First, as stated previously, healthcare exposure is commonly seen in these cases; thus, multidrug resistance often characterizes these pathogens. Second, therapy may include agents with increased toxicity risks such as aminogly- cosides (given in high dosages) and colistin. Third, because regimens that include >1 agent are often selected for use, the risks of drug-drug interactions and increased drug-related adverse events are problematic. Fourth, mortality is high in these infections, and medical-surgical approaches are often required for optimal management and favorable outcomes. Combination antibiotic therapy with a -lactam (penicillins, cephalosporins, or carbapenems) and either an aminoglycoside or fluoroquinolone for 6 weeks is reasonable.221 Consultation with an infectious diseases expert in IE should be sought because of the various mechanisms of antibiotic resistance that can be found in the non-HACEK Gram-negative aerobic bacilli. For example, several of these bacteria may harbor inducible -lactamases that could require supplemental laboratory screening, in addition to routine in vitro susceptibility testing. Medical therapy may be successful in right-sided P aerugi- nosa IE in 50% to 75% of cases. If the disease is refractory to anti- biotics, then partial tricuspid valvulectomy or vegetectomy 223 without valve replacement is indicated.224 Typically, these patients have been IDUs, and because of their high recidivism risk, avoid- ance of placement of prosthetic valves is desirable. Recommendations 1. Cardiac surgery is reasonable in combination with prolonged courses of combined antibiotic therapy for most patients with IE caused by non-HACEK Gram-negative aerobic bacilli, particularly P aeru- ginosa (Class IIb; Level of Evidence B). Table 16. 