DOI: 10.1128/AAC.01230-17
Article Figures & Data
Tables
- TABLE 1
Cumulative frequency distributions of nafithromycin MIC results against 4,739 bacterial isolates (all regions combined)
Organism or phenotype (MIC)c No. of isolates No. of isolates (cumulative %) with nafithromycin MIC (μg/ml) MIC50 (μg/ml) MIC90 (μg/ml) ≤0.002 0.004 0.008 0.015 0.03 0.06 0.12 0.25 0.5 1 2 4 8 16 >a S. aureus 716 1 (0.1) 39 (5.6) 562 (84.1) 27 (87.8) 3 (88.3) 2 (88.5) 0 (88.5) 2 (88.8) 80 (100.0) 0.06 >2 MSSA 468 28 (6.0) 409 (93.4) 20 (97.6) 1 (97.9) 2 (98.3) 0 (98.3) 2 (98.7) 6 (100.0) 0.06 0.06 MRSA 248 1 (0.4) 11 (4.8) 153 (66.5) 7 (69.4) 2 (70.2) 0 (70.2) 0 (70.2) 0 (70.2) 74 (100.0) 0.06 >2 TelithromycinS (≤1 μg/ml) 633 1 (0.2) 39 (6.3) 562 (95.1) 27 (99.4) 3 (99.8) 1 (100.0) 0.06 0.06 TelithromycinI (2 μg/ml) 3 1 (33.3) 0 (33.3) 0 (33.3) 2 (100.0) >2 TelithromycinR (≥4 μg/ml) 80 2 (2.5) 78 (100.0) >2 >2 ERYr (≥1 μg/ml), CLIs (≤0.5 μg/ml), D test−b 85 3 (3.5) 74 (90.6) 8 (100.0) 0.06 0.06 ERYr (≥1 μg/ml), CLIs (≤0.5 μg/ml), D test+b 110 11 (10.0) 93 (94.5) 4 (98.2) 0 (98.2) 1 (99.1) 0 (99.1) 0 (99.1) 1 (100.0) 0.06 0.06 CLINS (≥1 μg/ml) 85 1 (1.2) 2 (3.5) 1 (4.7) 0 (4.7) 2 (7.1) 79 (100.0) >2 >2 ERYs (≤0.5 μg/ml), CLIs (≤0.5 μg/ml) 436 1 (0.2) 25 (6.0) 395 (96.6) 14 (99.8) 1 (100.0) 0.06 0.06 S. pneumoniae 1,911 1 (0.1) 20 (1.1) 396 (21.8) 1014 (74.9) 224 (86.6) 162 (95.1) 88 (99.7) 6 (100.0) 0.015 0.06 PENs (≤2 μg/ml) 1,762 1 (0.1) 20 (1.2) 392 (23.4) 994 (79.9) 200 (91.2) 127 (98.4) 25 (99.8) 3 (100.0) 0.015 0.03 PENi (4 μg/ml) 133 4 (3.0) 18 (16.5) 21 (32.3) 29 (54.1) 59 (98.5) 2 (100.0) 0.06 0.12 PENr (≥8 μg/ml) 16 2 (12.5) 3 (31.2) 6 (68.8) 4 (93.8) 1 (100.0) 0.06 0.12 ERYs (≤0.25 μg/ml), CLIs (≤0.25 μg/ml) 1,173 19 (1.6) 371 (33.2) 765 (98.5) 14 (99.7) 3 (99.9) 1 (100.0) 0.015 0.015 ERYr (≥0.5 μg/ml), CLIs (≤0.25 μg/ml) 344 1 (0.3) 1 (0.6) 11 (3.8) 121 (39.0) 114 (72.1) 88 (97.7) 8 (100.0) 0.03 0.06 ERYr (≥0.5 μg/ml), CLIr (≥0.5 μg/ml) 394 14 (3.6) 128 (36.0) 96 (60.4) 71 (78.4) 79 (98.5) 6 (100.0) 0.03 