Abstract
Background
Apophysomyces species are emerging as the second most common agent of mucormycosis in India. It is worrisome as it affects predominantly immunocompetent host unlike other Mucorales. Unfortunately, the most common presentation is necrotising fasciitis which can be overlooked as bacterial infection.
Results
Seven cases of mucormycosis due to Apophysomyces species were detected in our hospital between January 2019 and September 2022. Mean age was 55 years and all were males. Six patients presented with necrotising soft tissue infection following accidental or iatrogenic trauma. In four cases, multiple fractures over the body were observed. Median days between admission to laboratory diagnosis was 9 days. All isolates were phenotypically identified as Apophysomyces variabilis. Multiple wound debridements, on an average two, was performed in all the cases and amputation performed in two patients. Three patients recovered, two could not be treated due to financial constraints and lost to followup and two patients died.
Conclusion
Through this series, we anticipate to upheave awareness among the orthopedician community about this emerging infection and contemplate it in appropriate case settings. All patients with necrotising soft tissue infection following trauma and significant degree of wound contamination with soil should be suspected for traumatic mucormycosis at the time of wound assessment.
Keywords: Apophysomyces, Necrotising fasciitis, Trauma
1. Introduction
Apophysomyces species are surging as the second most common agent of mucormycosis in India.1 It is perturbing as it affects largely immunocompetent host unlike other Mucorales. Regrettably, the most common presentation is necrotising fasciitis which can be overlooked as bacterial infection. So there is a consequential delay in diagnosis when appropriate samples and tests are not sought far. A recent review of literature has identified around 256 cases of mucormycosis reported globally so far due to this emerging fungus.2 This is definitely an understated condition due to dearth of clinical suspicion and diagnostic delay. Conventional endemic regions include India. This belt has been expanding with recent reports from western countries.3 Since 2019 we have regularly identified cases of mucormycosis due to Apophysomyces species complex at our center.4
2. Case series
Seven cases of mucormycosis due to Apophysomyces species were detected in our hospital between January 2019 and September 2022. Table 1 shows the clinical and epidemiological data of seven patients with mucormycosis caused by Apophysomyces species. Age ranged between 33 and 80 years with a median age of 55 years and all were males implying outdoor activity. There was no seasonal predilection of cases. All isolates caused cutaneous, subcutaneous and soft tissue infection. Six patients presented with necrotising soft tissue infection (cellulitis and fascitis) following accidental(5) or iatrogenic trauma(1). In four cases, multiple fractures over the body were observed. In two other patients, necrotising infection observed in left back and right leg. A young immunocompetent male developed post injection right gluteal abscess. In addition to trauma, comorbidities were noted in some cases. (Diabetes mellitus = 3). An elderly diabetic male patient presented with ulcer over left back for 15 days and reduced level of activity for 2 days without any history of trauma. Median days between admission to laboratory diagnosis was 9 days. Major reason for diagnostic delay was lack of clinical suspicion and appropriate samples (Wound swabs were sent rather than tissue). In most of the cases, fungal infection was not suspected and detected incidentally during routine bacterial culture of wound swabs. KOH mount from the samples showed broad hyaline aseptate fungal hyphae and SDA(Sabouraud's Dextrose agar) tube showed colonies with cotton candy appearance with typical stunted growth at the top unlike other Mucorales which are typically described as lid lifters. LPCB(Lactophenol cottonblue) mount from SDA revealed nonsporulating broad hyaline aseptate hyphae. Water agar was used for inducing sporulation. LPCB mount from water agar showed long unbranched sporangiophore with bell shaped apophysis, pear shaped sporangia and oblong sporangiospores (Fig. 1). All isolates were phenotypically identified as Apophysomyces variabilis. All the samples were histopathologically confirmed with sections showing areas of coagulative and liquefaction necrosis and densely tangled broad, aseptate hyphae. Multiple wound debridements, on an average two, was performed in all the cases and amputation performed in two patients. Conventional Amphotericin B was used in some of the cases (Topical amphotericin B instillation in one case) and injection posoconazole was used in one patient. Median duration of hospitalisation was 18 days. Three patients recovered (amputation in two cases), and were followed up for the next 12 months with good clinical improvement and resumed normal activities. Two elderly diabetics could not be treated due to financial constraints and lost to followup and two patients, one of them young and immunocompetent treated with multiple debridements and above knee amputation and another elderly diabetic male died within 32 and 16 days respectively.
Table 1.
