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A randomized, open study of high-dose ciprofloxacin (750 mg every 12 h) in uncomplicated falciparum malaria was conducted in Thailand. No patient completed the planned 1-week treatment course. Because of rising parasitemia (threefold higher at 36 h than on admission) and deterioration of clinical status, three individuals required quinine treatment 36 h after commencing ciprofloxacin; a fourth was given quinine at 54 h. The study was terminated early for safety reasons after only four ciprofloxacin and four control patients had been enrolled. Ciprofloxacin was well absorbed and efficiently entered erythrocytes; median plasma and red cell concentrations 90 min after the first dose were 4.0 (range, 3.7-6.8) and 5.1 (3.8-6.0) micrograms/ml, respectively. However, 50% inhibition of parasite growth in vitro required 6.6 micrograms/ml, (5.6-9.6). Ciprofloxacin should not be used alone to treat chloroquine-resistant falciparum malaria.

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Abstract.Reports ofdeteriorating quinine efficacy prompted us to investigate the ability ofquinine-tetracycline to clear parasites and feverfrom patientswith multiple drug-resistant Plasmodium fakiparum infections. Past and present treatment results were compared at two study sites along the Thai-Cambodian border. In northeastern Thailand, quinine tetracycline cleared parasites more quickly in 1990 than in 1987 (mean 3.4 and 4.0 days, respectively; P = 0.006). In southeastern Thailand, there were no significant differences between 1990 (n = 26) and 1981â€"1983 (n = 42) in the time taken to clear either parasites (median 96 and 93 hr,respectively; P = 0.35)or fever(mean 74 and 66 hr,respectively; P = 0.30). In vitro drug sensitivity testing revealed a two-fold decrease in susceptibility toquinine between 1983 and 1990 in isolates from the southeastern Thai-Cambodian border (mean inhibitory concentration 166 ng/ml and 320 ng/ml, respectively; P < 0.001). We conclude that oral quinine-tetracycline continues to reliably clear parasites and fever from falciparum malaria patients infected in eastern Thailand. Periodic re-evaluations are war ranted, however, since the decrease in in vitro susceptibility to quinine may be followed by an in vivo decay in the treatment response.