0.12 TelithromycinS (≤0.25 μg/ml) 1,707 1 (0.1) 20 (1.2) 396 (24.4) 1014 (83.8) 209 (96.1) 64 (99.8) 3 (100.0) 0.015 0.03 TelithromycinNS (≥0.5 μg/ml) 204 15 (7.4) 98 (55.4) 85 (97.1) 6 (100.0) 0.06 0.12 S. pyogenes 606 46 (7.6) 513 (92.2) 22 (95.9) 10 (97.5) 6 (98.5) 2 (98.8) 7 (100.0) 0.015 0.015 ERYs (≤0.25 μg/ml), CLIs (≤0.25 μg/ml) 542 42 (7.7) 483 (96.9) 16 (99.8) 1 (100.0) 0.015 0.015 ERYr (≥0.5 μg/ml), CLIs (≤0.25 μg/ml) 33 3 (9.1) 18 (63.6) 4 (75.8) 7 (97.0) 1 (100.0) 0.015 0.06 ERYr (≥0.5 μg/ml), CLIr (≥0.5 μg/ml) 31 1 (3.2) 12 (41.9) 2 (48.4) 2 (54.8) 5 (71.0) 2 (77.4) 7 (100.0) 0.06 0.5 H. influenzae 1002 2 (0.2) 2 (0.4) 6 (1.0) 42 (5.2) 428 (47.9) 455 (93.3) 56 (98.9) 5 (99.4) 6 (100.0) 4 4 β-Lactamase positive 210 5 (2.4) 90 (45.2) 99 (92.4) 14 (99.0) 1 (99.5) 1 (100.0) 4 4 β-Lactamase negative 792 2 (0.3) 2 (0.5) 6 (1.3) 37 (5.9) 338 (48.6) 356 (93.6) 42 (98.9) 4 (99.4) 5 (100.0) 4 4 M. catarrhalis 504 1 (0.2) 6 (1.4) 1 (1.6) 6 (2.8) 58 (14.3) 265 (66.9) 159 (98.4) 8 (100.0) 0.12 0.25 ↵a The MIC was greater than the highest concentration tested, which was 16 μg/ml for H. influenzae and 2 μg/ml for all other organisms.
↵b The D test was performed by broth microdilution as described in CLSI document M100-S26 (20).
↵c Abbreviations: MSSA, methicillin-susceptible S. aureus; MRSA, methicillin-resistant S. aureus; s, susceptible; i, intermediate; r, resistant; ERY, erythromycin; CLI, clindamycin; PEN, penicillin; ns, nonsusceptible.
- TABLE 2
Activities by geographic region for nafithromycin and comparator antimicrobial agents tested against selected clinical isolates
Organism or antimicrobial agent US EU LATAM APAC n MIC50f MIC90f % susceptible/% resistant n MIC50f MIC90f % susceptible/% resistant n MIC50f MIC90f % susceptible/% resistant n MIC50f MIC90f % susceptible/% resistant CLSIa EUCASTa CLSIa EUCASTa CLSIa EUCASTa CLSIa EUCASTa S. aureus 205 203 154 154 Nafithromycin 0.06 >2 0.06 0.06 0.06 >2 0.06 0.12 Telithromycin 0.12 >2 86.8/12.2 0.06 0.12 93.1/6.9 0.06 >2 81.2/18.2 0.06 0.25 