Table 1. In-vitro Susceptibility of O1 and O139 V. cholerae Strains Isolated from Patients Enrolled in Clinical Trials
|
Antimicrobial agent |
No. of strains |
MIC50 (ug/ml) |
MIC90 (ug/ml) |
Range |
Ref |
|
Tetracycline |
12 102 |
1.56 ND |
ND 0.250 |
1.25-2.5 0.06-0.5 |
14 42 |
|
Doxycycline |
260* |
ND |
0.125 |
ND |
54 |
|
Cotrimoxazole |
32 |
1.47 |
ND |
0.2-3.2 |
14 |
|
Lomefloxacin |
68 |
ND |
0.06 |
ND |
41 |
|
Ciprofloxacin |
100 260* 168† 14‡ |
ND ND 0.250 0.0230 |
0.007 0.003 ND ND |
0.0007-0.25 ND ND ND |
42 54 88 88 |
|
Norfloxacin |
32 |
ND |
ND |
0.008-0.016 |
97 |
|
Azithromycin |
123§ |
ND |
ND |
0.125 |
55 |
|
Erythromycin |
123§ |
ND |
ND |
1.0 |
55 |
ND= not done
* includes 130 O139 strains
† V.cholerae O1
‡ V. cholerae O139
§ V. cholerae O1 (103) and O139 (19): all attains were inhibited by that MIC. Peak azithromycin concentration in
stools were 1444 times higher than the MIC for azithromycin, while erythromycin concentration was only 180 times higher than the MIC
Table 2. Antimicrobial Regimens for the Treatment of Cholera [Download PDF]
|
Drug |
Dose Adults |
Children |
|
Tetracycline |
500 mg four times-a-day for 3 days |
50 mg/kg of body weight four times-a-day for 3 days |
|
Doxycycline |
300 mg as a single-dose |
Not evaluated |
|
Furazolidone |
100 mg. four times-a-day for 3 days |
5 mg/Kg of body weight per day four times-a-day for 3 days, or 7 mg/Kg as a single dose |
|
Cotrimoxazole |
160 mg of trimethoprim/800 mg of sulfamethoxazole twice-a-day for divided in 3 days |
8 mg of trimethoprim-40 mg of sulfamethoxazole/kg divided in two doses for 3 days |
|
Norfloxacin |
400 mg. twice-a-day for 3 days |
Not recommended |
|
Ciprofloxacin |
250 mg. once-a-day for 3 days or 1g single-dose |
Not recommended |
|
Azithromycin |
1g, single-dose |
20 mg/kg, single-dose |
Table 3. Results from Studies with Fluoroquinolones in Cholera
|
Quinolone |
Study Design |
Dosing Regimens |
No. of patients |
Duration of Diarrhea (h)* |
Clinical Cure, n (%) |
Bacteriological Cure, n (%) |
Ref |
|
Norfloxacin |
1.Randomized double-blind, and controlled
2. Open, randomized, and controlled
3. Open, non-controlled
4.Randomized controlled |
a. Norfloxacin, 400mg bid, 3 days b. TMP/SMX, 160/800 mg, bid, 3 days c. Placebo
a. Norfloxacin, 400 mg bid, 3 days b. Norfloxacin, 800 mg single-dose c. Tetracycline,500mg qid, 3 days
Norfloxacin, 800mg, single-dose
a. Norfloxacin 400mg, bid, 3 days in adults, or 7.5mg/Kg bid in children b. Tetracycline,500mg qid, 3 days in adults, or 12.5mg/Kg qid in children |
13
12
12
25
34
35
32
12
13 |
19.2 (4.4)
27.5 (4.0)
29.3 (4.5)
60.8 (18.4)
91.04 (50.1)
61.66 (23.2)
------
1.25 (NS) days
1.31 (NS) days |
NS†
NS
NS
25 (74)
13 (52)
27 (77)
NS
NS
NS
|
NS
NS
NS
34 (100)
19 (76)
31 (91)
32 (100)
NS
NS |
5
40
97
71 |
|
Lomefloxacin |
Open, non Controlled |
400 mg, once per day, 3 days |
68 |
49.6 (16.9) |
61 (90) |
48 (100) |
41 |
|
Ofloxacin |
Open, non controlled |
400 mg per day, 2 days |
42 |
NS |
NS‡ |
NS |
30 |
|
Fleroxacin |
Open, randomized and controlled |
400 mg per day, single dose |
100 |
NS |
100 (100) |
100 (100) |
8 |
|
Ciprofloxacin |
1. Open, non controlled
2. Open, non controlled
3. Open, non controlled
4. Open, randomized, and controlled
5.Randomized double-blind, and controlled
6.Randomized double-blind, and controlled
7. Open, non randomized
8.Randomized double-blind, and controlled
9. Open, randomized, controlled
|
500 mg, bid. 3 days
250 mg, bid, 3 days
1g per day, 2 days
a.Ciprofloxacin,500mg bid, 3 days b.Tetracycline,500mg qid, 3 days
a.Ciprofloxacin,250mg once-a-day, 3 days b.Tetracycline,500mg qid, 3 days
a. Ciprofloxacin,1g single-dose b. Doxycycline,300mg single-dose
Ciprofloxacin, 1g single-dose**
a.Ciprofloxacin, 1g single- dose b. Doxycycline,300mg single-dose
a. Ciprofloxacin, 1g single-dose b. Ciprofloxacin,500mg bid, 1day c. Doxycycline,100mg bid, 3 days d. Placebo |
20
21
7
15
12
100
102
66
64
16
59
71
21
19
21
13 |
53.6 (14)
48.3 (14.4)
NS
NS §
NS
51.2 (17.4)
48.0 (20.6)
NS ¶
NS
41 (19)
NS ¶
NS
1.9 (0.6)
2.5 (0.7)
2.8 (0.9)
4 (0.6) |
18 (90)
19 (90)
NS
14 (93)
5 (42)
84 (84)
91 (89)
62 (94)
47 (73)
NS ††
54 (92)
65 (92)
NS
NS
NS
NS |
20 (100)
21 (100)
NS
15 (100)
6 (50)
99 (99)
97 (95)
63 (95)
44 (69)
NS††
58 (98)
56 (79)
20 (95)
17 (90)
19 (91)
2 (15)
|
43
43
30
52
42
54
53
54
99
|
* Values are mean (SD) in hours, unless noted otherwise
† NS= not specified
‡ Volume of diarrhea and excretion of vibrio were significant reduced at the end of therapy
§ Patients in the ciprofloxacin group had shorten duration of diarrhea than patients in the tetracycline group (Kaplan-Meier survival curve, p=0.004 by log rank test)
¶ Ciprofloxacin group had shorten duration of diarrhea than single-dose doxycycline group in V. cholerae O1 infected patients, but not in V. cholerae O139 infected
patients (Kaplan-Meier survival curve, p=0.0451 and p=0.435 by log rank test, respectively)
** Studies conducted in O139 V. cholerae
†† Diarrhea stopped in all patients within 72 hours of therapy. Stool cultures were negative for V. cholerae O139 during the third day of therapy.