Synergy between amoxicillin and gentamicin in combination against a highly penicillin-resistant and -tolerant strain of Streptococcus pneumoniae in a mouse pneumonia model
| Autor: | E Azoulay-Dupuis, P Moine, Claude Carbon, E Vallée, J. P. Bédos, C Sauve, C Darras-Joly |
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| Rok vydání: | 1996 |
| Předmět: |
Time Factors
medicine.drug_class Injections Subcutaneous Penicillin Resistance Antibiotics Microbial Sensitivity Tests Penicillins medicine.disease_cause Microbiology Mice Streptococcus pneumoniae medicine Animals Pharmacology (medical) Lung Antibacterial agent Pharmacology biology business.industry Aminoglycoside Amoxicillin Drug Synergism Pneumonia Pneumococcal Streptococcaceae biology.organism_classification Anti-Bacterial Agents Penicillin Infectious Diseases Drug Therapy Combination Gentamicin Gentamicins business Half-Life Research Article medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 40:2147-2151 |
| ISSN: | 1098-6596 0066-4804 |
| Popis: | In vivo synergy with beta-lactam antibiotics and aminoglycosides has been studied only with penicillin-susceptible Streptococcus pneumoniae strains. We evaluated the interaction between amoxicillin (AMX) and gentamicin (GEN) on the basis of in vitro checkerboard and time-kill curves and of findings in a mouse model of acute bacteremic pneumonia due to a highly penicillin-resistant and -tolerant S. pneumoniae strain of serotype 19 (penicillin and AMX MICs of 4 micrograms/ml; gentamicin MIC of 16 micrograms/ml). Checkerboard results at 18 h of incubation showed indifference. With regard to AMX alone, in vitro time-kill curves demonstrated synergy between AMX (1 microgram/ml) and GEN (16 micrograms/ml) at 5 and 8 h of incubation and for AMX (16 micrograms/ml) in combination with GEN (16 micrograms/ml) at 3, 5, and 8 h of incubation. In leukopenic mice, pulmonary killing curves after a single drug injection demonstrated that AMX (100 mg/kg of body weight) with GEN (16 mg/kg) was more effective than AMX alone (P = 10(-4). With repeated-dose treatment, a synergy was apparent at 8 h after four injections with AMX (100 mg/kg) in combination with GEN (8 or 16 mg/kg) (P < or = 0.05). The cumulative survival rate with AMX (100 mg/kg) every 8 h, combined with GEN (4 or 8 mg/kg) every 8, 12, or 24 h, was better than with AMX alone. Combined use of AMX and GEN may be a valuable therapeutic alternative for pneumococcal pneumonia due to highly penicillin-resistant S. pneumoniae strains. |
| Databáze: | OpenAIRE |
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