Article Figures & Data
Figures
- Fig 1
Daptomycin structure (A) and interaction with the cytoplasmic membrane (B).
- Fig 2
MIC distributions for Gram-positive clinical isolates collected in Europe, North America, and South America in 2002, before the introduction of daptomycin for clinical use. (Based on data from reference 56.)
- Fig 3
Percent probability of pharmacokinetic-pharmacodynamic target attainment for area under the curve targets of 180 for S. aureus (A) and 48 for E. faecalis (B). Data were generated from Monte Carlo analysis by applying a total drug AUC/MIC criterion of 180 or 48 for efficacy, based on murine thigh and thigh and renal models for S. aureus and E. faecalis, respectively. A 4-mg/kg q24h dose of daptomycin with an AUC of 494 ± 75 μg · h/ml was used in this simulation.
- Fig 4
Mutations in MprF identified in daptomycin-NS S. aureus. MprF consists of an N-terminal flippase domain and a C-terminal phosphatidylglycerol lysylination domain. Mutations have been identified in both domains, as outlined in the following references: a, reference 96; b, reference 101; c, reference 88; d, reference 98; e, reference 103; f, reference 115; g, reference 90; h, reference 201; i, reference 94.
Tables
- Table 1
Daptomycin MIC breakpoints established by the CLSI, FDA, and EUCAST
Organism MIC breakpoint (μg/ml) established by a : CLSI FDA EUCAST S R S R S R Staphylococcus ≤1 ≤1 ≤1 >1 Enterococcus ≤4 ≤4 b Beta-hemolytic Streptococcus ≤1 ≤1 ≤1 >1 Viridans group Streptococcus, excluding S. pneumoniae ≤1 Corynebacterium ≤1 Lactobacillus ≤4 ↵a S, susceptible; R, resistant; CLSI, Clinical and Laboratory Standards Institute; FDA, Food and Drug Administration; EUCAST, European Committee on Antimicrobial Susceptibility Testing.
↵b Due to the lack of clinical data, the FDA clinical breakpoint is approved for vancomycin-susceptible E. faecalis alone.
- Table 2
Daptomycin cure rate of MRSA infections by daptomycin MIC a
Daptomycin MIC, μg/ml b Cure, n c Total, n d Cure rate, % (95% CI) e References ≤1 376 434 86.6 (83.4–89.8) 11, 12, 73, 202 – 217 2 15 31 48.4 (30.8–66.0) 12, 98, 202, 216 – 222 4 3 14 21.4 (0.0–42.9) 12, 216, 217 223, 224 ≥8 0 2 0 76, 77 ↵a MRSA, methicillin-resistant Staphylococcus aureus.
↵b MIC by broth microdilution, Etest, or automated method. The isolate with the highest MIC was included. Etest results were rounded up to the nearest dilutional integer for comparison.
↵c Microbiological or clinical cure. Where both were presented in a relevant study, the lower cure rate was chosen for a more conservative estimate.
↵d Data pooled from multiple studies and case reports, with additional data clarification by the study authors where possible. See Table S1 in the supplemental material for further details.
↵e 95% CI, 95% confidence interval.
- Table 3
Daptomycin cure rate of VRE infections by daptomycin MIC a
Daptomycin MIC, μg/ml b Cure, n c Total, n d Cure rate, % (95% CI) e References ≤1 6 7 85.7 (60.6–100) 79, 225 – 227 2 12 19 63.2 (37.5–88.9) 79, 225, 228 – 231 4 33 44 75.0 (52.3–97.7) 79, 225, 230 – 233 ≥8 0 5 0.0 75, 160, 183, 234, 235 ↵a VRE, vancomycin-resistant Enterococcus, including E. faecalis, E. faecium, E. raffinosus, and E. gallinarum.
↵b MIC by broth microdilution, Etest, or automated method. The isolate with the highest MIC was included. Etest results were rounded up to nearest dilutional integer for comparison.
↵c Microbiological or clinical cure. Where both were presented in a relevant study, the lower cure rate was chosen for a more conservative estimate.
↵d Data pooled from multiple studies and case reports, with additional data clarification by study authors where possible. See Table S2 in the supplemental material for further details.
↵e 95% CI, 95% confidence interval.
- Table 5
Mutations in the cardiolipin synthetase gene, cls, identified among daptomycin-nonsusceptible Enterococcus strains
Species and mutation Predicted Cls domain Daptomycin MIC (μg/ml) Reference Enterococcus faecium H215R Proximal to the PLD1 active site (within 10 Å) 48 a 164 H270R Spacer regions between PLD1 and PLD2 32 157 K60T Linker region 32 160 MPL insertion at 110 Linker region 24 a 164 N13I N-terminal transmembrane helix 32 a 164 N13S N-terminal transmembrane helix 192 157 N13T N-terminal transmembrane helix >256 160 R218Q HKD of PLD1 32 a 164 R218Q HKD of PLD1 48 a 164 R218Q HKD of PLD1 16 162 Enterococcus faecalis Deletion of K61 Linker region 12 164 R218Q HKD of PLD1 256 163 N77-Q79 del Linker region 256 163 R218Q HKD of PLD1 512 163 ↵a MIC measured by Etest.
- Table 6
Essential agreement and error rates for automated antimicrobial test systems versus the CLSI reference broth microdilution method a
Automated system Organism(s) n (no. NS) % EA % CA % ME % VME Reference BD Phoenix E. faecalis 39 (4) 82 87 14.2 0 236 E. faecium 46 (22) 98 100 0 0 236 S. aureus 63 (26) 98 100 0 0 236 CoNS 26 (1) 100 100 0 0 236 MicroScan E. faecalis 1311 (0) NR 99.6 0.4 237 E. faecium 362 (0) NR 91.2 8.8 237 Enterococcus 128 (17) 91–94 b 88 NR NR 238 S. aureus 161 (0) 97.5 100 0 191 Vitek 2 Enterococcus faecium 30 (3) NR 100 0 239 CoNS 100 (0) 98 99 1 196 S. aureus 270 (20) 80.7 95.4 5.4 10.7 196 S. aureus and S. agalactiae 751 (19) 97.2 96.8 3.0 3.3 240 Staphylococcus 184 (0) 98.2 100 241
Supplemental material
Files in this Data Supplement:
- Supplemental file 1 -
Correlations of MRSA daptomycin MIC (Table S1) and VRE daptomycin MIC (Table S2) with clinical outcomes in comparative studies.
PDF, 420K
- Supplemental file 1 -
