Therapeutic Responses to Quinine and Clindamycin in Multidrug-Resistant Falciparum Malaria

Therapeutic responses to clindamycin in combination with quinine were assessed in adult Thai patients with uncomplicated multidrug-resistant Plasmodium falciparum malaria. In total 204 patients were randomized to receive a 7-day oral treatment regimen of quinine (Q(7)) either alone (n = 68), in combination with clindamycin (Q(7)C(7); n = 68), or in combination with tetracycline (Q(7)T(7); n = 68). All patients had uncomplicated recoveries with no serious adverse effects. Fever clearance times for both of the two combination regimens (median of 47 h and range of 8 to 120 h for Q(7)C(7) and median of 36 h and range of 8 to 117 h for Q(7)T(7)) were significantly shorter than that for the Q(7)-only regimen (median, 56; range, 4 to 152 h) (P = 0.002). Parasite clearance times (overall mean ± standard deviation, 78 ± 23 h) were not significantly different between the three treatment groups (P = 0.98). The cure rates assessed at 28 days of follow-up were 100% for Q(7)C(7) and 98% for Q(7)T(7), whereas the cure rate was 87% for the Q(7)-only regimen (P ≤ 0.04). Clindamycin in combination with quinine is a safe and effective treatment for multidrug-resistant P. falciparum malaria. This combination may be of particular value in children and pregnant women, in whom tetracyclines are contraindicated.

本研究针对泰国成年单纯性耐多药恶性疟原虫（Plasmodium falciparum）疟疾患者，评估了克林霉素联合奎宁的治疗应答效果。总计204名患者被随机分配接受7天口服奎宁（Q(7)）治疗方案，分为三组：单纯奎宁组（n=68）、奎宁联合克林霉素组（Q(7)C(7)；n=68）以及奎宁联合四环素组（Q(7)T(7)；n=68）。所有患者均实现单纯性康复，未出现严重不良反应。两种联合治疗方案的退热时间均显著短于单纯奎宁组（Q(7)C(7)组退热时间中位数为47小时，范围8~120小时；Q(7)T(7)组中位数为36小时，范围8~117小时；单纯奎宁组中位数为56小时，范围4~152小时，P=0.002）。三组患者的疟原虫清除时间（总体均值±标准差为78±23小时）无显著统计学差异（P=0.98）。随访28天时评估的治愈率分别为：Q(7)C(7)组100%、Q(7)T(7)组98%，而单纯奎宁组治愈率为87%（P≤0.04）。克林霉素联合奎宁是治疗耐多药恶性疟原虫疟疾的安全有效方案，该联合疗法在四环素类药物禁忌的儿童及孕妇群体中可能具有特殊应用价值。