Recommendations

Data suggest that appropriate monotherapy is sufficient for the treatment of most Gram-negative infections.

The use of 2 agents to treat proven or suspected Gram-negative infections should be limited to the following situations:

• Empiric treatment of serious infections manifested by sepsis, including hypotension, pressor dependence, or mechanical ventilation (to broaden spectrum) until cultures return.

• Documented infection with a resistant Gram-negative organism (particularly Pseudomonas, Acinetobacter, Citrobacter, Enterobacter, and Serratia when antibiotic penetration to the site of infection is poor (pneumonia, osteomyelitis). Consideration should be given to stopping one of the agents after 5-7 days of therapy when the bacterial burden has decreased. Infectious Diseases consultation is highly recommended in such cases

The second agent should be from a different antimicrobial class if possible. Options include fluoroquinolone or aminoglycoside (depending on patient allergy/renal function, drug interactions etc.)

Double beta-lactam combinations (e.g. piperacillin/tazobactam + meropenem) should be avoided.