TABLE 2.

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

Bacterium group or antimicrobial agent (no. of isolates tested)MIC (μg/ml)% of isolates by category
50%90%RangeSusceptibleResistant
Citrobacter freundii (20)
    PPI-0903M0.1220.06->32a
    Cefepime≤0.120.25≤0.12-1100.00.0
    Ceftriaxone≤0.250.5≤0.25-1100.00.0
    Ceftazidime≤12≤1-4100.00.0
    Piperacillin-tazobactam2161->6490.010.0
    Imipenem≤0.51≤0.5-1100.00.0
    Levofloxacin0.060.25≤0.03->495.05.0
    Tobramycin0.510.25->1695.05.0
Enterobacter cloacaeb
    Wild type (23)
        PPI-0903M0.12320.03->32
        Cefepime≤0.122≤0.12-4100.00.0
        Ceftriaxone≤0.2516≤0.25->3287.0b8.7
        Ceftazidime≤1>16≤1->1687.0b13.0
        Piperacillin-tazobactam2128≤0.5-25687.013.0
        Imipenem≤0.51≤0.5-2100.00.0
        Levofloxacin≤0.031≤0.03->491.38.7
        Tobramycin0.520.25->1691.38.7
    ESBL-producing strains (15)
        PPI-0903M>32>324->32
        Cefepime16>168->1640.033.3
        Ceftriaxone>32>3216->320.086.7
        Ceftazidime>16>162->1633.353.3
        Piperacillin-tazobactam32>642->6440.026.7
        Imipenem≤0.5≤0.5≤0.5-893.30.0
        Levofloxacin>4>4≤0.03->433.353.3
        Tobramycin8>160.5->1626.746.7
E. coli
    Wild type (20)
        PPI-0903M0.060.12≤0.016-0.25
        Cefepime≤0.12≤0.12≤0.12100.00.0
        Ceftriaxone≤0.25≤0.25≤0.25100.00.0
        Ceftazidime≤1≤1≤1100.00.0
        Piperacillin-tazobactam120.25-4100.00.0
        Imipenem≤0.5≤0.5≤0.5100.00.0
        Levofloxacin≤0.03>4≤0.03->480.015.0
        Tobramycin0.520.25-890.00.0
    ESBL-producing strains (15)
        PPI-0903M>32>320.5->32
        Cefepime16>16≤0.12->1646.740.0
        Ceftriaxone>32>32≤0.25->3240.060.0
        Ceftazidime8>16≤1->1653.320.0
        Piperacillin-tazobactam8322->6486.76.7
        Imipenem≤0.5≤0.5≤0.5100.00.0
        Levofloxacin>4>4≤0.03->426.766.7
        Tobramycin16>160.5->1628.664.3
Klebsiella pneumoniae
    Wild type (21)
        PPI-0903M0.060.50.03-4
        Cefepime≤0.12≤0.12≤0.12-0.25100.00.0
        Ceftriaxone≤0.25≤0.25≤0.25100.00.0
        Ceftazidime≤1≤1≤1100.00.0
        Piperacillin-tazobactam240.5-25695.24.8
        Imipenem≤0.5≤0.5≤0.5100.00.0
        Levofloxacin0.060.5≤0.03->490.59.5
        Tobramycin0.50.5≤0.12-2100.00.0
    ESBL-producing strains (15)
        PPI-0903M>32>3232->32
        Cefepime8>162->1660.020.0
        Ceftriaxone>32>3216->320.066.7
        Ceftazidime>16>16≤1->1640.053.3
        Piperacillin-tazobactam8>2561->25658.841.2
        Imipenem≤0.5≤0.5≤0.5100.00.0
        Levofloxacin0.5>4≤0.03->460.026.7
        Tobramycin>16>160.5->1620.080.0
Morganella morganii (20)
    PPI-0903M0.060.120.03-0.5
    Cefepime≤0.12≤0.12≤0.12100.00.0
    Ceftriaxone≤0.25≤0.25≤0.25-0.5100.00.0
    Ceftazidime≤1≤1≤1100.00.0
    Piperacillin-tazobactam≤0.5≤0.5≤0.5-2100.00.0
    Imipenem24≤0.5-4100.00.0
    Levofloxacin≤0.030.12≤0.03-1100.00.0
    Tobramycin0.51≤0.12-2100.00.0
Proteus mirabilis
    Wild type (20)
        PPI-0903M0.120.120.03-4
        Cefepime≤0.12≤0.12≤0.12100.00.0
        Ceftriaxone≤0.25≤0.25≤0.25-0.5100.00.0
        Ceftazidime≤1≤1≤1100.00.0
        Piperacillin-tazobactam≤0.51≤0.5-2100.00.0
        Imipenem12≤0.5-2100.00.0
        Levofloxacin0.06>4≤0.03->480.020.0
        Tobramycin120.5-890.00.0
    ESBL-producing strains (10)
        PPI-0903M>32>324->32
        Cefepime>16>16>160.0100.0
        Ceftriaxone>32>321->3230.070.0
        Ceftazidime416≤1->1680.010.0
        Piperacillin-tazobactam12≤0.5-3290.00.0
        Imipenem120.25-2100.00.0
        Levofloxacin>4>42->410.080.0
        Tobramycin4>160.5->1660.040.0
Providencia spp./P. vulgaris (22)c
    PPI-0903M1>32c0.03->32
    Cefepime≤0.121≤0.12-8100.00.0
    Ceftriaxone≤0.254≤0.25-3290.99.1
    Ceftazidime≤1≤1≤1-8100.00.0
    Piperacillin-tazobactam≤0.54≤0.5-4100.00.0
