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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

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