Table 6.
MIC and susceptibility results for H. influenzae isolates by country
| Susceptibility |
|||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| MIC (mg/L) |
CLSI |
PK/PD |
EUCAST |
||||||||||
| Antimicrobial | Isolate group | n | 50% | 90% | min | max | %S | %I | %R | %S | %S | %I | %R |
| India | |||||||||||||
| AMCa,b | All | 135 | 0.5 | 4 | ≤0.015 | >256 | 97.0 | 0.0 | 3.0 | 89.6 (97.0) | 89.6 | 0.0 | 10.4 |
| BL− | 124 | 0.5 | 2 | ≤0.015 | 8 | 99.2 | 0.0 | 0.8 | 91.9 (99.2) | 91.9 | 0.0 | 8.1 | |
| BL+ | 11 | 2 | >256 | 0.03 | >256 | 72.7 | 0.0 | 27.3 | 63.6 (72.7) | 63.6 | 0.0 | 36.4 | |
| ampicillinc | All | 135 | 0.25 | 1 | ≤0.015 | 32 | 91.1 | 1.5 | 7.4 | NA | 91.1 | 0.0 | 8.9 |
| BL− | 124 | 0.25 | 0.5 | ≤0.015 | 2 | 99.2 | 0.8 | 0.0 | NA | 99.2 | 0.0 | 0.8 | |
| BL+ | 11 | 4 | 16 | 2 | 32 | 0.0 | 9.1 | 90.9 | NA | 0.0 | 0.0 | 100 | |
| azithromycind | All | 94 | 4 | 8 | ≤0.015 | >256 | 94.7 | 0.0 | 5.3 | NA | NA | NA | NA |
| BL− | 87 | 4 | 8 | ≤0.015 | >256 | 94.3 | 0.0 | 5.8 | NA | NA | NA | NA | |
| BL+ | 7 | 4 | 8 | ≤0.015 | 8 | 100 | 0.0 | 0.0 | NA | NA | NA | NA | |
| cefixime | All | 135 | 0.06 | 0.5 | ≤0.015 | >256 | 97.0 | 0.0 | 3.0 | 97.0 | 85.2 | 0.0 | 14.8 |
| BL− | 124 | 0.06 | 0.5 | ≤0.015 | >256 | 96.8 | 0.0 | 3.2 | 96.8 | 84.7 | 0.0 | 15.3 | |
| BL+ | 11 | 0.03 | 0.12 | ≤0.015 | 0.5 | 100 | 0.0 | 0.0 | 100 | 90.9 | 0.0 | 9.1 | |
| cefpodoxime | All | 134 | 0.06 | 1 | ≤0.015 | >256 | 97.0 | 0.0 | 3.0 | 89.5 | 78.4 | 11.2 | 10.5 |
| BL− | 123 | 0.12 | 1 | ≤0.015 | >256 | 96.7 | 0.0 | 3.3 | 88.6 | 78.1 | 10.6 | 11.4 | |
| BL+ | 11 | 0.06 | 0.5 | 0.03 | 0.5 | 100 | 0.0 | 0.0 | 100 | 81.8 | 18.2 | 0.0 | |
| cefuroximee,b | All | 134 | 0.5 | 1 | ≤0.015 | >256 | 99.3 | 0.0 | 0.8 | 90.3 | 17.9 | 72.4 | 9.7 |
| BL− | 123 | 0.5 | 1 | ≤0.015 | >256 | 99.2 | 0.0 | 0.8 | 91.9 | 18.7 | 73.2 | 8.1 | |
| BL+ | 11 | 1 | 2 | ≤0.015 | 4 | 100 | 0.0 | 0.0 | 72.7 | 9.1 | 63.6 | 27.3 | |
| ciprofloxacin | All | 135 | 0.5 | 8 | ≤0.015 | >32 | 76.3 | 0.0 | 23.7 | 76.3 | 59.3 | 0.0 | 40.7 |
| BL− | 124 | 0.5 | 8 | ≤0.015 | >32 | 75.0 | 0.0 | 25.0 | 75.0 | 58.1 | 0.0 | 41.9 | |
| BL+ | 11 | 0.25 | 1 | ≤0.015 | 8 | 90.9 | 0.0 | 9.1 | 90.9 | 72.7 | 0.0 | 27.3 | |
