Activity of Plazomicin (ACHN-490) against MDR clinical isolates of Klebsiella pneumoniae, Escherichia coli, and Enterobacter spp. from Athens, Greece Irene Galani1, Maria Souli 1 , George L. Daikos 2 , Zoi Chrysouli 1 , 1 2 1 Garyphalia Poulakou , Mina Psichogiou , Theofano Panagea , 3 4 5 5 Athina Argyropoulou , Ioanna Stefanou , George Plakias , Helen Giamarellou , George Petrikkos1 14th Department of Internal Medicine, Molecular Biology Section, Athens University School of Medicine, Greece, 2First Department of Propaedeutic Medicine, University of Athens, Greece, 3Laboratory of Microbiology, Evaggelismos Athens General Hospital, Greece, 4Department of Microbiology, Laikon General Hospital, Greece, 56th Department of Internal Medicine, Diagnostic and Therapeutic Center of Athens ‘Hygeia’, Greece The in vitro activity of plazomicin was evaluated against 300 multidrug resistant (MDR) (carbapenemase and/or ESBL-producing) isolates from four hospitals in Athens, an area where carbapenemase-producing organisms are endemic. Most of the isolates were also resistant to the legacy aminoglycosides with the MIC50/MIC90 to tobramycin, amikacin and gentamicin being 32/.32, 32/.32 and 4/.8 mg/ml, respectively. ACHN-490 retained activity (MICs(4 mg/ml) against all isolates of Klebsiella pneumoniae, Escherichia coli, and Enterobacter spp. tested with MIC50 and MIC90 of 1 and 2 mg/ml, respectively, irrespective of their MDR phenotype and it represents a promising alternative for the treatment of the most problematic Gram-negative pathogens. Keywords: Aminoglycosides, Multidrug resistant, VIM, KPC Introduction Bacterial resistance is an increasing threat to the successful treatment of both community- and hospi- tal-acquired infections (http://www.earss.rivm.nl) and antimicrobials potent against multidrug resistant (MDR) pathogens are urgently needed. Plazomicin (formerly ACHN-490) (Achaogen, South San Francisco, CA, USA) is a next-generation aminoglycoside, currently in early clinical develop- ment (FDA, http://clinicaltrials.gov/), with enhanced activity against many MDR Gram-negative bacteria and Staphylococcus aureus including methicillin resistant S. aureus isolates (MRSA) (MIC90, 2 mg/ ml).1 Plazomicin is not affected by any of known aminoglycoside-modifying enzymes, except AAC(29)- Ia, -Ib and -Ic (only found in Providencia spp), it retains the favourable bactericidal properties of the aminoglycoside class and has demonstrated potent in vivo efﬁcacy in two animal infection models.2 Methylation of 16S ribosomal RNA (rRNA) confers Correspondence to: I. Galani, 4th Department of Internal Medicine, University General Hospital ‘Attikon’, Rimini 1, 124 62 Chaidari, Greece. Email: egalani@med.uoa.gr MICs of .8 mg/ml for plazomicin, as well as high-level resistance to all parenterally administered aminoglycosides that are currently in clinical use.3,4 The compound is currently under development for the treatment of complicated urinary tract infections and acute pyelonephritis as a single agent. After intravenous administration of plazomicin to humans at a dose of 15 mg/kg, the maximum concentraration was 113 mg/ml, the area under the curve (0–24) was 239 hours mg/ml, the half-life was 3.0 hours and the steady-state volume of distribution was 0.24 l/kg.5 Human phase I and II studies to date have not reported nephrotoxicity or ototoxicity, and lack of ototoxicity has been reported in the guinea pig model.5 In the present work, we analyzed the in vitro activity of plazomicin against a collection of 300 MDR clinical isolates of Klebsiella pneumoniae, Escherichia coli, and Enterobacter spp. recently collected at four tertiary-care Hospitals in Athens, Greece, the University General Hospital Attikon, the Laikon and Evaggelismos General Hospitals, and the private Hospital Hygeia. 2012 Edizioni Scientifiche per l’Informazione su Farmaci e Terapia MORE OpenChoice articles are open access and distributed under the terms of the Creative Commons Attribution License 3.0 DOI 10.1179/1973947812Y.0000000015 Journal of Chemotherapy 2012 VOL. 24 NO. 4 191