608

Candidal Mediastinitis: An Emerging Clinical Entity

Cornelius J. Clancy, M. Hong Nguyen, From the University of Florida College of Medicine and the VeteransAdministration Medical Center, Gainesville, Florida; and the Dukeand Arthur J. Morris

University Medical Center, Durham, North Carolina

Candidal mediastinitis is rare. We report nine cases encountered at our institutions since 1985;seven cases were diagnosed since 1993. All cases followed thoracic surgery, with a median timefrom surgery to disease onset of 11 days (range, 6–100 days). All patients received prior antibiotictherapy. Common clinical manifestations were chest wall erythema in 4 cases (44%), drainage in 5(56%), fever in 4 (44%), and sternal instability in 4 (44%). Failure to obtain appropriate intraoperativespecimens for cultures and the dismissal of cultures positive for Candida as contaminants delayeddiagnosis in three cases (33%). Mediastinitis was complicated by contiguous or hematogenous spreadin seven cases (78%); five patients (56%) had two or more complications. The mortality rate was56%. Optimal therapy remains undefined, but on the basis of our experience, aggressive surgicaldebridement combined with antifungal therapy for at least 6 weeks is recommended. Prompt recogni-tion and institution of therapy appear to be the keys to improving prognosis.

Candida is a rare cause of mediastinitis, causing only 5% 1985 and 1996 were identified via infection control files andmedical record discharge code. Chart reviews determined thatof cases reported in the English-language literature [1–13].

Although an increase in individual case reports of candidal eight cases fulfilled our criteria for candidal mediastinitis (seeunder Inclusion Criteria). An additional case meeting the crite-mediastinitis has appeared in the literature since 1990 [14–

17], the understanding of the disease and its optimal manage- ria was identified in a prospective study of candidemia that weconducted [18].ment remain limited by the small number of reported cases,

the lack of a consistent definition of mediastinitis, incomplete We also reviewed the previously reported cases of candidalmediastinitis in the English-language literature from 1966 toclinical descriptions and accounts of therapy, and inadequate

long-term follow-up of patients. Given the high morbidity and 1996 by using MEDLINE. Key words used were Candida,fungus, mediastinitis, pericarditis, sternal, and osteomyelitis.mortality rates associated with candidal mediastinitis [14], a

comprehensive review of the clinical manifestations, naturalhistory, microbiology, therapy, and outcome of the disease is

Inclusion Criterianeeded.Our experience with five cases of candidal mediastinitis from Cases in our series met the following criteria: mediastinitis—

1995 to 1996 prompted us to conduct such a review. A search infection of the region within the thorax between the pleuralfor all cases at our institutions since 1985 confirmed the impres- sacs that is bounded inferiorly by the diaphragm, superiorly bysion of its increasing incidence: of nine cases identified, 78% the aperture of thorax, anteriorly by the sternum and costalwere diagnosed since 1993. In addition, we identified seven cartilages, and posteriorly by the thoracic vertebrae [19]; andcases previously reported in the English-language literature that Candida-positive culture of a specimen obtained intraopera-fulfilled our rigorous definition of candidal mediastinitis (see tively or by guided biopsy from within the mediastinum.under Methods). We present our series of nine cases and review Superficial wound infections following median sternotomythe literature to provide more complete insight into this emerg- or thoracotomy were excluded, as were cases of sternal osteo-ing clinical entity. myelitis, endocarditis, pericarditis, or empyema without evi-

dence of extension into the mediastinum.

Methods

ResultsPotential cases of candidal mediastinitis diagnosed at theUniversity of Florida College of Medicine (Gainesville) and the

From January 1985 to August 1996, eight cases of candidalVeterans Administration Medical Center (Gainesville) between

mediastinitis were identified at our institutions. The clinicaldata for these patients and another patient identified during ourprospective study of candidemia [18] are summarized in tables

Received 4 November 1996; revised 4 March 1997. 1 and 2. These nine cases formed the database for our analysis.Reprints or correspondence: Dr. M. Hong Nguyen, University of Florida Seven cases in our series were diagnosed since 1993. During

College of Medicine, Department of Medicine, P.O. Box 100277, JHMHC,this period, 3,061 cardiothoracic surgical procedures were per-Gainesville, Florida 32610.formed at our institutions; the incidence of candidal mediastin-

Clinical Infectious Diseases 1997;25:608–13This article is in the public domain. itis was 0.3%.

