Vibrio vulnificus causes life-threatening soft tissue and gastrointestinal infections including necrotizing fasciitis and primary septicemia. Broad-spectrum antibiotic therapy, such as cefepime, is indicated during empiric management of life-threatening infections. The activity of cefepime, cefepime with doxycycline, and cefepime with ciprofloxacin was determined against V. vulnificus M06-24/O, a prevalent clinical strain in the US.
Microbroth dilution assays were performed to assess in vitro susceptibilities for cefepime, doxycycline, and ciprofloxacin against V. vulnificus. For each antibiotic, time-kill studies were conducted to determine the minimum concentration needed to reduce bacterial growth by less than 2log10 compared to control at 48 hours. Using these concentrations, time-kill studies were performed for the combination of cefepime with doxycycline and cefepime with ciprofloxacin. Synergy was defined as achieving a greater than 2log10 reduction in bacterial growth compared to cefepime alone. All experiments were repeated twice and bacterial growth was measured in triplicate. Multiple comparisons analysis of variance testing was conducted to assess for significance at each time point (p<0.01).
The minimum inhibitory concentration (MIC) for cefepime was 0.25 μg/ml, doxycycline 0.125 μg/ml, and ciprofloxacin 0.03 μg/ml. The concentration with minimal inhibitory activity at 48 hours for cefepime was 0.25 μg/ml (Figure 1), doxycycline 0.125 μg/ml, and ciprofloxacin 0.015 μg/ml. The combination of cefepime and doxycycline decreased bacterial growth by greater than 2log10 compared to cefepime alone at 4, 24, 36, and 48 hours (p<0.01) (Figure 2). The combination of cefepime and ciprofloxacin decreased bacterial growth by greater than 2log10 compared to cefepime alone at 24, 36, and 48 hours (p<0.01) (Figure 3).
Empiric treatment of necrotizing fasciitis and sepsis with cefepime provides adequate coverage for V. vulnificus infection. Cefepime acts synergistically in vitro with doxycycline and ciprofloxacin. Addition of doxycycline or ciprofloxacin to cefepime during empiric treatment may improve clinical outcomes of V. vulnificus infection.
K. Satchell, None