TABLE 2

Antimicrobial activities of ceftobiprole and comparator agents when tested against bacterial isolates from European medical centers (2005 to 2010)

Organism (no. of isolates tested) and antimicrobial agentMIC% of isolates susceptible/intermediate/resistanta
MIC50MIC90RangeCLSIEUCAST
S. aureus (15,426)
    Ceftobiprole0.51≤0.06–4b/—/—99.5/0.0/0.5
    Oxacillin0.5>2≤0.25–>273.1/0.0/26.973.1/0.0/26.9
    Cefepime2>16≤0.12–>1673.1/0.0/26.973.1/0.0/26.9
    Ceftriaxone4>8≤0.25–>873.1/0.0/26.973.1/0.0/26.9
    Imipenem≤0.128≤0.12–>873.1/0.0/26.973.1/0.0/26.9
    Clindamycin≤0.25>2≤0.25–>288.6/0.1/11.388.1/0.5/11.4
    Erythromycin≤0.25>2≤0.25–>270.5/0.9/28.671.0/0.3/28.7
    Daptomycin0.250.5≤0.06–2>99.9/—/—>99.9/0.0/<0.1
    Gentamicin≤2≤2≤2–>892.5/0.5/7.091.9/0.0/8.1
    Levofloxacin≤0.5>4≤0.5–>471.6/0.6/27.871.6/0.6/27.8
    Linezolid12≤0.12–>8>99.9/0.0/<0.1>99.9/0.0/<0.1
    Tetracycline≤2≤2≤2–>891.7/0.6/7.791.4/0.0/8.6
    Tigecyclinec0.120.25≤0.03–1>99.9/—/—>99.9/0.0/<0.1
    Trimethoprim-sulfamethoxazole≤0.5≤0.5≤0.5–>299.0/0.0/1.099.0/<0.1/1.0
    Vancomycin11≤0.12–2100.0/0.0/0.0100.0/0.0/0.0
Oxacillin-susceptible S. aureus (11,279)
    Ceftobiprole0.250.5≤0.06–2—/—/—100.0/0.0/0.0
    Cefepime24≤0.12–16100.0/0.0/0.0100.0/0.0/0.0
    Ceftriaxone44≤0.25–>8100.0/0.0/0.0100.0/0.0/0.0
    Imipenem≤0.12≤0.12≤0.12–2100.0/0.0/0.0100.0/0.0/0.0
    Clindamycin≤0.25≤0.25≤0.25–>297.5/0.1/2.497.1/0.4/2.5
    Erythromycin≤0.25>2≤0.25–>285.1/0.8/14.185.4/0.4/14.2
    Daptomycin0.250.5≤0.06–1100.0/—/—100.0/0.0/0.0
    Gentamicin≤2≤2≤2–>898.1/0.2/1.797.7/0.0/2.3
    Levofloxacin≤0.5≤0.5≤0.5–>494.1/0.4/5.594.1/0.4/5.5
    Linezolid12≤0.12–2100.0/0.0/0.0100.0/0.0/0.0
    Tetracycline≤2≤2≤2–>894.5/0.4/5.194.2/<0.1/5.8
    Tigecyclinec0.120.25≤0.03–0.5100.0/—/—100.0/0.0/0.0
    Trimethoprim-sulfamethoxazole≤0.5≤0.5≤0.5–>299.6/0.0/0.499.6/<0.1/0.4
    Vancomycin11≤0.12–2100.0/0.0/0.0100.0/0.0/0.0
Oxacillin-resistant S. aureus (4,147)
    Ceftobiprole120.12–4—/—/—98.3/0.0/1.7
    Clindamycin≤0.25>2≤0.25–>264.2/0.2/35.663.6/0.6/35.8
    Erythromycin>2>2≤0.25–>230.9/1.1/68.031.6/0.4/68.0
    Daptomycin0.250.5≤0.06–2>99.9/—/—>99.9/0.0/<0.1
