FDC2018 Speaker Preview

Mandibular Osteomyelitis Associated to Candida Albicans in Marijuana and Heroin Abusers: Literature Review and Case Series

By Mikhail Daya, DMD*; Isabella Anderson, BS+; and, Jason Portnof, DMD, MD, FACS, FIDC**

Background: Osteomyelitis of the mandible is most commonly caused by bacterial infections and is rarely linked to fungal infections. Friedman et al. studied the relationship of multiple drugs, including marijuana, opioids, nicotine and alcohol, and its effect on the immune system. It’s important to consider potential risks and complications of patients who are immunocompromised and present a history of substance abuse. These complications include infections and osteomyelitis, which can be associated with multiple microorganisms, such as fungus. Candida albicans is commonly found in skin and mucosa of healthy individuals; however, it has been proven to cause disease in individuals who are immunocompromised.

Case Presentation: Two cases of mandibular osteomyelitis after routine dental extractions and a history of drug abuse, including heroin and marijuana, are presented in this case series. The patients were both male, ages included a 40-year-old (Patient A) and a 45-year-old (Patient B). Both patients underwent routine dental extractions performed by two different oral surgeons. Patient A underwent routine extraction of tooth No. 19 and Patient B had an extraction of erupted tooth No. 32. Due to recurrent infections and non-healing extraction sites, both patients were referred to the Department of Oral and Maxillofacial Surgery at Nova Southeastern University. Patients A and B underwent multiple courses of antibiotics as well as incision and drainage without resolution. Cultures of the infected sites were collected and analyzed for aerobes, anaerobes and fungus. In the final microbiology, both cases yielded positive results for Candida albicans.

Once the final microbiology yielded positive results for Candida albicans, Patient A was treated with irrigation and debridement, and Patient B underwent a right mandibular resection. Both patients also were treated in combination with antimicrobial therapy and fluconazole leading to complete resolution.

fig-1.jpg
Fig. 1: Patient A. – Initial presentation after extraction of tooth No. 19 (Note: penrose drain in left mandible).
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Fig. 2: Patient A. – Two-month follow-up, non-healing extraction site of tooth No. 19.
Fig. 3
Fig. 3: Patient B. – Non-healing extraction site of tooth No. 32, with radiolucent area affecting the inferior border and tooth No. 31.
Fig. 4
Fig. 4: Patient B. – Right mandibular resection due to chronic osteomyelitis, two-month follow-up with hardware in place, disease free.

 

Discussion: Osteomyelitis is defined as a progressive inflammatory condition of the bone and bone marrow.1,2 This rare condition can affect any bone, but is commonly seen in teeth bearing bones of the facial skeleton, due to direct access of microorganisms through infected teeth.5 In 2012, Slenker et al. studied 212 cases of Candida osteomyelitis. In this study, the most commonly affected sites were vertebrae and sternum. Interestingly, only six of them affected the facial skeleton.4

Infections of dental origin have been historically associated to bacterial microorganisms; however, in recent years there has been a trend in increasing infections associated to fungal pathogens.6 This increase in prevalence of Candida infections have been associated to contributing factors such as growth in population of immunosuppressed patients, invasive surgeries and overuse of broad-spectrum antibiotics.7

We show two cases of mandibular osteomyelitis after routine dental extraction in patients with a history of marijuana and heroin abuse as their only significant comorbidity. Friedman et al. demonstrated a correlation between marijuana and heroin abuse and a susceptibility to infections; this is due to the direct effect of these drugs over the immune response against pathogens.3 Marijuana is the common name given to Cannabis sativa; this plant has been widely used for recreational and medicinal purposes.3 Marijuana has been directly associated to increased susceptibility to infections because of its effect on immune cells, macrophages, lymphocytes and cytokines.9,10,11 On the other hand, heroin and other opioids have been linked to increase susceptibility to infection by direct exposure of pathogens through injections as well as their direct action in immune cells.12,13

Both cases presented here were treated with a combination of surgical debridement and fluconazole. The management of Candida osteomyelitis has not been well established due to the uncommon nature of this condition. Treatment recommendations for Candida osteomyelitis are based on case reports and case series. Amphotericin B (AmB) has been used widely in the past;14 however, more recent literature supports the use of fluconazole or echinocandin over AmB due to high toxicity rate.4,15,16 Recommendations of the Infectious Diseases Society of America include the use of different antifungal combinations and surgical debridement in selected cases.

