Table 1.
IC50 of Leishmania isolates and Leishmania guyanensis reference strain according to the medium used and the drug tested
| Species | Medium | Isolate number | Promastigote IC50 | Clinical outcome§ | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Amphotericin B | Azithromycin | Fluconazole | Meglumine antimoniate | Miltefosine | Paromomycin | Pentamidine | |||||||||||
| μg/mL | 95% CI | μg/mL | 95% CI | μg/mL | 95% CI | μg/mL | 95% CI | μg/mL | 95% CI | μg/mL | 95% CI | μg/mL | 95% CI | ||||
| L. guyanensis | R | 1 | 4.16 | 3.50–4.94 | > 3,000 | – | 3,759 | 3,252–4,345 | 9,510 | 8,768–10,316 | 3.91 | 3.25–4.34 | < 156.25 | – | 0.0013 | 0.012–0.014 | Sensitive presumed |
| 2 | 11.51 | 11.17–11.87 | > 3,000 | – | 5,000–10,000 | – | 7,500–15,000 | – | 3.9–7.8 | – | < 156.25 | – | 0.00078–0.0015 | – | Sensitive | ||
| 3 | 4.19 | 3.52–4.98 | 192.4 | 175.9–210.4 | 3,607 | 495.2–26,267 | 5,222 | 3,666–7,438 | < 3.9 | – | < 156.25 | – | 0.0011 | 0.0009–0.001 | – | ||
| 4 | 1.87 | 1.63–2.15 | – | – | – | – | 3,057 | 2,711–3,447 | < 3.9 | – | 1,211 | 982.7–1,492 | – | – | Sensitive | ||
| 5 | 1.56–3.12 | – | – | – | – | – | 2,781 | 2,103–3,676 | < 3.9 | – | > 5,000 | – | – | – | Sensitive presumed | ||
| 6 | 1.58 | 1.43–1.74 | – | – | – | – | 3,353 | 3,065–3,669 | < 3.9 | – | 701.8 | 542.7–907.4 | – | – | – | ||
| 7 | 5.38 | 4.70–6.16 | – | – | – | – | 3,034 | 2,860–3,218 | < 3.9 | – | 1,154 | 928.8–1,434 | 0.0065 | – | Sensitive | ||
| 8 | 1.89 | 1.61–2.21 | – | – | – | – | 2,562 | 1,009–6,504 | < 3.9 | – | 2,314 | 826.1–6,484 | > 0.01 | – | Resistant | ||
| 9 | 2.57 | 2.39–2.77 | – | – | – | – | 2,802 | 2,458–3,193 | < 3.9 | – | 953.4 | 365.1–2,489 | 0.004 | 0.004–0.005 | Sensitive | ||
| 10 | 0.78–1.56 | – | – | – | – | – | < 937.5 | – | 5.27 | 4.69–5.92 | < 156.25 | – | 0.0025 | 0.002–0.003 | Sensitive | ||
| 11 | 9.81 | 8.86–10.85 | – | – | – | – | 15,000–30,000 | – | 10.53 | 7.97–13.90 | 96.27 | 53.84–172.2 | 0.0056 | 0.005–0.006 | Sensitive presumed | ||
| 12 | 6.25–12.5 | – | – | – | – | – | 15,000–30,000 | – | 10.63 | 9.10–12.42 | 359.7 | 338.5–382.2 | 0.006 | 0.003–0.01 | – | ||
| 13 | 1.56–3.12 | – | – | – | – | – | 1,597 | 1,494–1,708 | – | – | 269.7 | 237.1–306.7 | 0.0094 | 0.003–0.02 | Resistant | ||
| 14 | 1.03 | 0.85–1.23 | – | – | – | – | < 937.5 | – | < 3.9 | – | 56.47 | 39.93–79.86 | 0.0059 | 0.005–0.006 | Sensitive | ||
| 15 | 3.76 | 3.12–4.53 | – | – | – | – | 1,875–3,750 | – | 6.64 | 5.33–8.26 | 98.12 | 89.52–107.5 | 0.0057 | 0.005–0.006 | Sensitive | ||
| Ref* | 1.4 | 1.31–1.492 | < 93.75 | – | 3,117 | 3,016–3,222 | 10,705 | 9,830–11,657 | 3.9–7.8 | – | 110 | 75.5–160.3 | 0.002119 | 0.0017–0.0025 | |||
| Isolates interval values in R medium† | 1.03–12.5 | 192.4–> 3,000 | 3,607–10,000 | < 937.5–30,000 | < 3.9–10.63 | < 156.25–> 5,000 | 0.001–> 0.01 | ||||||||||
| L. guyanensis | S | 16 | 6.25–12.5 | – | – | – | – | – | 15,000–30,000 | – | > 125 | – | 48.12 | 14.82–156.3 | 0.0041 | 0.003–0.004 | – |
| 17 | 23.89 | 0.3079–1,854 | – | – | – | – | > 30,000 | – | 10.6 | 9.17–12.26 | < 156.25 | – | 0.00312–0.00625 | – | Sensitive presumed | ||
| 18 | 6.25–12.5 | – | – | – | – | – | 13,339 | 10,841–16,412 | 7.6 | 6.89–8.39 | < 156.25 | – | 0.003 | 0.002–0.003 | Sensitive | ||
| 19 | > 25 | – | – | – | – | – | > 30,000 | – | > 125 | – | 267.3 | 241.9–295.2 | > 0.01 | – | Resistant | ||
| 20 | – | – | – | – | – | – | – | – | < 3.9 | – | < 156.25 | – | 0.00312–0.00625 | – | Sensitive presumed | ||
| 21 | 3.12–6.25 | – | – | – | – | – | – | – | 9.95 | 8.17–12.13 | < 156.25 | – | 0.0025 | 0.0022–0.0027 | Resistant | ||
