Table 1.
Antimicrobial phenotypes and molecular mechanisms of resistance found in the two XDR H. parainfluenzae isolatesa
| Antimicrobial | MIC (μg/ml) and interpretationb | Molecular mechanism(s) of resistance |
|---|---|---|
| β-lactams | PBP3: Lys276Asn, Ala307Asn, Val329Ile, Ser385Thr, Ile442F, Val511Ala, Asn526Lys (TEM-1 not expressed) | |
| Ampicillin | 8, R | |
| Amoxicillin | 6, R | |
| Amoxicillin-clavulanate | 4, R | |
| Cefuroxime | 32, R | |
| Ceftriaxone | 0.25, R | |
| Cefotaxime | 1.5, R | |
| Cefepime | 3, R | |
| Meropenem | 0.5, S (I) | |
| Macrolides | Mef(A); L4: Ala69Serc | |
| Erythromycin | >256, R | |
| Clarithromycin | >256, R | |
| Azithromycin | >256, R | |
| Quinolones | GyrA: Ser84Phe, Asp88Tyr; ParC: Ser84Phe | |
| Ciprofloxacin | >32, R | |
| Levofloxacin | >32, R | |
| Tetracycline | 32, R | Tet(M) |
| Trimethoprim-sulfamethoxazole | 0.25, S | |
| Rifampin | 0.75, S | |
| Chloramphenicol | 96, R | CatS |
Since the isolates are indistinguishable, the phenotypic and molecular backgrounds of resistance are the same.
Interpretation of MICs according to the EUCAST criteria (S, susceptible; I, intermediate; R, resistant) (8): for ampicillin, cefuroxime, rifampin, clarithromycin, levofloxacin, and tetracycline, S is a MIC of ≤1 μg/ml; for amoxicillin, amoxicillin-clavulanate, and chloramphenicol, S is a MIC of ≤2 μg/ml; for ceftriaxone, cefotaxime, and azithromycin, S is a MIC of ≤0.12 μg/ml; for cefepime, S is a MIC of ≤0.25 μg/ml; for meropenem, S is a MIC of ≤2 μg/ml, but in cases of meningitis (interpretation indicated in parentheses), S is a MIC of ≤0.25 μg/ml and R is a MIC of ≥2 μg/ml; for erythromycin, ciprofloxacin, and trimethoprim-sulfamethoxazole, S is a MIC of ≤0.5 μg/ml.
The Ala69Ser substitution was observed after comparison with H. influenzae Rd but not with H. parainfluenzae T3T1.