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A fatal case of rhinocerebral mucormycosis of the jaw after dental extractions and review of literature
G Model JIPH-832; No. of Pages 3
ARTICLE IN PRESS Journal of Infection and Public Health xxx (2017) xxx–xxx
Contents lists available at ScienceDirect
Journal of Infection and Public Health journal homepage: http://www.elsevier.com/locate/jiph
A fatal case of rhinocerebral mucormycosis of the jaw after dental extractions and review of literature Shilpa Prabhu a,∗ , Manaf Alqahtani b , Mohammed Al Shehabi a a
Department of Otorhinolaryngology, Royal Medical Services, Bahrain Defence Force Hospital, Bahrain Department of Pathology, Royal College of Surgeons in Ireland-Bahrain Medical University, Royal Medical Services, Bahrain Defence Force Hospital, Bahrain b
a r t i c l e
i n f o
Article history: Received 19 June 2017 Received in revised form 1 September 2017 Accepted 30 September 2017 Keywords: Mucormycosis Rhinocerebral Polymicrobial Diabetes mellitus Fungal infection Immune dysfunction
a b s t r a c t The purpose of presenting this case is to report a fatal case of rhinocerebral mucormycosis post-dental extraction in a patient with uncontrolled diabetes mellitus. Several cases of rhinocerebral mucormycosis have been reported, but mucocutaneous mucormycosis has not been commonly reported to be a part of polymicrobial wound infections at multifocal sites. To the best of author’s knowledge, this is the second case of polymicrobial rhinocerebral infection involving mucormycosis. © 2017 The Authors. Published by Elsevier Limited on behalf of King Saud Bin Abdulaziz University for Health Sciences. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).
Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Case report . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Operative details . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Post-operative course . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Competing interests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Ethical approval . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
Introduction Opportunistic infections are common in patients with uncontrolled diabetes, and over 50% of all mucormycosis cases occur in diabetic patients [1]. This is most likely due to a cellular innate immunity defect of the polymorphonuclear cells [2]. Although primary disease occurs in the paranasal sinuses, it may originate in
the oral cavity or teeth and often progresses intracranially via direct extension or angioinvasion. Rhinocerebral mucormycosis is rapidly fatal, with a mortality rate of 85% even when maximally treated with surgical debridement, antifungal therapy, and correction of underlying processes [3,4]. Case report
∗ Corresponding author at: Department of Otorhinolaryngology, Royal Medical Services, Bahrain Defence Force Hospital, P. O Box 28743, Bahrain. E-mail addresses: [email protected] (S. Prabhu), [email protected] (M. Alqahtani), [email protected] (M. Al Shehabi).
A 70-year-old male with a longstanding history of uncontrolled diabetes mellitus was brought to the emergency department with altered sensorium, vomiting, decreased oral intake and right facial swelling for one day. The patient had a right tooth extraction 3 days
https://doi.org/10.1016/j.jiph.2017.09.026 1876-0341/© 2017 The Authors. Published by Elsevier Limited on behalf of King Saud Bin Abdulaziz University for Health Sciences. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Please cite this article in press as: Prabhu S, et al. A fatal case of rhinocerebral mucormycosis of the jaw after dental extractions and review of literature. J Infect Public Health (2017), https://doi.org/10.1016/j.jiph.2017.09.026
G Model JIPH-832; No. of Pages 3 2
ARTICLE IN PRESS S. Prabhu et al. / Journal of Infection and Public Health xxx (2017) xxx–xxx
Operative details
Fig. 1. Blackish discoloration of right hard palate.
Patient underwent endoscopic sinus surgery and right hemimaxillectomy under general anaesthesia. Intraoperatively, black necrotic tissue was observed in both nasal cavities. This involved the inferior, middle, and superior turbinates, the septum, floor of the nose and the right 3/4th of the palate. Thick mucin was retrieved from both maxillary sinuses. White fungal spores were found in the right nasal cavity. Mucosa of all sinuses was blackish and necrotic. With a nasal endoscope and microdebrider, turbinectomy was performed. Uncinectomy, middle meatal antrostomy, ethmoidectomy and sphenoidectomy were performed on both sides. The mucosal linings of all sinuses were scraped, and the bone was exposed. Caldwell-Luc incision progressing to craniofacial flap elevation was performed; then, 3/4th of the palate was excised by right hemimaxillectomy. The upper right 3, upper right 4, and upper right 2 spaces were filled with ribbon gauze soaked in betadine. An orogastric tube was inserted, and the patient was kept under ICU care after surgery. Post-operative course
Fig. 2. Ct facial bones coronal section showing heterogeneous opacity in left maxillary sinus.
