Efficacy of Ciprofloxacin-Gentamicin Combination Therapy in Murine Bubonic Plague

Abstract

Potential benefits of combination antibiotic therapy for the treatment of plague have never been evaluated. We compared the efficacy of a ciprofloxacin (CIN) and gentamicin (GEN) combination therapy with that of each antibiotic administered alone (i) against Yersinia pestis in vitro and (ii) in a mouse model of bubonic plague in which animals were intravenously injected with antibiotics for five days, starting at two different times after infection (44 h and 56 h). In vitro, the CIN+GEN combination was synergistic at 0.5x the individual drugs’ MICs and indifferent at 1x- or 2x MIC. In vivo, the survival rate for mice treated with CIN+GEN was similar to that observed with CIN alone and slightly higher than that observed for GEN alone 100, 100 and 85%, respectively when treatment was started 44 h post challenge. 100% of survivors were recorded in the CIN+GEN group vs 86 and 83% in the CIN and GEN groups, respectively when treatment was delayed to 56 h post-challenge. However, these differences were not statistically significant. Five days after the end of treatment, Y. pestis were observed in lymph nodes draining the inoculation site (but not in the spleen) in surviving mice in each of the three groups. The median lymph node log10 CFU recovered from persistently infected lymph nodes was significantly higher with GEN than with CIN (5.8 vs. 3.2, p = 0.04) or CIN+GEN (5.8 vs. 2.8, p = 0.01). Taken as the whole, our data show that CIN+GEN combination is as effective as CIN alone but, regimens containing CIN are more effective to eradicate Y. pestis from the draining lymph node than the recommended GEN monotherapy. Moreover, draining lymph nodes may serve as a reservoir for the continued release of Y. pestis into the blood – even after five days of intravenous antibiotic treatment.

Multi‐Functional Polyurethane Hydrogel Foams with Tunable Mechanical Properties for Wound Dressing Applications

“…Zones of inhibition were observed for each formulation loaded with gentamicin and ciprofloxacin and those loaded with ciprofloxacin exhibited, on average, larger zones of inhibition than those containing gentamicin. This was due to the greater efficacy of ciprofloxacin compared to gentamicin, and not due to sample composition. Overall, there were no relationships between the zones of inhibition of PEG M w .…”

Curative Treatment of Severe Gram-Negative Bacterial Infections by a New Class of Antibiotics Targeting LpxC

“…LPC-058 was very active against Y. pestis , with a MIC similar to that of ciprofloxacin (0.03 µg/ml) (21, 22). LPC-069 was active against the same strains and species as LPC-058 but showed a lower level of activity, except when serum albumin was added to the culture medium (Fig.…”

Functional and Structural Analysis of HicA3-HicB3, a Novel Toxin-Antitoxin System of Yersinia pestis

“…Groups of 8-to 9-week-old female OF1 mice (Charles River, France) were inoculated intradermally with ϳ10 cells of Y. pestis CO92 or its ⌬hicA3B3 derivative, as described previously (30). Survival was monitored daily for 15 days after inoculation.…”