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609CID 1997;25 (September) Candida Mediastinal Wound Infection

Table 1. Clinical features of nine patients with candidal mediastinitis at the University of Florida College of Medicine (Gainesville) and theVeterans Administration Medical Center (Gainesville).

Time fromAge, sex/ surgery to Prior

Case year of onset of antibiotic Prior or concomitant Culture specimens positive forno. diagnosis Type of surgery mediastinitis therapy Clinical findings bacterial infection Candida

1 64 y, F/1985 Mitral and aortic 11 d Yes Chest wall erythema, Prior bacteremia with Intraoperative mediastinal fluid,valve drainage, and Proteus mirabilis blood, sternum, urinereplacement instability, fever and Enterococcus

2 Newborn, S/P Blalock-Taussig 6 d Yes Chest wall erythema, None Intraoperative mediastinal fluid,F/1985 shunt procedure drainage, and blood, chest tube, pericardial

instability, shock fluid, urine3 74 y, M/1993 CABG, VSD repair 8 d Yes Chest wall None Intraoperative mediastinal fluid/

tenderness, shock, thrombus, blood, sternum,fever, respiratory pleural fluiddistress

4 Newborn, Heart 6 d Yes Open sternum, shock None Intraoperative mediastinal fluid,M/1994 transplantation sternum; pleural, pericardial,

and peritoneal fluids5 59 y, M/1995 CABG 4 w Yes Chest wall erythema, None Intraoperative mediastinal fluid,

drainage, and chest tube drainageinstability

6 59 y, M/1995 Aortic valve 13 d Yes Chest wall erythema, None Intraoperative mediastinal fluid,replacement swelling, drainage, blood, sternum

instability, anddehiscence

7 9 mo, F/1995 Blalock-Taussig 100 d Yes Sternal instability and None Intraoperative mediastinal fluid/shunt procedure click, fever hematoma, polymeric

silicone band, thrombus fromgraft, sutures

8 72 y, M/1996 CABG 8 d Yes Sternal instability and Concomitant wound Intraoperative mediastinal fluidclick, persistent infection with and woundwound drainage Pseudomonas,

Acinetobacter, andStaphylococcusaureus

9 50 y, M/1996 Esophagectomy 26 d Yes Fever, subcutaneous None Percutaneous mediastinal fluidwith subsequent emphysema aspiration, chest tubeleak drainage

NOTE. In case 9, the patient was infected with Candida glabrata. All other patients were infected with Candida albicans. CABG Å coronary artery bypassgrafting; S/P Å status post; VSD Å ventricular septal defect.

Patient Demographics and Underlying Conditions received antibacterial agents postoperatively. Three (33%) ofnine patients were also treated with antibacterial agents for atIn our series, there were six adults and three children. Twoleast 4 days prior to surgery; all of these patients developedof the children were newborn infants. All three children hadmediastinitis shortly after surgery.congenital heart disease; two children underwent a Blalock-

Taussig shunt procedure, and the third underwent orthotopicheart transplantation. In the six adults, the most commonunderlying diseases (in descending order) were coronary ar- Clinical Manifestationstery disease (3 patients), valvular heart disease (2), and malig-nancy (1). The most common clinical manifestation was purulent

drainage from the sternum (56%) (table 1). Fever, sternalAll nine patients underwent thoracic surgery prior to thedevelopment of mediastinitis. The median time between sur- instability, and chest wall erythema were each noted in 44%

of patients. Other manifestations included shock (33% of pa-gery and the onset of mediastinitis was 11 days (range, 6–100days). Of note, the onset of mediastinitis in eight (89%) of tients), sternal click (22%), respiratory distress (11%), subcu-

taneous emphysema (secondary to esophageal rupture; 11%),nine patients occurred within 28 days of surgery; the onsetoccurred within 14 days in six (69%) of nine. All patients wound dehiscence (11%), and sternal tenderness (11%).

