Efficacy of Gatifloxacin in Experimental Escherichia coli Meningitis

Abstract

The effectiveness of gatifloxacin therapy (15 mg/kg every 5 h [q5h]) was compared with that of meropenem (75 mg/kg q5h) and cefotaxime (75 mg/kg q5h) therapy in experimental meningitis caused by a β-lactamase-producing strain of Escherichia coli. Gatifloxacin therapy was more rapidly bactericidal than cefotaxime but similar to meropenem therapy (bacterial killing rates at 5 h, 0.83 ± 0.26, 0.46 ± 0.3, and 0.73 ± 0.17 CFU/ml/h, respectively; P = 0.03 for gatifloxacin versus cefotaxime). At 10 h, seven of eight animals treated with gatifloxacin had <10 CFU/ml in their cerebrospinal fluid, compared with one of seven treated with cefotaxime therapy (P = 0.01). Gatifloxacin was at least as effective as currently available antibiotics in this model of E. coli meningitis.

Evaluation of antimicrobial regimens in a guinea-pig model of meningitis caused by Pseudomonas aeruginosa

“…The meropenem CSF concentration achieved in the guinea-pigs in the first 4 h ranged from 1.1 to 19.3 mg/L, in the same range as those measured in 48 samples of CSF from children with bacterial meningitis treated with meropenem, 40 mg/kg every 8 h, which ranged from 0 to 18.8 mg/l with a mean of 2.1 mg/L [30]. The meropenem peak CSF concentration in our model (16.8 AE 3.24 mg/ L) was higher than the peak achieved in an Escherichia coli meningitis model in rabbit with a dose of 75 mg/kg: 3.8 AE 0.8 mg/L [31]. The peak ceftazidime levels in CSF reported in five cases of P. aeruginosa meningitis ranged from 7.4 to 42 mg/L [7], close to that found in the present animal model: 9.8 to 44 mg/L.…”

Pasteurized whole milk confers reduced susceptibilities to the antimicrobial agents trimethoprim, gatifloxacin, cefotaxime and tetracycline via themarRABlocus inEscherichia coli

“…These antimicrobial agents represent distinct drug classes and have different mechanisms of actions (McDermott et al 2003). These agents also have significance in clinical therapy, such as trimethoprim (Juckett, 1999; Casewell et al 2003), gatifloxacin (Lutsar et al 1999), and cefotaxime (Wittmann et al 1997) or significance in agriculture for the purposes of growth promotion or prophylaxis in dairy calves, such as tetracycline (Constable & Morin, 2002).…”

Predicting efficacy of antiinfectives with pharmacodynamics and Monte Carlo simulation

“…Because the tissue concentrations of antibiotic might be different for each infection site, one can now predict that different therapeutic dosages of a single antibiotic might be necessary for each infection under consideration, with central nervous system infections like meningitis requiring some of the highest mg/kg doses in order to achieve cure. 25,26 This has in fact been the standard of practice for many years. On the other hand high cure rates of bloodstream infections are achieved at a lower dosage of antibiotic than with central nervous system infections, as we have much higher drug exposure profiles in the blood; children with urinary tract infections require a lower dosage of an antibiotic that is concentrated in and excreted by the kidneys than if treated with an antibiotic that is concentrated in and cleared by the liver.…”