TABLE 1.
MICs of baseline and after exposure to subinhibitory concentrations of MIN, RIF, and CHX
| Organism type and strain by susceptibility status | MIC (μg/ml) of individual agentsa |
MIC (μg/ml) of MIN, RIF, and CHX atb: |
|||
|---|---|---|---|---|---|
| Minocycline | Rifampin | Chlorhexidine | Baseline | Passage 20 | |
| Low-susceptibility organisms (n = 17) | |||||
| Vancomycin-resistant Enterococcus | |||||
| MDA 111 | 8 (I) | 16 (R) | 4 (R) | 2 | 1 |
| MDA 191 | 8 (I) | 4 (R) | 8 (R) | 2 | 2 |
| MDA 192 | 16 (R) | 16 (R) | 4 (R) | 2 | 2 |
| Carbapenem-resistant Enterobacteriaceae | |||||
| Klebsiella pneumoniae | |||||
| ATCC 1705 | 8 (I) | 32 (R) | 8 (R) | 1 | 1 |
| MDA 124 | 32 (R) | 32 (R) | 4 (R) | 2 | 1 |
| MDA 125 | 32 (R) | 32 (R) | 8 (R) | 1 | 1 |
| MDA 126 | 32 (R) | 32 (R) | 4 (R) | 1 | 2 |
| Escherichia coli | |||||
| MDA 122 | 8 (I) | 32 (R) | 1 (S) | 1 | 1 |
| Enterobacter cloacae | |||||
| MDA 166 | 8 (I) | >32 (R) | 16 (R) | 1 | 4 |
| MDA 167 | 32 (R) | 32 (R) | 16 (R) | 1 | 2 |
| MDA 121 | 4 (S) | 32 (R) | 8 (R) | <1 | 1 |
| Multidrug-resistant organisms | |||||
| Pseudomonas aeruginosa | |||||
| MDA 118 | 8 (I) | 8 (R) | 8 (R) | 2 | 1 |
| MDA 194 | 32 (R) | 32 (R) | 8 (R) | 4 | 2 |
| MDA 170 | 32 (R) | 32 (R) | 8 (R) | 1 | 1 |
| Other organisms | |||||
| Candida albicans | |||||
| MB 3655A | >16 (R) | >16 (R) | 4 (R) | 4 | 4 |
| Candida parapsilosis | |||||
| MB2247 | >16 (R) | >16 (R) | 4 (R) | 4 | 8 |
| Acinetobacter baumannii | |||||
| MB 2790 | 0.125 (S) | 4 (R) | 4 (R) | <1 | <1 |
| High-susceptibility organismsc (n = 12) | |||||
| Gram positive | |||||
| Staphylococcus aureus | |||||
| ATCC 25923 | 0.125 (S) | <0.031 (S) | 0.5 (S) | <0.031 | — |
| ATCC 43300 | 0.125 (S) | <0.031 (S) | 1 (S) | <0.031 | — |
| MDA 155 | <0.016 (S) | 1.0 (S) | 2 (S) | 0.0002 | — |
| MDA 148 | <0.016 (S) | >32 (R) | 2 (S) | 0.0002 | — |
| Staphylococcus epidermidis | |||||
| MB 123 | 0.125 (S) | >32 (R) | 1 (S) | 0.125 | — |
| MB 1915 | 0.125 (S) | >32 (R) | 1 (S) | 0.125 | — |
| Gram negative | |||||
| Acinetobacter baumannii | |||||
| MB 2875 | 0.125 (S) | 2 (I) | 2 (S) | <1 | <1 |
| MB 2767 | 0.031 (S) | 2 (I) | 2 (S) | <0.016 | — |
| Escherichia coli | |||||
| ATCC 25922 | 1 (S) | 8 (R) | 0.25 (S) | <1 | 1 |
| ATCC 35218 | 1 (S) | 8 (R) | 0.5 (S) | <1 | 1 |
| MDA 164 | 4 (S) | 16 (R) | 2 (S) | 1 | 2 |
| MDA 165 | 4 (S) | 16 (R) | 2 (S) | 1 | 1 |
Susceptibility testing for each component of MIN, RIF, and CHX before exposure. MICs to individual agents were then assigned susceptible (S), intermediate (I), or resistant (R) based on CLSI breakpoints for minocycline and rifampin (42) or EUCAST epidemiologic cutoffs for chlorhexidine (43). MIC breakpoints are defined as S ≤ 4, I = 8, R ≥ 16 for minocycline; S ≤ 1, I = 2, R ≥ 4 for rifampin; and S ≤ 2, R ≥ 4 for chlorhexidine.
MICs for triple combination MIN, RIF, and CHX in organisms at baseline and after 20 passages exposed to subinhibitory concentrations of MIN, RIF, and CHX.
For Staphylococcus aureus ATCC 25923 and ATCC 43300 and Acinetobacter baumannii MB 2767, the organisms were highly susceptible to the point that the MIC for MIN, RIF, and CHX was less that that of the testing limit; thus, no subinhibitory concentration could be achieved for passages to be conducted. For Staphylococcus aureus MDA 155 and MDA 148 and Staphylococcus epidermidis MB 123 and MB 1915, subinhibitory concentrations were established at baseline; however, organisms died after two passages and no further passages could be conducted. A dash indicates that a MIC at passage 20 could not be established.