Stearne L E, Kooi C, Goessens W H, Bakker-Woudenberg I A, Gyssens I C
Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center, Rotterdam, The Netherlands.
Antimicrob Agents Chemother. 2001 Jan;45(1):243-51. doi: 10.1128/AAC.45.1.243-251.2001.
To determine the efficacy of trovafloxacin as a possible treatment for intra-abdominal abscesses, we have developed an anaerobic time-kill technique using different inocula to study the in vitro killing of Bacteroides fragilis in pure culture or in mixed culture with either Escherichia coli or a vancomycin-resistant strain of Enterococcus faecium (VREF). With inocula of 5 x 10(5) CFU/ml and trovafloxacin concentrations of </=2 microg/ml, a maximum observed effect (E(max)) of >/=6.1 (log(10) CFU/ml) was attained with all pure and mixed cultures within 24 h. With inocula of 10(8) CFU/ml, a similar E(max) and a similar concentration to produce 50% of E(max) (EC(50)) for B. fragilis were found in both pure cultures and mixed cultures with E. coli. However, to produce a similar killing of B. fragilis in the mixed cultures with VREF, a 14-fold increase in the concentration of trovafloxacin was required. A vancomycin-susceptible strain of E. faecium and a trovafloxacin-resistant strain of E. coli were also found to confer a similar "protective" effect on B. fragilis against the activity of trovafloxacin. Using inocula of 10(9) CFU/ml, the activity of trovafloxacin was retained for E. coli and B. fragilis and was negligible against VREF. We conclude that this is a useful technique to study the anaerobic killing of mixed cultures in vitro and may be of value in predicting the killing of mixed infections in vivo. The importance of using mixed cultures and not pure cultures is clearly shown by the difference in the killing of B. fragilis in the mixed cultures tested. Trovafloxacin will probably be ineffective in the treatment of infections involving large numbers of enterococci. However, due to its ability to retain activity against large cultures of B. fragilis and E. coli, trovafloxacin could be beneficial in the treatment of intra-abdominal abscesses.
为确定曲伐沙星作为腹腔内脓肿可能治疗药物的疗效，我们开发了一种厌氧时间杀菌技术，使用不同接种量来研究其对脆弱拟杆菌在纯培养物中或与大肠杆菌或耐万古霉素屎肠球菌（VREF）混合培养时的体外杀菌作用。接种量为5×10⁵CFU/ml且曲伐沙星浓度≤2μg/ml时，在24小时内所有纯培养物和混合培养物均达到了≥6.1（log₁₀CFU/ml）的最大观察效应（E(max)）。接种量为10⁸CFU/ml时，在脆弱拟杆菌的纯培养物和与大肠杆菌的混合培养物中发现了相似的E(max)以及产生50%E(max)（EC₅₀）的相似浓度。然而，为在与VREF的混合培养物中对脆弱拟杆菌产生相似的杀菌效果，曲伐沙星浓度需要增加14倍。还发现一株对万古霉素敏感的屎肠球菌和一株对曲伐沙星耐药的大肠杆菌对脆弱拟杆菌抵抗曲伐沙星的活性也具有相似的“保护”作用。使用接种量为10⁹CFU/ml时，曲伐沙星对大肠杆菌和脆弱拟杆菌仍有活性，而对VREF的活性可忽略不计。我们得出结论，这是一种研究体外混合培养物厌氧杀菌的有用技术，可能对预测体内混合感染的杀菌情况有价值。在所测试的混合培养物中脆弱拟杆菌杀菌情况的差异清楚地表明了使用混合培养物而非纯培养物的重要性。曲伐沙星可能对涉及大量肠球菌的感染治疗无效。然而，由于其对大量脆弱拟杆菌和大肠杆菌培养物仍有活性，曲伐沙星可能对腹腔内脓肿的治疗有益。
