RESUMEN
BACKGROUND: Streptococcus pneumoniae is now the predominant pathogen causing meningitis. The resistance of S. pneumoniae to penicillin and third-generation cephalosporins has grown steadily. OBJECTIVES: To assess the antibiotic susceptibility of S. pneumoniae isolated from the cerebrospinal fluid of children with meningitis, and determine the antibiotic regimen appropriate for suspected bacterial meningitis in Israel. METHODS: The study group included 31 children with 35 episodes of meningitis hospitalized from 1998 to 2006. S. pneumoniae isolates from the cerebrospinal fluid were tested for susceptibility to penicillin and ceftriaxone. RESULTS: Of the 35 isolates, 17 (48.6%) showed resistance to penicillin (minimum inhibitory concentration > or = 0.12 microg/ml). Only 3 isolates (8.6%) showed intermediate resistance to ceftriaxone (> or = 0.5 and < (2 microg/ml), and none showed complete resistance (MIC > or = 2 microg/ml). The rates of antibiotic resistance were higher in children who were treated with antibiotics prior to admission (penicillin 88.9% vs. 34.6%, P = 0.007; ceftriaxone 22.2% vs. 3.8%, P = 0.156). CONCLUSIONS: The rate of penicillin resistance is high in children with S. pneumoniae meningitis in Israel, especially in those treated with oral antibiotics prior to admission. Resistance to ceftriaxone is infrequent though not negligible. On the basis of these findings, current recommendations to empirically treat all children with suspected bacterial meningitis with ceftriaxone in addition to vancomycin until the bacterial susceptibility results become available are justified also in Israel.
Asunto(s)
Antibacterianos/uso terapéutico , Ceftriaxona/uso terapéutico , Farmacorresistencia Bacteriana , Meningitis Neumocócica/tratamiento farmacológico , Penicilinas/uso terapéutico , Streptococcus pneumoniae/efectos de los fármacos , Antibacterianos/líquido cefalorraquídeo , Ceftriaxona/líquido cefalorraquídeo , Resistencia a las Cefalosporinas , Niño , Preescolar , Femenino , Hospitales/estadística & datos numéricos , Humanos , Lactante , Israel , Masculino , Meningitis Neumocócica/líquido cefalorraquídeo , Pruebas de Sensibilidad Microbiana/métodos , Pruebas de Sensibilidad Microbiana/estadística & datos numéricos , Resistencia a las Penicilinas , Penicilinas/líquido cefalorraquídeo , Streptococcus pneumoniae/aislamiento & purificación , Resultado del TratamientoRESUMEN
The bactericidal activities of monotherapy with trovafloxacin (-0.37 +/- 0.15 Delta log(10) CFU/ml. h), vancomycin (-0.32 +/- 0.12 Delta log(10) CFU/ml. h), and ceftriaxone (-0.36 +/- 0.19 Delta log(10) CFU/ml. h) for the treatment of experimental meningitis in rabbits due to a clinical penicillin-resistant pneumococcal strain (MIC, 4 mg/liter) were similar. The combination of ceftriaxone with trovafloxacin considerably improved the killing rates (-0.67 +/- 0.16 Delta log(10) CFU/ml. h) and was slightly superior to ceftriaxone with vancomycin (killing rate, -0.53 +/- 0. 22 Delta log(10) CFU/ml. h), the regimen most commonly used in clinical practice. In vitro, synergy was demonstrated between ceftriaxone and trovafloxacin by the checkerboard method (fractional inhibitory concentration index, 0.5) and by time-killing assays over 8 h.