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610 Clancy, Nguyen, and Morris CID 1997;25 (September)

Table 2. Therapy and outcome for nine patients with candidal mediastinitis at the University of Florida College of Medicine (Gainesville)and the Veterans Administration Medical Center (Gainesville).

Case Initial antifungal Response to Subsequentno. Complication(s) therapy Surgery treatment treatment Outcome

1 Fungemia, sternal None Debridement No clinical response NA Died at 2 dosteomyelitis

2 Fungemia, Amphotericin B Debridement, removal No clinical response Added flucytosine Died at 3 wpericarditis of hardware

3 Fungemia, sternal Amphotericin B Debridement, removal No clinical response Amphotericin B Died at 9 dosteomyelitis, of hardwareempyema

4 Sternal osteomyelitis, Fluconazole Debridement, removal No clinical response, Changed to Died at 2 mopericarditis, of graft with subsequent amphotericin Bempyema, MSOFperitonitis

5 None Amphotericin B Debridement, Clinical response Fluconazole Cured; 7-mofor 2 w resection of clot maintenance follow-up

(400 mg q.d.)6 Fungemia, sternal Amphotericin B Debridement, removal Clinical response Fluconazole (400 Cured; 14-mo

osteomyelitis for 2 w of surgical sternal mg q.d.) for 6 follow-upwire w

7 None Fluconazole (20 Debridement, removal Clinical response NA Cured; 9-momg b.i.d.) for of graft, sutures, follow-up6 w and polymeric

silicone bards8 Chronic wound None Five debridements, Persistent infection Fluconazole Ongoing

infection four vascular flap maintenance infection;procedures (600 mg q.d.) 5-mo

follow-up9 Empyema Amphotericin B None Relapse Liposomal Died at 2 mo

for 2 w amphotericin Band flucytosine

NOTE. MSOF Å multiple system organ failure; NA Å not applicable.

Microbiology this delay was due to failure to obtain appropriate intraoperativespecimens for culture (patients 1 and 5) or dismissal of cultures

All patients except one were infected with Candida albicans;positive for Candida as contaminants (patient 8).

one patient was infected with Candida glabrata. For eight(89%) of nine patients, Candida was isolated in pure culture.Cultures of specimens from within the mediastinum of all pa- Complicationstients were positive for Candida. Other positive culture speci-

Mediastinitis was complicated by either contiguous or hema-mens included blood (44% of cases), sternal bone (44%), pleu-togenous spread in seven (78%) of nine patients. Five (56%)ral fluid (22%), pericardial fluid (22%), urine (22%), thrombusof nine patients had two or more complications. Complications(22%), wound site (11%), and hardware (11%). One patientincluded fungemia (44% of patients), sternal osteomyelitishad prior bacteremia, and another had concomitant bacterial(44%), empyema (22%), pericarditis (22%), peritonitis (11%),infections of the mediastinum (table 1).chronic wound infection (11%), and infected thrombus (22%).

DiagnosisOutcome and Therapy

All patients had clinical evidence of mediastinitis. The diag-nosis was subsequently confirmed by cultures positive for Can- The overall mortality rate was 56%; four (80%) of five deaths

were directly attributable to candidal mediastinitis (tables 2dida. Chest radiographs were suggestive of mediastinitis in six(75%) of eight cases; these radiographs demonstrated a mass and 3).

Six patients were treated with combined surgical debride-or fluid collection in four cases and mediastinal air in two.For three patients, the diagnosis of candidal infection was ment and antifungal agents. Three of these patients died: two

received amphotericin B therapy (patients 2 and 3) and onenot made until at least 3 weeks after the onset of mediastinitis;

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611CID 1997;25 (September) Candida Mediastinal Wound Infection

Table 3. Outcome according to type of therapy for nine patients Seven (78%) of nine cases in this report were diagnosedwith candidal mediastinitis at the University of Florida College of since 1993, thus suggesting that mediastinitis due to CandidaMedicine (Gainesville) and the Veterans Administration Medical Cen- is an important emerging clinical entity. Our experience paral-ter (Gainesville).

