490High Dose Tigecycline for the Treatment of Multi-Drug Resistant Gram Negative Urinary Tract Infections

Background. Tigecycline is a glycylcycline derived from the tetracycline antibiotics with potent bacteriostatic activity against gram negative, gram positive, and anaerobic organisms. With only 15 to 22 percent of tigecycline excreted unchanged in the urine with a standard dose of 50 mg every 12 hours, clinicians have debated the use of tigecycline for the treatment of multi-drug resistant urinary tract infections (MDR UTIs) based on concerns about inadequate drug concentrations in the urine. Therefore, higher doses of tigecycline (100 mg every 12 hours) may be warranted to achieve higher urinary concentrations as the drug displays linear pharmacokinetics. The purpose of this study is to evaluate clinical outcomes using high-dose tigecycline for the treatment of MDR UTIs. Methods. A retrospective review was conducted on adult patients who received high dose tigecycline (100 mg every 12 hours) for the treatment of MDR UTIs between 2012 and 2013. Data was collected and analyzed to compare treatment success and failure rates, time to treatment success, length of hospital stay, incidence of Clostridium-difficile associated diarrhea, and incidence of nausea and vomiting. Results. Of the 107 patients with UTIs who were administered tigecycline, 7 patients were treated with high dose tigecycline. Twenty-eight percent of the patients were male with a median age of 58 years (range 30 – 79). The UTIs were most commonly caused by extended spectrum beta-lactamase Enterobacteriaceae (71%) followed by Klebsiella pneumoniae carbapenamases (43%). Overall, 86% and 14% of the patients who were treated with high dose tigecycline were found to have treatment success and treatment failure, respectively. Nausea and vomiting occurred in only 1 patient without the need for discontinuation of therapy. Conclusion. Although the sample size was small, high dose tigecycline appears to be an alternative for the treatment of MDR UTIs. However, larger, prospective studies are warranted to further characterize this relationship. Disclosures. All authors: No reported disclosures.