| clarithromycind | All | 108 | 16 | 64 | 0.06 | >256 | 66.7 | 19.4 | 13.9 | NA | NA | NA | NA |
| BL− | 99 | 16 | 64 | 0.06 | >256 | 65.7 | 19.2 | 15.2 | NA | NA | NA | NA | |
| BL+ | 9 | 8 | 32 | 1 | 32 | 77.8 | 22.2 | 0.0 | NA | NA | NA | NA | |
| levofloxacin | All | 135 | 0.5 | 8 | ≤0.015 | >32 | 85.2 | 0.0 | 14.8 | 85.2 | 79.3 | 0.0 | 20.7 |
| BL− | 124 | 0.5 | 8 | ≤0.015 | >32 | 84.7 | 0.0 | 15.3 | 84.7 | 78.2 | 0.0 | 21.8 | |
| BL+ | 11 | 0.5 | 1 | 0.03 | 8 | 90.9 | 0.0 | 9.1 | 90.9 | 90.9 | 0.0 | 9.1 | |
| ofloxacin | All | 135 | 0.5 | 8 | ≤0.015 | >32 | 80.7 | 0.0 | 19.3 | NA | 53.3 | 0.0 | 46.7 |
| BL− | 124 | 0.5 | >32 | ≤0.015 | >32 | 79.8 | 0.0 | 20.2 | NA | 51.6 | 0.0 | 48.4 | |
| BL+ | 11 | 0.5 | 2 | 0.06 | 8 | 90.9 | 0.0 | 9.1 | NA | 72.7 | 0.0 | 27.3 | |
| SXT | All | 135 | 4 | >32 | ≤0.015 | >32 | 23.0 | 13.3 | 63.7 | 23.0 | 23.0 | 5.2 | 71.9 |
| BL− | 124 | 4 | >32 | ≤0.015 | >32 | 25.0 | 13.7 | 61.3 | 25.0 | 25.0 | 4.8 | 70.2 | |
| BL+ | 11 | >32 | >32 | 1 | >32 | 0.0 | 9.1 | 90.9 | 0 | 0.0 | 9.1 | 90.9 | |
| South Korea | |||||||||||||
| AMCa,b | All | 72 | 4 | 32 | 0.25 | >256 | 62.5 (56.9)f | 0.0 0.0 | 37.5 (43.1)f | 38.9 (62.5) | 38.9 (31.9)f | 0.0 | 61.1 (68.1)f |
| BL− | 30 | 4 | 16 | 0.25 | >256 | 66.7 | 0.0 | 33.3 | 36.7 (66.7) | 36.7 | 0.0 | 63.3 | |
| BL+ | 42 | 4 | 32 | 0.5 | >256 | 59.5 | 0.0 | 40.5 | 40.5 (59.5) | 40.5 | 0.0 | 59.5 | |
| ampicillinc | All | 72 | 64 | >256 | 0.25 | >256 | 16.7 | 13.9 | 69.4 | NA | 16.7 | 0.0 | 83.3 |
| BL− | 30 | 2 | 16 | 0.25 | >256 | 26.7 | 30.0 | 43.3 | NA | 26.7 | 0.0 | 73.3 | |
| BL+ | 42 | >256 | >256 | 0.25 | >256 | 9.5 | 2.4 | 88.1 | NA | 9.5 | 0.0 | 90.5 | |
| azithromycind | All | 72 | 2 | 8 | 0.5 | >256 | 94.4 | 0.0 | 5.6 | NA | NA | NA | NA |
| BL− | 30 | 2 | 8 | 1 | >256 | 93.3 | 0.0 | 6.7 | NA | NA | NA | NA | |
| BL+ | 42 | 2 | 4 | 0.5 | 64 | 95.2 | 0.0 | 4.8 | NA | NA | NA | NA | |
| cefaclorb | All | 72 | 64 | >256 | 0.5 | >256 | 29.2 (27.8)f | 8.3 | 62.5 (63.9)f | 1.4 | NA | NA | NA |
| BL− | 30 | 32 | >256 | 0.5 | >256 | 30.0 | 13.3 | 56.7 | 3.3 | NA | NA | NA | |
| BL+ | 42 | 64 | >256 | 2 | >256 | 28.6 | 4.8 | 66.7 | 0 | NA | NA | NA | |
