Ertapenem for the Treatment of Osteomyelitis: A Retrospective Analysis of the Bone And Joint Infection Organization (BAJIO) Database. Medina Stella MD¹, Gnoni Martin MD¹, Mariko Cheick CRC¹, Harting Julie PharmD¹,³, Newman David PharmD², Kelley Robert PhD¹,Christensen Diana MD¹,², and Julio Ramirez MD¹². ¹Division of Infectious Diseases, University of Louisville, ²Robley Rex Veterans Affairs Medical Center, ³Sullivan College of Pharmacy all in Louisville, Kentucky. Bone And Joint Infection Organization (BAJIO) Group. ABSTRACT Background: There is limited data regarding ertapenem in the treatment of osteomyelitis. The objective of this study was to analyze data from patients receiving ertapenem for the treatment of osteomyelitis to further characterize clinical outcomes and adverse effects associated with ertapenem-prolonged therapy. Methods: This was a retrospective study of adult patients with diagnosis of osteomyelitis treated with ertapenem at the UofL Hospital and the VA Hospital in Louisville, KY. All patients from December 2010 to February 2013 with diagnosis of osteomyelitis treated with ertapenem for ≥ 2 weeks were reviewed. The diagnosis of osteomyelitis was confirmed using radiographic or histopathologic criteria, or positive bone culture. The microbiological diagnosis was confirmed with positive bone culture, deep tissue culture, or blood culture. A patient was a candidate for ertapenem if the osteomyelitis was polymicrobial. Results: A total of 33 patients were reviewed (79% males). Nine diabetic foot infections, 19 other locations, 3 PJI and 2 Septic arthritis. Median ertapenem days were 40 (18-76). Median follow up was 114 days (20547). Seventeen and 16 patients received 2 grams Q24 and 1 gram Q24 respectively. The success rate was 85%. Minor adverse effects were seen in 33% and were not related with the dose. Conclusion: ertapenem appears to be effective in the treatment of osteomyelitis. It possesses a favorable safety profile even with high doses. These findings warrant further research describing ertapenem use in bone infections. INTRODUCTION • Ertapenem is FDA approved for the treatment of complicated intraabdominal infections, complicated skin/skin structure infections, including diabetic foot infections without osteomyelitis, communityacquired pneumonia, complicated urinary tract infections (including pyelonephritis), acute pelvic infections (including postpartum endomyometritis), septic abortion, and postsurgical gynecologic infections and prophylaxis of surgical site infection following elective colorectal surgery.  • Ertapenem is a broad-spectrum carbapenem with a long half-life permitting once-daily dosing. • Ertapenem has activity against the most invasive bacterial pathogens except for methicillin-resistant Staphylococcus aureus (MRSA), Enterococci, Pseudomonas aeruginosa, and Acinetobacter baumannii.  • A prior study has shown 12 cases of osteomyelitis treated with ertapenem as the primary antimicrobial with a success rate of 50% among patients who received an average of six weeks of ertapenem. • There are few case reports with ertapenem for the treatment of osteomyelitis.[3,4] • A study of obese patients with vertebral osteomyelitis suggests that 1gr q 24 hs is suboptimal/sub therapeutic. • There are limited data regarding ertapenem in the treatment of osteomyelitis. • The objective of this study was to analyze data from patients receiving ertapenem for osteomyelitis to further characterize clinical outcomes and adverse effects associated with ertapenem-prolonged therapy. MATERIALS AND METHODS Study Design: • This was a secondary analysis of the BAJIO database examining osteomyelitis cases treated with ertapenem. • The database included patients from the University of Louisville Hospital and the Robley Rex Veterans Affairs Medical Center both in Louisville, Kentucky. Inclusion Criteria: • ≥18 years of age • Confirmed osteomyelitis: 1. Osteomyelitis confirmed by x-rays, computed tomography, magnetic resonance imaging, and/or nuclear medicine studies. 