For most of the last two decades gram positive infections have been the focus of attention concerning antibiotic resistance. More recently gram negative resistance has begun to outpace the pipeline of antibiotic development.
In serious infections multiple studies    have demonstrated the effect on survival of including the causative pathogen in the initial (“empiric”) antibiotic selection. This generally means very broad initial coverage with two or more agents. For gram positives, vancomycin coverage has become knee jerk. Decision making for gram negative coverage is now more complex. The clinician must take into account changing trends in resistance mechanisms, a wide variety of antibiotics and local resistance patterns.
This review outlines newly emerging resistance threats. Extended spectrum beta lactamases (ESBLs) and carbapenemases along with other resistance mechanisms may result in resistance to all commonly prescribed antibiotics, necessitating consideration of alternatives such as tygecycline or the older and largely abandoned class of polymyxin antibiotics. (More information on the polymyxins can be found here).
ESBLs concentrate in the periplasmic space of gram negative bacilli and consequently may overwhelm the beta lactamase inhibitors present in two currently available antibiotic combinations. For this reason, and because ESBLs inactivate late generation cephalosporins, carbapenems are increasingly included in initial therapy. A carbapenem review is referenced here. Additional posts from last year with recent literature citations can be found here and here.