TABLE 2.
Overview of the effects of ciprofloxacin risk concentration on P. aeruginosa clinical isolates and its association with their 3-day sub-MIC selective windowsa
| Phenotypic changes upon exposure to 0.04 μg/mL of CIP (fold-changes) |
|||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Strain | Relative CIP MSC (3 days) | CIP mIC of the parental strains | Fitnessb | 3-day evolved populations |
|||||||
| CIP mICc | Mutant selectionc |
Biofilm formationc | Elastase activityc | Pyocyanin productionc | Swarming motilityc | Cross-resistanced | |||||
| MIC | 2×MIC | ||||||||||
| Narrow sub-MIC selective window | |||||||||||
| GAL02-002 | 1/2 MIC | 0.25 | 1.0 | 2.4 | 30 | 2.3 | 1.3 | 0.8 | 1.1 | 2.2 | None |
| FQSE111010 | 1/5 MIC | 0.25 | 1.0 | 1.4 | 3.6 | 1.3 | 1.0 | 1.0 | 1.1 | 1.0 | None |
| FQSE06-0403 | 1/5 MIC | 0.19 | 1.0 | 5.4 | 1.7 × 109 | 1.2 × 109 | 1.7 | 1.0 | 0.9 | 0.9 | LEV, CAZ, AMK, FOF |
| CAT02-004 | 1/10MIC | 0.25 | 0.9 | 2.3 | 9.7 × 104 | 4.6 × 107 | 0.9 | 1.2 | 0.7 | 4.4 | None |
| Wide sub-MIC selective window | |||||||||||
| CLE03-004 | 1/25MIC | 0.094 | 0.3 | 13.3 | 2.1 × 104 | 7.9 × 104 | 1.3 | 1.0 | 0.8 | 1.1 | LEV, AMK, ATM |
| ICA01-004 | 1/25MIC | 0.064 | 0.6 | 13.9 | 7.7 × 105 | 9.3 × 105 | 0.9 | 0.9 | 0.9 | 0.3 | LEV, CAZ, AMK, ATM, IPM |
| AND04-004A | 1/25MIC | 0.064 | 0.5 | 10.4 | 1.6 × 107 | 2.6 × 108 | 1.0 | 0.4 | 1.0 | 0.1 | LEV, IPM |
| CAN01-002 | 1/25MIC | 0.094 | 0.9 | 7.8 | 3.9 × 105 | 1.6 × 107 | 0.8 | 0.3 | 0.8 | 0.9 | LEV |
| BAL04-002 | 1/50MIC | 0.094 | 0.4 | 10.0 | 5.5 × 105 | 3.3 × 106 | 1.1 | 1.0 | 1.0 | 0.8 | LEV, CAZ, ATM, FOF |
| FQSE11-0603 | 1/50MIC | 0.125 | 1.1 | 13,5 | 1.7 × 105 | 1.7 × 106 | 1.0 | 1.1 | 0.9 | 1.1 | LEV |
| PA14 | 1/200MIC | 0.064 | 0.6 | 23.7 | 8.6 × 104 | 9.1 × 104 | 0.6 | 0.8 | 0.7 | 0.2 | LEV |
The table summarizes the changes in phenotypic traits of the strains used in this study after 3 days in the presence of ciprofloxacin sub-MIC risk concentration. A statistically significant fold-change in a parameter (excepting CIP MIC fold-change) is highlighted in bold. An MSC of 1/2 of MIC to 1/10 of MIC is dubbed narrow sub-MIC selective window, whereas 1/25 of MIC to 1/200 of MIC is dubbed wide sub-MIC selective window. CIP, ciprofloxacin; LEV, levofloxacin; CAZ, ceftazidime; AMK, amikacin; ATM, aztreonam; IPM, imipenem; FOF, fosfomycin.
This parameter is measured as the average fold-change of the strain’s fitness in the presence of 0.04 μg/mL of ciprofloxacin for 30 h, with respect to the one in LBB for the same interval.
This parameter is measured as the average fold-change of the value of populations evolved under 0.04 μg/mL of ciprofloxacin for 3 days, with respect to the ones evolved in LBB for the same interval.
At least half the replicates must show ≥2-fold of the parental strain MIC to the antibiotic, as determined using MIC test strips that discern small differences, to be subsumed as a cross-resistance.