TABLE 1.

In vitro activities of PPI-0903M compared to those of selected antimicrobial agents when tested against gram-positive bacteria

Bacterium group or antimicrobial agent (no. of isolates tested)MIC (μg/ml)% of isolates by category
50%90%RangeSusceptibleResistant
Staphylococcus aureus
    Methicillin susceptible (73)a
        PPI-0903M0.250.250.03-0.5b
        Cefepime240.25-1698.60.0
        Ceftriaxone440.5-1698.60.0
        Piperacillin-tazobactam12≤0.12-4100.00.0
        Imipenem≤0.5≤0.5≤0.5100.00.0
        Levofloxacin0.120.50.06->493.24.1
        Vancomycin110.5-2100.00.0
        Linezolid220.5-2100.0
    Methicillin resistant (102)a
        PPI-0903M120.12-2
        Cefepime>16>161->16(26.5)c(60.8)c
        Ceftriaxone>32>324->32(11.8)c(60.8)c
        Piperacillin-tazobactam642560.5->256(20.6)c(79.4)c
        Imipenem2>8≤0.5->8(63.7)c(30.4)c
        Levofloxacin>4>40.12->410.887.3
        Vancomycin110.5-4100.00.0
        Linezolid220.25-2100.0
    h-VISA and VISA (100)d
        PPI-0903M120.25-4
        Cefepime>16>164->167.091.0
        Ceftriaxone>32>324->324.093.0
        Oxacillin>2>2≤0.25->212.088.0
        Piperacillin-tazobactam1282561->2565.095.0
        Imipenem>8>8≤0.5->812.080.0
        Levofloxacin>4>40.12->41.094.0
        Linezolid110.5->899.0
    Quinupristin-dalfopristin nonsusceptible (11)
        PPI-0903M110.25-1
        Cefepime>16>162->1618.263.6
        Ceftriaxone>32>328->329.172.7
        Oxacillin>8>88->80.0100.0
        Piperacillin-tazobactam>64>644->6416.783.3
        Imipenem>8>8≤0.06->836.463.6
        Levofloxacin4>41->49.190.9
        Vancomycin221-2100.00.0
        Linezolid120.5-2100.0
CoNS
    Methicillin susceptible (50)a
        PPI-0903M0.060.25≤0.016-0.5
        Cefepime120.25-2100.00.0
        Ceftriaxone240.5-8100.00.0
        Piperacillin-tazobactam0.251≤0.12-4100.00.0
        Imipenem≤0.5≤0.5≤0.5100.00.0
        Levofloxacin0.2510.06->490.08.0
        Vancomycin120.5-4100.00.0
        Linezolid110.5-2100.0
    Methicillin resistant (80)a
        PPI-0903M0.250.5≤0.016-2
        Cefepime481->16(92.5)c(6.3)c
        Ceftriaxone8324->32(55.0)c(5.0)c
        Piperacillin-tazobactam140.25-256(96.3)c(3.7)c
        Imipenem≤0.52≤0.5->8(92.5)c(6.3)c
        Levofloxacin4>40.06->437.555.0
        Vancomycin22≤0.12-2100.00.0
        Linezolid110.25-2100.0
    h-VIS (51)e
        PPI-0903M12≤0.016-2
        Cefepime>16>160.5->1631.462.7
        Ceftriaxone>32>321->3215.766.7
        Oxacillin>8>8≤0.25->89.890.2
        Piperacillin-tazobactam64>64≤0.5->6428.671.4
        Imipenem>8>8≤0.5->843.156.9
        Levofloxacin4>40.12->422.577.5
        Linezolid120.5-2100.0
    Quinupristin-dalfopristin nonsusceptible (15)
        PPI-0903M0.510.12-2
        Cefepime8>161->16(60.0)c(26.7)c
        Ceftriaxone32>328->32(33.3)c(40.0)c
        Oxacillin>8>80.5->80.0100.0
        Piperacillin-tazobactam4>641->64(53.8)c(46.2)c
        Imipenem1>8≤0.5->8(73.3)c(26.7)c
        Levofloxacin>4>41->49.172.7
        Vancomycin220.5-2100.00.0
        Linezolid121-2100.0
Streptococcus pneumoniae
    Penicillin susceptible (33)
        PPI-0903M≤0.016≤0.016≤0.016-0.06
        Cefepimef≤0.060.25≤0.06-0.5100.00.0
        Ceftriaxonef0.0160.060.016-0.5100.00.0
        Meropenem0.0160.03≤0.008-0.03100.00.0
        Levofloxacin110.5-1100.00.0
        Clarithromycin≤0.258≤0.25->3281.815.2
        Erythromycin≤0.258≤0.25->3281.812.1
        Vancomycin0.250.5≤0.06-0.5100.0
