Continuing the Fight Against Gram-Negative Infections: Help for Existing Carbapenems—Part 2

Extending the Life of Existing Carbapenems

Another prong in the battle against resistant Gram-negative infections is the addition of beta-lactamase inhibitors (BLIs) to restore or improve the activity of older carbapenems. Anne-Catrin Uhlemann, MD, PhD, reported that the addition of relebactam restored imipenem activity in 88% of CRE isolates, with susceptibility rates of 86.5% among Klebsiella pneumoniae isolates and 91% among Enterobacter spp. Isolates, both having MIC₉₀ values of 0.25 mg/mL.¹⁶ Likewise, Yunliang Zhang, PhD, reported that the addition of relebactam reduced the MIC₉₀ for imipenem by ≥32-fold among carbapenemase-producing carbapenem-resistant Enterobacteriaceae isolates recently collected from health care centers in central Indiana.¹⁷

The SMART surveillance program, which collected more than 5600 Enterobacteriaceae and 1400 Pseudomonas isolates from both ICU and non-ICU wards in 2015 through 2016, reported that, among imipenem-non-susceptible isolates, the addition of relebactam dropped the modal MIC for imipenem from 2 μg/mL to .5 μg/mL or less for Enterobacteriaceae and the MIC₉₀ for imipenem from 16 μg/mL to 2 μg/mL for Pseudomonas aeruginosa.^18,19 Susceptibility rates among the imipenem-non-susceptible isolates were restored to being susceptible in about 75% for Enterobacteriaceae and 80% for Pseudomonas aeruginosa. In Latin America, the SMART surveillance program found that relebactam restored imipenem susceptibility rates to 80.4% against Enterobacteriaceae isolates that were non-susceptible to imipenem, resulting in an overall susceptibility rate of 98.6% for all Enterobacteriaceae isolates.²⁰ The addition of relebactam dropped the MIC₉₀ for imipenem from 32 μg/mL to 4 μg/mL for imipenem-non-susceptible Pseudomonas aeruginosa isolates. The addition of relebactam restored 59.6% of imipenem non-susceptible isolates to being susceptible and an overall susceptibility rate of 85.3% for all Pseudomonas aeruginosa isolates.²⁰

Presentations at ASM Microbe also focused on vaborbactam in combination with meropenem. Mariana Castanheira, PhD, reported that the addition of vaborbactam dropped the MIC₉₀ for meropenem from more than 32 μg/mL to 1 μg/mL against carbapenemase-producing Enterobacteriaceae and KPC-producing Enterobacteriaceae.²¹

Contagion