舒巴坦单剂及舒巴坦与第三代头孢菌素联合对鲍曼不动杆菌的体外抗菌作用比较

In vitro activities of sulbactam alone and in combination withthe third-generation cephalosporins against Acinetobacter baumannii

目的比较舒巴坦(SB)单剂和舒巴坦联合第三代头孢菌素对鲍曼不动杆菌的体外抗菌活性,探讨舒巴坦在联合制剂中的实际作用。方法从临床分离的表型为对头孢哌酮(CPZ)、头孢他啶(CAZ)和头孢噻肟(CTX)3种第三代头孢菌素中1种以上耐药或中介的56株鲍曼不动杆菌分为3组。A组(27株)对上述2种以上药物耐药;B组(11株)仅对CPZ耐药;C组(18株)仅对CPZ或CTX中介。采用微量肉汤稀释法检测SB单剂以及SB分别联合上述3种第三代头孢菌素敏感和耐药折点浓度的最低抑菌浓度(MICs)。采用CPZ三维酶提取和抑制试验检测β-内酰胺酶,并选择对CPZ中介(A株)和耐药(B株)进行杀菌曲线试验。结果SB对B组和C组菌的MICs≤1μg/ml;SB对A组菌的MICs范围在4～64μg/ml之间,并且与CPZ、CAZ或CTX任一药物的敏感和耐药折点浓度联合,均不能使联合后SB的MICs低于单剂SB的MICs。在三维β-内酰胺酶抑制试验中,酶活性不能被SB抑制的菌株,其SB的MICs值高于酶活性能被SB抑制的菌株。杀菌曲线显示在SB和CPZ之间无协同作用。结论SB单剂对多重耐药的鲍曼不动杆菌有抗菌活性,这些菌株对联合制剂的敏感可能主要是SB在发挥杀菌作用。

Objective To compare the in vitro activity of sulbactam alone and in combination with the third-generation cephalosporins against Acinetobacter baumannii. Methods A total of 56 Acinetobacter baumannii resistant or intermediate to one or more than one of the three cephalosporins （cefoperazone, CFP; ceftazidime, CAZ and cefotaxime, CTX） were divided into three groups： Group A （27 isolates resistant to 2 or 3 of the above cephalosporins）, Group B： （11 isolates resistant only to CFP）, and Group C （18 isolates intermediate to CFP or CTX）. The MICs of SB alone and SB in combination with the concentration of resistant or susceptible breakpoint of CFP, CAZ or CTX were determined by the broth microdilution method and β-lactamases activities were detected by the three-dimensional extract test with CFP, and the two different strains （strain A intermediate to CFP, and strain B resistant to CFP） were selected for performing killing curves. Results The MICs of SB against the isolates of the B group and C group were ≤1μg/ml. The MICs of SB against the A group were 4- 64μg/ml. There was no decrease of MICs of SB in combination with resistant/susceptible concentration break point of any of CFP, CAZ or CTX versus the MIC when SB tested alone. The MICs of SB against isolates whose β-lactamases activities were not inhibited by SB were higher compared with those whose β-lactamases activities were inhibited by SB. Killing curves showed no synergy between CFP and SB. Conclusion Sulbactam alone was useful against muhiresistant Acinetobacter baumannii. These isolates were susceptible to the combinations mainly possibly due to the antimicrobial activity of sulbactam.