    Penicillin intermediate (53)
        PPI-0903M0.030.06≤0.016-0.12
        Cefepimef0.251≤0.06-495.92.0
        Ceftriaxonef0.250.50.03-1100.00.0
        Meropenem0.120.5≤0.008-0.582.20.0
        Levofloxacin110.12-2100.00.0
        Clarithromycin1>32≤0.25->3236.064.0
        Erythromycin2>32≤0.25->3236.064.0
        Vancomycin0.250.50.12-298.0
    Penicillin resistant (50)
        PPI-0903M0.120.250.06-0.5
        Cefepimef120.25-478.02.0
        Ceftriaxonef12≤0.008-882.08.0
        Meropenem110.25-22.155.3
        Levofloxacin110.5-1100.00.0
        Clarithromycin8>32≤0.25->3212.086.0
        Erythromycin8>32≤0.25->3212.088.0
        Vancomycin0.250.50.12-0.5100.0
    Levofloxacin nonsusceptible (22)
        PPI-0903M≤0.0160.12≤0.016-0.12
        Cefepime≤0.060.5≤0.06-1100.00.0
        Ceftriaxone0.030.5≤0.008-1100.00.0
        Penicillin≤0.031≤0.03-268.29.1
        Clarithromycin2>32≤0.25->3240.959.1
        Erythromycin4>32≤0.25->3240.959.1
        Vancomycin0.250.50.12-0.5100.0
    Multidrug resistant (23)g
        PPI-0903M0.120.250.12-0.5
        Cefepimef120.5-473.94.3
        Ceftriaxonef14≤0.008-873.913.0
        Meropenem110.5-10.065.2
        Levofloxacin110.5-495.70.0
        Vancomycin0.250.50.12-0.5100.00.0
β-Haemolytic group A streptococci (22)
    PPI-0903M≤0.016≤0.016≤0.016
    Cefepime≤0.12≤0.12≤0.12100.00.0
    Ceftriaxone≤0.25≤0.25≤0.25100.00.0
    Penicillin≤0.016≤0.016≤0.016-0.03100.00.0
    Meropenem≤0.008≤0.008≤0.008100.0
    Ertapenem≤0.06≤0.06≤0.06-0.12100.0
    Levofloxacin0.510.25-1100.00.0
    Erythromycin≤0.06≤0.06≤0.06->890.59.5
    Vancomycin0.250.50.25-0.5100.0
β-Haemolytic group B streptococci (26)
    PPI-0903M≤0.016≤0.016≤0.016
    Cefepime≤0.12≤0.12≤0.12100.00.0
    Ceftriaxone≤0.25≤0.25≤0.25100.00.0
    Penicillin0.060.120.03-0.12100.00.0
    Meropenem0.060.060.03-0.12100.0
    Ertapenem≤0.06≤0.06≤0.06-0.12100.0
    Levofloxacin0.510.25-1100.00.0
    Erythromycin≤0.062≤0.06->873.126.9
    Vancomycin0.50.50.25-0.5100.0
Other β-haemolytic streptococci (20)
    PPI-0903M≤0.016≤0.016≤0.016-0.03
    Cefepime≤0.120.5≤0.12-0.5100.00.0
    Ceftriaxone≤0.25≤0.25≤0.25100.00.0
    Penicillin≤0.0160.06≤0.016-0.06100.00.0
    Meropenem0.0160.12≤0.008-0.12100.0
    Ertapenem≤0.060.25≤0.06-0.5100.0
    Levofloxacin0.50.50.25-1100.00.0
    Erythromycin≤0.06≤0.06≤0.06-295.05.0
    Vancomycin0.250.50.25-1100.0
Levofloxacin-resistant β-haemolytic streptococci (10)h
    PPI-0903M≤0.016≤0.016≤0.016-0.03
    Cefepime≤0.120.25≤0.12-0.25100.00.0
    Ceftriaxone≤0.25≤0.25≤0.25100.00.0
    Penicillin0.030.06≤0.016-0.12100.00.0
    Erythromycin≤0.06>8≤0.06->880.020.0
    Vancomycin0.50.50.25-1100.0
Viridans group streptococci
    Penicillin susceptible (32)
        PPI-0903M≤0.0160.03≤0.016-1
        Cefepime≤0.120.25≤0.12-0.5100.00.0
        Ceftriaxone≤0.25≤0.25≤0.25-0.5100.00.0
        Meropenem0.030.06≤0.008-0.12100.0
        Ertapenem≤0.060.12≤0.06-0.5100.0
        Levofloxacin0.510.06-2100.00.0
        Erythromycin≤0.061≤0.06->878.118.7
        Vancomycin0.510.25-1100.0
    Penicillin intermediate (53)
        PPI-0903M0.030.12≤0.016-0.5
        Cefepime0.51≤0.12-490.61.9
        Ceftriaxone0.52≤0.25-490.61.9
        Meropenem0.1210.06-188.0
        Ertapenem0.252≤0.06-288.5
        Levofloxacin1>40.5->485.510.9
        Erythromycin14≤0.06->835.852.8
        Vancomycin0.50.50.25-1100.0
    Penicillin resistant (52)
        PPI-0903M0.2510.03-8
        Cefepime481->1621.253.8