Clinical and epidemiological data of seven patients with mucormycosis caused by Apophysomyces species.
| Case number | Month/Year | Age/sex/occupation/Education | Presentation | Comorbidity | Mode of injury | Surgical Treatment | Antifungal therapy | Outcome | Time to fungus detection after admission(Days) | Duration of hospitalisation(Days) |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | January/2019 | 35/M/Plumber/Primary school | Brought to emergency on mechanical ventilation | Nil | Motor vehicle collision with a wall and then a tree. | Multiple wound debridements, shoulder disarticulation | Topical and intravenous Amphotericin B(100 mg twice daily for 30 days) | Recovered after 102 days of hospitalisation | 14 | 102 |
| with alleged history of trauma, initially treated in a private hospital.Polytrauma with right brachial plexus injury, right clavicle, scapula and humerus fractures, multiple rib fractures, right hemopneumothorax, bilateral lower lobe of lung contusion, hemoperitoneum, liver laceration and T12 | ||||||||||
| vertebrae fracture. | ||||||||||
| 2 | July/2019 | 33/M/Construction worker/Primary school | Necrotizing wound infection following soft tissue and bony injuries to the right lower limb. Managed initially at a local hospital with fixation of the fracture (interlocking nailing of right femur) and wound debridement. Referred to the present hospital with worsening wound infection. | Nil | Hit by a truck while riding a bicycle and fall in the bushes withmassive contamination of the wounds by soil and plant debris | Wound debridement twice and above knee amputation | Conventional Amphotericin B started 100 mg twice daily for 12 days until death | Died 32 days after trauma | 10 | 23 |
| 3 | August/2019 | 58/M/Agricultural worker/Secondary school | Blackish discoloration and extensive ulceration with fracture of left femur shaft, right superior and inferior pubic rami following accidental trauma | Nil | Sustained injury while digging a well(Agricultural with active soil exposure) | Wound debridement with vacuum dressing | Tab Fluconazole 150 mg once daily | Recovered after 22 days of hospitalisation | 12 | 23 |
| 4 | September/2019 | 36/M/Construction worker/higher secondary school | Blackish discoloration and ulceration on the left buttock at the site of intramuscular injection elsewhere | Nil | Post intramuscular injection of diclofenac | Radical wound debridement of gluteal maximus muscle and vacuum dressing, followed by two more sessions of debridement | liposomal amphotercin B started was stopped due to drug induced nephrotoxicity and switched to injection posoconazole for two weeks | Discharged after 5 days of hospitalisation | 3 | 5 |
| 5 | April/2022 | 74/M/Retired teacher/bachelor Degree | Necrotizing wound infection following degloving injury of the right lower limb. | T2DM | Fall while riding two wheeler with visible mud over the limb | Wound debridement twice | No antifungals due to financial constraints | Lost to followup | 8 | 14 |
| 6 | May/2022 | 80/M/Retired bank clerk/Master degree | Ulcer over left side of back for 15 days, decreased level of activity for two days | T2DM | Nil | Radical wound debridement | No antifungals initiated due to morbid status | Lost to followup | 3 | 4 |
| 7 | September/2022 | 70/M/Agricultural worker/Primary school | Multiple fractures with hypovolemic shock-fracture right femur, lt tibial plateau, right ilium, left sacroiliac joint dehiscence, | T2DM | Injury while using ploughing machine(power tiller) and visible soil in injured parts | D2-ORIF right femur, D8- percutaneous si jt fixation and both lower limb Wound debridement on D14 | No antifungals initiated due to delay in diagnosis and above knee amputation advised by orthopedician on D15 was deferred due to morbid status, | Died | 16 | 18 |
| fracture right proximal fibula, right ankle medial malleolus |
RTA-Road traffic accident, T2DM-Type 2 Diabetes Mellitus, ORIF-Open reduction and internal fixation.
Fig. 1.
1A& 1B-Multiple fractures in an elderly male after sustaining injury with power driller with deep lacerations over the left leg and scalp. 1C-LPCB mount from water agar showing bell shaped apophysis. 1D-Wet mount from water agar showing oblong sporangiospores.
3. Discussion
Mucorales are progressively perceived as paramount causes of necrotizing wound infections following injuries. In a review of 122 cases of posttraumatic mucormycosis(PTM) reported between 1993 and 2013, remarkable number (n = 23) was reported in Middle East/India.5 Male preponderence(67.2%)observed with a median age of 38 years. Mode of injuries include traffic accident, domestic accidents, natural disaster, agronomic accident and animal or insect bite. Apophysomyces(31.7%) and Lichthemia (21.1%) species were the most frequent pathogens. 91% underwent surgery with additional debridements performed for 69.7% cases with a median of two procedures per patient. Antifungal treatment included amphotericin B deoxycholate in 44.3% and L-AmB in 36.9%. 74.4% patients had a favorable outcome.
