112) as illustrated in Fig. 1. DAP demonstrated potent bactericidal activity against all susceptible strains with a log10 CFU/mL decrease of 3.5 ± 0.8 log10 CFU/mL. A bactericidal effect was also noted for two H 89 mutant strains (D712 and A8091). However, after the initial kill within the first 8 h, significant BV-6 in vivo regrowth of 1.5 log10 CFU/mL increase from starting inoculum occurred in

the other two mutants. VAN demonstrated activity against all parent isolates within the first 8 h, but kill was not sustained over the complete duration of the experiment against R6491. Against R6387, VAN demonstrated bacteriostatic activity with 2.3 ± 0.1 log10 CFU/mL reduction, but no appreciable activity was noted against any of the other mutants. TEI only displayed

activity against one of the eight strains tested (A8090) with 2.4 ± 0.1 log10 CFU/mL reduction over 24 h. All remaining strains with TEI demonstrated minimal to no activity (0–<1 log10 CFU/mL reduction). BI 10773 purchase Table 1 Minimum inhibitory concentration (MIC) (Etest) data summary   MIC range (mg/L) MIC50 (mg/L) MIC90 (mg/L) CPT 0.125–1.5 0.38 1 DAP 0.03–4 0.25 2 TEI 0.25–16 1.5 8 VAN 0.19–8 1 6 CPT ceftaroline, DAP daptomycin, TEI teicoplanin, VAN vancomycin Table 2 Correlation coefficients   R compared to VAN R compared to TEI R compared to DAP CPT  MIC90 −0.912* −0.963* −0.936*  MIC50 −0.858* −0.847* −0.818*  MIC −0.535* −0.386* −0.483* DAP  MIC90 0.943* 0.947* –  MIC50 0.959* 0.957* –  MIC 0.666* 0.632* – TEI  MIC90 0.971* – –  MIC50 0.997* – –  MIC 0.789* – – CPT ceftaroline, DAP daptomycin, MIC minimum inhibitory concentration, TEI teicoplanin, VAN vancomycin * P < 0.05 Table 3 Minimum inhibitory concentrations for isogenic strain pairs Strain pairs MICs (mg/L) parent/mutant CPT DAP TEI VAN R6911/R6913 0.5/0.5 2/4 4/4 2/8 R6491/R6387 1/1 0.5/0.5 0.125/4 1/2 D592/D712 1/1 0.5/4 0.5/2 2/4 A8090/A8091 0.5/0.5 0.25/1 0.5/4 1/8 CPT ceftaroline, DAP daptomycin, TEI teicoplanin, VAN vancomycin Fig. 1 Time–kill evaluation Galactosylceramidase results. Closed circles ceftaroline, open triangles daptomycin, closed triangles teicoplanin, open diamonds vancomycin, closed

squares drug-free control Discussion The results of this study demonstrate that as the VAN MIC increased, a linear increase in MIC was also observed for DAP and TEI. This positive correlation was more pronounced with the two glycopeptides, but was only slightly less for DAP. Although not previously reported with TEI, we observed the same “seesaw effect” with TEI that has previously been demonstrated with VAN and DAP [15]. Additionally, the CPT MIC appeared to decrease as the glyco- and lipopeptide MIC increased. In our time–kill evaluations, CPT was more active against isolates with reduced susceptibility to glyco- and lipopeptide antimicrobials than to the parent strains. Of note, the CPT MIC did remain the same from parent to mutant, while the MIC for the other agents increased.