Antimicrobial Effects of Varied Combinations of Meropenem, Sulbactam, and Colistin on a Multidrug-Resistant Acinetobacter baumannii Isolate That Caused Meningitis and Bacteremia

Meropenem (MEM; 2g/8hr; minimum inhibitory concentration [MIC] = 256 mg/L) plus sulbactam (SUL; 1g/8hr; MIC = 128 mg/L) (two-drug-therapy period), and subsequent additional intravenous colistin (COL; 2.5mg/kg/12hr) and intraventricular (COL, 5mg/day; MIC = 1 mg/L) (three-drug-therapy period) were sequentially used in a patient with postneurosurgery bacteremic meningitis due to a multidrug-resistant Acinetobacter baumannii (MDRAB) isolate (AB(1)). We detected 4- to 32-fold increases in peak or trough cerebrospinal fluid bactericidal titer and serum bactericidal titer in three-drug-therapy period when comparing to those in two-drug-therapy period. The time-kill study with MEM, SUL, and COL alone or varied combinations (all at 1 x MIC) against AB(1) and another genetically nonrelated MDRAB isolate (AB(134) [MICs of MEM = 64 mg/L, SUL = 16 mg/L, and COL = 1 mg/L]) was performed. The two-drug combinations (MEM + SUL, MEM. + COL, and SUL + COL) each elicited different inhibitory effect on AB(1) and AB(134) at 6 hr. Bacterial regrowth at 24 hr was observed in the experiments in which the MDRAB isolate was inhibited earlier by COL alone (AB(1) and AB(134)), by MEM plus SUL (AB(1)), and by MEM plus COL (AB(134)), but not in SUL plus COL, and MEM + SUL + COL. Combined use of COL with MEM and/or SUL may provide good therapeutic options, even though MEM and SUL are in vitro resistance to the MDRAB.