Table 1.
Antibiotic prophylaxis efficacy against Francisella tularensis infection in mice.
| Drugs | Dosage, route$ | Duration | Time before or post-infection | Survival rate in animals depending on treatment time | Statistical significance versus untreated controls (100% death rates) or between antibiotics when specified |
|---|---|---|---|---|---|
| Barnes et al. (2021), Balb/c mice, Schu S4, aerosol, ~300 CFU | |||||
| Finafloxacin | 23.1 mg/kg tid, po | 3 days | 1 dpi$ | 100% at 35 dpi | p < 0.0001 |
| 7 days | 1 dpi | 100% at 35 dpi | P < 0.0001 | ||
| 3 days | 3 dpi | 0% at 35 dpi | NS, but delayed death | ||
| 7 days | 3 dpi | 50% at 35 dpi | More active than ciprofloxacin for 7 days (p < 0.01%) | ||
| Ciprofloxacin | 30 mg/kg bid, ip | 3 days | 1 dpi | 100% at 35 dpi | P < 0.0001 |
| 7 days | 1 dpi | 100% at 35 dpi | P < 0.0001 | ||
| 3 days | 3 dpi | 0% at 35 dpi | NS | ||
| 7 days | 3 dpi | 10% at 35 dpi | NS | ||
| Grossman et al. (2017)£, BALB/c mice, Schu S4, aerosol, ~1,000 CFU | |||||
| TP-271 fluorocycline (MIC = 0.03 μg/mL) | 3 mg/kg od, ip | 21 days | 1 dpi | 80% at 21 dpi and 50.4% at 37 dpi | P < 0.001 for both |
| 3 dpi | 89% at 21 dpi and 37 dpi | p < 0.0001 for both; more active than doxycycline at 37 dpi (p = 0.01) | |||
| 6 mg/kg od, ip | 21 days | 1 dpi | 100% at 21 dpi and 37 dpi | p < 0.0001 for both | |
| 3 dpi | 100% at 21 dpi and 89% at 37 dpi | p < 0.0001 for both | |||
| 12 mg/kg od, ip | 21 days | 1 dpi | 100% at 21 dpi and 80% at 37 dpi | p < 0.0001 for both | |
| 3 dpi | 100% at 21 dpi and 37 dpi | p < 0.0001 for both; more active than doxycycline at 37 dpi (p = 0.007) | |||
| 18 mg/kg od, ip | 21 days | 1 dpi | 100% at 21 dpi and 37 dpi | p < 0.0001 for both | |
| 3 dpi | 100% at 21 dpi and 37 dpi | p < 0.0001 for both; more active than doxycycline at 37 dpi (p = 0.01) | |||
| doxycycline | 40 mg/kg bid, ip | 21 days | 1 dpi | 84% at 21 dpi and 73.9% at 37 dpi | p < 0.0001 for both |
| 3 dpi | 100% at 21 dpi and 22% at 37 dpi | p < 0.0001 for both | |||
| Hamblin et al. (2014), BALB/c mice, LVS, intranasal, 6 × 104 CFU | |||||
| Ciprofloxacin | 50 mg/Kg, po | single dose | 3 or 4 dpi | 100% at 21 dpi | p < 0.05 |
| Hamblin et al. (2014), BALB/c mice, Schu S4, aerosol, 10 CFU | |||||
| Ciprofloxacin | 50 mg/Kg, po | Single dose | 1 dpi | 0% at 28 dpi | NS |
| 50 mg/Kg bid, po | 3 days | 1 dpi | 0% at 28 dpi, delayed death | NS | |
| 50 mg/Kg bid, po | 5 days | 1 dpi | 18% at 28 dpi, delayed death | NS | |
| Crane et al. (2012), C57 Bl/6 mice, Schu S4, intranasal, 50 CFU | |||||
| Levofloxacin | 40 mg/kg, ip | 14 days | 1, 2, or 3 dpi | 100% at 30 dpi | p < 0.05 for both |
| 5 mg/kg, ip | 14 days | 1, 2, or 3 dpi | 100, 100, and 60% at 30 dpi | p < 0.05 for all | |
| Rotem et al. (2012), BALB/c mice, LVS, intranasal, 105 CFU | |||||
| Ciprofloxacin | 50 mg/Kg bid, ip | 7 days | 1, 2, or 3 dpi | 100, 100, 100% | p < 0.05 |
| Doxycycline | 40 mg/Kg bid, ip | 14 days | 1, 2, or 3 dpi | 100, 100, 100% | p < 0.05 |
| Rotem et al. (2012), BALB/c mice, Schu S4, intranasal, 102 CFU | |||||
