Original Article
Fungal osteomyelitis and soft tissue infections: Simple solutions to
uncommon scenarios
Ravi Chavan1, Aditya Menon1, Rajeev Soman1, Camilla Rodrigues1, Anjali Shetty1, Ravi Bhadiyadra1,
Vikas M Agashe1
1
P.D. Hinduja Hospital and Medical Research Centre, Mahim, Mumbai, India
Abstract
Introduction: Fungal osteoarticular/soft tissue infections (FOaSI) are an uncommon entity with protracted course due to variability in clinical
picture, slow progression; resulting in misdiagnosis with empirical therapy. Recent studies have shown an alarming emergence of FOaSI in
immunocompetent individuals with high mortality rates. This study recommends a protocol for managing these complex and confusing
scenarios.
Methodology: We have retrospectively analysed patients with FOaSI between January 2014 and December 2016, with a minimum 12 months
follow up.
Results: 8 cases (6 male, 2 female) with a mean age of 42.88 years (26-53) presented to us 45 days (3-365) after initial symptoms. They
underwent mean 3 procedures before being diagnosed with a fungal infection. Deep tissue cultures grew 9 fungi and 6 bacteria, commonest
fungus being Candida sp (n = 4), treated with appropriate antifungals and antibiotics. Infection remission was achieved in 7/8 (87.5%) cases at
27.1 months (19-45) follow-up with 1 mortality. Excellent functional results as per our criteria were seen in 5 cases (62.5%) with 1 talus
excision, 1 ray amputation and 1 mortality.
Conclusions: This study highlights the significance of implementing a simple rule such as obtaining fungal cultures in every case of bone and
soft tissue infections. Standardisation of treatment may not be the ideal solution, since different fungi have different growth patterns and
invasiveness. A simple protocol of customising the medico- surgical treatment with an open ended discussion between the surgeons,
microbiologists, pathologists and infectious disease specialists forms the cornerstone to success.
Key words: Fungal osteomyelitis; mycosis; fungal soft tissue infection; open fractures; mucormycosis; candida osteomyelitis.
J Infect Dev Ctries 2020; 14(9):1033-1039. doi:10.3855/jidc.11449
(Received 08 February 2020 – Accepted 18 June 2020)
Copyright © 2020 Chavan et al. This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly cited.
Introduction
Fungal osteoarticular/soft tissue infections (FOaSI)
are an uncommon entity with protracted course due to
variability in clinical picture, slow progression, rarity;
resulting in misdiagnosis with empirical therapy [1].
Normally, fungal infections follow an indolent,
protracted course lasting over months to years;
however, recent studies have shown an alarming
emergence of FOaSI in immunocompetent individuals
with high mortality rates [2–6]. Till date, there is no
consensus on the diagnostic and management protocol.
There are very few reports in English literature
analysing the characteristics of FOaSI and their
outcomes; our retrospective analysis attempts to
recommend a protocol for managing these complex and
often confusing scenarios.
Methodology
We have retrospectively analysed patients with
FOaSI between January 2014 and December 2016, with
a minimum 12 months follow up.
Inclusion criteria were:
1. Complete records (covering clinical details,
operation notes, cultures, antibiotics) in the
Electronic Medical Record Department
(eMRD) after presenting to our centre;
2. Clinical photographs or radiographs at
presentation and on achieving infection
remission;
3. Minimum follow up of 12 months after the
discontinuation of antifungals;
4. Lost to follow up before follow up period of 12
months (considered treatment failure).
Exclusion criteria were:
1. Unavailability of above mentioned records. All
the patients were treated by a single
Chavan et al. – Management of fungal infections in Orthopaedics
orthopaedic surgeon. A team comprising of
infectious
disease
specialist
(ID),
microbiologist,
histopathologist,
plastic
surgeon and other specialists as needed helped
in managing these patients at a tertiary referral
centre with intensive care facilities (ICU).
The protocol included:
1. Detailed history - mode of injury, probable site
and extent of contamination in open fractures,
treatment received, fixation details, whether
external fixation was done, antibiotics/
antifungals received, factors responsible for
immunocompromised state if any;
2. Good clinical examination- assess scars of the
primary injury, scar/scars of osteosynthesis,
sinuses, signs of infection, deformities,
abnormal mobility;
3. Analyzing photographs and imaging studies of
the primary injury whenever available- to
locate the possible site/ extent of soft tissue
injury in an open fracture, which would give an
indication of the primary site of contamination;
4. Relevant imaging and hematological studies;
5. Preoperative referral to the Infectious Disease
(ID) specialist who would study the
circumstances around the primary injury, index
surgery and current picture and then
recommend appropriate microbiological tests
for the intra operative tissue samples and
empirical antibiotics till availability of reports;
6. Avoiding negative cultures- In cases where the
general condition of the patient permitted,
antibiotic free interval of at least three weeks
prior to debridement was preferable.
