Table 4.

Activities of Ro 63-9141 and reference compounds against experimental septicaemias in mice

Strain (CFU/mouse) and compound MIC (μg/ml)ED50a (mg/kg s.c.)
MSSA Smith (2 × 107)
 Ro 63-91410.25<0.2
 Cefepime10.89 (0.55–1.5)
 Ceftriaxone40.89 (0.55–1.5)
 Meropenem≤0.120.22 (0.095–0.53)
 Vancomycin10.73 (0.46–1.2)
MRSA I-6 (5 × 107)
 Ro 63-914122.4 (1.4–4.0)
 Cefepime>16>25
 Ceftriaxone>16>25
 Meropenem>16>25
 Vancomycin26.7 (4.8–9.4)
Streptococcus pyogenes β15 (1 × 106)
 Ro 63-9141≤0.06<0.2
 Cefepime≤0.06<0.2
 Ceftriaxone≤0.06<0.2
 Meropenem≤0.060.27 (0.19–0.38)
 Vancomycin0.50.70 (0.37–1.2)
Penicillin-susceptible Streptococcus pneumoniae4241 (2 × 102)
 Ro 63-9141≤0.06<0.2
 Benzylpenicillin≤0.06<0.4
 Cefepime≤0.06<0.2
 Ceftriaxone≤0.06<0.2
 Meropenem≤0.060.34 (0.19–0.60)
 Vancomycin0.50.69 (0.43–1.1)
Penicillin-resistant Streptococcus pneumoniae1/37 (1 × 106)
 Ro 63-91410.51.1 (0.80–1.5)
 Benzylpenicillin11.1 (6.5–18)
 Cefepime0.54.2 (3.0–5.9)
 Ceftriaxone13.1 (1.7–5.1)
 Meropenem0.251.8 (1.1–2.9)
 Vancomycin0.50.44 (0.27–0.72)
Penicillin-resistant Streptococcus pneumoniae536 (1 × 106)
 Ro 63-914110.6 (0.35–1.0)
 Benzylpenicillin2>12
 Ceftriaxone12.1 (1.5–3.0)
 Meropenem11.8 (1.1–2.9)
Penicillin-resistant Streptococcus pneumoniae 23 F-CTR (5 × 104)
 Ro 63-914111.0 (0.75–1.5)
 Benzylpenicillin1>12
 Ceftriaxone48.8 (6.1–13)
 Meropenem0.51.2 (0.70–2.0)
Escherichia coli 25922 (5 × 103)
 Ro 63-9141≤0.06<0.2
 Cefepime≤0.06<0.2
 Ceftriaxone≤0.06<0.2
 Meropenem≤0.06<0.2
Klebsiella pneumoniae 418 (1 × 103)
 Ro 63-9141≤0.06<0.4
 Cefepime≤0.06<0.4
 Ceftriaxone≤0.06<0.4
 Meropenem≤0.06<0.4
Enterobacter cloacae MRW (2 × 106)
 Ro 63-914143.8 (2.2–6.0)
 Cefepime21.1 (0.8–1.5)
 Ceftriaxone>32>25
 Meropenem≤0.060.22 (0.13–0.36)
Citrobacter freundii 1982 (1 × 107)
 Ro 63-914111.5 (0.92–2.3)
 Cefepime10.45 (0.19–1.1)
 Ceftriaxone>32>25
 Meropenem≤0.06<0.2
Serratia marcescens 69438 (5 × 103)
 Ro 63-91410.250.68 (0.41–1.2)
 Cefepime0.12<0.2
 Ceftriaxone0.25<0.4
 Meropenem≤0.060.45 (0.27–0.72)
Proteus vulgaris 1028 (1 × 106)
 Ro 63-9141>32>12
 Cefepime0.50.28 (0.09–0.84)
 Ceftriaxone0.12<0.2
 Meropenem≤0.06<0.4
Proteus mirabilis 2117 (2 × 106)
 Ro 63-9141≤0.060.35 (0.19–0.59)
 Cefepime0.12<0.4
 Ceftriaxone≤0.06<0.2
 Meropenem0.124.4 (3.0–6.4)
Pseudomonas aeruginosa BA (1 × 105)
 Ro 63-914184.0 (2.1–8.0)
 Cefepime41.0 (0.73–1.5)
 Ceftriaxone328.8 (6.1–13)
 Meropenem2<0.4
  • a ED50 after s.c. administration, with 95% confidence interval in brackets.