    Gentamicin≤2>8≤2–>877.2/1.4/21.476.2/0.0/23.8
    Levofloxacin>4>4≤0.5–>410.4/1.0/88.610.4/1.0/88.6
    Linezolid120.25–>8>99.9/0.0/<0.1>99.9/0.0/<0.1
    Tetracycline≤2>8≤2–>884.0/1.3/14.783.6/0.1/16.3
    Tigecyclinec0.120.25≤0.03–1>99.9/—/—>99.9/0.0/<0.1
    Trimethoprim-sulfamethoxazole≤0.5≤0.5≤0.5–>297.3/0.0/2.797.3/0.0/2.7
    Vancomycin11≤0.12–2100.0/0.0/0.0100.0/0.0/0.0
Coagulase-negative staphylococci (5,563)d
    Ceftobiprole12≤0.06–8—/—/——/—/—
    Oxacillin>2>2≤0.25–>223.7/0.0/76.323.7/0.0/76.3
    Cefepime4>16≤0.12–>1623.7/0.0/76.323.7/0.0/76.3
    Ceftriaxone>8>8≤0.25–>823.7/0.0/76.323.7/0.0/76.3
    Imipenem0.25>8≤0.12–>823.7/0.0/76.323.7/0.0/76.3
    Clindamycin≤0.25>2≤0.25–>271.6/1.0/27.469.1/2.5/28.4
    Erythromycin>2>2≤0.25–>236.3/0.3/63.436.4/0.2/63.4
    Daptomycin0.250.5≤0.06–499.8/—/—99.8/0.0/0.2
    Gentamicin≤2>8≤2–>858.8/8.2/33.052.2/0.0/47.8
    Levofloxacin4>4≤0.5–>442.3/4.8/52.942.3/4.8/52.9
    Linezolid11≤0.12–>899.8/0.0/0.299.8/0.0/0.2
    Tetracycline≤2>8≤2–>884.4/1.4/14.279.8/1.4/18.8
    Tigecyclinec0.120.25≤0.03–0.5—/—/—100.0/0.0/0.0
    Trimethoprim-sulfamethoxazole≤0.5>2≤0.5–>260.9/0.0/39.160.9/1.8/37.3
    Vancomycin12≤0.12–4100.0/0.0/0.0100.0/0.0/0.0
Enterococcus faecalis (3,968)
    Ceftobiprole0.54≤0.06–>8—/—/——/—/—
    Ampicillin≤12≤1–>1699.6/0.0/0.499.4/0.2/0.4
    Daptomycin11≤0.06–4100.0/—/——/—/—
    Levofloxacin1>4≤0.5–>465.4/0.6/34.0—/—/—
    Linezolid120.12–>899.8/0.1/0.199.8/0.1/0.1
    Tigecyclinec0.120.25≤0.03–199.9/—/—99.9/0.1/<0.1
    Teicoplanin≤2≤2≤2–>899.1/<0.1/0.999.0/0.0/1.0
    Vancomycin120.25–>1698.7/0.1/1.298.7/0.0/1.3
Enterococcus faecium (2,222)
    Ceftobiprole>8>80.12–>8—/—/——/—/—
    Ampicillin>8>8≤1–>87.1/0.0/92.96.4/0.7/92.9
    Daptomycin22≤0.06–4100.0/—/——/—/—
    Levofloxacin>4>4≤0.5–>412.7/4.5/82.8—/—/—
    Linezolid120.25–>899.6/0.2/0.299.8/0.0/0.2
    Tigecyclinec0.060.12≤0.03–0.599.9/0.1/—99.9/0.1/0.0
    Teicoplanin≤2>8≤2–>881.0/1.5/17.579.8/0.0/20.2
    Vancomycin1>16≤0.12–>1675.3/1.5/23.275.3/0.0/24.7
Streptococcus pneumoniae (4,443)
    Ceftobiprole≤0.060.5≤0.06–2—/—/—99.3/0.0/0.7
    Penicilline≤0.032≤0.03–>495.0/4.8/0.2—/—/—
    Penicillinf≤0.032≤0.03–>471.1/12.0/16.971.1/23.9/5.0