before in a private hospital, after which blood-stained pus leaked from his mouth. On examination, the patient had right cheek swelling with right eye proptosis, eyelid swelling, conjunctival chemosis, limited extraocular movement and an unreactive right pupil. Nasal examination revealed blackish discolouration bilaterally throughout the nasal mucosa. Oral cavity examination showed blackish discolouration of the right hard palate and right alveolar ridge, extending to the right buccal mucosa (Fig. 1). The extraction site was difficult to identify. Patient underwent urgent computerized tomography (CT) scan of the facial bones. This showed air foci inside an ill-defined soft tissue opacity in the right buccal region, extending to the medial right nostril, as well as an alveolar process of the maxilla pointed inferiorly and extending to the periorbital region superiorly, with pre-septal orbital fat stranding. The orbital walls were fairly intact. Heterogeneous opacities were observed in both sides of the maxillary sinuses, ethmoid sinuses and in the nasal cavities, extending to the posterior choana (Fig. 2). Severe bilateral rarefaction of the turbinates was noted. A brain MRI found no brain abscess or mass lesion in the brain, but the right side of the cavernous sinus was slightly larger than the left. Cavernous sinus thrombosis was not visualized, as scans were done without intravenous contrast due to an electrolyte imbalance. The patient was given 5 mg/kg intravenous liposomal amphotericin and other supportive medications, including diabetic control. The patient was taken for urgent endoscopic sinus surgery and debridement under general anaesthesia.
After surgery, the patient was kept under ICU care. Tissue culture showed the presence of Rhizomucor, Klebsiella pneumoniae, and Candida albicans. In vitro antifungal sensitivity was determined by the microbroth dilution method according to CLSI 2016 (Clinical and Laboratory Standards Institute). The MIC (minimum inhibitory concentration) values obtained with various antifungal drugs at 24 and 48 h. The Rhizomucor strain was susceptible to amphotericin B, itraconazole and posaconazole, with MIC values less than 1 mg. The Klebsiella pneumonia was sensitive to cefuroxime, levofloxacin, ciprofloxacin, trimethoprim/sulfamethoxazole, gentamycin, amikacin, piperacillin/tazobactam, ceftazidime, ceftriaxone and moxifloxacin. The Candida albicans found to be susceptible to amphotericin B and caspofungin but resistant to fluconazole using E test – Epsilometer test (AB Biodisk, Solna, Sweden). Histopathology of oral and nasal tissues confirmed invasive zygomycosis (mucormycosis) with extensive angioinvasion and neural invasion. The patient received intravenous piperacillin, tazobactam, metronidazole, anidulafungin and liposomal amphotericin b. The patient underwent daily debridement of necrotic tissues. Necrotic tissues had begun spreading to the nose externally. Despite all these measures, the patient died from cardiac arrest secondary to sepsis on the 10th day after admission. Discussion Diabetes mellitus increases susceptibility to infections, both the most common infections as well as some that uniquely afflict diabetes patients (e.g., rhinocerebral mucormycosis) [5]. This may be due to abnormal phagocytosis, persistent reduction of blood flow, and cell-mediated immune abnormalities characteristic of diabetes [6]. This explains the greater probability of concurrent infection by multiple organisms, as found in this patient. Rao et al. reported Klebsiella pneumonia to be the second most common organism (12.9%) infecting the maxillofacial space in diabetic patients (Streptococcus is the most common) [7]. In a study by Suárez et al, 74.8% of 107 diabetic patients had oral candidiasis; this study did not distinguish between colonization and disease [8]. The third organism, Rhizomucor, which was identified in this case, belongs to the mucoraceae family. In approximately 50% of mucormycosis infections, diabetes mellitus was the predisposing factor due to the greater availability of glucose, lower pH and subsequent decreased serum inhibitory activity against the pathogen and
Please cite this article in press as: Prabhu S, et al. A fatal case of rhinocerebral mucormycosis of the jaw after dental extractions and review of literature. J Infect Public Health (2017), https://doi.org/10.1016/j.jiph.2017.09.026
G Model JIPH-832; No. of Pages 3
ARTICLE IN PRESS S. Prabhu et al. / Journal of Infection and Public Health xxx (2017) xxx–xxx
