Abstract
Background
Plazomicin (PLZ) approved by FDA in June of 2018, is an aminoglycoside class antibacterial indicated for the treatment of adults with complicated urinary tract infections (cUTI) including pyelonephritis caused by Enterobacterales. It is used in patients who have limited or no alternative treatment options, e.g. CRE and MDRO patients. The drug has bactericidal activity, it is active against organisms producing ESBL, Carbapenemase and aminoglycoside-modifying enzymes. The purpose of this study was to compare ETEST® PLZ bioMérieux to the broth microdilution reference method (BMD) for Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca and pneumoniae, Morganella morganii, Providencia stuartii, Proteus mirabilis and vulgaris and Serratia marcescens isolates.
Methods
A total of 598 isolates were tested by ETEST® (PLZ) and BMD at four clinical trial sites.
Isolates were subcultured on tryptic soy or Columbia agar plates supplemented with 5% sheep blood. Suspensions of the isolates were prepared in 0.85% saline, which were used to inoculate BMD and Mueller Hinton agar for ETEST®. Results were read after 16-20 hours incubation at 35°C +2°C in ambient air. QC organisms were tested with each run following CLSI QC guidelines.
Results were analyzed using FDA breakpoints for PLZ (Susceptible <2 µg/mL, Intermediate 4 µg/mL, Resistant >8 µg/mL).
Performance was evaluated using FDA performance criteria, EA and CA (≥ 90%), major error rate (≤3.0%) and very major error rate (≤2.0%).
Results
Table 1.
Table 1. Performance for Plazomicin ETEST® PLZ for Enterobacterales
| EA | CA | Very Major Error Rate | Major Error Rate | Minor Error Rate |
| 99.0% (592/598) | 92.8% (555/598) | 1.9%(1/53) | 0.0%(0/478) | 7.0% (42/598) |
Table 2.
MIC distribution BMD and ETEST® PLZ (mode MIC in bold)
| MIC/Interp µg/ml | ≤0.016S | 0.032S | 0.064S | 0.125S | 0.25S | 0.5S | 1S | 2S | 4I | 8R | 1R | 32R | 64R | 128R | ≥256R |
| BMD | 0 | 0 | 0 | 5 | 122 | 172 | 98 | 81 | 67 | 15 | 7 | 1 | 0 | 1 | 29 |
| ETEST® PLZ | 0 | 0 | 0 | 5 | 59 | 232 | 93 | 94 | 65 | 11 | 7 | 3 | 0 | 0 | 30 |
Conclusion
ETEST® PLZ clinical performance met the FDA acceptance criteria and was found useful for determining Plazomicin MIC of Enterobacterales, including ESBL, CRE (MBL, KPC, Oxa-48), high level AmpC and aminoglycoside resistant strains. Percent susceptibility of Plazomicin is at 80% among the 598 isolates tested, the mode MIC is 0.5 ug/ml as Susceptible.
Disclosures
Tom Armstrong, BS, bioMérieux (Employee) Laurine Blanchard, PhD, bioMérieux (Employee) Michael Kresken, PhD, bioMérieux (Scientific Research Study Investigator, Research Grant or Support) Gilles Zambardi, biomerieux (Employee) Marion Pompilio, BioMérieux (Employee)