Administering antibiotics for surgical site
prophylaxis only after deep tissue cultures were
obtained;
7. Debridement
beyond
the
infection
(Oncosurgical debridement)- It comprised of
incision with a margin of clean non- infected
tissue, excision of the previous surgical scar, all
sinuses and drain sites with intervening skin
with the intention of enbloc resection of
infected soft tissues; going deep up to the bone
and implant maintaining a clean margin all
around. Removal of all macroscopic infected
tissue, exploration of the site of open injury,
implant removal where indicated, removal of
biofilm present on the surface and undersurface
of the plate and within screw holes, fracture site
and medullary canal, reaming of medullary
canal in selected cases, excision of necrotic
J Infect Dev Ctries 2020; 14(9):1033-1039.
bone till pin point bleeding edges finally
leaving a bed of macroscopically clean, healthy
tissue and bone;
8. Biopsy- Procuring at least 5 to 6 deep tissue
sample for gram staining, culture (aerobic,
anaerobic,
fungal,
tuberculous)
and
histopathology either by open surgical or image
guided biopsy;
9. Suitable stabilization, if necessary;
10. Early soft tissue cover either with primary
closure over a drain if possible or later by the
plastic and reconstructive surgeon with skin
grafts or flaps, as necessary;
11. Antibiotic administration- Empirical (before
culture reports) and targeted antibiotics after
final antibiotic susceptibility pattern selected
by the ID specialist in collaboration with the
microbiologist and histopathologist;
12. Negative pressure wound therapy (NPWT) and
appropriate local antibiotics were used when
indicated for source control in severe
infections.
Infection remission was defined as no clinical and
radiological signs and symptoms of persistent infection,
with normal haematological workup at 12 months
follow up after stopping medication. The outcomes
were graded based on the last follow up.
Excellent results were defined as a combination of:
1. Remission of infection for a minimum 12
months after the discontinuation of antibiotics/
antifungals;
2. No local relapse or distant spread by the same
organism at any stage during the follow up and;
3. Radiological union at fracture site (where
applicable).
Failure was defined as any one of the following:
1. Persistence or recurrence of infection at the
primary site;
2. Amputation/excision in unsalvageable cases;
3. Distant focus of infection by the same
organism;
4. Non- union;
5. Patients lost to follow up within 12 months
from the last surgery, irrespective of the wound
status;
6. Mortality attributed directly or indirectly to the
infection.
Results
Eight cases (six male, two female) with a mean age
of 42.88 years (26 - 53) were managed during the study
period and fulfilled the inclusion criteria. The patient
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Chavan et al. – Management of fungal infections in Orthopaedics
J Infect Dev Ctries 2020; 14(9):1033-1039.
demography, aetiology and clinical presentation were
as described in Table 1. Patients presented to us at a
median 45 days (3 - 365) after initial symptoms. 6/8 had
osteoarticular involvement, while two had soft tissue
infections. They underwent a mean of three procedures
before being diagnosed with a fungal infection. Four
were being treated for bacterial infections prior to being
diagnosed with a fungal infection. One patient was
being treated for infection with Actinomycosis based on
a histopathology report. Following presentation to our
institute, 7/8 cases underwent radical debridement to
obtain deep tissue cultures, while the 8th case with rib
osteomyelitis underwent ultrasound (USG) guided
aspiration. We adhered to the protocol of sending
tissues for bacterial, tubercular, fungal cultures and
histopathology in all cases. A total of 15 organisms
were isolated (9 fungi and 6 bacteria) with mixed
bacterial and fungal infections in 3 (Table 1). The
commonest fungi was Candida sp (n=4), while the
commonest bacteria was Pseudomonas aeruginosa
(n=3). Antifungals were administered for a mean 2.8
months as prescribed by the ID specialist (Table 1).
Appropriate antibiotics were given for those with a
mixed infection for 6 weeks. Infection remission was
achieved in 7/8 (87.5%) cases at a mean follow up of
27.1 months (19 - 45) with one mortality secondary to
septicaemia during the course of hospitalisation.
Excellent results as per our criteria were seen in 5 cases
(62.5%). There were three failures, the first was a 60
Figure 1. Gangrenous changed bilateral feet.
Figure 2. Bilateral lower limb debridement.
Table 1. Patient demography, aetiology, clinical presentation, Culture results and Antifungal therapy details.
