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Dr. Mui reports no financial relationships relevant to this field of study.
Plazomicin is a next-generation aminoglycoside with potent in-vitro activity against Gram-negative aerobic organisms, including extended spectrum beta-lactamase (ESBL) and carbapenemase-producing Enterobacteriaceae and in-vitro activity against some Gram-positive organisms. On June 26, the Food and Drug Administration (FDA) approved plazomicin for treating complicated urinary tract infections, including pyelonephritis. In a Phase III trial, researchers compared plazomicin to meropenem (with the option to switch to oral levofloxacin) for the primary composite cure endpoint of microbiologic eradication and clinical cure at the end of therapy. In the non-inferiority trial, plazomicin achieved higher microbiological eradication at the test-of-cure visit.1,2
In a Phase III, open-label study consisting of a randomized, open-label cohort and a separate single-arm, observational cohort, investigators examined the efficacy and safety of plazomicin plus meropenem or tigecycline compared to colistin plus meropenem or tigecycline in patients who had serious infections caused by carbapenem-resistant Enterobacteriaceae (CREs), the primary endpoint of all-cause mortality and significant disease-related complications favored patients treated with plazomicin compared to colistin (23.5% vs. 50%; -26.5 (-51.2, 0.7). The secondary endpoint of all-cause mortality at day 28 was lower for the plazomicin group compared to colistin (11.8% vs. 40%; -28.2 (-52.5, -0.07).3,4
MICROBIOLOGY
Plazomicin exhibited in vitro activity that was more potent against most Gram-negative and Gram-positive pathogens than amikacin, gentamicin, and tobramycin. The FDA susceptibility breakpoint for plazomicin against Enterobacteriaceae is ≤ 2 mcg/mL, with isolates with an MIC of 4 mcg/mL considered intermediate and ≥ 8 mcg/mL considered resistant. Plazomicin’s MIC50 and MIC90 values are comparable or lower than comparator aminoglycosides against Escherichia coli, Klebsiella pneumoniae, Citrobacter spp., Enterobacter spp., and Serratia spp. (MIC90 values in the range of 0.5-2 mcg/mL). Plazomicin is less active against Proteus mirabilis and indole-positive Proteus spp. (MIC90 values of 4-8 mcg/mL).5-14
Plazomicin has less activity against nonfermentative bacteria (MIC90 values of 16-32 mcg/mL for Pseudo-monas aeruginosa and 16 mcg/mL for Acinetobacter spp.)...