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ABSTRACTCeftobiprole medocaril, a new cephalosporin, is highly active against a broad spectrum of Gram-positive and Gram-negative clinical pathogens, including methicillin-resistant Staphylococcus aureus(MRSA) and penicillin-resistant pneumococci. In this study, we tested ceftobiprole against various Gram-negative pathogens in a rabbit meningitis model and determined its penetration into the cerebrospinal fluid (CSF). In this animal model, ceftobiprole produced an antibacterial activity similar to that of cefepime against an Escherichia colistrain, a Klebsiella pneumoniaestrain, and a β-lactamase-negative Haemophilus influenzaestrain. Against a β-lactamase-positive H. influenzaestrain, ceftobiprole was significantly superior. The penetration of ceftobiprole through inflamed meninges reached about 16% of serum levels compared to about 2% of serum levels through uninflamed meninges.

Objectives: To test the efficacy of daptomycin, a cyclic lipopeptide antibiotic, against a methicillin-susceptible Staphylococcus aureus strain in experimental rabbit meningitis and to determine its penetration into non-inflamed and inflamed meningesResults: Over a treatment period of 8 h, daptomycin (15 mg/kg) was significantly superior to the comparator regimen vancomycin (−4.54 ± 1.12 log10/mL for daptomycin versus −3.43 ± 1.17 log10/mL for vancomycin). Daptomycin managed to sterilize 6 out of 10 CSFs compared with 4 out of 10 for vancomycin. The penetration of daptomycin into inflamed meninges was ∼5% and ∼2% into non-inflamed meninges.Conclusions: The superior bactericidal activity of daptomycin was confirmed in vivo and in time-killing assays in vitro.

ABSTRACTThe penetration of telavancin was 2% into inflamed meninges and ca. 1‰ into noninflamed meninges after two intravenous injections (30 mg/kg of body weight). In experimental meningitis, telavancin was significantly superior to vancomycin combined with ceftriaxone against a penicillin-resistant pneumococcal strain. Against a methicillin-sensitive staphylococcal strain, telavancin was slightly but not significantly superior to vancomycin.

ABSTRACTThe penetration of daptomycin, a new lipopeptide antibiotic, into inflamed meninges ranged between 4.37 and 7.53% (mean, 5.97%). Daptomycin was very efficacious in the treatment of experimental pneumococcal meningitis, producing a decrease of −1.20 ± 0.32 Δlog10CFU/ml · h in the bacterial titer of Streptococcus pneumoniaeagainst a penicillin-resistant strain and of −0.97 ± 0.32 Δlog10CFU/ml · h against a penicillin- and quinolone-resistant strain found in cerebrospinal fluid (CSF). For both strains, daptomycin was significantly superior to the standard regimen of a combination of ceftriaxone with vancomycin, sterilizing 9 of 10 CSF samples after 4 h. In vitro, daptomycin produced highly bactericidal activity in concentrations above the MIC.

ABSTRACTBMS 284756 penetrated well into inflamed meninges (44% ± 11%) and produced good bactericidal activity (−0.82 ± 0.22 Δlog10CFU/ml · h) in the treatment of experimental meningitis in rabbits due to a penicillin-sensitive strain. BMS 284756 monotherapy had a greater potency than the standard regimen of ceftriaxone and vancomycin (−0.49 ± 0.08 Δlog10CFU/ml · h) against a penicillin-resistant strain (MIC, 4 mg/liter). Even against a penicillin- and quinolone-resistant strain, BMS 284756 showed good bactericidal activity (−0.52 ± 0.12 Δlog10CFU/ml · h). The antibacterial activity of BMS 284756 was confirmed by time-killing assays over 8 h in vitro.

Grepafloxacin, a new fluoroquinolone, produced bactericidal activity comparable to that of vancomycin and ceftriaxone in the treatment in rabbits of meningitis caused by a pneumococcal strain highly resistant to penicillin (MIC 4 mg/L) (triangle uplog(10) cfu/mL*h for grepafloxacin, -0.32 +/- 0.15; dose, 15 mg/kg iv; triangle uplog(10) cfu/mL*h for vancomycin, -0.39 +/- 0.18; dose, 2 x 20 mg/kg iv; triangle uplog(10) cfu/mL*h for ceftriaxone, -0.32 +/- 0. 12; dose, 125 mg/kg iv). Higher doses of grepafloxacin (30 mg/kg and 2 x 50 mg/kg) did not improve the killing rates. The combination of grepafloxacin with vancomycin was not significantly superior to monotherapies (P > 0.05). In vitro, grepafloxacin was bactericidal at concentrations above the MIC. Using concentrations around the MIC, addition of vancomycin to grepafloxacin showed synergic activity.

Cefepime, a broad-spectrum, fourth-generation cephalosporin, showed excellent CSF penetration with levels ranging between 10 and 16 mg/L after two intravenous injections (100 mg/kg). The bactericidal activity of cefepime (-0.60 +/- 0.28 Deltalog(10) cfu/mL/h) was superior to that of ceftriaxone (-0.34 +/- 0.23 Deltalog(10) cfu/mL/h, P < 0.05) and vancomycin (-0.39 +/- 0.19 Deltalog(10) cfu/mL/h, P < 0.05) in the treatment of rabbits with meningitis caused by an isolate highly resistant to penicillin (MIC of penicillin G: 4 mg/L). The addition of vancomycin to both cephalosporins did not significantly increase the killing rate compared with monotherapies (P > 0.05). Similar results were obtained in time-killing experiments in vitro.

ABSTRACTIn this study, the efficacy of ceftaroline fosamil was compared with that of cefepime in an experimental rabbit meningitis model against two Gram-negative strains (Escherichia coliQK-9 and Klebsiella pneumoniae1173687). The penetration of ceftaroline into inflamed and uninflamed meninges was also investigated. Both regimens were bactericidal, but ceftaroline fosamil was significantly superior to cefepime against K. pneumoniaeand E. coliin this experimental rabbit meningitis model (P< 0.0007 against K. pneumoniaeand P< 0.0016 against E. coli). The penetration of ceftaroline was approximately 15% into inflamed meninges and approximately 3% into uninflamed meninges.

ABSTRACTCeftaroline is a new cephalosporin with bactericidal activity against resistant Gram-positive organisms, including methicillin-resistant Staphylococcus aureus(MRSA) and penicillin-resistant Streptococcus pneumoniae, as well as common Gram-negative organisms. This study tested the prodrug, ceftaroline fosamil, against a penicillin-sensitive and a penicillin-resistant strain of S. pneumoniaein an experimental rabbit meningitis model. The penetration of ceftaroline into inflamed meninges was approximately 14%. Ceftaroline fosamil was slightly superior to ceftriaxone against the penicillin-sensitive strain and significantly superior to the combination of ceftriaxone and vancomycin against the penicillin-resistant strain.

We found positive results for leucocyte esterase in the dipstick test in two patients with acute leukaemia who had had documented aplasia for several days. They were treated with imipenem [...]

ABSTRACTPreincubation of pneumococci with sub-MIC concentrations of ceftriaxone (1/16× MIC), cefotaxime (1/8× MIC), and meropenem (1/4× MIC) alone or combined with levofloxacin (1/8× MIC) over 6 h prevents the emergence of levofloxacin-resistant mutants after 96 h of incubation but does not affect the intracellular accumulation of levofloxacin in two penicillin-resistant pneumococcal strains, suggesting a link between the mechanism of action of β-lactams and the emergence of quinolone-induced resistance in pneumococci.