91.6/8.4 Clindamycin ≤0.25 >2 86.3/13.7 86.3/13.7 ≤0.25 ≤0.25 92.6/7.4 91.6/7.4 ≤0.25 >2 81.2/18.8 80.5/18.8 ≤0.25 ≤0.25 91.6/8.4 90.9/8.4 Erythromycin 4 >16 40.5/49.3 42.0/56.1 0.25 >16 73.9/23.2 73.9/25.6 0.25 >16 57.8/36.4 57.8/39.6 0.25 >16 74.0/21.4 74.0/24.7 Linezolid 1 1 100.0/0.0 100.0/0.0 1 1 100.0/0.0 100.0/0.0 1 1 100.0/0.0 100.0/0.0 1 1 100.0/0.0 100.0/0.0 Oxacillin 1 >2 53.7/46.3 53.7/46.3 0.5 >2 75.4/24.6 75.4/24.6 0.5 >2 63.6/36.4 63.6/36.4 0.5 >2 69.5/30.5 69.5/30.5 Trimethoprim-sulfamethoxazole ≤0.5 ≤0.5 98.5/1.5 98.5/1.5 ≤0.5 ≤0.5 99.5/0.5 99.5/0.5 ≤0.5 ≤0.5 99.4/0.6 99.4/0.0 ≤0.5 ≤0.5 97.4/2.6 97.4/1.9 Vancomycin 1 1 100.0/0.0 100.0/0.0 1 1 100.0/0.0 100.0/0.0 1 1 100.0/0.0 100.0/0.0 1 1 100.0/0.0 100.0/0.0 MRSA 95 50 56 47 Nafithromycin 0.06 >2 0.06 >2 0.06 >2 0.06 >2 Telithromycin 0.12 >2 76.8/23.2 0.12 >2 76.0/24.0 0.12 >2 51.8/46.4 0.06 >2 72.3/27.7 Clindamycin ≤0.25 >2 76.8/23.2 76.8/23.2 ≤0.25 >2 74.0/26.0 72.0/26.0 ≤0.25 >2 51.8/48.2 50.0/48.2 ≤0.25 >2 72.3/27.7 70.2/27.7 Erythromycin >16 >16 18.9/70.5 20.0/78.9 >16 >16 34.0/60.0 34.0/66.0 >16 >16 37.5/62.5 37.5/62.5 >16 >16 34.0/57.4 34.0/61.7 Linezolid 1 1 100.0/0.0 100.0/0.0 1 1 100.0/0.0 100.0/0.0 1 1 100.0/0.0 100.0/0.0 1 1 100.0/0.0 100.0/0.0 Trimethoprim-sulfamethoxazole ≤0.5 ≤0.5 96.8/3.2 96.8/3.2 ≤0.5 ≤0.5 98.0/2.0 98.0/2.0 ≤0.5 ≤0.5 100.0/0.0 100.0/0.0 ≤0.5 1 91.5/8.5 91.5/6.4 Vancomycin 1 1 100.0/0.0 100.0/0.0 0.5 1 100.0/0.0 100.0/0.0 1 1 100.0/0.0 100.0/0.0 1 1 100.0/00 100.0/0.0 S. pneumoniae 712 698 250 251 Nafithromycin 0.015 0.06 0.015 0.03 0.015 0.06 0.015 0.06 Telithromycin 0.015 0.5 99.9/0.0 82.7/2.7 0.015 0.12 99.9/0.0 94.8/1.0 0.015 0.25 100.0/0.0 90.8/3.2 0.015 0.25 100.0/0.0 91.2/0.0 Amoxicillin-clavulanate ≤1 4 88.5/7.2b ≤1 2 92.6/5.2b ≤1 8 79.2/12.8b ≤1 8 79.7/16.3b Ceftriaxone ≤0.06 1 81.6/6.3c 81.6/0.8 ≤0.06 1 84.2/7.2c 84.2/1.0 0.12 2 69.2/13.6c 69.2/0.8 0.12 2 64.1/19.5c 64.1/4.8 93.7/0.8b 92.8/1.0b 86.4/0.8b 80.5/4.8b Clindamycin ≤0.25 >2 82.2/16.6 83.4/16.6 ≤0.25 >2 80.8 18.2 81.8 18.2 ≤0.25 >2 78.4/21.6 78.4/21.6 ≤0.25 >2 68.5 30.7 69.3 30.7 Erythromycin 0.25 >16 50.0/49.0 50.0/49.0 ≤0.12 >16 74.1/25.4 74.1/25.4 ≤0.12 >16 62.8/37.2 62.8/37.2 ≤0.12 >16 57.0/42.2 57.0/42.2 Penicillin ≤0.06 2 58.1/13.6d 58.1/41.9c ≤0.06 2 68.5/11.9d 68.5/31.5c 0.12 4 49.2/26.8d 49.2/50.8c ≤0.06 4 51.8/29.1d 51.8/48.2c 93.5/0.6e 95.0/0.7e 88.4/0.4e 84.5/2.4e Trimethoprim-sulfamethoxazole ≤0.5 >4 67.8/20.1 75.4/20.1 ≤0.5 >4 70.6/20.1 76.1/20.1 1 >4 48.8/39.6 53.6/39.6 ≤0.5 >4 56.6/34.7 64.5/34.7 Penicillin-resistant S. pneumoniae 4 5 1 6 Nafithromycin 0.03 0.06 0.06 Telithromycin 0.25 100.0/0.0 50.0/25.0 0.25 100.0/0.0 60.0/40.0 100.0/0.0 0.0/0.0 0.25 100.0/0.0 66.7/0.0 Amoxicillin-clavulanate >8 0.0/100.0b >8 0.0/80.0b 0.0/100.0b >8 0.0/83.3b Ceftriaxone 8 0.0/100.0c 0.0/75.0 8 0.0/80.0c 0.0/60.0 0.0/100.0c 0.0/0.0 4 0.0/83.3c 0.0/66.7 0.0/75.0b 20.0/60.0b 0.0/0.0b 16.7/66.7b Clindamycin ≤0.25 50.0/50.0 50.0/50.0 >2 20.0/80.0 20.0/80.0 0.0/100.0 0.0/100.0 >2 0.0/100.0 0.0/100.0 Erythromycin 8 0.0/100.0 0.0/100.0 >16 0.0/100.0 0.0/100.0 0.0/100.0 0.0/100.0 >16 0.0/100.0 0.0/100.0 Penicillin 8 0.0/100.0d 0.0/100.0c 8 0.0/100.0d 0.0/100.0c 0.0/100.0d 0.0/100.0c 8 0.0/100.0d 0.0/100.0c 0.0/100.0e 0.0/100.0e 0.0/100.0e 0.0/100.0e Trimethoprim-sulfamethoxazole 4 0.0/100.0 0.0/100.0 >4 0.0/60.0 40.0/60.0 0.0/100.0 0.0/100.0 >4 0.0/100.0 0.0/100.0 Erythromycin-resistant and clindamycin-resistant S. pneumoniae 127 134 54 79 Nafithromycin 0.03 0.12 0.03 0.12 0.03 0.12 0.03 0.12 Telithromycin 0.06 0.5 100.0/0.0 66.9/6.3 0.03 0.5 99.3/0.0 79.9/5.2 0.12 0.5 100.0/0.0 64.8/9.3 0.06 0.5 100.0/0.0 77.2/0.0 Amoxicillin-clavulanate ≤1 8 57.5/33.9b ≤1 8 79.1/16.4b 4 8 46.3/40.7b 4 8 45.6/46.8b Ceftriaxone 1 2 48.8/28.3c 48.8/1.6 0.5 2 51.5/24.6c 51.5/3.7 1 2 29.6/31.5c 29.6/1.9 2 4 19.0/50.6c 19.0/12.7 71.7/1.6b 75.4/3.7b 68.5/1.9b 49.4/12.7b Clindamycin >2 >2 0.0/92.9 7.1/92.9 >2 >2 0.0/94.8 5.2/94.8 >2 >2 0.0/100.0 0.0/100.0 >2 >2 0.0/97.5 2.5/97.5 Erythromycin >16 >16 0.0/100.0 0.0/100.0 >16 >16 0.0/100.0 0.0/100.0 >16 >16 00.0/100.0 0.0/100.0 >16 >16 0.0/98.7 0.0/98.7 Penicillin 1 4 15.0/44.9d 15.0/85.0c 0.5 4 20.9/38.1d 20.9/79.1c 2 4 9.3/64.8d 9.3/90.7c 2 4 6.3/68.4d 6.3/93.7c 66.9/1.6e 82.8/3.0e 63.0/1.9e 55.7/7.6e Trimethoprim-sulfamethoxazole 2 >4 37.8/49.6 47.2/49.6 1 >4 43.3/41.8 53.7/41.8 4 >4 29.6/59.3 35.2/59.3 >4 >4 25.3/64.6 32.9/64.6 Telithromycin- nonsusceptible S. pneumoniae 123 36 23 22 Nafithromycin 0.06 0.12 0.12 0.12 0.12 0.12 0.12 0.12 Telithromycin 0.5 1 99.2/0.0 0.0/15.4 0.5 1 97.2/0.0 0.0/19.4 0.5 1 100.0/0.0 0.0/34.8 0.5 0.5 100.0/0.0 0.0/0.0 Amoxicillin-clavulanate ≤1 8 61.8/26.8b 4 8 47.2/41.7b 8 8 8.7/65.2b 8 8 27.3/59.1b Ceftriaxone 0.5 2 54.5/23.6c 54.5/2.4 1 2 22.2/44.4c 22.2/8.3 2 2 8.7/60.9c 8.7/0.0 2 2 18.2/54.5c 18.2/9.1 76.4/2.4b 55.6/8.3b 39.1/0.0b 45.5/9.1b Clindamycin ≤0.25 >2 65.9/31.7 68.3/31.7 >2 >2 25.0/75.0 25.0/75.0 >2 >2 17.4/82.6 17.4/82.6 >2 >2 18.2/81.8 18.2/81.8 Erythromycin 16 >16 0.0/100.0 0.0/100.0 >16 >16 0.0/100.0 0.0/100.0 >16 >16 0.0/100.0 0.0/100.0 >16 >16 0.0/100.0 0.0/100.0 Penicillin 1 4 41.5/40.7d 41.5/58.5c 2 4 19.4/69.4d 19.4/80.6c 4 4 0.0/87.0d 0.0/100.0c 4 4 18.2/81.8d 18.2/81.8c 72.4/1.6e 55.6/5.6e 39.1/4.3e 40.9/9.1e Trimethoprim-sulfamethoxazole 1 >4 48.8/41.5 56.9/41.5 >4 >4 16.7/66.7 27.8/66.7 >4 >4 13.0/87.0 13.0/87.0 >4 >4 13.6/81.8 13.6/81.8 S. pyogenes n = 202 n = 203 n = 102 n = 99 Nafithromycin 0.015 0.015 0.015 0.015 0.015 0.015 0.015 0.03 Telithromycin 0.015 0.03 97.0/2.5 0.015 0.03 96.6/3.0 0.015 0.015 99.0/0.0 0.015 0.03 98.0/2.0 Clindamycin ≤0.25 ≤0.25 92.6/5.9 94.1/5.9 ≤0.25 ≤0.25 95.1/4.9 95.1/4.9 ≤0.25 ≤0.25 97.1/2.9 97.1/2.9 ≤0.25 ≤0.25 97.0/3.0 97.0/3.0 Erythromycin ≤0.12 8 83.2/16.8 83.2/16.8 ≤0.12 0.25 91.1/8.9 91.1/8.9 ≤0.12 ≤0.12 93.1/5.9 93.1/5.9 ≤0.12 ≤0.12 94.9/5.1 94.9/5.1 Penicillin ≤0.06 ≤0.06 100.0/0.0 100.0/0.0 ≤0.06 ≤0.06 100.0/0.0 100.0/0.0 ≤0.06 ≤0.06 100.0/0.0 100.0/0.0 ≤0.06 ≤0.06 100.0/0.0 100.0/0.0 Erythromycin-resistant and clindamycin-resistant S. pyogenes 15 10 3 3 Nafithromycin 0.015 0.25 0.12 0.5 0.015 