Conclusion: Although mandibular osteomyelitis is most commonly caused by bacterial microorganisms, special attention must be given to patients with medical histories of immunosuppression and illicit drug use of cannabis and opiates. Patients who do not respond to broad-spectrum antibiotics might benefit from bacterial cultures, fungal cultures and sensitivity. In cases of positive fungal microorganisms, anti-fungal treatment with an antifungal agent such as oral fluconazole is indicated if fungal organisms are yielded in the culture.

 

*Oral and Maxillofacial Surgery Chief Resident at Nova Southeastern University, Broward Health Medical Center, Joe DiMaggio Children’s Hospital.
+Fourth-year Dental Student at Nova Southeastern University
**Oral and Maxillofacial Surgery Associate Professor and Craniofacial Director at Nova Southeastern University and Joe DiMaggio Children’s Hospital.

Dr. Portnof will be speaking at the 2018 Florida Dental Convention in Orlando in June. He is presenting his course, “Opioid Disorder in Dental Patients,” on Thursday, June 21 at 9:30 a.m. and 12:30 p.m. To register, go to floridadentalconvention.com.

 

References:

  1. Dym H, Zeidan J. Microbiology of Acute and Chronic Osteomyelitis and Antibiotic Treatment. Dent Clin North Am 2017; 61(2):271-282.
  2.  Kushner GM. Osteomyelitis and osteoradionecrosis. In: Miloro M, editor. Peterson’s principles of oral and maxillofacial surgery. Lewiston (ME): BC Decker; 2004. pp 300-324.
  3. Friedman H, Newton C, Klein TW. Microbial Infections, Immunomodulation, and Drugs of Abuse. Clin Microbiol Rev 2003; 16(2):209-219.
  4. Slenker AK, Keith SW, Horn DL. Two hundred and eleven cases of Candida osteomyelitis: 17 case reports and a review of the literature. Diagn Microbiol Infect Dis 2012; 73(1):89-93.
  5. Baur DA, Altay MA, Flores-Hidalgo A, Ort Y, Quereshy FA. Chronic osteomyelitis of the mandible: Diagnosis and management — an institution’s experience over 7 years. J Oral Maxillofac Surg 2015; 73(4):655-665.
  6. Sanz-Rodriguez C, Hernandez-Surmann F, Bueno AG, Goizueta C, Noguerado A. Candida and bacterial mandibular osteomyelitis in an AIDS patient. Eur J Clin Microbiol Infect Dis 1988; 17(7):531-532.
  7. Blumberg HM, Jarvis WR, Soucie JM, Edwards JE, Patterson JE, Pfaller MA, et al. Risk factors for candidal bloodstream infections in surgical intensive care unit patients: The NEMIS Prospective Multicenter Study. The National Epidemiology Mycosis Survey. Clin Infect Dis 2001; 33(2):177-186.
  8. Daya M, Mederos H, McClure S. Refractory Odontogenic Infection Associated to Candida Albicans: A Case Report. Clin Surg 2017; 2:1397.
  9. Baldwin GC, Tashkin DP, Buckley DM, Park AN, Dubinett SM, Roth MD. Marijuana and cocaine impair alveolar macrophage function and cytokine production. Am J Respir Crit Care Med 1997; 156(5):1606-1613.
  10. Derocq J, Segui M, Marchand J, LeFur G, Casellas P. Cannabinoids enhance human B-cell growth at low nanomolar concentrations. FEBS Lett 1995; 369:177-182.
  11. Srivastava MD, Srivastava BI, Brouhard B. Delta9 tetrahydrocannabinol and cannabidiol alter cytokine production by human immune cells. Immunopharmacology 1998; 40(3):179-185.
  12. Donahoe RM. Drug abuse and AIDS: causes for the connection. NIDA Res Monogr 1990; 96:181-191.
  13. McCarthy L, Wetzel M, Sliker JK, Eisenstein TK, Rogers TJ. Opioids, opioid receptors, and the immune response. Drug Alcohol Depend 2001; 62(2):111–123.
  14. Miller DJ, Mejicano GC. Vertebral osteomyelitis due to Candida species: case report and literature review. Clin Infect Dis 2001; 33(4):523-530.
  15. Neofytos D, Huprikar S, Reboli A, Schuster M, Azie N, Franks B, et al. Treatment and outcomes of Candida osteomyelitis: review of 53 cases from the PATH Alliance (R) registry. Eur J Clin Microbial Infect Dis 2014; 33(1):135-141.
  16. Mora-Duarte J, Betts R, Rotstein C, Colombo AL, Thompson-Moya L, Smietana J, et al. Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med 2002; 347(25):2020-2029.
  17. Pappas P, Kauffman C, Andes D, Clancy C, Marr K, Ostrosky-Zeichner L, et al. Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis 2016; 62(4): e1-e50.

 

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