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Epidemiology and Surveillance

In Vitro Activity of Plazomicin against Gram-Negative and Gram-Positive Isolates Collected from U.S. Hospitals and Comparative Activities of Aminoglycosides against Carbapenem-Resistant Enterobacteriaceae and Isolates Carrying Carbapenemase Genes

Mariana Castanheira, Andrew P. Davis, Rodrigo E. Mendes, Alisa W. Serio, Kevin M. Krause, Robert K. Flamm
Mariana Castanheira
aJMI Laboratories, North Liberty, Iowa, USA
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Andrew P. Davis
aJMI Laboratories, North Liberty, Iowa, USA
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Rodrigo E. Mendes
aJMI Laboratories, North Liberty, Iowa, USA
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Alisa W. Serio
bAchaogen, South San Francisco, California, USA
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Kevin M. Krause
bAchaogen, South San Francisco, California, USA
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Robert K. Flamm
aJMI Laboratories, North Liberty, Iowa, USA
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DOI: 10.1128/AAC.00313-18
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Tables

  • TABLE 1

    Antimicrobial activity of plazomicin tested against 4,825 clinical isolates collected in 70 U.S. hospitals during 2014 to 2015

    Organism or group (no. of isolates)aNo. (cumulative %) of isolates at MIC (μg/ml) of:MIC50 (μg/ml)MIC90 (μg/ml)
    ≤0.060.120.250.51248163264128>128
    Enterobacteriaceae (4,362)25 (0.6)308 (7.6)971 (29.9)1,764 (70.3)822 (89.2)317 (96.4)121 (99.2)13 (99.5)11 (99.8)2 (99.8)3 (99.9)1 (99.9)4 (100.0)0.52
        Klebsiella pneumoniae (1,506)18 (1.2)246 (17.5)621 (58.8)580 (97.3)34 (99.5)4 (99.8)1 (99.9)0 (99.9)0 (99.9)0 (99.9)0 (99.9)1 (99.9)1 (100.0)0.250.5
        Escherichia coli (1,346)1 (0.1)6 (0.5)75 (6.1)641 (53.7)534 (93.4)81 (99.4)6 (99.9)0 (99.9)0 (99.9)0 (99.9)0 (99.9)0 (99.9)2 (100.0)0.51
        Klebsiella oxytoca (359)2 (0.6)17 (5.3)92 (30.9)214 (90.5)27 (98.1)4 (99.2)1 (99.4)0 (99.4)0 (99.4)0 (99.4)1 (99.7)0 (99.7)1 (100.0)0.50.5
        Enterobacter cloacae species complex (104)0 (0.0)14 (13.5)30 (42.3)51 (91.3)8 (99.0)1 (100.0)0.50.5
        Enterobacter aerogenes (120)2 (1.7)6 (6.7)41 (40.8)53 (85.0)16 (98.3)1 (99.2)1 (100.0)0.51
        Serratia marcescens (107)0 (0.0)1 (0.9)5 (5.6)37 (40.2)52 (88.8)9 (97.2)3 (100.0)12
        Citrobacter freundii species complex (159)0 (0.0)5 (3.1)42 (29.6)91 (86.8)18 (98.1)2 (99.4)1 (100.0)0.51
        Citrobacter koseri (145)2 (1.4)12 (9.7)63 (53.1)58 (93.1)6 (97.2)3 (99.3)1 (100.0)0.250.5
        Morganella morganii (118)0 (0.0)7 (5.9)31 (32.2)38 (64.4)31 (90.7)6 (95.8)2 (97.5)2 (99.2)1 (100.0)24
        Providencia spp. (158)0 (0.0)1 (0.6)0 (0.6)18 (12.0)27 (29.1)54 (63.3)44 (91.1)5 (94.3)8 (99.4)0 (99.4)1 (100.0)24
        Proteus mirabilis (124)0 (0.0)2 (1.6)5 (5.6)23 (24.2)72 (82.3)20 (98.4)2 (100.0)24
        Proteus vulgaris group (116)0 (0.0)9 (7.8)46 (47.4)48 (88.8)12 (99.1)0 (99.1)1 (100.0)24
    Pseudomonas aeruginosa (103)0 (0.0)1 (1.0)3 (3.9)1 (4.9)3 (7.8)17 (24.3)49 (71.8)17 (88.3)7 (95.1)4 (99.0)0 (99.0)0 (99.0)1 (100.0)416
    Acinetobacter spp. (95)1 (1.1)0 (1.1)7 (8.4)14 (23.2)17 (41.1)25 (67.4)7 (74.7)11 (86.3)4 (90.5)4 (94.7)1 (95.8)0 (95.8)4 (100.0)216
    Coagulase-negative staphylococci (72)17 (23.6)21 (52.8)26 (88.9)8 (100.0)0.120.5
    Staphylococcus aureus (69)0 (0.0)14 (20.3)51 (94.2)2 (97.1)2 (100.0)0.50.5
        MRSA (30)0 (0.0)9 (30.0)18 (90.0)2 (96.7)1 (100.0)0.50.5
    Streptococcus pneumoniae (66)0 (0.0)4 (6.1)32 (54.5)30 (100.0)3264
    Enterococcus spp. (58)0 (0.0)1 (1.7)8 (15.5)7 (27.6)9 (43.1)5 (51.7)8 (65.5)16 (93.1)4 (100.0)1664
    • ↵a MRSA, methicillin-resistant S. aureus.