| Ciprofloxacin | 50 mg/Kg bid, ip | 7 days | 1, 2, or 3 dpi | 100, 100, 70% | p < 0.05 |
| Ciprofloxacin | 50 mg/Kg bid, ip | 10 days | 3dpi | 100%, no relapse | p < 0.05 |
| Doxycycline | 40 mg/Kg bid, ip | 14 days | 1, 2, or 3 dpi | 90, 30, 0% | p < 0.05 for 1 and 2 dpi; NS for 3 dpi |
| Doxycycline | 40 mg/Kg bid, ip | 21 days | 3 dpi | 10% | NS |
| Sutherland et al. (2012), BALB/cJ mice, Schu S4, intranasal, 50 CFU | |||||
| Gentamicin | 5 mg/Kg/day, ip | 10 days | 6hpi, 12hpi, 1dpi, 2dpi | 0% at 25 dpi with death time like untreated control | NS |
| 10 mg/Kg/day, ip | 10 days | 6hpi, 12hpi, 1dpi, 2dpi | 0% for 12 hpi, 1 dpi, and 2 dpi; and 20% for 6 hpi, at 25 dpi | ||
| 20 mg/Kg/day, ip | 10 days | 12hpi, 1dpi, 2dpi | 100% for 12 hpi and 1 dpi only | ||
| 40 mg/Kg/day, ip | 10 days | 6hpi, 12hpi, 1dpi, 2dpi | 100% | ||
| Peterson et al. (2010), BALB/c mice, Schu S4, intranasal, 1.7 × 102 CFU | |||||
| Levofloxacin | 0.1 mg/kg/day, ip | 13 days | 1 dpi | 54% at 26 dpi | NS |
| 0.5–10 mg/kg/day, ip | 13 days | 1 dpi | 100% at 26 dpi (except 90% at 1 mg/Kg/day) | p < 0.05 | |
| 40 mg/kg/day, ip | 13 days | 1, 2, 3, 4 or 5 dpi | 100, 100, 100, 80, and 0% at 70 dpi | p < 0.05 for 1, 2, 3, and 4 dpi; NS for 5 dpi | |
| Klimpel et al. (2008), BALB/c mice, Schu S4, intranasal, ~100 CFU | |||||
| Levofloxacin | 50, 25, 12.5, and 6.25 mg/kg/day, ip | 13 days | 1 dpi | 100% | p < 0.0001 |
| 40 mg/kg/day, ip | 13 days | 1, 2, 3, 4, or 5 dpi | 100, 100, 100, 80, and 0% at 40 dpi | p < 0.0001 for 1, 2, 3, and 4 dpi; NS for 5 dpi | |
| Steward et al. (2006), BALB/c mice, Schu S4, aerosol, 1.5×104 CFU | |||||
| Ciprofloxacin | 100 mg/Kg bid, po | 14 days | 6 hpi$, or 1 or 2 dpi | 0% at 42 dpi | |
| Moxifloxacin | 100 mg/Kg bid, po | 14 days | 6 hpi, or 1 or 2 dpi | 53, 12, and 35% at 42 dpi | More active than ciprofloxacin (p < 0.01) |
| Gatifloxacin | 100 mg/Kg bid, po | 14 days | 6 hpi, or 1 or 2 dpi | 53, 41, and 65% at 42 dpi | More active than ciprofloxacin (p < 0.01) except for 1 dpi |
| Piercy et al. (2005), BALB/c mice, Schu S4, subcutaneous, 106 CFU | |||||
| Ciprofloxacin | 100 mg/kg tid, po | 14 days | 6 hpi, or 1 or 2 dpi | 94, 67, and 0% at 42 dpi | P < 0.001 for 6 hpi and 1 dpi; NS for 2 dpi |
| Moxifloxacin | 100 mg/kg tid, po | 14 days | 6 hpi, or 1 or 2 dpi | 100, 100, and 62% at 42 dpi | p < 0.001 for 6 hph, and 1 and 2 dpi; more active than ciprofloxacin for 1 and 2 dpi (p < 0.05) |
| Gatifloxacin | 100 mg/kg tid, po | 14 days | 6 hpi, or 1 or 2 dpi | 100, 96, and 84% at 42 dpi | p < 0.001 for 6 hpi, and 1 and 2 dpi; more active than ciprofloxacin for 1 and 2 dpi (p < 0.05) |
| Russell et al. (1998) §, Porton outbred mice, Schu S4, intraperitoneal, ~10–103 CFU | |||||
| Doxycycline subcutaneous | 40 mg/Kg bid, sc | 7 days | 48 h before challenge | 73.3% at 24 dpi | |
| 20 mg/Kg bid, sc | 7 days | 48 h before challenge | 13.3% at 24 dpi | ||
| 40 mg/Kg bid, sc | 5 days | 1 dpi | 93.3% at 24 dpi | ||
| 20 mg/Kg bid, sc | 5 days | 1 dpi | 60% at 24 dpi | ||
| Ciprofloxacin subcutaneous | 40 mg/Kg bid, sc | 7 days | 48 h before challenge | 100% at 24 dpi | |