In our case series of PTM, all were males with a median age of 55 years. Mode of injuries were motor vehicle collision, agricultural accidents and iatrogenic trauma. All the patients encountered surgical debridement, with amputation in two cases and one patient refused to undergo amputation due to moribund state. In three patients, antifungals were not commenced due to moribund condition and financial hardship. Though there is no role of fluconazole against Mucorales, it was used in a case due to lack of knowledge among clinicians.
PTM being an uncommon infection, without controlled studies to steer management, perspectives delineated by Rodriguez et al. grounded in direct battleground circumstance perpetuate that crucial therapy includes aggressive and frequent surgical debridement with topical antifungal therapy.6 Following a diagnosis of mucormycosis, therapy was amalgamated with liposomal amphotericin B.
4. Conclusion
Regardless of India being aboriginal for this unusual fungus by case reports, series and environmental studies, it is hapless that many clinicians are still unaware of this life threatening fungus.2,7,8 Foremost, knowledge is crucial among clinicians, especially surgeons, orthopedicians and trauma physicians. Through this series, we anticipate to upheave awareness among the orthopedician community about this emerging infection and contemplate it in appropriate case settings. All patients with necrotising soft tissue infection following trauma and significant degree of wound contamination with soil should be suspected for traumatic mucormycosis at the time of wound assessment and rapid diagnostic tests are indispensable.
Despite the recommendations to use liposomal preparation in place of conventional Amphotericin B, in the current series, the latter was used due to financial constraints.9 In a case of iatrogenic gluteal abscess, cure was reported with just surgical debridement and salvage therapy of posoconazole. The high mortality can be reduced with early clinical suspicion, laboratory diagnosis and management.
Funding
“This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors”.
Informed consent obtained from the patients.
Declaration of competing interest
None.
Acknowledgement
None.
References
- 1.Prakash H., Ghosh A.K., Rudramurthy S.M., et al. A prospective multicenter study on mucormycosis in India: epidemiology, diagnosis, and treatment. Med Mycol. 2019;57:395–402. doi: 10.1093/mmy/myy060. [DOI] [PubMed] [Google Scholar]
- 2.Samaddar A., Shrimali T., Sharma A. Mucormycosis caused by Apophysomyces species: an experience from a tertiary care hospital in Western India and systematic review of global cases. Mycoses. 2022;10 doi: 10.1111/myc.13538. [DOI] [PubMed] [Google Scholar]
- 3.Chakrabarti A., Shivaprakash M.R., Curfs-Breuker I., Baghela A., Klaassen C.H., MeisJF Apophysomyceselegans:Epidemiology,amplifiedfragmentlengthpolymorphismtyping,andinvitroantifungalsusceptibilitypattern. J Clin Microbiol. 2010;48:80–85. [Google Scholar]
- 4.Priya P., Ganesan V., Rajendran T., Geni V.G. Mucormycosis in a tertiary care center in south India: a 4-year experience. Indian J Crit Care Med. 2020;24(3):168–171. doi: 10.5005/jp-journals-10071-23387. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Lelievre L., Garcia-Hermoso D., Abdoul H., et al. Posttraumatic mucormycosis: a nationwide study in France and review of the literature. Medicine (Baltim) 2014 Nov;93(24):395–404. doi: 10.1097/MD.0000000000000221. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Rodriguez C.J., Tribble D.R., Malone D.L., et al. Treatment of suspected invasive fungal infection in war wounds. Mil Med. 2018;183(Suppl. 2):142–146. doi: 10.1093/milmed/usy079. [DOI] [PubMed] [Google Scholar]
- 7.Pamidimukkala U., Sudhaharan S., Kancharla A., et al. Mucormycosis due to Apophysomyces species complex- 25 years' experience at a tertiary care hospital in southern India. Med Mycol. 2020;58(4):425–433. doi: 10.1093/mmy/myz081. [DOI] [PubMed] [Google Scholar]
- 8.Prakash H., Ghosh A.K., Rudramurthy S.M., et al. The environmental source of emerging Apophysomyces variabilis infection in India. Med Mycol. 2016;54:567–575. doi: 10.1093/mmy/myw014. [DOI] [PubMed] [Google Scholar]
- 9.Cornely O.A., Arikan-Akdagli S., Dannaoui E., et al. ESCMID and ECMM joint clinical guidelines for the diagnosis and management of mucormycosis 2013. Clin Microbiol Infect. 2014;2:5–26. doi: 10.1111/1469-0691.12371. [DOI] [PubMed] [Google Scholar]