1. Suggestive radiologic indices augmented by histologic evaluation of bone and/or positive cultures for bacteria in bone biopsy specimens. • A patient was a candidate for ertapenem if the osteomyelitis was polymicrobial either by culture or clinical suspicion. RESULTS (Cont’d) RESULTS • For the primary endpoint of clinical success, 27/30 evaluable patients (90%) achieved success, 3 patients were lost to follow-up. Table 2: Pathogenic isolates from clinically evaluable patients with osteomyelitis. ___________________________________________________________________________________________________________________________ • A total of 33 patients were evaluated for adverse events and discontinuations of ertapenem Organism (s) No. (%) (n = 36) ___________________________________________________________________________________________________________________________ Enterobacteriaceae Enterobacter cloacae Escherichia coli Klebsiella Serratia marcescens Citrobacter Proteus mirabilis 13/36 (36%) 5 3 2 1 1 1 • The incidence of adverse events between the 1g and 2g dosing strategies did not differ statistically. Staphylococcus aureus Methicillin-resistant Methicillin-susceptible 4/36 (11%) 3 1 • Ertapenem was discontinued in 5 patients due to an adverse event. Discontinuations between the 1g and 2g groups did not differ statistically. Staphylococcus coagulase negative 5/36 (14%) Streptococcus species Streptococcus viridans Streptococcus anginosus group Other streptococcal species 7/36 (20%) 2 1 4 Anaerobic bacteria Bacteroides fragilis group 1/36 (3%) 1 Enterococcus faecalis Vancomycin resistant 3/36 (8%) 0 Other GNR 3/36 (8%) • Dosing regimens for ertapenem were 1g administered once daily (n = 16), or 2g administered once daily (n = 17). Mean length of treatment was 39.3 days (18-76). • Approximately 27% experienced some adverse event. Nausea and vomiting 3 (8%), eosinophilia 3 (8%), neutropenia 1(3%), hyperbilirubinemia 1 (3%), and diarrhea 1 (3%). Table 1: Demographic and laboratory data for 33 cases of osteomyelitis treated with Ertapenem _________________________________________________________________________________________________________________________ Exclusion Criteria for Primary Outcome: Variable • Those not receiving ≥2 continuous weeks of ertapenem _________________________________________________________________________________________________________________________ Study Definitions and Outcomes: 1- Primary outcome: - Clinical success = resolution of disease measured clinically and with decreased ESR and CRP, without need for alteration in antibiotic therapy or repeat surgical intervention 2- Secondary outcomes: - Adverse events = enumerated and compared by dosing strategy (1g daily versus 2 g daily) = side effects or laboratory aberrations in patients on ertapenem Statistics: • Fisher’s exact test or Chi-squared test, as appropriate, for comparisons between ertapenem dosing groups • Clinical success was described as the number (%) of those clinically evaluable who were coded as successes. • Microsoft Excel™ 2010 was used for all calculations. • P-values ≤0.05 were considered significant. No./%ª (n = 33) Demographic data Age, mean (SD) 49.6 (33) Male sex 26 (79%) Caucasian 25 (76%) African-American 8 (24%) Comorbidities Hypertension 18 (55%) Current smoker 12 (36%) Diabetes 11 (33%) Orthopedic hardware 10 (30%) Peripheral neuropathy 8 (24%) Peripheral arterial disease 6 (18%) Chronic renal disease 2 (6%) Current alcohol use 3 (9%) Coronary artery disease 3 (9%) Current steroid use 3 (9%) Cirrhosis 1 (3%) Site of Infection/Surgical intervention Diabetic foot 9 (27%) Other site 19 (57%) Mandible 9 (27%) PJI 3 (9%) Septic arthritis 2 (6%) Laboratory data upon diagnosis WBC (cells/mm³), Median (IQR) 11.6 (3.5-21.9.) ESR (mm/hr), Median (IQR) 62.82 (0-140) CRP (mg/dl), Median (IQR) 8.91 (0.09-32.59) Procalcitonin, Median (IQR) 0.77 (0.05-3.7) --------------------------------------------------------------------------------SD: standard deviation; WBC: white blood cell count; IQR: interquartile range; ESR: erythrocyte sedimentation rate; CRP: C-reactive protein. ªAll values are given as No. (% of total patients) unless otherwise specified. ªAll values are given as No. of a given isolate (% of total bacterial isolates). CONCLUSIONS • Ertapenem appeared to be efficacious for the treatment of polymicrobial osteomyelitis. • Ertapenem possesses a favorable safety profile, even with high doses. • These findings warrant further research describing ertapenem use in bone infections. REFERENCES  http://www.invanz.com/ertapenem_sodium/invanz/hcp/index.xhtml  Goswami ND, et al. Ertapenem for the treatment of osteomyelitis. 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