1. Mandible Osteomyelitis: Retrospective Analysis of the Bone and Joint Infection (BAJIO) Database Julie A. Harting, PharmD 1,2, Cheick O. Mariko, CRC 1, Rob Kelly, PhD 1, and Diana Christensen, MD 1 1 Division of Infectious Diseases, University of Louisville School of Medicine and 2 Sullivan College of Pharmacy, both in Louisville, KY ABSTRACT Background: Infectious Disease Guidelines for diabetic foot and prosthetic joint infections have been published, but data are lacking regarding management of other bone infections, particularly those in the mandible. The primary objectives were to describe the etiology and microbiology in patients with mandible osteomyelitis. The secondary objective was to evaluate the end-of treatment, and 30-day outcomes. Methods: This was a retrospective cohort study of adult patients at the University of Louisville Hospital. All patients with a diagnosis of mandible osteomyelitis by Infectious Disease, confirmed using radiographic or histopathologic criteria or positive bone culture, from January 2010 to March 2013 were included. Patients received 4-6 weeks of IV antibiotics and were followed at the end therapy, and 1-3-6-12 months after induction therapy. Success was defined as clinical improvement, decrease in ESR and CRP, and no need for further debridement. Results: From 300 osteomyelitis cases, 9% (n= 27) were recorded in the mandible. Etiologies included abscess 63%, prosthetic-related 22%, postsurgical 85%, tooth extraction 37%, and bisphosphonate usage 26%. Sixteen (59%) were polymicrobial, In patients with bone cultures, the most common pathogen was Streptococcus sp, particularly Streptococcus anginosus. One patient was bacteremic. 21 (78%) required surgical intervention. 100% had success at end-of-therapy. Seventeen (63%) patients were seen at 30 days with a success rate of 70%. Conclusion: Although etiologies vary greatly in this subset of patients, pathogenic organisms most commonly represented normal flora from the oral cavity. A combined multi-disciplinary management approach by Oromaxillofacial Surgery and Infectious Disease led to a high rate of treatment success. INTRODUCTION MATERIALS AND METHODS REFERENCES RESULTS Study Design: Retrospective case series of patients in the BAJIO database at the University of Louisville hospital and the Robley Rex Veterans Affairs Medical Center in Louisville, Kentucky. Cases were collected from January 2010 to March 2013. The BAJIO database is a multi-center, real-time, database of all patients diagnosed with osteomyelitis (including diabetic foot), prosthetic joint infection, or septic joint by the Bone & Joint Infectious Disease Program team. Members of the team include an ID Attending, ID Fellow, Pharmacist, Podiatry Resident, and Medical and Pharmacy students. Although data is analyzed retrospectively, patient cases are created and followed prospectively to capture the most accurate data and guide clinical decisions. IRB approval has been obtained. Inclusion Criteria: ≥18 years of age Diagnosis of mandible osteomyelitis confirmed by: X-ray, computed tomography, magnetic resonance imaging, and/or nuclear medicine studies. Histologic evaluation of bone documenting presence of osteomyelitis Positive bone cultures collected from the operating room Study Definitions: Clinical Success Improvement in clinical symptoms of infection Decreased pain, drainage, edema Absence of fever during treatment duration Closure of a sinus tract or surrounding wound Decrease in laboratory markers of infection, ESR and CRP, to normal range No need for further debridement Statistics: Clinical success was described as the number (%) of those clinically evaluable who were coded as successes. Microsoft Excel™ 2010 for all calculations P-values ≤ 0.05 were considered significant. CONCLUSIONS From a total of ~300 cases of osteomyelitis, 9% (n = 27) were in the mandible. Twenty-one (78%) underwent surgical intervention Pathogenesis Pathogenesis of infection was highly varied among the patient population. Patients could have more than one etiology. (Table 1) RESULTS (Cont’d) Osteomyelitis is an infection of the bone and/or marrow. (1) Data are lacking regarding treatment of osteomyelitis beyond diabetic foot, orthopedic, and vertebral infections. Studies regarding the mandible are limited to case reports and small case series