increased expression of some host receptors that mediate invasion of human epithelial cells [1]. The patient in this case underwent a right tooth extraction 3 days prior to the event. This may have been an entry point for the polymicrobial infection. In one study, univariate analysis of 324 patients who underwent invasive oral surgery showed a statistically significant correlation between surgical site infection and diabetes [9]. Polymicrobial rhinocerebral infection is not mentioned much in literature, as this is only the second case ever reported to the best of author’s knowledge. The first case was a 50-year-old male patient with uncontrolled diabetes who worked as a farmer and developed rhinocerebral mucormycosis following a tooth infection. Histopathology of a tissue biopsy showed non-septate mucormycotic hyphae at 90◦ . Similar to what was observed in this patient; Klebsiella and Candida were detected in the cultured pus [10]. Despite the polymicrobial findings in this case report, we find mucormycosis to be the most important, as this is the most common organism responsible for typical clinical features such as facial swelling, ophthalmologic symptoms and blackish necrotic debris [11]. In this case patient was started on anidulafungin and liposomal amphotericin b depending on sensitivity of Rhizomucor and Candida albicans. However other antifungals like those in azole group can be initiated but in our case Candida albicans was resistant to azoles [11,12]. An aggressive multidisciplinary approach was undertaken, involving an otorhinolaryngologist, maxillofacial surgeon, neurosurgeon, intensivist, diabetologist and infectious diseases specialists. The mainstay of the treatment strategy was surgical debridement, including endoscopic sinus and maxillectomy with supporting antifungal and antibacterial medications. Despite all these measures, there is a high mortality rate of 50–85% associated with rhinocerebral mucormycosis even when aggressive surgery is done [3,11,12]. Conclusion More data are necessary to inform management of polymicrobial rhinocerebral infections, including mucormycosis in diabetic patients. This manuscript provides additional information on the subject to help improve the protocol for polymicrobial rhinocerebral infection management.
3
Funding No funding sources. Competing interests None declared. Ethical approval Not required. References [1] Shipton WA. The biology of fungi impacting human health; 2014. p. 72. [2] Geerlings SE, Hoepelman AI. Immune dysfunction in patients with diabetes mellitus. FEMS Immunol Med Microbiol 1999;26(December (3–4)):259–65. [3] Palejwala SK, Zangeneh TT, Goldstein SA. An aggressive multidisciplinary approach reduces mortality in rhinocerebral mucormycosis. J Surg Neurol Int 2016;7(May):61. [4] Abdel Motaleb Hesham Y, Mohamed Mostafa S, Mobarak Fahmy A. A fatal outcome of rhino-orbito-cerebral mucormycosis following tooth extraction: a case report. J Int Oral Health 2015;7(Suppl. 1):68–71. [5] Casqueiro J, Casqueiro J, Alves C. Infections in patients with diabetes mellitus: a review of pathogenesis. Indian J Endocrinol Metab 2012;16(March (Suppl. 1)):S21–36. [6] Chang Shin, Yoo Kil-Hwa, Yoon Sung Hwan, Ha Jiwon, Jung Seunggon, Kook Min-Suk, et al. Odontogenic infection involving the secondary fascial space in diabetic and non-diabetic patients: a clinical comparative study. J Korean Assoc Oral Maxillofac Surg 2013;39(August (4)):175–81. [7] Rao DD, Desai A, Kulkarni RD, Gopalkrishnan K, Rao CB. Comparison of maxillofacial space infection in diabetic and nondiabetic patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;110:7–12. [8] Suárez B, Alvarez MI, de Bernal M, Collazos A. Candida species and other yeasts in the oral cavities of type 2 diabetic patients in Cali, Colombia. Colomb Med 2013;44(1):26–30. [9] Shigeishi H, Ohta K, Takechi M. Risk factors for postoperative complications following oral surgery. J Appl Oral Sci 2015;23(July–August (4)):419–23. [10] Sree Vijayabala G, Annigeri Rajeshwari G, Sudarshan Ramachandran. Mucormycosis in a diabetic ketoacidosis patient. Asian Pac J Trop Biomede 2013;3(October (10)):830–3. [11] Rapidis AD. Orbitomaxillary mucormycosis (zygomycosis) and the surgical approach to treatment: perspectives from a maxillofacial surgeon. Clin Microbiol Infect 2009;15(Suppl. 5):98–102. [12] Papadogeorgakis Nikolaos, Parara Eleni, Petsinis Vassilios, Vourlakou Christina. A case of successfully treated rhinocerebral mucormycosis: dental implications. Int J Dent 2010;2010:273127. Published online 2011 Feb 15.
