TABLE 2.
Antimicrobial susceptibility profiles of 46 baseline multidrug-resistant or carbapenem-resistant Pseudomonas aeruginosa isolates from 46 patients receiving cefiderocol in the compassionate use program by using CLSI breakpointsa
| Antimicrobial agent | MICb90 (μg/mL) | MIC range (μg/mL) | Interpretation (no. [%]) |
||
|---|---|---|---|---|---|
| S | I | R | |||
| Cefiderocolc,d (n = 46) | 4 | ≤0.03 to 16 | 42 (91) | 3 (7) | 1 (2) |
| Amikacin (n = 43) | >64 | ≤4 to >64 | 22 (51) | 7 (16) | 14 (33) |
| Aztreonam (n = 43) | >32 | 2 to >32 | 5 (12) | 12 (28) | 26 (60) |
| Cefepime (n = 46) | >16 | 2 to >64 | 4 (9) | 11 (24) | 31 (67) |
| Ceftazidime-avibactam (n = 46) | >64 | 1 to >64 | 14 (30) | NA | 32 (70) |
| Ceftolozane-tazobactam (n = 46) | >64 | 0.5 to >64 | 9 (20) | 2 (4) | 35 (76) |
| Ciprofloxacin (n = 46) | >4 | ≤0.25 to >8 | 3 (7) | 2 (4) | 41 (89) |
| Colistin (n = 46) | 2 | ≤0.5 to >8 | NA | 45 (98) | 1 (2) |
| Imipeneme (n = 43) | >64 | 1 to >64 | 7 (16) | 1 (2) | 35 (81) |
| Meropeneme (n = 46) | >64 | 0.25 to >64 | 4 (9) | 3 (7) | 39 (85) |
CLSI, Clinical and Laboratory Standards Institute; FDA, U.S. Food and Drug Administration; I, intermediate; R, resistant; S, susceptible; NA, not applicable.
MIC values were obtained by broth microdilution method at a central laboratory according to CLSI.
Four patients had P. aeruginosa isolates with cefiderocol MIC values of >4 μg/mL. These four patients were eligible for compassionate use based on the following reasons: one patient with a cefiderocol MIC of 16 μg/mL had CR Acinetobacter baumannii coinfection with no alternative treatment option, one patient with a cefiderocol MIC of 8 μg/mL had Achromobacter xylosoxidans coinfection with no alternative treatment option, and two patients with cefiderocol MICs of 8 μg/mL had a locally tested cefiderocol-susceptible P. aeruginosa isolate before treatment initiation, and later, the central laboratory confirmed cefiderocol resistance in the current analysis.
Based on FDA breakpoints (S, ≤1 μg/mL; I, 2 μg/mL; R, ≥4 μg/mL) as follows: susceptible, 63%, n = 29; intermediate, 20%, n = 9; and resistant, 17%, n = 8.
Three isolates were susceptible to meropenem and imipenem, but the patient had another carbapenem-resistant Gram-negative pathogen at baseline (A. baumannii, n = 1; A. xylosoxidans: n = 1; and Klebsiella pneumoniae, n = 1).