| 22 | 3.1 | – | – | – | – | – | < 937.5 | – | 6.66 | 5.92–7.50 | < 156.25 | – | 0.0033 | 0.002–0.005 | – | ||
| 23 | 3.12–6.25 | – | – | – | – | – | > 30,000 | – | 7.8–15.6 | – | < 156.25 | – | 0.0026 | 0.001–0.004 | Sensitive | ||
| 24 | 3.12–6.25 | – | – | – | – | – | 18,699 | 4,757–73,501 | 11.7 | 10.81–12.66 | < 156.25 | – | 0.0036 | 0.0033–0.0039 | Intermediate | ||
| 25 | 6.25–12.5 | – | – | – | – | – | – | – | 3.09 | 2.57–3.72 | 98.52 | 34.45–281.7 | 0.0015 | 0.0013–0.0019 | Intermediate | ||
| 26 | 3.92 | – | – | – | – | – | < 937.5 | – | 1.55 | 0.17–13.96 | < 156.25 | – | 0.0033 | 0.002–0.004 | – | ||
| 27 | 4.93 | 4.82–5.04 | 102.3 | 88.52–118.2 | 3,145 | 2,995–3,303 | 18,642 | 8,707–39,913 | < 3.9 | – | 738.9 | 425.7–1,283 | 0.00312–0.00625 | – | – | ||
| Ref | 2.08 | 0.002–2,044 | < 93.75 | – | < 312.5 | – | < 937.5 | – | 8.85 | 4.9–15.9 | 186.8 | 134.6–259.2 | 0.002329 | 0.00084–0.0064 | |||
| Isolates interval values in S medium† | 3.1–> 25 | 102.3 | 3,145 | < 937.5–> 30,000 | < 3.9–> 125 | 48.12–738.9 | 0.0015–> 0.01 | ||||||||||
| L. guyanensis | R-BH | 28 | 6.25–12.5 | – | 187.5–375 | – | 2,500–5,000 | – | 13,130 | 12,902–13,362 | 3.52 | 3.24–3.82 | 159.8 | 134.5–189.9 | 0.00312–0.00625 | – | Sensitive presumed |
| 29 | 4.41 | 4.11–4.73 | 35.15 | 17.68–69.89 | 2,993 | 2,951–3,035 | 7,349 | 4,966–10,875 | < 3.9 | – | 358.1 | 275.5–465.4 | 0.0015–0.00312 | – | – | ||
| 30 | 13.31 | 12.71–13.94 | 83.72 | 74.91–93.58 | 3,327 | 3,244–3,411 | – | – | 1.61 | 0.52–5.01 | 714.3 | 611.7–834.2 | 0.0035 | 0.003–0.004 | Sensitive presumed | ||
| 31 | > 25 | – | 177.7 | 139.3–226.5 | 4,638 | 3,505–6,138 | > 30,000 | – | < 3.9 | – | 4,461 | 303.6–65,551 | 0.0028 | 0.002–0.003 | – | ||
| 32 | 3.29 | 3.21–3.37 | < 93.75 | – | 2,011 | 1,893–2,137 | 4,744 | 3,343–6,730 | < 3.9 | – | – | – | 0.0015–0.00312 | – | – | ||
| 33 | 7.83 | 7.38–8.31 | < 93.75 | – | 2,500–5,000 | – | – | – | – | – | – | – | – | – | Intermediate | ||
| Ref | 2.39 | 2.27–2.54 | < 93.75 | – | 2,992 | 2,773–3,228 | 10,635 | 9,424–12,001 | 6.2 | 5.9–6.52 | 77.89 | 46.15–131.5 | 0.002537 | 0.0023–0.0027 | |||
| Isolates interval values in R–BH medium† | 3.29–> 25 | < 93.75–375 | 2,011–5,000 | 4,744–> 30,000 | 1.61–3.52 | 159.8–4,461 | 0.001–0.006 | ||||||||||
| Leishmania braziliensis | R–BH | 34 | 1.27 | 1.08–1.48 | 83.31 | 59.73–116.2 | 830.7 | 687.6–1,004 | – | – | 3 | 1.31–6.85 | – | – | 0.0016 | 0.001–0.002 | – |
| L. braziliensis | R | 35 | < 0.78 | – | – | – | – | – | – | – | < 3.9 | – | < 156.25 | – | 0.00625–0.0125 | – | – |
| Leishmania amazonensis | R–BH | 36 | 8.35 | 7.77–8.98 | < 93.75 | – | 3,105 | 2,983–3,232 | 9,822 | 9,384–10,282 | 1.95 | 0.45–8.29 | 129.6 | 122.1–137.5 | 0.00312–0.00625 | – | – |
| Total isolates interval values‡ | < 0.78–> 25 | < 93.75–> 3,000 | 830.7–10,000 | 4,744–> 30,000 | < 3.9–> 125 | < 156.25–> 5,000 | 0.001–> 0.01 | ||||||||||
IC50 = 50% inhibitory concentration; R = RPMI 1640 medium; R-BH = RPMI 1640 medium + L-Biopterin and Hemin Chloride; S = Schneider medium (+ L-Biopterin and Hemin Chloride).
*
Ref = Leishmania guyanensis reference strain.
†
Isolates interval values for each medium according to the drug tested.
‡
Isolates interval values for all medium included, according to the drug tested.
§
Sensitive, cured after one course of pentacarinat; sensitive presumed, presumed cured after one course of pentacarinat (did not consult again); intermediate, cured after two courses of pentacarinat; resistant, cured after three or more courses of pentacarinat.