Please cite this article in press as: Prabhu S, et al. A fatal case of rhinocerebral mucormycosis of the jaw after dental extractions and review of literature. J Infect Public Health (2017), https://doi.org/10.1016/j.jiph.2017.09.026
ARTICLE IN PRESS Journal of Infection and Public Health xxx (2017) xxx–xxx
Contents lists available at ScienceDirect
Journal of Infection and Public Health journal homepage: http://www.elsevier.com/locate/jiph
A fatal case of rhinocerebral mucormycosis of the jaw after dental extractions and review of literature Shilpa Prabhu a,∗ , Manaf Alqahtani b , Mohammed Al Shehabi a a
Department of Otorhinolaryngology, Royal Medical Services, Bahrain Defence Force Hospital, Bahrain Department of Pathology, Royal College of Surgeons in Ireland-Bahrain Medical University, Royal Medical Services, Bahrain Defence Force Hospital, Bahrain b
a r t i c l e
i n f o
Article history: Received 19 June 2017 Received in revised form 1 September 2017 Accepted 30 September 2017 Keywords: Mucormycosis Rhinocerebral Polymicrobial Diabetes mellitus Fungal infection Immune dysfunction
a b s t r a c t The purpose of presenting this case is to report a fatal case of rhinocerebral mucormycosis post-dental extraction in a patient with uncontrolled diabetes mellitus. Several cases of rhinocerebral mucormycosis have been reported, but mucocutaneous mucormycosis has not been commonly reported to be a part of polymicrobial wound infections at multifocal sites. To the best of author’s knowledge, this is the second case of polymicrobial rhinocerebral infection involving mucormycosis. © 2017 The Authors. Published by Elsevier Limited on behalf of King Saud Bin Abdulaziz University for Health Sciences. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).
Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Case report . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Operative details . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Post-operative course . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Competing interests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Ethical approval . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
Introduction Opportunistic infections are common in patients with uncontrolled diabetes, and over 50% of all mucormycosis cases occur in diabetic patients [1]. This is most likely due to a cellular innate immunity defect of the polymorphonuclear cells [2]. Although primary disease occurs in the paranasal sinuses, it may originate in
the oral cavity or teeth and often progresses intracranially via direct extension or angioinvasion. Rhinocerebral mucormycosis is rapidly fatal, with a mortality rate of 85% even when maximally treated with surgical debridement, antifungal therapy, and correction of underlying processes [3,4]. Case report
∗ Corresponding author at: Department of Otorhinolaryngology, Royal Medical Services, Bahrain Defence Force Hospital, P. O Box 28743, Bahrain. E-mail addresses: [email protected] (S. Prabhu), [email protected] (M. Alqahtani), [email protected] (M. Al Shehabi).
A 70-year-old male with a longstanding history of uncontrolled diabetes mellitus was brought to the emergency department with altered sensorium, vomiting, decreased oral intake and right facial swelling for one day. The patient had a right tooth extraction 3 days
https://doi.org/10.1016/j.jiph.2017.09.026 1876-0341/© 2017 The Authors. Published by Elsevier Limited on behalf of King Saud Bin Abdulaziz University for Health Sciences. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Please cite this article in press as: Prabhu S, et al. A fatal case of rhinocerebral mucormycosis of the jaw after dental extractions and review of literature. J Infect Public Health (2017), https://doi.org/10.1016/j.jiph.2017.09.026
G Model JIPH-832; No. of Pages 3 2
ARTICLE IN PRESS S. Prabhu et al. / Journal of Infection and Public Health xxx (2017) xxx–xxx
Operative details
Fig. 1. Blackish discoloration of right hard palate.
Patient underwent endoscopic sinus surgery and right hemimaxillectomy under general anaesthesia. Intraoperatively, black necrotic tissue was observed in both nasal cavities. This involved the inferior, middle, and superior turbinates, the septum, floor of the nose and the right 3/4th of the palate. Thick mucin was retrieved from both maxillary sinuses. White fungal spores were found in the right nasal cavity. Mucosa of all sinuses was blackish and necrotic. With a nasal endoscope and microdebrider, turbinectomy was performed. Uncinectomy, middle meatal antrostomy, ethmoidectomy and sphenoidectomy were performed on both sides. The mucosal linings of all sinuses were scraped, and the bone was exposed. Caldwell-Luc incision progressing to craniofacial flap elevation was performed; then, 3/4th of the palate was excised by right hemimaxillectomy. The upper right 3, upper right 4, and upper right 2 spaces were filled with ribbon gauze soaked in betadine. An orogastric tube was inserted, and the patient was kept under ICU care after surgery. Post-operative course
Fig. 2. Ct facial bones coronal section showing heterogeneous opacity in left maxillary sinus.
