Ceftazidime-Avibactam for Treatment of Carbapenem-Resistant Enterobacteriaceae Bacteremia: Table 1.

To the Editor—The Centers for Disease Control and Prevention (CDC) has estimated that >2 million people in the United States are infected each year with antibiotic-resistant bacteria. Among antibiotic-resistant bacteria, carbapenem-resistant Enterobacteriaceae (CRE) have been described as an urgent threat by the CDC 1. Yearly, nearly 9300 healthcare-associated Enterobacteriaceae infections are caused by CRE 1. Approximately 50% of patients who acquire bloodstream infections from CRE die from the infection, stressing the importance of developing and identifying more effective treatment options 1. Ceftazidime/avibactam (C/A) is a new β-lactam/β-lactamase inhibitor combination that was recently approved for use in the United States in February 2015 2. Avibactam is a novel non–β-lactam/β-lactamase inhibitor that inhibits extended-spectrum beta-lactamases, Amp C β-lactamases, and class A carbapenemases of the Klebsiella pneumoniae carbapenemase family restoring the activity of ceftazidime against Enterobacteriaceae producing these enzymes 2, 3. Currently, C/A is approved for treatment of complicated intra-abdominal infections when used in combination with metronidazole, as well as complicated urinary tract infections 4. Interest for utilization of C/A for CRE bacteremia is piqued due to established efficacy of cephalosporins for treatment of serious infections, limitations of currently available treatment options, and historically poor clinical outcomes 1. However, data in support of the use of C/A for patients with CRE bacteremia susceptible to C/A are lacking. We recently successfully treated 3 patients with CRE bacteremia with C/A. All isolates demonstrated in vitro susceptibility to C/A. Among the 3 patients, 2 had severe infections: 1 patient was in septic shock, and the other had suspected CRE endocarditis with persistently positive blood cultures and findings of a new mitral valve vegetation on a transthoracic echocardiogram. Doses were adjusted according to the patients' estimated renal function based on manufacturer recommendations. In 2 of the 3 patients, C/A was started after identification of a CRE pathogen but prior to availability of in vitro susceptibilities to the antibiotic. All patients were successfully discharged without a 30-day readmission despite having an infection caused by an extremely resistant pathogen. A summary of the 3 patient cases is provided in Table 1. Characteristics of Patients With Carbapenem-Resistant Enterobacteriaceae Bacteremia Treated With Ceftazidime/Avibactam Abbreviations: C/A, ceftazidime/avibactam; CAD, coronary artery disease; CHF, congestive heart failure; CKD, chronic kidney disease; DM, diabetes mellitus; MIC, minimum inhibitory concentration; UTI, urinary tract infection. a Ceftazidime/avibactam was administered for 16 days during the hospital stay with the remaining doses to be administered at a skilled nursing facility. Characteristics of Patients With Carbapenem-Resistant Enterobacteriaceae Bacteremia Treated With Ceftazidime/Avibactam Abbreviations: C/A, ceftazidime/avibactam; CAD, coronary artery disease; CHF, congestive heart failure; CKD, chronic kidney disease; DM, diabetes mellitus; MIC, minimum inhibitory concentration; UTI, urinary tract infection. a Ceftazidime/avibactam was administered for 16 days during the hospital stay with the remaining doses to be administered at a skilled nursing facility. Unfortunately, but perhaps predictably, CRE prevalence has been increasing. Although it is still relatively uncommon in most of the acute care hospitals in the United States, the rate of CRE has increased from 1.2% reported to the National Nosocomial Infection Surveillance system in 2001 to 4.2% reported to the National Healthcare Safety Network in 2011 5. Current treatment options for CRE bacteremia often involve polymyxin-based regimens, which are difficult to dose and are associated with significant risks of neurological and renal toxicity. Although C/A is not currently approved for treatment of patients with CRE bacteremia, our positive experience with this agent is encouraging and suggests that C/A could be considered if in vitro sensitivities demonstrate susceptibility. Acknowledgments. The authors thank Dr Eileen Tang for her careful input and review of the manuscript. Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.