Journal
BMC INFECTIOUS DISEASES
Volume 19, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s12879-019-3801-1
Keywords
Plazomicin; K; pneumoniae; Carbapenemase; Greece
Categories
Funding
- ACHAOGEN INC. (South San Francisco, CA, USA)
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BackgroundTo evaluate the in vitro activities of plazomicin and comparator aminoglycosides and elucidate the underlying aminoglycoside resistance mechanisms among carbapenemase-producing K. pneumoniae isolates collected during a nationwide surveillance study in Greek hospitals.MethodsThree hundred single-patient carbapenemase-producing K. pneumoniae isolates were studied, including 200 KPC-, 50 NDM-, 21 VIM-, 14 KPC & VIM-, 12 OXA-48-, two NDM & OXA- and one KPC & OXA-producing isolates. Susceptibility testing was performed by broth microdilution, and minimum inhibitory concentrations (MICs) interpreted per EUCAST breakpoints. Carbapenemase-, aminoglycoside modifying enzyme- and 16S rRNA methylase- encoding genes were detected by PCR.ResultsOf 300 isolates tested, 5.7% were pandrug resistant and 29.3% extensively drug resistant. Plazomicin inhibited 87.0% of the isolates at 2mg/L, with MIC50/MIC90 of 0.5/4mg/L. Apramycin (a veterinary aminoglycoside) inhibited 86.7% of the isolates at 8mg/L and was the second most active drug after plazomicin, followed by gentamicin (S, 43%; MIC50/MIC90, 4/>256) and amikacin (S, 18.0%; MIC50/MIC90, 32/128). Twenty-three (7.7%) isolates (16 KPC-, 6 VIM- and one KPC & OXA-48-producers) exhibited MICs 64mg/L for plazomicin, and harbored rmtB (n=22) or armA (n=1). AAC(6)-b was the most common aminoglycoside modifying enzyme (84.7%), followed by AAC(3?)-IIa (25.3%), while those two enzymes were co-produced by 21.4% of the isolates.ConclusionsPlazomicin retains activity against most carbapenemase-producing K. pneumoniae isolated from Greek hospitals, with MICs consistently lower than those of the other aminoglycosides, even in the presence of aminoglycoside modifying enzymes. Dissemination of 16S- rRNA methylases in 8% of the isolates is an unwelcome event that needs strict infection control measures and rigorous stewardship interventions.
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