before in a private hospital, after which blood-stained pus leaked from his mouth. On examination, the patient had right cheek swelling with right eye proptosis, eyelid swelling, conjunctival chemosis, limited extraocular movement and an unreactive right pupil. Nasal examination revealed blackish discolouration bilaterally throughout the nasal mucosa. Oral cavity examination showed blackish discolouration of the right hard palate and right alveolar ridge, extending to the right buccal mucosa (Fig. 1). The extraction site was difficult to identify. Patient underwent urgent computerized tomography (CT) scan of the facial bones. This showed air foci inside an ill-defined soft tissue opacity in the right buccal region, extending to the medial right nostril, as well as an alveolar process of the maxilla pointed inferiorly and extending to the periorbital region superiorly, with pre-septal orbital fat stranding. The orbital walls were fairly intact. Heterogeneous opacities were observed in both sides of the maxillary sinuses, ethmoid sinuses and in the nasal cavities, extending to the posterior choana (Fig. 2). Severe bilateral rarefaction of the turbinates was noted. A brain MRI found no brain abscess or mass lesion in the brain, but the right side of the cavernous sinus was slightly larger than the left. Cavernous sinus thrombosis was not visualized, as scans were done without intravenous contrast due to an electrolyte imbalance. The patient was given 5 mg/kg intravenous liposomal amphotericin and other supportive medications, including diabetic control. The patient was taken for urgent endoscopic sinus surgery and debridement under general anaesthesia.
After surgery, the patient was kept under ICU care. Tissue culture showed the presence of Rhizomucor, Klebsiella pneumoniae, and Candida albicans. In vitro antifungal sensitivity was determined by the microbroth dilution method according to CLSI 2016 (Clinical and Laboratory Standards Institute). The MIC (minimum inhibitory concentration) values obtained with various antifungal drugs at 24 and 48 h. The Rhizomucor strain was susceptible to amphotericin B, itraconazole and posaconazole, with MIC values less than 1 mg. The Klebsiella pneumonia was sensitive to cefuroxime, levofloxacin, ciprofloxacin, trimethoprim/sulfamethoxazole, gentamycin, amikacin, piperacillin/tazobactam, ceftazidime, ceftriaxone and moxifloxacin. The Candida albicans found to be susceptible to amphotericin B and caspofungin but resistant to fluconazole using E test – Epsilometer test (AB Biodisk, Solna, Sweden). Histopathology of oral and nasal tissues confirmed invasive zygomycosis (mucormycosis) with extensive angioinvasion and neural invasion. The patient received intravenous piperacillin, tazobactam, metronidazole, anidulafungin and liposomal amphotericin b. The patient underwent daily debridement of necrotic tissues. Necrotic tissues had begun spreading to the nose externally. Despite all these measures, the patient died from cardiac arrest secondary to sepsis on the 10th day after admission. Discussion Diabetes mellitus increases susceptibility to infections, both the most common infections as well as some that uniquely afflict diabetes patients (e.g., rhinocerebral mucormycosis) [5]. This may be due to abnormal phagocytosis, persistent reduction of blood flow, and cell-mediated immune abnormalities characteristic of diabetes [6]. This explains the greater probability of concurrent infection by multiple organisms, as found in this patient. Rao et al. reported Klebsiella pneumonia to be the second most common organism (12.9%) infecting the maxillofacial space in diabetic patients (Streptococcus is the most common) [7]. In a study by Suárez et al, 74.8% of 107 diabetic patients had oral candidiasis; this study did not distinguish between colonization and disease [8]. The third organism, Rhizomucor, which was identified in this case, belongs to the mucoraceae family. In approximately 50% of mucormycosis infections, diabetes mellitus was the predisposing factor due to the greater availability of glucose, lower pH and subsequent decreased serum inhibitory activity against the pathogen and
Please cite this article in press as: Prabhu S, et al. A fatal case of rhinocerebral mucormycosis of the jaw after dental extractions and review of literature. J Infect Public Health (2017), https://doi.org/10.1016/j.jiph.2017.09.026
