Russell P, Eley S M, Ellis J, Green M, Bell D L, Kenny D J, Titball R W
CBD Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
J Antimicrob Chemother. 2000 Jun;45(6):813-8. doi: 10.1093/jac/45.6.813.
Melioidosis and glanders are caused by the closely related species Burkholderia pseudomallei and Burkholderia mallei, respectively. Whereas melioidosis is a significant cause of morbidity in south-east Asia, glanders is extremely rare. The efficacies of ciprofloxacin and doxycycline were assessed against a strain of B. pseudomallei and a strain of B. mallei which were susceptible to both antimicrobials in vitro. Porton outbred mice and Syrian hamsters were given 40 mg/kg of either doxycycline or ciprofloxacin twice daily by sc injection according to one of three regimens: dosing starting 48 h before challenge and continuing for 5 days postchallenge; 5 days' therapy starting immediately after challenge; 5 days' therapy starting 24 h after challenge. Mice were challenged ip with B. pseudomallei 4845 and hamsters were challenged ip with B. mallei 23344. Antimicrobial efficacy was determined by the shift in the median lethal dose (MLD). Ciprofloxacin prophylaxis and immediate therapy both raised the MLD of B. pseudomallei to 4 x 10(6) cfu from 19 cfu in untreated animals, but therapeutic ciprofloxacin only raised the MLD to 180 cfu. The results for doxycycline were similar. Ciprofloxacin prophylaxis raised the MLD of B. mallei 23344 to 4.6 x 10(5) cfu compared with 4 cfu in untreated controls. Immediate therapy raised the MLD to 7.0 x 10(4) cfu and therapy raised the MLD to 1.6 x 10(3) cfu. All regimens of doxycycline protected hamsters against challenges of up to 2 x 10(7) cfu. Despite using a susceptible strain of B. pseudomallei, neither antimicrobial was effective when used therapeutically. The timely administration of either antimicrobial, however, was effective in preventing symptomatic infection. Doxycycline was the superior of the two antimicrobials against experimental glanders although relapse did occur in treated animals approximately 4-5 weeks after challenge.
类鼻疽和鼻疽分别由密切相关的伪鼻疽伯克霍尔德菌和鼻疽伯克霍尔德菌引起。类鼻疽是东南亚地区发病的一个重要原因，而鼻疽极为罕见。评估了环丙沙星和多西环素对一株体外对这两种抗菌药物均敏感的伪鼻疽伯克霍尔德菌和一株鼻疽伯克霍尔德菌的疗效。根据三种方案之一，通过皮下注射给波特on远交系小鼠和叙利亚仓鼠每日两次给予40mg/kg的多西环素或环丙沙星：在攻毒前48小时开始给药并在攻毒后持续5天；攻毒后立即开始5天治疗；攻毒后24小时开始5天治疗。小鼠经腹腔注射伪鼻疽伯克霍尔德菌4845，仓鼠经腹腔注射鼻疽伯克霍尔德菌23344。通过半数致死剂量（MLD）的变化来确定抗菌疗效。环丙沙星预防和立即治疗均将伪鼻疽伯克霍尔德菌的MLD从未经治疗动物的19cfu提高到4×10⁶cfu，但治疗性环丙沙星仅将MLD提高到180cfu。多西环素的结果相似。环丙沙星预防将鼻疽伯克霍尔德菌23344的MLD提高到4.6×10⁵cfu，而未经治疗的对照组为4cfu。立即治疗将MLD提高到7.0×10⁴cfu，治疗将MLD提高到1.6×10³cfu。所有多西环素方案均保护仓鼠免受高达2×10⁷cfu的攻毒。尽管使用的是对环丙沙星敏感的伪鼻疽伯克霍尔德菌菌株，但两种抗菌药物在治疗时均无效。然而，及时给予任何一种抗菌药物在预防症状性感染方面均有效。在针对实验性鼻疽方面，多西环素是两种抗菌药物中更优的一种，尽管在攻毒后约4 - 5周治疗动物中确实发生了复发。