| 20 mg/Kg bid, sc | 7 days | 48 h before challenge | 100% at 24 dpi | ||
| 40 mg/Kg bid, sc | 5 days | 1 dpi | 100% at 24 dpi | ||
| 20 mg/Kg bid, sc | 5 days | 1 dpi | 93.3% at 24 dpi | ||
| Russell et al. (1998) §, Porton outbred mice, Schu S4, intraperitoneal, 105–107 CFU | |||||
| Doxycycline subcutaneous | 40 mg/Kg bid, sc | 7 days | 48 h before challenge | 93.3 at 24 dpi | |
| 20 mg/Kg bid, sc | 7 days | 48 h before challenge | 53.3% at 24 dpi | ||
| 40 mg/Kg bid, sc | 5 days | 1 dpi | 60% at 24 dpi | ||
| 20 mg/Kg bid, sc | 5 days | 1 dpi | 33.3% at 24 dpi | ||
| 40 mg/Kg bid, sc | 10 days | 1 dpi | 100% at 24 dpi | ||
| Ciprofloxacin subcutaneous | 40 mg/Kg bid, sc | 7 days | 48 h before challenge | 73.3% at 24 dpi | |
| 20 mg/Kg bid, sc | 7 days | 48 h before challenge | 53.3% at 24 dpi | ||
| 40 mg/Kg bid, sc | 5 days | 1 dpi | 46.6% at 24 dpi | ||
| 20 mg/Kg bid, sc | 5 days | 1 dpi | 73.3% at 24 dpi | ||
| 40 mg/Kg bid, sc | 10 days | 1 dpi | 100% at 24 dpi | ||
| Di Ninno et al. (1993), BALB/c mice, LVS, 102 CFU intranasal or 103 CFU intravenous | |||||
| Ciprofloxacin | 1 mg, iv | Single dose | 1, 2, 3, and 7 days before infection | 8, 0, 12, 0% | NS |
| Ciprofloxacin | 1 mg, in | Single dose | 1, 2, 3, and 7 days before infection | 0, 12, 0, 12% | NS |
| Liposomal ciprofloxacin | 1 mg, iv | Single dose | 1, 2, 3, and 7 days before infection | 92, 100, 25, 0% | More active than ciprofloxacin for 1 and 2 days before infection (p < 0.005) |
| Liposomal ciprofloxacin | 1 mg, in | Single dose | 1, 2, 3, and 7 days before infection | 92, 83, 100, 63% | More active than ciprofloxacin for 1, 2 and 3 days before infection (p < 0.005), and for 7 days before infection (p < 0.01) |
| Ciprofloxacin | 1 mg, iv | Single dose | 1, 2, 3, or 7 dpi | 0, 25, 0, 12% | |
| Ciprofloxacin | 1 mg, in | Single dose | 1, 2, 3, or 7 dpi | 50, 0, 25, 0% | |
| Liposomal ciprofloxacin | 1 mg, iv | Single dose | 1, 2, 3, or 7 dpi | 75, 88, 0, 0% | More active than ciprofloxacin for 1 and 2 dpi (p < 0.005) |
| Liposomal ciprofloxacin | 1 mg, in | Single dose | 1, 2, 3, or 7 dpi | 83, 100, 63, 50% | More active than ciprofloxacin for 2 dpi (p < 0.005) and 1 and 3 dpi (p < 0.01) |
$: hpi: hours post-infection; dpi: days post-infection; od: once a day; bid: twice a day; tid: three times a day; po: orally; ip: intraperitoneally; in: intranasally; sc: subcutaneously; iv: intravenously. £: the original manuscript indicates the percentages of surviving animals at end of treatment (21 dpi) and among them the percentage of animals that were still alive at 37 dpi (16 days after treatment cessation). §: in this study, antibiotic efficacy was evaluated with different challenge doses (~10 to 107 CFU) of Schu S4. Here, we have combined data obtained in animals exposed to low doses (10–103 CFU) or high doses (105–107 CFU) of Schu S4 strain, corresponding to 15 animals for each prophylactic treatment group. The LD50 (i.e., lethal dose 50%, corresponding to the dose of the tested compound at which half the tested animals are killed) was determined to be close to 1 CFU.