Age/
Gender
1
26/M
2
51/M
3
40/M
4
38/F
5
35/M
6
40/M
7
53/M
8
60/F
Clinical presentation
Diagnosis
Comorbidities
Wound over dorsolateral
Open fracture
aspect of foot with
None
talus
extruded talus
Severe pain, swelling
Osteomyelitis
None
over right costal margin
ribs
Pain, swelling over left Osteomyelitis
None
ribs
costal margin
Multiple non healing
Non healing Systemic lupus
ulcers over both legs
ulcers
erythematosus
Infected nonSinus over right leg with
union right
foul smelling discharge
None
tibia
and soft tissue loss
diaphysis
Wound over right
proximal thigh medial
Open fracture
None
aspect and inguinal
femur
region with foul smelling
discharge
Osteomyelitis
Pain and swelling base of
right second
None
second toe
toe
Diabetes
mellitus,
Non healing ulcers
Bilateral wet
peripheral
bilateral foot and leg
gangrene
vascular
with gangrenous changes
disease
Immunocompromising
factors
Culture Results
Antifungal
Duration
(months)
None
Curvularia lunata,
Pseudomonas aeruginosa,
Acinetobacter baumannii
Voriconazole
4
None
Aspergillus flavus
Voriconazole
4
None
Aspergillus flavus
Voriconazole
3
None
Candida pasapsilosis
Fluconazole
3
None
Candida haemoloni
Anidulafungin
1
None
Candida albicans,
Pseudomonas aeruginosa
Fluconazole
1
Renal transplant,
immunosuppressive
therapy
Alternaria alternate
Voriconazole
6
None
Candida albicans,
Andiulafungin,
Mucormycosis,
Posiconazole
Pseudomonas aeruginosa
15 days
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Chavan et al. – Management of fungal infections in Orthopaedics
Figure 3. Recurrence of soft tissue necrosis.
J Infect Dev Ctries 2020; 14(9):1033-1039.
Figure 4. Talus excised and ankle temporarily stabilised with K
Wire.
year old known diabetic with peripheral vasculopathy.
She presented with bilateral lower limb diabetic
gangrene (Figure 1) and was managed with
debridement and negative pressure wound therapy
(Figure 2). The tissue cultures grew pseudomonas
aeruginosa and was treated with appropriate
antibiotics. The patient and relatives refused the
surgical recommendation of bilateral below knee
amputation which was advised taking into account the
poor wound status, decreased vascularity. The wound
Figure 5. Nodule over base of 2nd toe.
condition deteriorated 15 days after the primary
debridement and cultures subsequently grew Candida
albicans and Mucor (Figure 3). She was started on
Anidulafungin and Posaconazole by the ID specialist.
Subsequent bilateral below knee amputation was done
considering the invasiveness of Mucor infection and the
mortality associated with it. However, the patient died
due to septic shock secondary to gangrenous diabetic
foot. The second patient had a talus excision (Figure 4).
The third patient was a 53-year-old male who presented
with complaints of recurrent swelling and mild pain
over the base of second toe of left foot since 1 year
(Figure 5). There was no history of recurrent fever,
injury, thorn prick or discharging sinus. Patient had
undergone renal transplant 4 years ago and was on
immunosuppressive therapy. Excision biopsy done
elsewhere was indicative of Actinomycotic infection on
histopathology. Tissue cultures were negative. He had
a recurrence in spite of 3 months of doxycycline and
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Chavan et al. – Management of fungal infections in Orthopaedics
presented to our institute at this stage. On exploration;
a blackish, soft, irregular shaped mass partly adherent
to skin extending in to dorsal surface through 1st web
was excised. Histopathology showed several colonies
of pigmented fungus in dermal and subcutaneous tissue
with dense granulomatous inflammation and necrosis
surrounding these colonies. The cultures grew
Alternaria alternata, a saprophytic pigmented fungus
(Figure 6). He had a locally recurrent nodule 7 months
following debridement in spite of 6 months of
Voriconazole therapy. The nodule was excised and
Voriconazole continued. The nodule recurred locally 4
months later. Considering the immunosuppressive state
and a slow growing fungal infection with a possibility
of metastasis; 2nd ray amputation was done to prevent
further recurrence. Voriconazole was continued for a
further 6 months. There was no local or distant
recurrence 36 months after the ray amputation (Figure
7).
Discussion
Fungi rarely affect the musculoskeletal system, and
have been notorious in causing chronic, low grade,
persistent infections [5,6]. Delay in diagnosis can have
effects ranging from contiguous spread of infection to
haematogenous seeding with high mortality rates, more
so in immunocompromised patients [2,7–9]. There have
been increasing reports of fungal osteomyelitis in
immunocompetent
patients,
which
can
be
haematogenous or due to direct inoculation [1,6,10]. All
except one patient were immunocompetent in our study.
