Division of Infectious Diseases, Department of Internal Medicine, Chosun University College of Medicine, Clinical Research Institute, Gwangju, South Korea.
Int J Antimicrob Agents. 2010 Aug;36(2):155-8. doi: 10.1016/j.ijantimicag.2010.03.022. Epub 2010 May 15.
Typhoid fever is a systemic intracellular infection caused by Salmonellaenterica serotype Typhi. The emergence and spread of nalidixic acid-resistant S. Typhi (NARST) is challenging for clinicians in many countries owing to the lack of suitable treatment options. The aim of this study was to identify in vitro synergistic combinations of antibiotics against S. Typhi. In vitro time-kill studies were performed on three clinical NARST isolates and one type strain of nalidixic acid-susceptible S. Typhi (NASST) ATCC 9992 with ciprofloxacin, cefotaxime and azithromycin in various combinations. The combination of ciprofloxacin (0.012-0.375 microg/mL) and cefotaxime (0.063-0.125 microg/mL) against all three NARST strains and the NASST strain was significantly more effective in vitro in reducing bacterial counts by >or=3log(10) colony-forming units at 24h and showed synergistic effects. Combination therapy with ciprofloxacin and cefotaxime might be the treatment of choice for patients with typhoid fever. The combination of a fluoroquinolone and a beta-lactam, which are directed against different targets, may improve efficacy compared with a fluoroquinolone alone and may reduce the chance of fluoroquinolone-resistant mutants emerging in patients with severe typhoid fever.
伤寒是由伤寒沙门氏菌血清型 Typhi 引起的全身性细胞内感染。由于缺乏合适的治疗选择，许多国家的临床医生都面临着耐萘啶酸伤寒沙门氏菌（NARST）的出现和传播的挑战。本研究旨在确定针对伤寒沙门氏菌的体外协同抗生素组合。对三种临床 NARST 分离株和一种萘啶酸敏感伤寒沙门氏菌（NASST）ATCC 9992 进行了体外时间杀伤研究，用环丙沙星、头孢噻肟和阿奇霉素进行了各种组合。对三种 NARST 菌株和 NASST 菌株，环丙沙星（0.012-0.375 μg/mL）和头孢噻肟（0.063-0.125 μg/mL）的组合在 24 小时内减少细菌计数>或=3log（10）菌落形成单位的效果明显更有效，表现出协同作用。对于伤寒患者，联合使用环丙沙星和头孢噻肟可能是治疗的首选。联合使用针对不同靶点的氟喹诺酮类药物和β-内酰胺类药物可能比单独使用氟喹诺酮类药物更有效，并且可能减少严重伤寒患者中氟喹诺酮类耐药突变体出现的机会。