        Ceftriaxone4161->329.858.8
        Meropenem240.5-416.7
        Ertapenem481-811.1
        Levofloxacin120.5->494.23.8
        Erythromycin2>8≤0.06->811.578.8
        Vancomycin0.510.25-1100.0
    Levofloxacin nonsusceptible (20)
        PPI-0903M0.060.25≤0.016-1
        Cefepime0.254≤0.12-875.015.0
        Ceftriaxone≤0.252≤0.25-1675.06.2
        Penicillin0.064≤0.03-1655.015.0
        Erythromycin0.54≤0.06->3245.040.0
        Vancomycin0.510.25-1100.0
Quinupristin-dalfopristin nonsusceptible streptococci (6)i
    PPI-0903M≤0.016≤0.016-8
    Cefepime≤0.12≤0.12->1650.050.0
    Ceftriaxone32≤0.25->3240.060.0
    Penicillin0.12≤0.016->3250.050.0
    Levofloxacin11->483.316.7
    Erythromycin>8>80.0100.0
    Vancomycin0.50.25-0.5100.0
Enterococcus faecalis
    Vancomycin-susceptible (22)
        PPI-0903M2160.5->32
        Ceftriaxone>32>32>32
        Ampicillin≤2≤2≤2-8100.00.0
        Imipenem14≤0.5-8
        Levofloxacin2>40.5->454.545.5
        Teicoplanin≤2≤2≤2100.00.0
        Linezolid220.5->886.413.6
    Vancomycin resistant (22)
        PPI-0903M481-16
        Ceftriaxone>32>32>32
        Ampicillin≤24≤2->1695.54.5
        Imipenem241->8
        Levofloxacin>4>4>40.0100.0
        Teicoplanin8>16≤2->1650.045.5
        Linezolid121->895.54.5
Enterococcus faecium
    Vancomycin-susceptible (11)
        PPI-0903M16>320.5->32
        Ceftriaxone>32>3216->32
        Ampicillin>16>16≤2->1627.372.7
        Imipenem>8>82->8
        Levofloxacin>4>41->418.20.0
        Teicoplanin≤2≤2≤2100.00.0
        Linezolid121-2100.00.0
    Vancomycin resistant (vanA) (13)
        PPI-0903M>32>3216->32
        Ceftriaxone>32>32>32
        Ampicillin>16>16>160.0100.0
        Imipenem>8>8>8
        Levofloxacin>4>42->47.792.3
        Linezolid121-2100.00.0
Linezolid-resistant enterococci (10)j
    PPI-0903M16>321->32
    Ceftriaxone>32>32>32
    Ampicillin>16>16≤2->1640.060.0
    Imipenem>8>80.5->8
    Levofloxacin>4>41->410.090.0
    Vancomycin2>160.5->1650.040.0
    Teicoplanin≤2>16≤2->1660.040.0
Bacillus spp. (20)k
    PPI-0903M480.06-32
    Cefepime>16>162->16
    Ceftriaxone32>32≤0.25->32
    Penicillin32>32≤0.016->32
    Ampicillin16>16≤2->16
    Imipenem≤0.54≤0.5-8
    Levofloxacin0.120.250.06->4
    Vancomycin11≤0.12-1
  • a Oxacillin was used in the susceptibility test to categorize staphylococcal isolates as methicillin susceptible or resistant.

  • b —, no breakpoints have been established by the CLSI/NCCLS (3).

  • c Oxacillin-resistant S. aureus should be considered resistant to all β-lactams according to CLSI/NCCLS (3) recommendations.

  • d Includes 19 well-characterized vancomycin-intermediate S. aureus (VISA) strains and 81 hetero (h)-VISA strains, using the PAP method and results reported in an evaluation of AZD2563, an oxazolidinone (16).

  • e Isolates with vancomycin MIC at 4 μg/ml.

  • f Breakpoints for nonmeningitis isolates were applied (3).

  • g Resistant to penicillin, erythromycin, clarithromycin, clindamycin, tetracycline, and trimethoprim/sulfamethoxazole.

  • h Includes one group A, five group B, one group C, two group G, and one ungrouped β-haemolytic strain.

  • i Includes four S. mitis and two S. bovis strains.

  • j Includes four E. faecalis strains and six E. faecium strains. Resistances confirmed as having G2576U ribosomal target mutations.

  • k Includes 11 Bacillus cereus strains, one B. circulans strain, and eight Bacillus spp. strains.