident, A.

corymbifera was also observed from a drainage catheter

and fungal growth could be seen macroscopically on

the patients abdominal wound and on the surface of

abdominal organs, which showed signs of necrosis

(Figs. 1 and 2). The situation was further complicated

by the development of pulmonary infiltrates. Tracheal

secretions now turned sanguineous and purulent.

Although an intravenous antimycotic treatment with

amphotericin B (initially 40 mg/day; then 80 mg/day)

and flucytosine (2 g/day) was started 14 days after the

accident in addition to daily surgical debridement, the

patient died in therapy-refractory multi-organ failure

4 days later, 18 days after the accident.

Several tissue specimens were subjected to histo-

pathological and microbiological examination. Clinico-

chemical infection markers during disease showedelevated leukocyte counts (day 1, 8.2; day 17,

29.5 mm(3 [normal, 4.3/10.5 mm(3]) and C-reactive

protein values (day 1,B/1.0 mg/ml; day 7, 17.4 mg/ml;

day 17, 21.2 mg/ml [normal,B/10.0 mg/ml]).

Histopathology

Microscopy of skin, soft tissue and muscles from the

patients abdomen stained with Gomoris methenamin-

Fig. 1 The patients abdominal site in a

case of wound infection due to Absidia

corymbifera and Candida albicans.

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silver stain (GMS) showed invasive pseudohyphae

suggesting a yeast-like fungus, in addition to broad,

irregularly branched, non-septate hyphae, characteris-

tic of zygomycetes (Fig. 3). In samples from the surface

of the wound sporangia could be seen (Fig. 4).

Microbiology

Fungal isolation and identification

During the patients intensive care treatment, tracheal

secretions, wound fluids, tissue specimens and blood-

Fig. 2 Macroscopically visible fungal

growth at the margin of the patients wound.

Fig. 3 Tissue section showing pseudohy-

phae from the yeast Candida albicans in

addition to coenocytic hyphae from the

mould Absidia corymbifera (GMS )/100).


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cultures (Becton Dickinson, Germany) were sent for

microbiological examination. For fungal culture Candi-

Select agar (CSA; BioRad, Germany) (2 days at 378C)

and Sabourauds glucose agar (SGA) (10 days at 308C)

were used. Fungal growth was observed on SGA and

CSA after incubation for 2/3 days. No growth was

observed from the blood cultures, but abdominal

wound secretions yielded C. albicans as well as A.

corymbifera . The yeast grew in typical colonies on

SGA, with blue colour on CSA, which is indicative ofC. albicans. With the API 32C Identification System

(Api Biomerieux, France) the identification as C.

albicans was confirmed. The mould was woolly and

whitish-grey in colour; the reverse of the culture was

whitish. It was identified by morphological criteria and

thermotolerance at 508C, as described by De Hoog et

al. [2]. A. corymbifera was deposited in the culture

collection of the Centraalbureau voor Schimmelcul-

tures, Utrecht, the Netherlands, as CBS 112528.

Discussion

Infections due to C. albicans currently are common

diseases in intensive care patients. Probable risk factors

of the patient described in this article may have been

the antibacterial therapy and the prolonged abdominal

surgery as well as the leakage of gastrointestinal

contents. The aetiological agent mostly is one of the

patients indigenous yeasts colonizing the respiratory

and gastrointestinal tracts.

The situation in infections due to zygomycetes is

different. In older literature [6,11,12] most described

cases concerned colonisation of nasal sinuses, even-

tually leading to direct or vascular invasion of the

brain. Major risk factors for such rhinocerebral

mycoses are ketoacidosis as a consequence of diabetes

mellitus or alcohol abuse and deferoxamine therapy for

iron overload [11,12]. More recently, zygomycosis is

increasingly seen in haematological malignancies [5,13].

Most of the infections are pulmonary or disseminated[6]. Localized infections after traumatic inoculation of

the fungi have also been observed [14]. Clinical

manifestation depends on the route of infection [3].

In the case described here, nothing is known about

the previous fungal colonization of the patients

mucosal surfaces and there was no indication of

diabetes mellitus, alcohol abuse, or traumatic inocula-

tion of the zygomycete. The patient had no damage of

the skin; all traumatic lesions were located subcuta-

neously. Inoculation of A. corymbifera therefore might

have occurred during or after surgery, possibly when

the abdomen was left open after the compartment

syndrome. Immunocompromized patients undergoing

major surgery are at an increased risk, as infectious

sporangiospores may spread nosocomially by various

means [4,15,16]. Co-infections with other microorgan-

isms may also be a predisposing factor for infection

with zygomycetes [14,16/18].