    Amoxicillin-clavulanate≤12≤1–>1693.9/3.1/3.0—/—/—
    Cefepime≤0.121≤0.12–1695.7/4.0/0.395.7/4.0/0.3
    Ceftriaxone≤0.251≤0.25–3295.5/4.0/0.583.5/16.0/0.5
    Erythromycin≤0.25>2≤0.25–>269.0/0.4/30.669.0/0.4/30.6
    Clindamycin≤0.25>1≤0.25–>179.1/0.6/20.379.7/0.0/20.3
    Levofloxacin11≤0.5–>498.3/0.2/1.598.3/0.0/1.7
    Linezolid11≤0.12–2100.0/—/—100.0/0.0/0.0
    Tetracycline≤2>8≤2–>874.4/1.2/24.474.4/<0.1/25.6
    Tigecyclinec≤0.030.06≤0.03–191.0/—/——/—/—
    Trimethoprim-sulfamethoxazole≤0.5>2≤0.5–>270.2/11.0/18.877.1/4.1/18.8
    Vancomycin11≤1–1100.0/—/—100.0/0.0/0.0
β-Hemolytic streptococci (2,981)g
    Ceftobiprole≤0.06≤0.06≤0.06–0.25—/—/——/—/—
    Penicillin≤0.030.06≤0.03–0.12100.0/—/—100.0/0.0/0.0
    Cefepime≤0.12≤0.12≤0.12–299.9/—/—100.0/0.0/0.0
    Ceftriaxone≤0.25≤0.25≤0.25–499.9/—/—100.0/0.0/0.0
    Clindamycin≤0.25≤0.25≤0.25–>291.9/0.5/7.692.4/0.0/7.6
    Erythromycin≤0.25>2≤0.25–>282.0/1.0/17.082.0/1.0/17.0
    Daptomycin≤0.060.25≤0.06–0.5100.0/—/—100.0/0.0/0.0
    Levofloxacin≤0.51≤0.5–>499.6/0.0/0.495.6/4.0/0.4
    Linezolid110.25–2100.0/—/—100.0/0.0/0.0
    Tetracycline4>8≤2–>849.5/2.6/47.949.3/0.2/50.5
    Tigecyclinec≤0.030.06≤0.03–0.5>99.9/—/—>99.9/<0.1/0.0
    Trimethoprim-sulfamethoxazole≤0.5≤0.5≤0.5–>2—/—/—99.0/0.4/0.6
    Vancomycin0.250.5≤0.12–1100.0/—/—100.0/0.0/0.0
Viridans group streptococci (1,264)h
    Ceftobiprole≤0.060.25≤0.06–>8—/—/——/—/—
    Penicillin0.061≤0.03–>477.5/17.0/5.584.3/10.2/5.5
    Cefepime≤0.121≤0.12–>1692.1/3.4/4.588.1/0.0/11.9
    Ceftriaxone≤0.251≤0.25–>892.2/3.2/4.688.8/0.0/11.2
    Daptomycin0.250.5≤0.06–299.8/—/——/—/—
    Clindamycin≤0.25>2≤0.25–>288.0/0.3/11.788.3/0.0/11.7
    Erythromycin≤0.25>2≤0.25–>261.6/2.2/36.2—/—/—
    Levofloxacin12≤0.5–>496.8/1.1/2.1—/—/—
    Linezolid11≤0.12–2100.0/—/——/—/—
    Tetracycline≤2>8≤2–>862.2/2.2/35.6—/—/—
    Tigecyclinec≤0.030.06≤0.03–0.599.9/—/——/—/—
    Vancomycin0.51≤0.12–1100.0/—/—100.0/0.0/0.0
Enterobacteriaceae (17,480)i
    Ceftobiprole≤0.06>8≤0.06–>8—/—/—83.4/0.0/16.6
    Ampicillin>8>8≤1–>828.5/3.8/67.728.5/0.0/71.5
    Amoxicillin-clavulanate8>8≤1–>862.6/10.9/26.562.6/0.0/37.4
    Piperacillin-tazobactam232≤0.5–>6488.0/5.9/6.184.3/3.7/12.0