lels an increase in individual case reports appearing in theliterature since 1990 [14–17]. Whether the increase in caseNo. of patients with

reports represents a true increase in the incidence of the diseaseStable condition or simply an increase in the recognition of Candida as a sig-while receiving nificant pathogen in the postsurgical population is not apparent.

antifungal ChronicAlthough Candida has been implicated in outbreaks of woundTherapy Death treatment infection Cureinfection following sternotomy [41, 42], there was no evidence

Antifungal alone 1 0 0 0 that our increased number of cases was due to such an outbreak.Surgical debridement Our cases occurred at two institutions, and no epidemiological

alone 1 0 1 0 links between cases were found.Combined debridement

All of our cases and six (86%) of seven previously reportedand antifungal 3 1 0 2cases followed thoracic surgery, which has been identified asthe major predisposing factor for mediastinitis. In the era beforecardiothoracic surgery, perforation of the esophagus was theleading cause of mediastinitis. In our series, only one patientreceived fluconazole therapy (patient 4). All three patients had

multiple complications of candidal mediastinitis: fungemia (2 developed candidal mediastinitis as a complication of an esoph-ageal leak.patients), pericarditis (2), sternal osteomyelitis (2), empyema

(2), and peritonitis (1). The three surviving patients were treated All our patients received antibacterial agents postoperativley;three (33%) of nine patients also received antibacterial therapywith fluconazole alone (one patient) or with amphotericin B

for 2 weeks followed by fluconazole for at least 6 weeks for at least 4 days immediately prior to surgery. Prior receiptof antibacterial agents has been well established to be associ-(two patients). These patients were doing well at 9-, 7-, and

14-month follow-ups, respectively. ated with candidemia and with nosocomial infection due toCandida.Two patients who were treated with surgical debridement

alone either died (patient 1) or developed chronic infection that One of the most surprising findings in our series was thatsix (67%) of nine cases occurred relatively early (within 14ultimately required therapy with an antifungal agent (patient

8). The diagnosis was delayed for both patients: for patient 1, days) after surgery. These observations suggest that the portalof entry is often direct intraoperative inoculation; indeed, directappropriate specimens for culture were not obtained during the

initial surgery, and for patient 8, cultures positive for Candida inoculation was the attributed portal of entry in all patients inour series and in 15 (94%) of all 16 cases reviewed.were dismissed as contaminants.

One patient who was treated with antifungal therapy alone The most common clinical manifestations of candidal medi-astinitis were chest wall drainage, erythema, sternal instability,died despite treatment with liposomal amphotericin B and flu-

cytosine (patient 9). fever, and shock. These findings were indistinguishable fromthose of bacterial mediastinitis. As such, Candida should beconsidered as a possible etiologic agent in any case of medi-astinitis, especially those cases occurring in the setting of priorDiscussionuse of broad-spectrum antibiotics or those that do not respondto surgical debridement and therapy with antibacterial agents.Candidal mediastinitis is a rare clinical entity. The largest

review of candidal mediastinitis, published in 1990, included An appropriate level of suspicion is crucial to early diagno-sis. All debrided or aspirated material should be sent for micro-39 cases previously reported in the English-language literature

[14]. Many of these cases, however, were superficial wound biological and histopathologic studies. The failure to appropri-ately obtain culture specimens from patients or the dismissalinfections following sternotomy or infections of the sternum,

costal cartilages, heart, pericardium, or pleura rather than true of cultures positive for Candida as contaminants led to delayin diagnosis in three (33%) of our nine cases; all of theseinfections involving the mediastinum [20–27]. In addition, sev-

eral reports failed to adequately provide clinical details, localize patients died or subsequently developed chronic infectionsrequiring multiple debridements and long-term antifungalthe precise site of infection, describe the method for diagnosis,

or offer compelling evidence that Candida was contributing to therapy.The mortality rate of 56% in our series was similar to thatdisease [6, 7, 9, 14, 28–36]. We could identify only seven

reports published since 1966 that provided a complete case of 43% in the previous case reports. In our series, four (80%)of five patients with multiple (at least two) complications ofdescription of a well-documented diagnosis of candidal medi-

astinitis [14–17, 37–40] (table 4). To this body of experience, candidal mediastinitis died; one (25%) of four with no or onlyone complication died. All survivors in our series and the pre-we add our series of nine cases.

