Cottagnoud Philippe, Täuber Martin G.
*Department of Internal Medicine, Inselspital, Freiburgstrasse, 3010 Bern, Switzerland.
Curr Infect Dis Rep. 2003 Aug;5(4):329-336. doi: 10.1007/s11908-003-0011-0.
The continuous increase of resistant pathogens causing meningitis has limited the efficacy of standard therapeutic regimens. Due to their excellent activity in vitro and their good penetration into the cerebrospinal fluid (CSF), fluoroquinolones appear promising for the treatment of meningitis caused by gram-negative microorganisms, ie, Neisseria meningitidis and nosocomial gram-negative bacilli. The newer fluoroquinolones (moxifloxacin, gemifloxacin, gatifloxacin, and garenoxacin) have excellent activity against gram-positive microorganisms. Studies in animal models and limited clinical data indicate that they may play a future role in the treatment of pneumococcal meningitis. Analysis of pharmacodynamic parameters suggests that CSF concentrations that produce a C(peak)/minimal bactericidal concentration (MBC) ratio of at least 5 and concentrations above the MBC during the entire dosing interval are a prerequisite for maximal bactericidal activity in meningitis. Of interest, newer fluoroquinolones act synergistically with vancomycin and beta-lactam antibiotics (ceftriaxone, cefotaxime, meropenem) against penicillin-resistant pneumococci in experimental rabbit meningitis, potentially providing a new therapeutic strategy. Clinical trials are needed to further explore the usefulness of quinolones as single agents or in combination with other drugs in the therapy of pneumococcal meningitis.
引起脑膜炎的耐药病原体不断增加，限制了标准治疗方案的疗效。由于氟喹诺酮类药物在体外具有出色的活性，且能很好地穿透脑脊液（CSF），因此在治疗由革兰氏阴性微生物引起的脑膜炎方面显示出前景，即脑膜炎奈瑟菌和医院获得性革兰氏阴性杆菌。新型氟喹诺酮类药物（莫西沙星、吉米沙星、加替沙星和加雷沙星）对革兰氏阳性微生物具有出色的活性。动物模型研究和有限的临床数据表明，它们可能在未来的肺炎球菌性脑膜炎治疗中发挥作用。药效学参数分析表明，脑脊液浓度产生的C（峰值）/最低杀菌浓度（MBC）比值至少为5，且在整个给药间隔期间浓度高于MBC，是脑膜炎中最大杀菌活性的先决条件。有趣的是，在实验性兔脑膜炎中，新型氟喹诺酮类药物与万古霉素和β-内酰胺类抗生素（头孢曲松、头孢噻肟、美罗培南）对耐青霉素肺炎球菌具有协同作用，这可能提供一种新的治疗策略。需要进行临床试验，以进一步探索喹诺酮类药物作为单一药物或与其他药物联合用于肺炎球菌性脑膜炎治疗的有效性。