    Imipenem12≤0.5-4100.00.0
    Levofloxacin0.06>4≤0.03->472.713.6
    Tobramycin140.25-1690.94.5
Serratia marcescens (20)
    PPI-0903M0.520.12-8
    Cefepime≤0.120.25≤0.12-0.5100.00.0
    Ceftriaxone≤0.251≤0.25-8100.00.0
    Ceftazidime≤1≤1≤1100.00.0
    Piperacillin-tazobactam140.5-16100.00.0
    Imipenem≤0.51≤0.5-2100.00.0
    Levofloxacin0.120.50.06-2100.00.0
    Tobramycin240.5-1690.05.0
Haemophilus influenzae
    β-lactamase negative (23)
        PPI-0903M≤0.016≤0.016≤0.016
        Cefepime≤0.060.12≤0.06-0.12100.00.0
        Ceftriaxone≤0.008≤0.008≤0.008-0.016100.00.0
        Ampicillin≤0.51≤0.5-1100.00.0
        Piperacillin-tazobactam≤0.12≤0.12≤0.12100.00.0
        Meropenem0.030.120.016-0.25100.00.0
        Levofloxacin≤0.03≤0.03≤0.03100.00.0
        Azithromycin120.5-2100.0
    β-Lactamase positive (24)
        PPI-0903M≤0.016≤0.016≤0.016-0.25
        Cefepime≤0.060.12≤0.06-1100.00.0
        Ceftriaxone≤0.0080.016≤0.008-0.06100.00.0
        Ampicillin>4>42->40.097.1
        Piperacillin-tazobactam≤0.12≤0.12≤0.12100.00.0
        Meropenem0.030.060.016-0.12100.00.0
        Levofloxacin≤0.03≤0.03≤0.03100.00.0
        Azithromycin120.25-895.8a
    BLNAR (30)d
        PPI-0903M≤0.0160.03≤0.016-0.03
        Cefepime0.250.5≤0.06-1100.00.0
        Ceftriaxone0.0160.6≤0.008-2100.00.0
        Piperacillin-tazobactam≤1≤1≤1100.00.0
        Levofloxacin≤0.03≤0.03≤0.03100.00.0
        Azithromycin12≤0.12-4100.0
M. catarrhalis (25)e
    PPI-0903M0.060.12≤0.016-0.12
    Cefepime0.251≤0.06-2100.00.0
    Ceftriaxone0.060.5≤0.008-1100.00.0
    Ampicillinf≤0.52≤0.5->44.096.0
    Amoxicillin-clavulanic acid≤0.060.25≤0.06-0.5100.00.0
    Levofloxacin≤0.03≤0.03≤0.03100.00.0
    Azithromycin≤0.5≤0.5≤0.5100.0
Neisseria meningitidis (10)
    PPI-0903M≤0.016≤0.016≤0.016
    Cefepime≤0.12≤0.12≤0.12
    Ceftriaxone≤0.25≤0.25≤0.25
    Penicillin≤0.0160.25≤0.016-0.25
    Ampicillin≤1≤1≤1
    Piperacillin-tazobactam≤0.5≤0.5≤0.5
    Imipenem≤0.5≤0.5≤0.5
    Levofloxacin≤0.03≤0.03≤0.03-0.06
Acinetobacter baumannii (20)
    PPI-0903M16>322->32
    Cefepime8>162->1655.035.0
    Ceftriaxone16>320.5->3235.035.0
    Ceftazidime8>162->1650.025.0
    Ampicillin-sulbactam4322->3270.025.0
    Piperacillin-tazobactam32>256≤0.12->25640.045.0
    Imipenem≤0.51≤0.5->895.05.0
    Levofloxacin1>40.06->450.050.0
    Tobramycin1>160.5->1665.020.0
Alcaligenes spp. (10)g
    PPI-0903M>32>3216->32
    Cefepime>16>1616->16
    Ceftriaxone>32>3216->32
    Ceftazidime4>162->16
    Piperacillin-tazobactam2>64≤0.5->64
    Imipenem2>81->8
    Levofloxacin240.12->4
    Tobramycin>16>168->16
Pseudomonas aeruginosa (20)
    PPI-0903M16>324->32
    Cefepime281-1695.00.0
    Ceftriaxone>32>328->3215.060.0
    Ceftazidime28≤1-8100.00.0
    Piperacillin-tazobactam4162-25695.05.0
    Imipenem18≤0.5->885.010.0
    Levofloxacin0.5>40.25->475.025.0
    Tobramycin0.5>16≤0.12->1675.025.0
Stenotrophomonas maltophilia (10)
    PPI-0903M>32>3232->32
    Cefepime16>164->16
    Ceftriaxone>32>3232->32
    Ceftazidime8>16≤1->16
    Piperacillin-tazobactam>256>2568->256
    Imipenem>8>8>8
    Levofloxacin120.25->4
    Tobramycin>16>1616->16
    Trimethoprim-sulfamethoxazole≤0.5≤0.5≤0.5100.00.0
  • a —, no breakpoints have been established by the CLSI/NCCLS (3).

  • b 13% of isolates produced a stably derepressed AmpC enzyme.

  • c Two Proteus vulgaris and two Providencia stuartii isolates had PPI-0903M MICs of >32 μg/ml.

  • d BLNAR, β-lactamase-negative ampicillin-resistant strains.

  • e Haemophilus influenzae breakpoints were applied (3).

  • f Interpreted by β-lactamase production or a penicillin MIC at ≤0.06 μg/ml, susceptible (one strain [4.0%] was β-lactamase test negative).

  • g Includes eight A. xylosoxidans strains, one A. faecalis strain, and one Alcaligenes sp. strain.