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612 Clancy, Nguyen, and Morris CID 1997;25 (September)

Table 4. Summary of clinical data on seven patients with candidal mediastinitis previously reported in the English-language literature.

InitialUnderlying antifungal Response to Subsequent

[Reference(s)] condition(s) Complication(s) therapy Surgery therapy therapy Outcome

[37] Esophagectomy, repair Fungemia Miconazole None Persistent Amphotericin B Cured; 15-moof esophagotracheal infection and flucytosine follow-upfistula

[38] CABG Sternal osteomyelitis Ketoconazole Four debridements None Amphotericin B Stable conditionand whiledebridements, receivingketoconazole maintenancemaintenance therapy; 9-mo

follow-up[39] Heart transplant None Amphotericin B Debridements, None Added flucytosine Cured; 9-mo

repair of follow-upruptured aorticaneurysm

[14, 40] CABG, repeated Sternal osteomyelitis, Amphotericin B Debridements, Persistent Muscle flap Cured; 9-mothoracotomy due to pericarditis, pericardial infection procedure follow-uphemorrhage empyema stripping

[15] Boerhaave’s syndrome, Fungemia, empyema Amphotericin B Debridements, None NA Died at 1 moesophageal repair esophageal

repair[16] Cardiac surgery for None Amphotericin B Two None NA Died at 1 mo

congenital heart debridements,disease muscle flap

procedure[17] Anterior cervical Fungemia Amphotericin B Debridements, No clinical NA Died at 15 d

fixation for spinal esophageal responseinjury repair

NOTE. CABG Å coronary artery bypass graft; NA Å not applicable.

viously reported cases had significant morbidity, with pro- combining surgical and antifungal treatment appear to be themost important determinants of satisfactory outcome.longed hospitalizations, repeated debridements, and clinical

relapses.It is important to stress that the follow-ups in several pre-

Conclusionsviously reported cases were relatively short; therefore, any re-ports of cure must be interpreted with caution. It is not uncom- Increased recognition of Candida species as causes of blood-mon for apparently healed sternal wounds, in particular, to stream infection has been paralleled by increased appreciationrecrudesce months after cessation of therapy. As an example, of the role of these organisms in other nosocomial infectiousa 42-year-old man with candidal mediastinitis associated with processes. Candidal mediastinitis is one such process that haspericarditis and sternal osteomyelitis was described as cured recently emerged as a significant cause of mortality and mor-at a 9-month follow-up after two therapeutic courses of ampho- bidity, particularly in patients undergoing thoracic surgery.tericin B and aggressive surgical debridement [40]. A subse- This entity should be suspected in any patient with infectionquent report noted that 16 months later, his sternal wound of the mediastinum, especially those cases occurring in theinfection recurred, and further therapy was required [14]. setting of broad-spectrum antibiotic use or those that do not

Evaluation of the optimal therapy for candidal mediastinitis respond to aggressive surgical debridement and therapy withis limited by shortcomings in the literature, particularly incom- antibacterial agents. It is of paramount importance that appro-plete descriptions of antifungal regimens. On the basis of our priate samples from any patient with suspected mediastinitisexperience, however, therapy combining aggressive surgical be sent for microbiological and histopathologic studies. Delaydebridement with antifungal agents is the preferred approach in diagnosis has been associated with poor outcome, includingto management of these infections. Early diagnosis offers the chronic wound infection, local extension involving the pericar-best chance to reduce subsequent morbidity and mortality. Vas- dium, pleural sac, and sternal bone, and hematogenous seeding.cular flaps have been touted as essential for cure [14], but Mediastinitis complicated by these processes often is associated

with a fatal prognosis. The optimal therapy for candidal medi-in our experience, prompt diagnosis and aggressive therapy

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