Asunto(s)
Antiinfecciosos/uso terapéutico , Ceftriaxona/uso terapéutico , Fluoroquinolonas , Meningitis Neumocócica/tratamiento farmacológico , Naftiridinas/uso terapéutico , Infecciones Neumocócicas/tratamiento farmacológico , Animales , Antiinfecciosos/líquido cefalorraquídeo , Antiinfecciosos/farmacología , Ceftriaxona/líquido cefalorraquídeo , Ceftriaxona/farmacología , Cefalosporinas/líquido cefalorraquídeo , Cefalosporinas/farmacología , Cefalosporinas/uso terapéutico , Modelos Animales de Enfermedad , Sinergismo Farmacológico , Quimioterapia Combinada , Meningitis Neumocócica/líquido cefalorraquídeo , Meningitis Neumocócica/microbiología , Pruebas de Sensibilidad Microbiana , Naftiridinas/líquido cefalorraquídeo , Naftiridinas/farmacología , Resistencia a las Penicilinas , Infecciones Neumocócicas/líquido cefalorraquídeo , Infecciones Neumocócicas/microbiología , Conejos , Streptococcus pneumoniae/efectos de los fármacosRESUMEN
The treatment of meningitis caused by strains of Streptococcus pneumoniae with decreased susceptibility to third-generation cephalosporins is an increasingly frequent and difficult problem. In this study a rabbit model of meningitis was used to determine the efficacy of ceftriaxone at different dosages, and to establish the effect of the addition of dexamethasone to the chemotherapeutic regimen. Groups of eight rabbits were inoculated with 10(6) cfu/mL of a cephalosporin- resistant strain of S. pneumoniae (MIC of cefotaxime/ceftriaxone 2 mg/L). Eighteen hours after inoculation, ceftriaxone (50 or 100 mg/kg/day) with or without dexamethasone (0. 25 mg/kg/ day) was administered for a period of 48 h. The ceftriaxone dose of 50 mg/kg/day was not fully effective in this model (therapeutic failure rate 28%). With a dose of 100 mg/kg/day there were no therapeutic failures and all CSF cultures were below the level of detection at 48 h. CSF ceftriaxone concentrations, area under the time-concentration curve and time above the MIC were not significantly different with or without dexamethasone. However, concomitant use of dexamethasone resulted in higher CSF bacterial counts and a higher number of therapeutic failures (57% with the 50 mg/kg/day dose and 28% with the 100 mg/kg/day dose). Increasing doses of ceftriaxone might be an effective mode of therapy for meningitis caused by S. pneumoniae with MIC = 2 mg/L. However, in contrast to cephalosporin-sensitive cases, in cases caused by ceftriaxone-resistant strains, concomitant use of dexamethasone was associated with a higher failure rate even when a higher dosage of ceftriaxone was used.
Asunto(s)
Antiinflamatorios/uso terapéutico , Ceftriaxona/uso terapéutico , Cefalosporinas/uso terapéutico , Dexametasona/uso terapéutico , Meningitis Neumocócica/tratamiento farmacológico , Meningitis Neumocócica/microbiología , Streptococcus pneumoniae/efectos de los fármacos , Animales , Antiinflamatorios/líquido cefalorraquídeo , Área Bajo la Curva , Ceftriaxona/líquido cefalorraquídeo , Resistencia a las Cefalosporinas , Cefalosporinas/líquido cefalorraquídeo , Dexametasona/líquido cefalorraquídeo , Quimioterapia Combinada , Femenino , Meningitis Neumocócica/líquido cefalorraquídeo , Pruebas de Sensibilidad Microbiana , ConejosRESUMEN
In a rabbit model of meningitis caused by a pneumococcus highly resistant to penicillin (MIC, 4 microg/ml), meropenem, a broad-spectrum carbapenem, was bactericidal (-0.48+/-0.14 deltalog10 cfu/ml h) and slightly superior to ceftriaxone (-0.34+/-0.23 deltalog10 cfu/ml x h) and vancomycin (-0.39+/-0.19 deltalog10 cfu/ml x h). Although the combination of vancomycin with ceftriaxone was significantly more active than ceftriaxone alone (-0.55+/-0.19 deltalog10 cfu/ml x h), only an insignificant gain was observed by the addition of vancomycin to meropenem (-0.55+/-0.28 deltalog10 cfu/ml x h).