| cefuroximee,b | All | 72 | 16 | >256 | 0.5 | >256 | 40.3 (37.5)f | 4.2 | 55.6 (58.3)f | 16.7 | 0.0 | 16.7 | 83.3 |
| BL− | 30 | 4 | >256 | 0.5 | >256 | 50.0 | 6.7 | 43.3 | 16.7 | 0.0 | 16.7 | 83.3 | |
| BL+ | 42 | 32 | >256 | 0.5 | >256 | 33.3 | 2.4 | 64.3 | 16.7 | 0.0 | 16.7 | 83.3 | |
| clarithromycind | All | 72 | 16 | 64 | 4 | >256 | 50.0 | 37.5 | 12.5 | NA | NA | NA | NA |
| BL− | 30 | 16 | 64 | 8 | 64 | 53.3 | 33.3 | 13.3 | NA | NA | NA | NA | |
| BL+ | 42 | 32 | 64 | 4 | >256 | 47.6 | 40.5 | 11.9 | NA | NA | NA | NA | |
| levofloxacin | All | 72 | 0.015 | 0.03 | ≤0.015 | 1 | 100 | 0.0 | 0.0 | 100 | 100 | 0.0 | 0.0 |
| BL− | 30 | 0.015 | 0.03 | ≤0.015 | 1 | 100 | 0.0 | 0.0 | 100 | 100 | 0.0 | 0.0 | |
| BL+ | 42 | 0.015 | 0.03 | ≤0.015 | 0.5 | 100 | 0.0 | 0.0 | 100 | 100 | 0.0 | 0.0 | |
| SXT | All | 72 | 0.12 | >32 | ≤0.015 | >32 | 59.7 | 1.4 | 38.9 | 59.7 | 59.7 | 0.0 | 40.3 |
| BL− | 30 | 0.06 | >32 | 0.03 | >32 | 73.3 | 3.3 | 23.3 | 73.3 | 73.3 | 0.0 | 26.7 | |
| BL+ | 42 | 0.25 | >32 | ≤0.015 | >32 | 50.0 | 0.0 | 50.0 | 50.0 | 50.0 | 0.0 | 50.0 | |
| Singapore | |||||||||||||
| AMCa,b | All | 60 | 1 | 4 | 0.06 | 16 | 93.3 | 0.0 | 6.7 | 86.7 (93.3) | 86.7 (76.7)f | 0.0 | 13.3 (23.3)f |
| BL− | 49 | 1 | 4 | 0.06 | 16 | 91.8 | 0.0 | 8.2 | 85.7 (91.8) | 85.7 | 0.0 | 14.3 | |
| BL+ | 11 | 1 | 2 | 0.5 | 4 | 100 | 0.0 | 0.0 | 90.9 (100) | 90.9 | 0.0 | 9.1 | |
| ampicillinc | All | 60 | 0.5 | >256 | 0.03 | >256 | 63.3 | 15.0 | 21.7 | NA | 63.3 | 0.0 | 36.7 |
| BL− | 49 | 0.5 | 2 | 0.03 | 32 | 77.6 | 18.4 | 4.1 | NA | 77.6 | 0.0 | 22.5 | |
| BL+ | 11 | >256 | >256 | 64 | >256 | 0.0 | 0.0 | 100 | NA | 0.0 | 0.0 | 100 | |
| azithromycind | All | 60 | 2 | 4 | 0.12 | 16 | 98.3 | 0.0 | 1.7 | NA | NA | NA | NA |
| BL− | 49 | 2 | 4 | 0.12 | 8 | 100 | 0.0 | 0.0 | NA | NA | NA | NA | |
| BL+ | 11 | 2 | 4 | 1 | 16 | 90.9 | 0.0 | 9.1 | NA | NA | NA | NA | |
| cefaclorb | All | 60 | 4 | 256 | 0.03 | >256 | 75.0 (73.3)f | 1.7 | 23.3 (25.0)f | 5.0 | NA | NA | NA |
| BL− | 49 | 4 | >256 | 0.03 | >256 | 71.4 | 2.0 | 26.5 | 2.0 | NA | NA | NA | |
| BL+ | 11 | 4 | 8 | 0.12 | 256 | 90.9 | 0.0 | 9.1 | 18.2 | NA | NA | NA | |
