1. A rare case of Candida parapsilosis osteomyelitis in a diabetic woman with basal cell carcinoma BACKGROUND Candida parapsilosis is the most common non-albicans candida (NAC) infection worldwide (third in the USA after C. glabrata). It is not an obligate human pathogen, and has been isolated from nonhuman sources such as domestic animals, insects, soil, and marine environments. It is less virulent than C. albicans, but the incidence of invasive C. parapsilosis is rising (4% between 1997-2000 to 7% between 2001-05) (Pfaller et al.). It has a high affinity for parenteral nutrition, frequently colonizes the hands of health care workers, forms biofilm on prosthetic surfaces and central venous catheters, causes pathology in immuno- compromised and low birth weight neonates and is a rare cause of osteomyelitis. Other NAC species have specific risk factors, such as C. krusei to azole prophylaxis and along with C. tropicalis to neutropenia and BMT; C. glabrata to azole prophylaxis, surgery and urinary or vascular catheters; C. lusitaniae and C. guilliermondii to previous polyene (amphotericin B or nystatin) use; and C. rugosa to burns (Krcemery et al). Mortality NAC have similar mortality to C. albicans. C. parapsilosis has the lowest mortality (4%), and the highest are C. tropicalis and C. glabrata with 40–70%. Other NAC species including C. krusei are associated with similar overall mortality to C. albicans (20–40%) (Krcmery et al.). TREATMENT Generally C. parapsilosis is very susceptible to polyenes (amphotericin B) and azoles (fluconazole, ketoconazole, itraconazole, voriconazole, and posaconazole), but is less susceptible to echinocandins (van Asbeck et al.). In vitro susceptibility testing should be performed for most species of NAC in addition to removal of any foreign body to optimize management. Treatment for candida osteomyelitis: Oral fluconazole (400 mg) daily for 6 to 12 months, or Lipid formulation of amphotericin B (3 to 5 mg/kg IV daily) for at least 2 weeks Followed by: Oral fluconazole (400 mg) for a total of 6 to 12 months DISCUSSION This 71 year old female with uncontrolled diabetes mellitus with a large basal cell carcinoma and C. parapsilosis osteomyelitis was treated with fluconazole but unfortunately required an above the knee amputation. CASE REPORT A 71 year old female with uncontrolled diabetes mellitus presented with profound weakness and was unable to bear weight on her right leg for the past week. Initially, she noted a small ulcerative lesion on her right posterior calf 15 years ago, which had been slowly growing and now was foul smelling. She had not been to a doctor in over 20 years but had treated it with herbal salves. On admission, she was afebrile and slightly tachycardic. The right lower extremity was malodorous with a circumferential ulcerated lesion that extended below her knee to her ankle and involved all three layers of the dermis with visible bone, purulent drainage, patchy granulation tissue, and maggots throughout. Notable labs were hematocrit of 16, WBC of 45,000, creatinine 2.08, glucose 51, and lactic acid of 10. A CT of the right tibia showed osteomyelitis associated with large excoriation defect of the subcutaneous tissues overlying anterior tibial and medial calf (figure 3). She was empirically started on vancomycin, piperacillin/tazobactam and clindamycin. She was taken to the operating room for debridement and fasciotomy. Multiple tissue biopsies of the leg showed ulcerative basal cell carcinoma with positive margins and bone culture grew 4+ Candida parapsilosis (figure 1, 2a and 2b). She was started on fluconazole. Radiation oncology did not recommend radiation therapy and so on post-operative day 16, she agreed to have an above the knee amputation. Figure 1: Right leg wound gram stain showing budding yeast without pseudohyphae. The germ tube test was negative suggesting this was not C. albicans but results of the VITEK® YBC, a commercial identification panel of physiological tests, confirmed the diagnosis of Candida parapsilosis. Microscopically, unlike C. albicans and C. tropicalis, which can exist in multiple morphogenetic forms, C. parapsilosis does not form true hyphae and exists in either a yeast phase or a pseudohyphal form. Figure 3. Coronal CT image of right lower extremity showing periosteal reaction. Circumferential calf skin defect most severe anteromedially to the tibia. Periosteal reaction about the proximal tibia reflects osteomyelitis. Catherine P. Benziger, MD 1, Tony Trinh, MD 2, Sheila Dunaway, MD 2 1 UNIVERSITY OF WASHINGTON INTERNAL MEDICINE RESIDENCY PROGRAM, SEATTLE, WA; 2 HARBORVIEW MEDICAL CENTER, SEATTLE, WA REFERENCES Pfaller, M et al., Bloodstream Infections Due to Candida Species: SENTRY Antimicrobial Surveillance Program in North America and Latin America, 1997-1998. Antimicrob Agents Chemother. 2000; 44:3. Krcmery, V et al., Non-albicans Candida spp. causing fungaemia: pathogenicity and antifungal resistance. J Hospital Infection 2002; 50:4. Trofa, D. et al. Candida parapsilosis, an emerging fungal pathogen. Clin Microbiol Rev 2008 21:4. Van Asbeck, E et al. Candida parapsilosis: a review of its epidemiology, pathogenesis, clinical aspects, typing and antimicrobial susceptibility. Crit Rev Microbiol 2009; 35:4. CONCLUSIONS C. parapsilosis forms biofilm on prosthetic surfaces and central venous catheters, frequently affects immuno- compromised and low birth weight neonates, and is a rare cause of osteomyelitis. C. parapsilosis is the second most common candida infection worldwide after C. albicans (third in the USA after C. glabrata). C. parapsilosis is very susceptible to fluconazole and often requires 6-12 months of treatment for osteomyelitis. Figure 2a. Right leg anterior tibia biopsy Invasive carcinoma, basal cell (infiltrative and focally metatypical/baso-squamous) at previous excision edge. Sections of tibia show basal cell carcinoma with extensive squamous differentiation involving the bone and adjacent soft tissue. Figure 2b. Right leg wound excision showing invasive basal cell carcinoma at ulcer edge with NP pancytokeratin stain. PathologyRadiology Microbiology Image borrowed from Trofa et al.