    Cefepime≤0.52≤0.5–>1693.1/1.6/5.388.2/3.5/8.3
    Ceftazidime≤116≤1–>1687.6/1.8/10.683.5/4.1/12.4
    Imipenem0.251≤0.12–>894.4/3.8/1.898.2/1.4/0.4
    Aztreonam≤0.1216≤0.12–>1686.6/2.1/11.383.6/5.1/11.3
    Colistin≤0.5>4≤0.5–>4—/—/—87.3/0.0/12.7
    Amikacin≤4≤4≤4–>3298.5/0.8/0.796.9/1.6/1.5
    Gentamicin≤28≤2–>889.7/0.8/9.588.7/1.0/10.3
    Levofloxacin≤0.5>4≤0.5–>480.9/2.6/16.579.3/1.6/19.1
    Tetracycline≤2>8≤2–>862.0/3.1/34.9—/—/—
    Tigecyclinec0.251≤0.03–>498.7/1.2/0.195.0/3.7/1.3
    Trimethoprim-sulfamethoxazole≤0.5>2≤0.5–>271.9/0.0/28.171.9/22.4/5.7
Acinetobacter spp. (1,146)j
    Ceftobiprole>8>8≤0.06–>8—/—/——/—/—
    Cefepime16>16≤0.12–>1636.5/14.1/49.4—/—/—
    Ceftazidime>16>16≤1–>1629.4/7.5/63.1—/—/—
    Piperacillin-tazobactam>64>64≤0.5–>6434.3/0.0/65.7—/—/—
    Imipenem2>8≤0.12–>853.9/2.6/43.550.7/5.8/43.5
    Aztreonam>16>16≤0.12–>168.2/15.9/75.9—/—/—
    Colistin≤0.51≤0.5–>498.7/0.0/1.398.7/0.0/1.3
    Amikacin>32>32≤4–>3242.7/3.6/53.740.5/2.2/57.3
    Gentamicin>8>8≤2–>835.8/3.2/61.035.8/0.0/64.2
    Levofloxacin>4>4≤0.5–>431.8/8.7/59.529.8/2.0/68.2
    Tetracycline>8>8≤2–>838.6/6.1/55.3—/—/—
    Trimethoprim-sulfamethoxazole>2>2≤0.5–>237.0/0.0/63.037.0/53.7/9.3
Pseudomonas aeruginosa (3,434)
    Ceftobiprole2>8≤0.06–>8—/—/—64.6k/—/35.4
    Cefepime416≤0.12–>1678.6/11.7/9.778.6/0.0/21.4
    Ceftazidime2>16≤1–>1675.4/5.2/19.475.4/0.0/24.6
    Piperacillin-tazobactam8>64≤0.5–>6472.4/11.1/16.572.4/0.0/27.6
    Imipenem2>8≤0.12–>870.2/4.8/25.075.0/7.8/17.2
    Aztreonam8>16≤0.12–>1666.6/13.7/19.73.4/76.9/19.7
    Colistin12≤0.5–>499.5/0.3/0.299.5/0.0/0.5
    Amikacin≤416≤4–>3291.2/3.3/5.586.2/5.0/8.8
    Gentamicin≤2>8≤2–>878.8/3.1/18.178.8/0.0/21.2
    Levofloxacin≤0.5>4≤0.5–>469.2/5.7/25.162.0/7.2/30.8
  • a Criteria as published by the CLSI (2013) (16) and EUCAST (2013) (17) and the EUCAST breakpoints recently established for ceftobiprole for S. aureus (susceptible, ≤2 μg/ml; resistant, >2 μg/ml), S. pneumoniae (susceptible, ≤0.5 μg/ml; resistant, >0.5 μg/ml), and Enterobacteriaceae (susceptible, ≤0.25 μg/ml; resistant, >0.25 μg/ml) and non-species-specific breakpoints (susceptible, ≤4 μg/ml; resistant, >4 μg/ml) (18).

