Discussion
Mediastinitis is a rare but potentially lethal complication of heart
transplantation, occurring in 1-10% of cases with Staphylococcusspp. and Enterobacter spp. as the most common pathogens. [4]
Our patient presented with two rare pathogens of mediastinitis, A.
fumigatus and A. baumannii .
Aspergillus has been recognized as a major opportunistic pathogen
and accounts for the most common mycoses in cardiac transplant
recipients. [1] Diagnosis can be challenged by discriminating
colonization from invasive infection and because strains morphologically
identified as putative A. fumigatus are recognized as different
species by molecular methods with decreased antifungal susceptibility.
[5] This may lead to a delay of targeted treatment resulting in an
excessive mortality. Despite negative blood cultures, invasive infection
could be documented by numerous intraoperative specimens from the
sternum, native and transplanted aorta including anastomosis, all
intrathoracic organs and the thoracic wall. Microbiology uniformly
showed characteristic culture and genomic sequencing documented hyphae
consistent with Aspergillus on microscopic examination, positive
serum galactomannan test and the presence of A. fumigatus . Hence,
a diagnosis of invasive aspergillosis could be made in accordance with
the definition of the US Centres for Disease Control. [6]
A. fumigatus mediastinitis in our patient developed within the
usual time of onset of invasive aspergillosis reported to be between 36
and 52 days post transplantation. [1] Besides recent cardiac
transplantation, the current patient presented with previously reported
risk factors for fungal infections such as postoperative wound
discharge, renal failure, administration of multiple antibiotics,
ventricular assist device before surgery, as well as severe malnutrition
and diabetes mellitus. [1, 3]
Given the unique extent of the disease, the basic principle of therapy
[6], i.e. intravenous antifungal treatment, tapering of
immunosuppression and surgical re-exploration alone was thought not to
be sufficient. With regards to the pathology of invasive aspergillosis
resulting in infarction and necrosis of affected organs and poor drug
delivery to tissue, our treatment regime was based on the conviction of
the necessity to clean large surfaces without blood supply from thick
layers of fungal material not only mechanically but also with local
antiseptics.
A combination of repeated debridements with an open chest treatment,
cavity baths with aqueous voriconazole and chlorhexidine, intravenous
administration of voriconazole and caspofungin and lastly a chest wall
reconstruction by a muscle flap plasty were necessary leading to
successful recovery.
A combined systemic antifungal therapy was started with caspofungin and
voriconazole, the latter guided by testing susceptibility and serum
concentration. Voriconazole, a triazole with activity against yeasts and
molds including Aspergillus spp. [7] performed superior when
compared with amphotericin B, and is now recommended as primary
treatment of invasive aspergillosis including its uncommon
manifestations such as mediastinitis and osteomyelitis. [6, 8]
Voriconazole was administered systemically in the only two reported
surviving cases of Aspergillus mediastinitis after OHT. [2,
4] Monitoring of its serum levels is recommended in transplanted
patients because of impaired renal function and significant interactions
with cyclosporine, tacrolimus and sirolimus [1, 6]. In the current
case, oral voriconazole was continued for 12 months to prevent relapse
of infection, which has been reported to occur several months after
seemingly successful treatment. The role of combined primary or salvage
antifungal therapy is uncertain and warrants a prospective, controlled
clinical trial. [6]
The use of topical voriconazole in addition to its intravenous
administration has recently been found to be effective in cases ofAspergillus keratitis and endophtalmitis when administered
intravitreally [9-11]. Biocidal activity of chlorhexidine againstA. fumigatus was reported when applied topically at a
concentration of 0.06% for 30 to 60 minutes and its stable and lasting
adherence on human tissue without being absorbed. [12] In addition,
effectiveness of topical chlorhexidine was confirmed in the treatment of
fungal keratitis without any adverse effects. [13] Based on this
data, we decided to use chlorhexidine in the same way as the
voriconazole solution as local antifungal treatment.
After the fourth surgical session, examinations revealed a sterile
condition with respect to A. fumigatus . However, a superinfection
with a multi-drug resistant A. baumannii was reported.
Mediastinits due to A. baumannii is rare, with \soutonly two
reported cases in immunocompetent subjects, successfully treated with
ampicillin-sulbactam and a pan-resistant type with tigecycline. [14,
15] Notably, only one case of multi-drug resistant A. baumanniiin sternal wound after OHT has been reported. Favourable outcome was
achieved with extensive debridement, systemic colistin and minocycline
as well as wound irrigation with 5% chlorhexidine and NPWT dressing.
[16] Safe and effective topical use of colistin 0.19% has been
reported in the treatment of corneal infection by multi-drug resistantPseudomonas aeruginosa . [17] Hence, we used diluted colistin
as described above in combination with intravenous colistin. Lastly,
after the completion of topical antimicrobial therapy, a rotationallatissimus dorsi muscle flap into the thoracic cavity and
complete closure of the sternum resulted in a restitutio ad
integrum .