0.5 Telithromycin 0.015 2 66.7/33.3 0.5 >2 40.0/50.0 0.015 66.7/0.0 2 33.3/66.7 Clindamycin >2 >2 0.0/80.0 20.0/80.0 >2 >2 0.0/100.0 0.0/100.0 >2 0.0/100.0 0.0/100.0 >2 0.0/100.0 0.0/100.0 Erythromycin >16 >16 0.0/100.0 0.0/100.0 >16 >16 0.0/100.0 0.0/100.0 8 0.0/100.0 0.0/100.0 >16 0.0/100.0 0.0/100.0 Penicillin ≤.06 ≤0.06 100.0/0.0 100.0/0.0 ≤0.06 ≤0.06 100.0/0.0 100.0/0.0 ≤0.06 100.0/0.0 100.0/0.0 ≤0.06 100.0/0.0 100.0/0.0 H. influenzae 398 402 100 102 Nafithromycin 4 4 4 4 2 4 2 4 Telithromycin 2 4 96.7/1.3 0.5/1.3 2 4 98.8/0.5 0.0/0.5 2 4 98.0/1.0 0.0/1.0 2 4 99.0/1.0 99.0/1.0 Amoxicillin-clavulanate ≤1 2 99.7/0.3 99.0/1.0 ≤1 ≤1 100.0/0.0 99.3/0.7 ≤1 ≤1 100.0/0.0 99.0/1.0 ≤1 4 97.1/2.9 85.3/14.7 Ampicillin ≤0.25 >8 72.4/26.9 72.4/27.6b ≤0.25 >8 84.1/13.9 84.1/15.9b ≤0.25 >8 78.0/21.0 78.0/22.0b 1 >8 65.7/26.5 65.7/34.3b Azithromycin 0.5 2 98.7/ 2.3/1.3 0.5 1 100.0/0.0 3.0/0.0 0.5 1 99.0/ 4.0/1.0 0.5 1 99.0/ 2.0/1.0 Ciprofloxacin ≤0.03 ≤0.03 100.0/0.0 99.5/0.5 ≤0.03 ≤0.03 99.8/ 99.3/0.7 ≤0.03 ≤0.03 100.0/0.0 100.0/0.0 ≤0.03 ≤0.03 97.1/ 96.1/3.9 Clarithromycin 4 8 93.2/1.8 2.8/0.0 4 8 97.0/0.7 2.8/0.0 4 8 99.0/1.0 4.0/0.0 4 8 97.1/2.0 2.0/0.0 Trimethoprim-sulfamethoxazole ≤0.5 >4 65.6/27.4 65.6/32.7 ≤0.5 >4 68.4/25.1 68.4/29.6 ≤0.5 ≥4 71.0/24.0 71.0/28.0 ≤0.5 >4 59.8/38.2 59.8/39.2 M. catarrhalis 197 202 54 51 Nafithromycin 0.12 0.25 0.12 0.25 0.12 0.25 0.25 0.25 Telithromycin 0.06 0.12 99.0/0.0 0.12 0.12 100.0/0.0 0.06 0.12 100.0/0.0 0.12 0.25 100.0/0.0 Amoxicillin-clavulanate ≤1 ≤1 100.0/0.0 100.0/0.0 ≤1 ≤1 100.0/0.0 100.0/0.0 ≤1 ≤1 100.0/0.0 100.0/0.0 <1 <1 100.0/0.0 100.0/0.0 Azithromycin 0.03 0.06 100.0/0.0 100.0/0.0 0.03 0.06 100.0/0.0 100.0/0.0 ≤0.03 0.06 100.0/0.0 100.0/0.0 0.03 0.06 100.0/0.0 100.0/0.0 Clarithromycin ≤0.12 ≤0.12 100.0/0.0 100.0/0.0 ≤0.12 ≤0.12 100.0/0.0 99.5/0.0 ≤0.12 ≤0.12 100.0/0.0 100.0/0.0 ≤0.12 ≤0.12 100.0/0.0 98.0/0.0 Trimethoprim-sulfamethoxazole ≤0.5 ≤0.5 94.4/0.0 94.4/3.6 ≤0.5 ≤0.5 94.6/0.0 94.6/0.5 ≤0.5 ≤0.5 100.0/0.0 100.0/0.0 ≤0.5 ≤0.5 98.0/0.0 98.0/0.0