  • b —, no breakpoint has been established.

  • c U.S. FDA breakpoints (26) were applied as CLSI criteria.

  • d Includes S. auricularis (16 strains), S. capitis (201 strains), S. caprae (six strains), S. carnosus (one strain), S. chromogenes (four strains), S. cohnii (12 strains), S. epidermidis (2,673 strains), S. haemolyticus (467 strains), S. hominis (492 strains), S. intermedius (six strains), S. lentus (three strains), S. lugdunensis (92 strains), S. saprophyticus (67 strains), S. schleiferi (nine strains), S. sciuri (12 strains), S. simulans (25 strains), S. succinus (one strain), S. warneri (115 strains), S. xylosus (79 strains), Staphylococcus of undetermined species (two strains), and coagulase-negative staphylococci of undetermined species (1,280 strains).

  • e Criteria as published by the CLSI (2013) (16) for “penicillin parenteral (nonmeningitis).”

  • f Criteria as published by the CLSI (2013) (16) for “penicillin (oral penicillin V).”

  • g Includes S. dysgalactiae (126 strains), S. equi (three strains), S. equisimilis (13 strains), S. pyogenes (1,170 strains), S. agalactiae (1,227 strains), group C Streptococcus (108 strains), group F Streptococcus (nine strains), group G Streptococcus (320 strains), and beta-hemolytic streptococci of undetermined species (five strains).

  • h Includes S. acidominimus (four strains), S. alactolyticus (one strain), S. anginosus (155 strains), S. anginosus group (57 strains), S. bovis group (103 strains), S. canis (one strain), S. constellatus (53 strains), S. equinus (eight strains), S. gallolyticus (22 strains), S. gordonii (12 strains), S. infantis (one strain), S. intermedius (27 strains), S. mitis group (218 strains), S. mutans (nine strains), S. oralis (134 strains), S. parasanguinis (39 strains), S. porcinus (one strain), S. salivarius (75 strains), S. sanguinis (75 strains), S. sobrinus (one strain), S. thermophilus (two strains), S. uberis (three strains), S. vestibularis (17 strains), Streptococcus of undetermined species (19 strains), alpha-hemolytic streptococci of undetermined species (19 strains), and viridans group streptococci of undetermined species (208 strains).

  • i Includes Citrobacter amalonaticus (three strains), C. braakii (11 strains), C. farmeri (two strains), C. freundii (236 strains), C. koseri (144 strains), C. sedlakii (one strain), C. youngae (one strain), Enterobacter aerogenes (384 strains), E. amnigenus (nine strains), E. asburiae (five strains), E. cancerogenus (three strains), E. cloacae (1,385 strains), E. gergoviae (one strain), E. hormaechei (two strains), E. intermedius (one strain), E. sakazakii (six strains), E. taylorae (one strain), Escherichia coli (9,609 strains), E. vulneris (one strain), Hafnia alvei (31 strains), Klebsiella ornithinolytica (nine strains), K. oxytoca (743 strains), K. ozaenae (seven strains), K. planticola (one strain), K. pneumoniae (2,625 strains), K. terrigena (two strains), Leclercia adecarboxylata (one strain), Morganella morganii (284 strains), Pantoea agglomerans (12 strains), Proteus mirabilis (733 strains), P. penneri (two strains), P. vulgaris (93 strains), Providencia alcalifaciens (1 strain), P. rettgeri (16 strains), P. stuartii (35 strains), Rahnella aquatilis (one strain), Raoultella ornithinolytica (two strains), R. planticola (one strain), Salmonella spp. (152 strains), Serratia fonticola (three strains), S. liquefaciens (31 strains), S. marcescens (637 strains), S. odorifera (four strains), S. plymuthica (six strains), S. rubidaea (one strain), Shigella sonnei (two strains), Yersinia enterocolitica (four strains), Citrobacter of undetermined species (16 strains), Enterobacter of undetermined species (112 strains), Escherichia of undetermined species (4 strains), Klebsiella of undetermined species (20 strains), Kluyvera of undetermined species (1 strain), Morganella of undetermined species (1 strain), Pantoea of undetermined species (4 strains), Proteus of undetermined species (32 strains), Providencia of undetermined species (17 strains), and Serratia of undetermined species (29 strains).

  • j Includes Acinetobacter baumannii (925 strains), A. calcoaceticus (19 strains), A. haemolyticus (eight strains), A. junii (three strains), A. lwoffii (58 strains), A. nosocomialis (one strain), A. pittii (seven strains), A. radioresistens (one strain), A. ursingii (three strains), and Acinetobacter of undetermined species (121 strains).

  • k EUCAST non-species-specific breakpoint (18).