The major zygomycetes causing infections in humans

belong to the genera Rhizopus, Rhizomucor, Mucor,

Fig. 4 Tissue sections from the surface of

the wound showing sporangia of Absidiacorymbifera (GMS )/100).


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and Absidia , but a variety of members of other genera

have occasionally been reported [4]. It has been

assumed that the first described human case of

zygomycosis, from the 1800s, was due to A. corymbi-

fera [4]. This fungus grows more rapidly at 378C than at

258C and tolerates temperatures up to 528C, which

distinguishes it from other Absidia species [2,19].

Thermotolerance may be an important virulence factor

for human infection.

Cutaneous infections with A. corymbifera can be

visible as grey-black plaques that rapidly increase in

size over a 24-h period [14]. In the patient described

here, fungal growth was visible macroscopically, mainly

at the margin of the patients wounds, where local

necrosis and acidosis may have favoured fungal devel-

opment. Arterial invasion and thrombosis is a common

condition in zygomycosis and can result in ischaemia

and gangrene [20]. Conditions favourable to germina-

tion of A. corymbifera include low pH, high glucose

content [21], increased iron [22] and decreased phago-cytic defence [23]. The angioinvasive property of these

fungi is another virulence factor that may be respon-

sible for high lethality [7].

In our patient, the infection can only be assumed as

hospital acquired. Cutaneous zygomycosis is a rare but

serious infection in trauma patients with wounds

contaminated by environmental debris or soil. In this

case, the patient was traumatised, but fungal inocula-

tion during the accident was unlikely, because there was

internal damage only.

For the definite diagnosis of zygomycosis, the detec-

tion of the non-septate hyphae in tissue sections and

confirmation by culture is necessary [24]. Neitherserological tests nor PCR-based specific tools are

commercially available. In this patient, the first isolate

ofA. corymbifera was judged as fungal contamination.

Daily surgery and twice daily rinsing with amphoter-

icin-B-containing solution were performed until further

microbiological probes and histopathology confirmed

the infection due to A. corymbifera . Four days later, the

patient died due to multiorgan failure; a change of

therapeutic regimen was being discussed.

Treatment of infections due to A. corymbifera is

difficult; in -vitro test results often do not correlate with

in -vivo sufficiency. In -vitro synergy of amphotericin B

with rifampicin has been shown [25,26] but proved to

be ineffective in a 3-year-old boy with haematological

neoplasia who suffered from cerebral zygomycosis [27].

Another patient with a localized infection of his foot

following trauma was cured with local and systemic

ketoconazole associated with hyperbaric oxygen ther-

apy [28]. Invasive cutaneous A. corymbifera infection

was successfully treated in an allogeneic bone marrow

transplant patient with liposomal amphotericin B for

6 weeks and surgical debridement [9]. One patient with

catheter-related cutaneous infection was cured with

liposomal amphotericin B and granulocyte growth-

stimulating factor after removal of the catheter and

tissue debridement [10], and healing has been reported

in one case of a kidney infection after kidney trans-

plantation with transplantectomy alone [15]. All of

these reports describe only single cases; the mortality

rate in zygomycosis is still very high. For successful

treatment it seems to be most important that the

patient recovers immunologically and that the necrotic

tissue is removed. In addition, drug administration

should be performed as early as possible. Although rare

reports suggest that fluconazole may be effective [28/

30], in -vitro tests usually show resistance of Mucorales

to azole compounds. However, the new antifungal

compound posaconazole shows a high in -vitro activity

against zygomycetes compared with the other azoles

tested [1] and has been used successfully in thetreatment of Mucor infection in an immunosuppressed

mouse model [31]. This might indicate that posacona-

zole may be sufficient in the treatment of zygomycete

infections also. Furthermore, the first single cases of

the effectiveness of echinocandins (FK463) in the

eradication of invasive mucormycosis have been re-

ported [32].

Today, optimal treatment consists of aggressive

surgical debridement additionally to intravenous ad-

ministration of amphotericin B [8], especially lipid

formulations, if possible [33].

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