  • TABLE 2

    Activities of plazomicin and comparator agents tested against Enterobacteriaceae isolates

    Organism group (no. of isolates tested) and antimicrobial agentMIC50 (μg/ml)MIC90 (μg/ml)MIC range (μg/ml)% S using CLSI breakpointsa% S using EUCAST breakpointsa
    Enterobacteriaceae (4,362)
        Plazomicin0.52≤0.06–>128
        Amikacin14≤0.25–>3298.998.0
        Gentamicin0.54≤0.06–>890.389.2
        Tobramycin0.54≤0.12–>890.387.1
        Ceftazidime0.1216≤0.015–>3287.985.4
        Meropenem0.030.06≤0.015–>3297.697.9
        Piperacillin-tazobactam216≤0.5–>6492.089.2
        Colistin≤0.5>8≤0.5–>884.0
        Tigecycline0.251≤0.06–499.0b95.7
        Levofloxacin≤0.12>4≤0.12–>482.979.5
    CRE (97)
        Plazomicin0.51≤0.06–>128
        Amikacin16320.5–>3264.946.4
        Gentamicin2>80.12–>856.750.5
        Tobramycin>8>80.12–>813.411.3
        Ceftazidime>32>3216–>320.00.0
        Meropenem16>321–>322.17.2
        Piperacillin-tazobactam>64>6432–>640.00.0
        Colistin≤0.5>8≤0.5–>878.1
        Tigecycline0.510.12–2100.0b94.8
        Levofloxacin>4>4≤0.12–>418.611.3
    Isolates carrying blaKPC genes (87)
        Plazomicin0.251≤0.06–>128
        Amikacin16320.5–>3263.242.5
        Gentamicin4>80.12–>855.248.3
        Tobramycin>8>80.12–>811.59.2
        Ceftazidime>32>324–>321.10.0
        Meropenem16>320.5–>323.410.3
        Piperacillin-tazobactam>64>6464–>640.00.0
        Colistin≤0.5>8≤0.5–>878.2
        Tigecycline0.510.12–2100.0b96.6
        Levofloxacin>4>4≤0.12–>414.99.2
    Carbapenemase-negative isolates (26)
        Plazomicin0.510.12–2
        Amikacin4160.5–3292.384.6
        Gentamicin1>80.25–>869.269.2
        Tobramycin2>80.25–>857.750.0
        Ceftazidime>32>320.25–>3219.215.4
        Meropenem2320.03–3223.153.8
        Piperacillin-tazobactam>64>641–>6419.215.4
        Colistin≤0.5>8≤0.5–>875.0
        Tigecycline0.520.06–2100.088.5
        Levofloxacin2>4≤0.12–>450.034.6
    • ↵a Criteria reported by the CLSI (14) and EUCAST (15). S, susceptible.

    • ↵b Breakpoints from the FDA website (16).

  • TABLE 3

    Activities of plazomicin and comparator aminoglycosides against phenotypes and genotypes of Enterobacteriaceae isolates and other Gram-negative species

    Organism phenotype or genotypeSource of breakpoint criteria for aminoglycoside resistance (no. of isolates)a% of isolates inhibited by plazomicin at ≤4 μg/mlMIC50/MIC90 (μg/ml)
    PlazomicinAmikacinGentamicinTobramycin
    EnterobacteriaceaeNA (4,362)99.20.5/21/40.5/40.5/4
        Amikacin resistantCLSI (14)64.31/>128>32/>32>8/>8>8/>8
    EUCAST (50)90.00.5/432/>322/>8>8/>8
        Gentamicin resistantCLSI (377)96.60.5/22/8>8/>8>8/>8
    EUCAST (424)95.50.5/22/8>8/>8>8/>8
        Tobramycin resistantCLSI (292)96.90.5/24/32>8/>8>8/>8
    EUCAST (423)96.50.5/24/32>8/>8>8/>8
        CRENA (97)99.00.5/116/322/>8>8/>8
            CPE (all carrying blaKPC)NA (87)98.90.25/116/324/>8>8/>8
            Carbapenemase negativeNA (26)100.00.5/14/161/>82/>8
    Pseudomonas aeruginosaNA (103)71.84/162/82/80.5/1
    Acinetobacter baumanniiNA (99)65.22/324/>321/>81/>8
    • ↵a NA, not applicable.

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In Vitro Activity of Plazomicin against Gram-Negative and Gram-Positive Isolates Collected from U.S. Hospitals and Comparative Activities of Aminoglycosides against Carbapenem-Resistant Enterobacteriaceae and Isolates Carrying Carbapenemase Genes
Mariana Castanheira, Andrew P. Davis, Rodrigo E. Mendes, Alisa W. Serio, Kevin M. Krause, Robert K. Flamm
Antimicrobial Agents and Chemotherapy Jul 2018, 62 (8) e00313-18; DOI: 10.1128/AAC.00313-18

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In Vitro Activity of Plazomicin against Gram-Negative and Gram-Positive Isolates Collected from U.S. Hospitals and Comparative Activities of Aminoglycosides against Carbapenem-Resistant Enterobacteriaceae and Isolates Carrying Carbapenemase Genes
Mariana Castanheira, Andrew P. Davis, Rodrigo E. Mendes, Alisa W. Serio, Kevin M. Krause, Robert K. Flamm
Antimicrobial Agents and Chemotherapy Jul 2018, 62 (8) e00313-18; DOI: 10.1128/AAC.00313-18
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    • ABSTRACT
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KEYWORDS

aminoglycosides
plazomicin
carbapenem-resistant Enterobacteriaceae

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