Cefazolin plus minocycline against a clinical isolate of Vibrio vulnificus: in vitro and animal studies.
Cefotaxime plus minocycline has been shown to have synergistic activity against Vibrio vulnificus; however, the clinical role of cefazolin in combination with minocycline in immunocompromised hosts has not been established. Therefore, antimicrobial susceptibility of the V. vulnificus clinical isolate Vv05191 was studied by the agar dilution method. Antibacterial activity of cefazolin, minocycline, and a combination of the two drugs was investigated by time-kill studies in vitro and further examined for therapeutic efficacy in a murine model. When cefazolin at a combination of 4 mg/L (1/2 x MIC) was combined with minocycline at a concentration of 0.03 mg/L (1/2 x MIC), sustained inhibitory activity was noted until 24 h. In BALB/cByJ mice with cyclophosphamide-induced neutropenia, an inoculum of 1.5 x 10(8) CFU caused death within 96 h when the infected mice were treated by cefazolin (400 mg/kg every 3 h), while 6.3% of mice survived when treated by minocycline (4 mg/kg stat, then 2 mg/kg every 12 h). However, 62.5% of mice survived for 96 h when mice were treated by cefazolin (400 mg/kg every 3 h) plus minocycline (4 mg/kg stat, then 2 mg/kg every 12 h) (P = 0.002, log rank test). In conclusion, cefazolin in combination with minocycline exhibits in vitro synergistic antibacterial activity against V. vulnificus and provides a therapeutic advantage in neutropenic mice with V. vulnificus infection.
Tang
Hung-Jen
HJ
Department of Medicine, Chi Mei Medical Center, Tainan, Taiwan, Republic of China.
Ko
Wen-Chien
WC
Chuang
Yin-Ching
YC
Chen
Chi-Chung
CC
Chiang
Shyh-Ren
SR
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D002437:Cefazolin / Q000494:pharmacology* / Q000627:therapeutic use*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability; D008911:Minocycline / Q000494:pharmacology* / Q000627:therapeutic use*; D016019:Survival Analysis; D013997:Time Factors; D014735:Vibrio Infections / Q000188:drug therapy / Q000382:microbiology*; D041261:Vibrio vulnificus / Q000187:drug effects* / Q000302:isolation & purification
D000900:Anti-Bacterial Agents; D008911:Minocycline; D002437:Cefazolin