with particular pathogens. Management of infection relies on a multidisciplinary, collaborative approach, particularly surgical removal of infected and dead bone. (2) Treatment durations for osteomyelitis are long, ~6 weeks, and require high-dose intravenous antibiotic therapy. It is difficult to fully eradicate infection, so there must be an infrastructure for long-term follow-up to monitor for relapse or recurrence. (3) The human oral cavity is normally colonized with a variety of gram positive, gram negative, and anaerobic bacteria, not all of which are pathogenic or have been documented to cause bone infections. Osteomyelitis of the mandible can occur from a variety of etologies causing compromise to the mandible periosteum. Organisms inhabiting the human oral cavity were the most common pathogens associated with mandible osteomyelitis. Streptococcus sp. were the most common species. Empiric coverage in culture-negative patients should include coverage against gram positive, gram negative and anaerobic bacteria. Streptococcus anginosus, the most prevalent pathogen, is known to form abscesses and be invasive. Penicillins are the drug of choice. Empiric antimicrobial treatment for Staphylococcus aureus is usually not necessary unless metallic hardware is present in the mandible. Because Actinomyces sp did not grow in culture and are not typically processed for antimicrobial susceptibility, the presence of gram positive rods and histopathologic evidence of infection warrants empiric therapy. Penicillins are the drug of choice. Culture negative In these cases, antimicrobial selection was driven by gram stain, histopathologic evidence of a pathogen, or knowledge of human oral flora. The high frequency of surgical debridement and collaboration with the Oromaxillofacial Surgery Service at University Hospital contributed to the clinical success in out patients. Oromaxillofacial Surgery Infectious Disease Plastics Internal Medicine or Oncology Treatment Success The most common species by culture was Streptococcus sp., particularly Streptococcus anginosus. (Table 2) Clinical Outcomes All patients (100%) had clinical success at the end-of-therapy. Seventeen (63%) patients had documentation of outcome at 30-days with a success rate of 70% Ten (37%) patients were considered lost-to-follow-up Table 1: Pathogenesis of infection Etiology # of Patients (%) n = 27 Adjacent SSTI/Abscess17 (63%) Prosthetic-related6 (22%) Post-surgical23 (85%) Following tooth extraction10 (37%) Evidence of native pathological fracture1 (4%) Bisphosphonate-induced osteonecrosis of the jaw7 (26%) Table 2: Number of Isolates Collected in Patients with Mandible Osteomyelitis Gram StainPathogen# of Isolates Gram PositiveStreptococcus, Viridans Group3 Streptococcus anginosus6 Streptococcus, alpha-hemolytic2 Streptococcus, beta-hemolytic1 Peptostreptococcus sp. (anaerobe)1 Staphylococcus aureus5 Staphylococcus sp (Coagulase negative)3 Enterococcus sp3 Gram NegativePrevotella sp. (anaerobe)4 Pseudomonas aeruginosa3 Klebsiella sp.3 Citrobacter sp1 E. Coli1 YeastCandida sp.1 Microbiology (cont.) Infections caused by Actinomyces sp. (n = 3) were always identified by presence of gram-positive rods on gram stain and/or histopathologic. No cultures were cultivated in the laboratory. Staphylococcus aureus infections occurred in patients with pre-existing hardware in the mandible 75% of the time. Ohl, C. Principles and Practice in Infectious Diseases.7 th edtn. Philadelphia. Churchill Livingstone. 2010. Lew D, et al. Osteomyelitis. Lancet 2004;364:369-79 Spellburg B, Lipsky B. Systemic Antibiotic Therapy for Chronic Osteomyelitis in Adults. CID 2012;54(3);393-407 Note: Table only lists pathogens grown in the laboratory. Other pathogens, example, Actinomyces sp., were diagnosed via other methodologies Microbiology Ten (37%) infections were culture-negative. Sixteen (59%) infections were polymicrobial. Gram stain results contained > 2 organisms in over half of the patients (Figure 1), indicating presence of polymicrobial infection. Gram positive cocci and gram positive rods were the most prevalent. Figure 1: Gram Stain Results STUDY OBJECTIVES Primary Objective Describe the pathogenesis and microbiology of mandible osteomyelitis in this series of patients Secondary Objective Evaluate the end-of-treatment and 30-day outcomes