Ciprofloxacin Treatment of Drug-Resistant Falciparum Malaria

Abstract

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.

In Vitro Activities of Antibiotics against Plasmodium falciparum Are Inhibited by Iron

“…The IC 50 for tetracyclines in our experiments was close to those reported by other authors: 39 M for oxytetracycline (6), 32 M for tetracycline (55), and 11 M for doxycycline (40). Doxycycline and minocycline were the most potent tetracyclines.…”

“…Inhibition of activity was more pronounced for minocycline and oxytetracycline. The ratio of the antibiotic IC 50 with FeCl 3 to that of the antibiotic IC 50 without FeCl 3 was greater than 2 for minocycline combined with 750 M FeCl 3 and for oxytetracycline combined with 1,000 M FeCl 3 . The IC 50 of desferrioxamine was 4-to Ͼ10-fold higher when combined with FeCl 3 .…”

“…Macrolide antibiotics, such as erythromycin and azithromycin, also have both in vitro activity against P. falciparum (11,13) and clinical activity (42,48). Similarly, fluoroquinolones were also proven to have antimalarial activity in vitro (19,56) and in vivo (50).…”

“…In all living organisms, iron is an essential growth element (50). This metallic compound is needed for the catalysis of DNA synthesis and for a variety of enzymes concerned in electron transport and energy metabolism.…”

Antimicrosporidial activity of (fluoro)quinolones in vitro and in vivo

“…These compounds are structurally related to antimalarial quinolones, and a few fluoroquinolones, including trovafloxacin, ciprofloxacin, enoxacin, ofloxacin, and norfloxacin were shown to inhibit Plasmodium falciparum and Trypanosoma brucei brucei growth in vitro (Divo et al 1988, Tripathi et al 1993, Nenortas et al 1998, Hamzah et al 2000. Norfloxacin also was reported to be effective for treating P. falciparum and Plasmodium vivax infections in India (Sarma 1989, Tripathi et al 1993), but ciprofloxacin was ineffective against multidrug resistant P. falciparum infections in Thailand (Watt et al 1991). Trovafloxacin, grepafloxacin, gatifloxacin, and moxifloxacin were among the most effective of 24 (fluoro)quinolones tested for their ability to inhibit Toxoplasma gondii replication in vitro (Gozalbes et al 2000).…”