Nationwide epidemiology of carbapenem resistant Klebsiella pneumoniae isolates from Greek hospitals, with regards to plazomicin and aminoglycoside resistance.
Irene Galani,Konstantina Nafplioti,Panagiota Adamou,Ilias Karaiskos,Helen Giamarellou,Maria Souli +5 more
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Plazomicin retains activity against most carbapenemase-producing K. pneumoniae isolated from Greek hospitals, with minimum inhibitory concentrations consistently lower than those of the other aminoglycosides, even in the presence of am inoglycoside modifying enzymes.Abstract:
To 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. Three 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. Of 300 isolates tested, 5.7% were pandrug resistant and 29.3% extensively drug resistant. Plazomicin inhibited 87.0% of the isolates at ≤2 mg/L, with MIC50/MIC90 of 0.5/4 mg/L. Apramycin (a veterinary aminoglycoside) inhibited 86.7% of the isolates at ≤8 mg/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 ≥64 mg/L for plazomicin, and harbored rmtB (n = 22) or armA (n = 1). AAC(6′)-Іb 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. Plazomicin 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.read more
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Epidemiology of β-Lactamase-Producing Pathogens.
Karen Bush,Patricia A. Bradford +1 more
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TL;DR: There is a continued need for innovation and new-class antibacterial agents in order to provide effective therapeutic options against infections specifically caused by XDR and PDR Gram-negative bacteria.
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Plazomicin: A Next-Generation Aminoglycoside
Kristy M. Shaeer,Monika T Zmarlicka,Elias B. Chahine,Nicholas Piccicacco,Nicholas Piccicacco,Jonathan C. Cho +5 more
TL;DR: Despite limited efficacy and safety data, plazomicin is indicated for the treatment of cUTIs in adults with limited or no alternative treatment options, using a dosage regimen of 15 mg/kg intravenously every 24 hours for 4–7 days.
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Treatment of Carbapenem-Resistant Enterobacteriaceae Infections in Children.
TL;DR: A framework for antibiotic treatment of CRE infections in children is provided, highlighting relevant microbiologic considerations and summarizing available data related to the evaluation of FDA-approved antibiotics (as of September 2019) with CRE activity, including carbapenems, ceftazidime-avibactam, meropenem-vaborbactam and plazomicin.
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