Watt G, Chouriyagune C, Ruangweerayud R, Watcharapichat P, Phulsuksombati D, Jongsakul K, Teja-Isavadharm P, Bhodhidatta D, Corcoran K D, Dasch G A, Strickman D
Department of Medicine, US Army Component, AFRIMS, Bangkok, Thailand.
Lancet. 1996 Jul 13;348(9020):86-9. doi: 10.1016/s0140-6736(96)02501-9.
Rickettsia tsutsugamushi, the aetiological agent of scrub typhus, is common in Asia and readily infects visitors to areas where disease transmission occurs. Rapid defervescence after antibiotic treatment is so characteristic that it is used as a diagnostic test for R tsutsugamushi infection. Reports from local physicians that patients with scrub typhus in Chiangrai, northern Thailand responded badly to appropriate antibiotic therapy prompted us to do a prospective clinical evaluation and antibiotic susceptibility testing of human rickettsial isolates.
The clinical response to doxycycline treatment in patients with early, mild scrub typhus in northern Thailand was compared with the results of treatment in Mae Sod, western Thailand. Prototype and naturally occurring strains of R tsutsugamushi were tested for susceptibility to chloramphenicol and doxycycline in mice and in cell culture.
By the third day of treatment, fever had cleared in all seven patients from Mae Sod, but in only five of the 12 (40%) from Chiangrai (p < 0.01). Median fever clearance time in Chiangrai (80 h; range 15-190) was significantly longer than in Mae Sod (30 h; range 4-58; p < 0.005). Conjunctival suffusion resolved significantly more slowly in Chiangrai (p < 0.05). Antibiotics prevented death in mice infected by Chiangrai strains of R tsutsugamushi less often than after infection by the prototype strain (p < 0.05). Only one of three Chiangrai strains tested in cell culture was fully susceptible to doxycycline.
Chloramphenicol-resistant and doxycycline-resistant strains of R tsutsugamushi occur in Chiangrai, Thailand. This is the first evidence of naturally occurring antimicrobial resistance in the genus Rickettsia.
恙虫病东方体是恙虫病的病原体，在亚洲很常见，容易感染疾病传播地区的游客。抗生素治疗后迅速退热是恙虫病东方体感染的一个显著特征，因此被用作诊断试验。泰国北部清莱当地医生报告称，恙虫病患者对适当的抗生素治疗反应不佳，这促使我们对人类立克次体分离株进行前瞻性临床评估和抗生素敏感性测试。
比较了泰国北部早期轻症恙虫病患者接受多西环素治疗的临床反应与泰国西部湄索患者的治疗结果。在小鼠和细胞培养中测试了恙虫病东方体的原型菌株和自然发生菌株对氯霉素和多西环素的敏感性。
治疗第三天时，湄索的7名患者均已退热，但清莱的12名患者中只有5名（40%）退热（p<0.01）。清莱的中位退热时间（80小时；范围15 - 190小时）显著长于湄索（30小时；范围4 - 58小时；p<0.005）。清莱患者结膜充血消退明显更慢（p<0.05）。与感染原型菌株相比，抗生素预防泰国清莱菌株感染小鼠死亡的效果较差（p<0.05）。在细胞培养中测试的3株清莱菌株中，只有1株对多西环素完全敏感。
泰国清莱存在氯霉素耐药和多西环素耐药的恙虫病东方体菌株。这是立克次体属自然发生抗菌耐药性的首个证据。