| cefuroximee,b | All | 60 | 1 | 8 | 0.06 | >256 | 85.0 | 10.0 | 5.0 | 60.0 | 1.7 | 58.3 | 40.0 |
| BL− | 49 | 1 | 8 | 0.06 | >256 | 85.7 | 10.2 | 4.1 | 57.1 | 2.0 | 55.1 | 42.9 | |
| BL+ | 11 | 1 | 8 | 0.5 | 16 | 81.8 | 9.1 | 9.1 | 72.7 | 0.0 | 72.7 | 27.3 | |
| ciprofloxacin | All | 60 | 0.015 | 0.25 | ≤0.015 | 0.5 | 100 | 0.0 | 0.0 | 100 | 100 | 0.0 | 0.0 |
| BL− | 49 | 0.015 | 0.25 | ≤0.015 | 0.5 | 100 | 0.0 | 0.0 | 100 | 100 | 0.0 | 0.0 | |
| BL+ | 11 | 0.015 | 0.25 | ≤0.015 | 0.5 | 100 | 0.0 | 0.0 | 100 | 100 | 0.0 | 0.0 | |
| clarithromycind | All | 60 | 8 | 32 | 0.25 | >256 | 83.3 | 8.3 | 8.3 | NA | NA | NA | NA |
| BL− | 49 | 8 | 32 | 0.25 | 64 | 87.8 | 6.1 | 6.1 | NA | NA | NA | NA | |
| BL+ | 11 | 8 | 64 | 2 | >256 | 63.6 | 18.2 | 18.2 | NA | NA | NA | NA | |
| levofloxacin | All | 60 | 0.015 | 0.12 | ≤0.015 | 0.5 | 100 | 0.0 | 0.0 | 100 | 100 | 0.0 | 0.0 |
| BL− | 49 | 0.015 | 0.12 | ≤0.015 | 0.25 | 100 | 0.0 | 0.0 | 100 | 100 | 0.0 | 0.0 | |
| BL+ | 11 | 0.015 | 0.03 | ≤0.015 | 0.5 | 100 | 0.0 | 0.0 | 100 | 100 | 0.0 | 0.0 | |
| moxifloxacin | All | 60 | 0.03 | 0.06 | ≤0.015 | 2 | 98.3 | 0.0 | 1.7 | 98.3 | 98.3 | 0.0 | 1.7 |
| BL− | 49 | 0.03 | 0.12 | ≤0.015 | 0.25 | 100 | 0.0 | 0.0 | 100 | 100 | 0.0 | 0.0 | |
| BL+ | 11 | 0.015 | 0.06 | ≤0.015 | 2 | 90.9 | 0.0 | 9.1 | 90.9 | 90.9 | 0.0 | 9.1 | |
| ofloxacin | All | 60 | 0.06 | 0.06 | ≤0.015 | 2 | 100 | 0.0 | 0.0 | NA | 98.3 | 0.0 | 1.7 |
| BL− | 49 | 0.06 | 0.25 | ≤0.015 | 0.5 | 100 | 0.0 | 0.0 | NA | 100 | 0.0 | 0.0 | |
| BL+ | 11 | 0.06 | 0.06 | 0.03 | 2 | 100 | 0.0 | 0.0 | NA | 90.9 | 0.0 | 9.1 | |
| SXT | All | 60 | 0.12 | >32 | ≤0.015 | >32 | 63.3 | 3.3 | 33.3 | 63.3 | 63.3 | 1.7 | 35.0 |
| BL− | 49 | 0.12 | >32 | ≤0.015 | >32 | 67.4 | 4.1 | 28.6 | 67.4 | 67.4 | 2.0 | 30.6 | |
| BL+ | 11 | 8 | >32 | 0.03 | >32 | 45.5 | 0.0 | 54.6 | 45.5 | 45.5 | 0.0 | 54.6 | |
| Thailand | |||||||||||||
| AMCa,b | All | 263 | 1 | 2 | 0.06 | 16 | 97.7 (93.5)f | 0.0 | 2.3 (6.5)f | 90.5 (97.7) | 90.5 (81.4)f | 0.0 | 9.5 (18.6)f |
| BL− | 167 | 1 | 2 | 0.06 | 16 | 98.2 | 0.0 | 1.8 | 93.4 (98.2) | 93.4 | 0.0 | 6.6 | |
| BL+ | 96 | 1 | 4 | 0.12 | 16 | 96.9 | 0.0 | 3.1 | 85.4 (96.9) | 85.4 | 0.0 | 14.6 | |
