**2. Global resistance and global economic impact**

The preantibiotic era is a reality for many parts around the world, especially among the developed countries, driven in part by antibiotic overuse and misuse. Increasing antibiotic resistance is a global threat to patients worldwide and an economic burden. According to the U.S. Centers for Disease Control and Prevention (CDC), each year in the United States, drug-resistant bacteria cause approximately 2 million cases of illnesses and contribute to 23,000 deaths. A key driver has been the inappropriate use of antibiotics, which as an avoidable cost and burden to healthcare dollars, ranges from \$27 billion to 42 billion annually [1, 2]. The Infectious Diseases Society of America (IDSA) white paper entitled "Bad Bugs, No Drugs" commented on the declining research investments in antimicrobial development, as did an update on this article from clinical infectious disease (CID) in 2009 [3]. These papers identified certain Gram-negative bacteria that are particularly problematic pathogens, which tend to "escape" the activity of many antibiotics. These problematic pathogens are known as, the "ESKAPE" pathogens, which include: *Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species* and can *Clostridium difficile* is also include to the list. In addition to the "ESKAPE" pathogens, the prevalence of *C. difficile* infection (CDI) has risen dramatically in just the last 2 decades. Since 2001, surveillance data has shown a dramatic increase. The number of CDI cases (any diagnosis) per 10,000 hospital discharges increased from 25.0 to 40.0, a 60% increase. However, over the next 4 years (2001–2005), a 92% increase was observed (from 40.0 to 76.9) [3–5]. The CDC has placed these resistant pathogens into three categories: urgent, serious, and concerning threat levels. Several recent efforts have attempted to raise awareness and focus attention on antibiotic overuse in healthcare including: the World Health Organization, the CDC, and White House. The White House issued executive order 13,676: combating antibiotic-resistant bacteria, which is a roadmap to guide the nation that was issued by President Obama on September 18, 2014. This executive order will implement the *National Action Plan for Combating Antibiotic-Resistant Bacteria*, a plan that intends to have major reductions in the occurrence of urgent and serious threating pathogens, including methicillin-resistant *S. aureus* (MRSA), carbapenemresistant *Enterobacteriaceae* (CRE), and *C. difficile* [6]. Recent studies have demonstrated that critically ill patients colonized with multidrug-resistant pathogens also have a high prevalence of being infected with that particular organism. In such, antimicrobial resistance (AMR) as an independent risk factor also increases morbidity and mortality [7, 8].