Asunto(s)
Quimioterapia Combinada/uso terapéutico , Meningitis Neumocócica/tratamiento farmacológico , Streptococcus pneumoniae/efectos de los fármacos , Tienamicinas/uso terapéutico , Vancomicina/uso terapéutico , Animales , Ceftriaxona/líquido cefalorraquídeo , Ceftriaxona/farmacología , Ceftriaxona/uso terapéutico , Cefalosporinas/líquido cefalorraquídeo , Cefalosporinas/farmacología , Cefalosporinas/uso terapéutico , Recuento de Colonia Microbiana , Modelos Animales de Enfermedad , Quimioterapia Combinada/líquido cefalorraquídeo , Quimioterapia Combinada/farmacología , Meningitis Neumocócica/microbiología , Meropenem , Pruebas de Sensibilidad Microbiana , Resistencia a las Penicilinas , Conejos , Tienamicinas/líquido cefalorraquídeo , Tienamicinas/farmacología , Vancomicina/líquido cefalorraquídeo , Vancomicina/farmacologíaRESUMEN
The fluoroquinolone trovafloxacin was bactericidal (0.47 +/- 0.23 delta log10 CFU/ml x h after 10 mg/kg of body weight and 0.78 +/- 0.15 delta log10 CFU/ml x h after 30 mg/kg) in the treatment of experimental meningitis caused by a highly penicillin-resistant (MIC and minimum bactericidal concentration = 4 and 4 microg/ml) strain of Streptococcus pneumoniae. Combinations with ampicillin and rifampin were indifferent compared to single drugs.
Asunto(s)
Antiinfecciosos/uso terapéutico , Fluoroquinolonas , Meningitis Neumocócica/tratamiento farmacológico , Naftiridinas/uso terapéutico , Ampicilina/líquido cefalorraquídeo , Ampicilina/uso terapéutico , Animales , Antibacterianos/líquido cefalorraquídeo , Antibacterianos/uso terapéutico , Antiinfecciosos/sangre , Antiinfecciosos/líquido cefalorraquídeo , Ceftriaxona/líquido cefalorraquídeo , Ceftriaxona/uso terapéutico , Pruebas de Sensibilidad Microbiana , Naftiridinas/sangre , Naftiridinas/líquido cefalorraquídeo , Resistencia a las Penicilinas , Conejos , Rifampin/líquido cefalorraquídeo , Rifampin/uso terapéutico , Streptococcus pneumoniae/efectos de los fármacosRESUMEN
We evaluated the pharmacokinetics and therapeutic efficacy of ampicillin combined with sulbactam in a rabbit model of meningitis due to a beta-lactamase-producing strain of Escherichia coli K-1. Ceftriaxone was used as a comparison drug. The MIC and MBC were 32 and greater than 64 micrograms/ml (ampicillin), greater than 256 and greater than 256 micrograms/ml (sulbactam), 2.0 and 4.0 micrograms/ml (ampicillin-sulbactam [2:1 ratio, ampicillin concentration]) and 0.125 and 0.25 micrograms/ml (ceftriaxone). All antibiotics were given by intravenous bolus injection in a number of dosing regimens. Ampicillin and sulbactam achieved high concentrations in cerebrospinal fluid (CSF) with higher dose regimens, but only moderate bactericidal activity compared with that of ceftriaxone was obtained. CSF bacterial titers were reduced by 0.6 +/- 0.3 log10 CFU/ml/h with the highest ampicillin-sulbactam dose used (500 and 500 mg/kg of body weight, two doses). This was similar to the bactericidal activity achieved by low-dose ceftriaxone (10 mg/kg), while a higher ceftriaxone dose (100 mg/kg) produced a significant increase in bactericidal activity (1.1 +/- 0.4 log10 CFU/ml/h). It appears that ampicillin-sulbactam, despite favorable CSF pharmacokinetics in animals with meningitis, may be of limited value in the treatment of difficult-to-treat beta-lactamase-producing bacteria, against which the combination shows only moderate in vitro activity.