baumannii infections (Boucher et al., 2009). Select antibiotic combinations reportedly show synergy, that is, significantly greater activity provided by two antibiotics combined than the sum of each antibiotic’s activity, against MDR A. baumannii infections (Rahal, 2006). Examples of such combinations include imipenem (IMP)–rifampin (RIF) (Tripodi et al., 2007; Song et al., 2009; Panchón-Ibáñez et al., 2010), carbapenem–colistin (COL) (Timurkaynak et al., 2006), COL–RIF (Hogg et al., 1998; Giamarellos-Bourboulis

et al., 2001; HIF-1 pathway Timurkaynak et al., 2006; Li et al., 2007; Tripodi et al., 2007), and COL–doxycycline (DOX) (Timurkaynak et al., 2006). Two small clinical studies showed very good and limited efficacy of COL–RIF and IMP–RIF combinations, respectively, for patients with A. baumannii infections (Motaouakkil et al., 2006; Saballs et al., 2006). The mechanism of synergy between antibiotic combinations against

MDR A. baumannii, however, is undetermined. For example, A. baumannii is intrinsically resistant to RIF, and we hypothesized that the reported synergistic effect of combinations containing RIF comes from RIF potentiating the other antibiotic by interfering with mRNA production. Acinetobacter baumannii strains infamously carry a multitude of antibiotic resistance determinants, either on their chromosome or on their plasmids (Perez et al., 2007), and it is conceivable that not all strains or even strains within the same clone respond to antibiotic combinations equally. During 2006 and 2007, Cedars-Sinai Medical see more Center in Los Angeles, CA, USA, experienced an outbreak of MDR A. baumannii. The outbreak was terminated by a ‘bundle approach’ of strict infection control measures (Murthy et al., 2008). To provide insight into approaches for treatment of MDR A. baumannii, we evaluated dual combinations of antibiotics for possible synergy against our outbreak strains of MDR A. baumannii using Etest. Abiraterone mouse Although the correlation between the Etest and time-kill methods for in vitro testing of antimicrobial combinations on A. baumannii

is reported as 72% (Bonapace et al., 2000), we chose Etest because it is less labor-intensive than time-kill assays and may facilitate rapid clinical decisions. Additionally, our study aimed to determine whether our clonal strains would respond to antibiotic combinations equally and to investigate the effects of β-lactamases (blas) and other antibiotic resistance determinants in select strains on their response to these antibiotic combinations. We screened for β-lactamase genes, including blaTEM, blaSHV, blaPER, blaADC, blaIMP, blaVIM, blaOXA-23,blaOXA-Ab (housekeeping gene belonging to the blaOXA-51/69 families), and blaOXA-58, and for the genes encoding aminoglycoside-modifying enzymes (AMEs) including aphA6, aadA1, aadB, aacC1, and aacC2 (Hujer et al., 2006).