In vitro and in vivo activity of meropenem and sulbactam against a multidrug-resistant Acinetobacter baumannii strain.
OBJECTIVE
The potential therapeutic role of meropenem combined with sulbactam against a clinical endemic isolate of multidrug-resistant Acinetobacter baumannii, Ab-153, was investigated.


METHODS
The antimicrobial susceptibility of Ab-153 to various drugs was studied by the agar dilution method and Etest strips. The antibacterial activity of meropenem and sulbactam were investigated by a time-kill study in vitro and further examined for therapeutic efficacy in vivo in a murine model.


RESULTS
In the time-kill study, at a concentration of 0.5 x MIC (4 mg/L) of meropenem, 1 x MIC (8 mg/L) of sulbactam and both in combination, only the combination demonstrated bactericidal effects and there was at least a 5 log(10) reduction in bacterial colony counts after 48 h, compared with either drug alone. BALB/c mice infected with 2.1-2.6 x 10(7) cfu of Ab-153 were treated with 20 mg/kg meropenem every 8 h, 40 mg/kg sulbactam every 8 h or both in combination. The survival rate of mice in the combination group was significantly higher than that in the meropenem-treated or sulbactam-treated group (87% versus 35%, P = 0.0004; 87% versus 30%, P = 0.0002).


CONCLUSIONS
Meropenem in conjunction with sulbactam can exhibit more potent antimicrobial activity against Ab-153 than meropenem or sulbactam alone.
Ko
Wen-Chien
WC
Department of Medicine, National Cheng Kung University Medical College, Tainan, Taiwan.
Lee
Hsin-Chun
HC
Chiang
Shyh-Ren
SR
Yan
Jing-Jou
JJ
Wu
Jiunn-Jong
JJ
Lu
Chin-Li
CL
Chuang
Yin-Ching
YC
D000151:Acinetobacter Infections / Q000188:drug therapy* / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000187:drug effects*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D004338:Drug Combinations; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D000077731:Meropenem; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D013407:Sulbactam / Q000494:pharmacology* / Q000627:therapeutic use*; D016019:Survival Analysis; D013845:Thienamycins / Q000494:pharmacology* / Q000627:therapeutic use*
D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D013845:Thienamycins; D000077731:Meropenem; D013407:Sulbactam