The effects of metronidazole and of pentavalent antimony (P) on the movement and multiplication of
Leishmania promastigotes were compared.
Leishmania was isolated from the skin of a Japanese man who had spent time in Saudi Arabia. The promastigotes were cultured at 25°C in test tubes that contained 1.3 m/ of NNN medium and 1.0 m/ of 0.85w/v% NaCl. Metronidazole or P was added to cultures by one of two protocols. Either promastigotes were cultured with the drug of choice from the initial day and these cultures were called initial-day cultures. Alternatively, promastigotes were cultured for 3 days initially without drugs and then a drug was included from the 4th day. These cultures were called 4th-day cultures. The movement and multiplication of promastigotes were observed for at least 14 days after initial exposure to either drug.
(1) Promastigotes were alive in the tubes that contained 1 mg of metronidazole or P until the 14th day of exposure to either drug in both initial-day cultures and 4th-day cultures, but their movements were not observed in the tubes that contained 5 mg, 7 mg or 9 mg of metronidazole or P after a 14-day exposure to either drug in both cultures.
(2) In a clinical setting, P is injected as 600 mg (defind here as 1 arbitrary unit) per adult per day and metronidazole is given at a dose of 750 mg (1.25 units), 1, 500 mg (2.50 units) or 22, 500 mg (3.75 units). P at 0.5 mg, 1 mg, 1.5 mg and 2 mg was regarded in separate tests as equivalent to 1 unit and metronidazole at 1.00, 1.25, 2.50 and 3.75 times each dose of P was added to promastigotes. As shown in tube No. 3 in Table 4 and tube No. 3 and No. 4 in Table 5, the parasites survived in the presence of 1 mg or 1.5 mg (1 unit) of P, but their movements were not observed in the presence of 2.5 mg or 3.75 mg (2.5 units) and 3.75 or 5.625 mg (3. 75 units) of metronidazole in initial-day cultures. In 4th-day cultures, as shown in Table 5, the parasites also survived with 1.5 mg (1 unit) of P, but their movements were not observed with 3.75 mg (2.5 units) and 5.625 mg (3.75 units) of metronidazole. In these conditions, the effects of metronidazole were superior to the effects of pentavalent antimony.
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