[Comparison of in vitro activity of 4 oral beta-lactams on microorganisms responsible for broncho-pulmonary infections in children]. / Activité comparée in vitro de quatre bêtalactamines orales vis-à-vis de germes responsables d'infections broncho-pulmonaires en pédiatrie.

MIC 90 and MBC 90 of amoxicillin, cefaclor, cefadroxil and cefuroxime axetil have been determined by the microdilution method against 48 organisms responsible of acute respiratory tract infections in children: 17 E. coli, 15 K. pneumoniae, 16 H. influenzae. An inoculum effect and an inhibitory index in blood and bronchial secretions were determined. An inoculum effect was more important for amoxicillin and cefadroxil than for cefuroxime axetil and cefaclor. Against H. influenzae, cefuroxime axetil and cefaclor have a similar activity. Against Enterobacteria, cefuroxime axetil has the lowest MIC 90 and MBC 90 and the highest inhibitory index.

Early synergistic killing activity at concentrations attainable in CSF of amoxicillin or cefotaxime and aminoglycosides against Haemophilus influenzae.

Rapid eradication of bacteria from the CSF is critical for the outcome of Haemophilus influenzae meningitis in children. In 15 patients studied, the mean H. influenzae colony counts in CSF were 10(5) CFU/ml (range: 10(2) to 10(9) CFU/ml). Time-kill curves were determined for amoxicillin and cefotaxime alone and in combination with gentamicin or amikacin, against 60 clinical isolates of H. influenzae at concentrations equivalent to those found in CSF following systemic administration. Against beta-lactamase-negative strains (n = 44) a bactericidal effect was observed at 18 h for amoxicillin alone, at 5 h for amoxicillin plus aminoglycosides and at 2.5 h for cefotaxime with or without aminoglycosides. Against beta-lactamase-positive strains a bactericidal effect was observed at 18 h for cefotaxime, at 5 h for amoxicillin plus aminoglycosides and at 2.5 h for cefotaxime plus aminoglycosides. It appears that despite low concentrations of gentamicin or amikacin in the CSF, the accelerated killing of H. influenzae provides a rationale for the initial use of the combination of cefotaxime and aminoglycosides in the initial treatment of H. influenzae meningitis.

[Evaluation of the bactericidal curves of beta-lactam and aminoglycoside combinations at the concentrations obtained in the cerebrospinal fluid in Haemophilus influenzae meningitis]. / Intérêt des courbes de bactéricidie des associations beta-lactamines-aminosides aux concentrations obtenues dans le liquide céphalorachidien dans les méningitis à Haemophilus influenzae.

The prognosis and sequelae of patients with Haemophilus influenzae meningitis were related to concentrations of bacteria in the cerebrospinal fluid (CSF). Rapid bacterial killing and rapid reduction of organisms in vivo in CSF are critical to the outcome. In our patients colony counts of Haemophilus influenzae in CSF were 10(2)/ml - 10(9)/ml (mean 10(5)/ml). Killing kinetics were determined for amoxicillin and cefotaxime, alone and in combination with amikacin, against 35 clinical strains of Haemophilus influenzae (43% beta-lactamase-positive) at concentrations of these antibiotics comparable to those attained in the CSF following systemic administration. Antibiotics concentrations were: amoxicillin: 5 mg/ml, cefotaxime: 3.8 mg/l, amikacin: 1.8 mg/l. Mean killing curves with beta-lactamase-negative strains showed that a bactericidal effect was observed at 18 h for amoxicillin, at 5 h for cefotaxime, at 5 h for amoxicillin plus amikacin and at 2 h 30 for cefotaxime plus amikacin. Against beta-lactamase-positive strains a bactericidal effect was observed at 5 h for cefotaxime, at 2 h 30 for cefotaxime plus amikacin and at 18 h for amoxicillin plus amikacin. The finding of significantly increased killing rates of Haemophilus influenzae by amikacin at low concentration in the presence of either ampicillin or cefotaxime suggests that combined therapy may be beneficial in the treatment of meningitis caused by Haemophilus influenzae.