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increased expression of some host receptors that mediate invasion of human epithelial cells [1]. The patient in this case underwent a right tooth extraction 3 days prior to the event. This may have been an entry point for the polymicrobial infection. In one study, univariate analysis of 324 patients who underwent invasive oral surgery showed a statistically significant correlation between surgical site infection and diabetes [9]. Polymicrobial rhinocerebral infection is not mentioned much in literature, as this is only the second case ever reported to the best of author’s knowledge. The first case was a 50-year-old male patient with uncontrolled diabetes who worked as a farmer and developed rhinocerebral mucormycosis following a tooth infection. Histopathology of a tissue biopsy showed non-septate mucormycotic hyphae at 90◦ . Similar to what was observed in this patient; Klebsiella and Candida were detected in the cultured pus [10]. Despite the polymicrobial findings in this case report, we find mucormycosis to be the most important, as this is the most common organism responsible for typical clinical features such as facial swelling, ophthalmologic symptoms and blackish necrotic debris [11]. In this case patient was started on anidulafungin and liposomal amphotericin b depending on sensitivity of Rhizomucor and Candida albicans. However other antifungals like those in azole group can be initiated but in our case Candida albicans was resistant to azoles [11,12]. An aggressive multidisciplinary approach was undertaken, involving an otorhinolaryngologist, maxillofacial surgeon, neurosurgeon, intensivist, diabetologist and infectious diseases specialists. The mainstay of the treatment strategy was surgical debridement, including endoscopic sinus and maxillectomy with supporting antifungal and antibacterial medications. Despite all these measures, there is a high mortality rate of 50–85% associated with rhinocerebral mucormycosis even when aggressive surgery is done [3,11,12]. Conclusion More data are necessary to inform management of polymicrobial rhinocerebral infections, including mucormycosis in diabetic patients. This manuscript provides additional information on the subject to help improve the protocol for polymicrobial rhinocerebral infection management.
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Funding No funding sources. Competing interests None declared. Ethical approval Not required. References [1] Shipton WA. The biology of fungi impacting human health; 2014. p. 72. [2] Geerlings SE, Hoepelman AI. Immune dysfunction in patients with diabetes mellitus. FEMS Immunol Med Microbiol 1999;26(December (3–4)):259–65. [3] Palejwala SK, Zangeneh TT, Goldstein SA. An aggressive multidisciplinary approach reduces mortality in rhinocerebral mucormycosis. J Surg Neurol Int 2016;7(May):61. [4] Abdel Motaleb Hesham Y, Mohamed Mostafa S, Mobarak Fahmy A. A fatal outcome of rhino-orbito-cerebral mucormycosis following tooth extraction: a case report. J Int Oral Health 2015;7(Suppl. 1):68–71. [5] Casqueiro J, Casqueiro J, Alves C. Infections in patients with diabetes mellitus: a review of pathogenesis. Indian J Endocrinol Metab 2012;16(March (Suppl. 1)):S21–36. [6] Chang Shin, Yoo Kil-Hwa, Yoon Sung Hwan, Ha Jiwon, Jung Seunggon, Kook Min-Suk, et al. Odontogenic infection involving the secondary fascial space in diabetic and non-diabetic patients: a clinical comparative study. J Korean Assoc Oral Maxillofac Surg 2013;39(August (4)):175–81. [7] Rao DD, Desai A, Kulkarni RD, Gopalkrishnan K, Rao CB. Comparison of maxillofacial space infection in diabetic and nondiabetic patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;110:7–12. [8] Suárez B, Alvarez MI, de Bernal M, Collazos A. Candida species and other yeasts in the oral cavities of type 2 diabetic patients in Cali, Colombia. Colomb Med 2013;44(1):26–30. [9] Shigeishi H, Ohta K, Takechi M. Risk factors for postoperative complications following oral surgery. J Appl Oral Sci 2015;23(July–August (4)):419–23. [10] Sree Vijayabala G, Annigeri Rajeshwari G, Sudarshan Ramachandran. Mucormycosis in a diabetic ketoacidosis patient. Asian Pac J Trop Biomede 2013;3(October (10)):830–3. [11] Rapidis AD. Orbitomaxillary mucormycosis (zygomycosis) and the surgical approach to treatment: perspectives from a maxillofacial surgeon. Clin Microbiol Infect 2009;15(Suppl. 5):98–102. [12] Papadogeorgakis Nikolaos, Parara Eleni, Petsinis Vassilios, Vourlakou Christina. A case of successfully treated rhinocerebral mucormycosis: dental implications. Int J Dent 2010;2010:273127. Published online 2011 Feb 15.
Please cite this article in press as: Prabhu S, et al. A fatal case of rhinocerebral mucormycosis of the jaw after dental extractions and review of literature. J Infect Public Health (2017), https://doi.org/10.1016/j.jiph.2017.09.026