The outcome of bone infections primarily depends on
aggressive surgical debridement and procuring
representative deep tissue samples. This, however, does
not seem to hold true for all cases of FOaSI. Literature
shows studies with variable results in spite of adequate
debridement; the reasons can be manifold- negative
J Infect Dev Ctries 2020; 14(9):1033-1039.
Figure 7. Healed 2nd ray amputation with no local recurrence.
culture, inconclusive histopathology, microscopic
invasion of fungi in the tissues and vasculature beyond
what seems to be macroscopically normal tissue, poor
bone
penetration
of
antifungals
and
immunocompromised state amongst others [2–5,7,10–
13]. This variability in results is distinctly highlighted
in our case who underwent a second ray amputation
following local recurrence [14]. This case highlights the
need for a prolonged follow- up of patients with fungal
infections due to the propensity for recurrences.
Institutes all over the world are battling to setup a
systematic protocol to ensure early detection and good
outcomes. However, there is yet no consensus on the
Figure 6. Gross Image of Lesion and Microscopic images of Alterneria alternate.
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Chavan et al. – Management of fungal infections in Orthopaedics
duration of therapy or the need for adjuvant surgery. A
recent prospective observational study on Candida
osteomyelitis published by Neofytos et al, had multiple
cases with sequential change in the antifungal drug and
observed shorter duration of antifungal therapy (AFT)
in those undergoing a surgical intervention [11]. None
of the patients were on AFT for more than 90 days for
various reasons. Thus, there was a lack of consensus on
the duration of AFT and no guidelines were laid down
at the end of the study. Our study highlights the same,
with AFT duration ranging from 30 to 180 days, with
treatment being individualised on a case to case basis.
Contrary to the finding by Neofytos et al, where they
found shorter durations in those undergoing surgery;
Dietl et al, questioned the basis of surgical debridement
in Candida osteomyelitis of the sternum following
cardiac surgery [7]. They reported worse outcomes in
those subjected to debridement followed by a flap with
local recurrence in all. They have proposed long term
AFT as the first line of management and not radical
surgical debridement. 7/8 of our cases were subjected
to radical debridement. 6/7 had either an open wound
with discharging sinus or non-healing ulcers which
warranted surgical debridement. The seventh case had
excruciating pain over the costal margin with rib
osteomyelitis and soft tissue abscess on MRI, for which
he was explored. The only patient who did not undergo
debridement had pain over the left costal margin with
osteomyelitis of the ribs. There was a history of injury
with a piece of wood 2 years prior and patient was
clinically stable. An ultrasound guided biopsy was done
with a strong suspicion of FOaSI. Tissue cultures grew
Aspergillus flavus. He responded favourably to 3
months of Voriconazole and had an infection free
follow up of 22 months. It has been postulated that
FOaSI can arise from three primary routes, namelyhematogenous seeding, direct inoculation and
contiguous spread of infection [6]. 4 cases in our series
probably had direct inoculation (3 open injuries, 1
penetrating injury with a piece of wood), while the other
4 most likely had a hematogenous infection (1
immunocompromised, 3 immunocompetent). Delay in
diagnosis and aggressive management is known to be
associated with high mortality rates as seen in one of
our cases [2]. Mortality rate in non- disseminated
mucormycosis can be as high as 33% as described in a
recent case report where the patient had to undergo a
hip disarticulation following an open fracture of the
tibia [15]. Our study is limited by its retrospective
nature, varied etiopathogenesis and diverse treatment
strategies.
J Infect Dev Ctries 2020; 14(9):1033-1039.
Conclusions
In spite of the limitations mentioned, this study
clearly highlights the significance of implementing a
simple rule such as obtaining fungal cultures in every
case of bone and soft tissue infections, since we are
seeing increasing rates of FOaSI in immunocompetent
individuals when least suspected. Moreover, fungal
infections must be suspected in cases of open injuries
with soil contamination, prolonged hospitalisation,
farmyard injuries and penetrating injuries with
vegetation like a thorn prick. Standardisation of
treatment may not be the ideal solution, since different
fungi have different growth patterns and invasiveness,
ranging from relatively benign slow growing fungi to
invasive mucormycosis and aspergillosis. A simple
protocol of customising the medico- surgical treatment
with an open ended discussion between the surgeons,
microbiologists, pathologists and infectious disease
specialists forms the cornerstone to success as seen in
our series.
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Corresponding author
Aditya Menon
P.D. Hinduja Hospital and Medical Research Centre
SVS Rd, Mahim West, Shivaji Park,
Mumbai, Maharashtra 400016, India
Tel:
Fax:
Email: docmenon83@gmail.com
Conflict of interests: No conflict of interests is declared.
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