| ampicillinc | all | 263 | 1 | >256 | 0.03 | >256 | 51.7 | 8.8 | 39.5 | na | 51.7 | 0.0 | 48.3 |
| BL− | 167 | 0.5 | 2 | 0.03 | 32 | 80.8 | 12.0 | 7.2 | na | 80.8 | 0.0 | 19.2 | |
| BL+ | 96 | >256 | >256 | 0.5 | >256 | 1.0 | 3.1 | 95.8 | na | 1.0 | 0.0 | 99.0 | |
| azithromycind | all | 263 | 2 | 4 | 0.06 | 16 | 99.6 | 0.0 | 0.4 | na | na | na | na |
| BL− | 167 | 2 | 4 | 0.06 | 8 | 100 | 0.0 | 0.0 | na | na | na | na | |
| BL+ | 96 | 2 | 4 | 0.5 | 16 | 99.0 | 0.0 | 1.0 | na | na | na | na | |
| cefuroximee,b | all | 263 | 0.5 | 2 | 0.03 | 32 | 96.2 (92.4)f | 1.5 | 2.3 (6.1)f | 79.5 | 7.2 | 72.4 (66.9)f | 20.5 (25.9)f |
| BL− | 167 | 0.5 | 4 | 0.03 | 16 | 95.2 | 2.4 | 2.4 | 79.0 | 10.1 | 69.1 | 20.8 | |
| BL+ | 96 | 0.5 | 2 | 0.06 | 32 | 97.9 | 0.0 | 2.1 | 80.2 | 2.1 | 78.1 | 19.8 | |
| clarithromycind | all | 263 | 16 | 32 | 1 | 128 | 79.5 | 19.8 | 0.8 | na | na | na | na |
| BL− | 167 | 16 | 32 | 1 | 128 | 81.4 | 17.4 | 1.2 | na | na | na | na | |
| BL+ | 96 | 16 | 32 | 1 | 32 | 76.0 | 24.0 | 0.0 | na | na | na | na | |
| levofloxacin | all | 263 | 0.015 | 0.03 | ≤0.015 | >256 | 99.6 | 0.0 | 0.4 | 99.6 | 99.2 | 0.0 | 0.8 |
| BL− | 167 | 0.015 | 0.03 | ≤0.015 | >256 | 99.4 | 0.0 | 0.6 | 99.4 | 98.8 | 0.0 | 1.2 | |
| BL+ | 96 | 0.015 | 0.03 | ≤0.015 | 1 | 100 | 0.0 | 0.0 | 100 | 100 | 0.0 | 0.0 | |
min, minimum; max, maximum; S, susceptible; I, intermediate; AMC, amoxicillin/clavulanic acid; BL−, β-lactamase negative; BL+, β-lactamase positive; NA, no breakpoint data available (NA for azithromycin and clarithromycin by EUCAST because Etest® breakpoints in CO2 not available); SXT, trimethoprim/sulfamethoxazole.
aPK/PD susceptibility at high dose is shown in parentheses.
bIn clinical settings, isolates of BLNAR are considered resistant to amoxicillin/clavulanic acid, cefaclor and cefuroxime (see main text).
cClinically all β-lactamase-positive H. influenzae should be considered resistant.
dbioMérieux Etest® breakpoints for incubation in CO2.
eBreakpoints used are for cefuroxime axetil.
fClinical susceptibility to amoxicillin/clavulanic acid or cefuroxime reduced (data in parenthesis) due to corrections according to BLNAR (see main text).