Table 1.
List of studied P. aeruginosa isolates with antibiotic susceptibility profiles, antibiotics received by patients, genomic variations found between the earliest isolate and late isolates of each patient, and clinical evolution.
Isolate | Clinical specimen | Days of mechanical ventilation | Sequence Type | MICs (mg/L)a | Antibiotic treatment (initiation day)a | Genomic variationb | Coding region change | Amino acid changec | Clinical evolution | |||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
TIC | TCC | PIP | CAZ | IPM | CIP | |||||||||
Patient 1 ( strain PA-VAP-1 ) | ||||||||||||||
1A | BAL | 3 days | 1027 | 16 | 16 | ≤4 | 2 | 2 | ≤0.25 | CAZ (day 6) | — | death in intensive care unit | ||
1B | BAL | 14 days | 1027 | 16 | 16 | ≤4 | ≤1 | 2 | ≤0.25 | — | ||||
1C | BAL | 14 days | 1027 | >64 | >64 | >64 | 32 | 2 | ≤0.25 | IPM/AN (day 17) | SNP | ampD: 358 G > T | AmpD: Glu120* | |
SNP | gacA: 601 T > G | GacA: Ser201Ala | ||||||||||||
Patient 2 ( strain PA-VAP-2 ) | ||||||||||||||
2A | BAL | 4 days | 2960 | 32 | 32 | 8 | 4 | 0.5 | ≤0.25 | CAZ/CS (day 5) | — | death in intensive care unit | ||
2B | BAL | 27 days | 2960 | 64 | 32 | 16 | 4 | ≥16 | ≤0.25 | INS | oprD: 672_673insC | OprD: Tyr225fs | ||
SNP | groEL: 560 C > T | GroEL: Pro187Leu | ||||||||||||
2C | BAL | 27 days | 2960 | 32 | 32 | 16 | 4 | 0.5 | ≤0.25 | FEP/CS (day 30) | SNP | groEL: 560 C > T | GroEL: Pro187Leu | |
SNP | pilM: 808 C > T | PilM: Gln270* | ||||||||||||
INS | pilE: 208_209insTCGG | PilE: Thr70fs | ||||||||||||
Patient 3 ( strain PA-VAP-3 ) | ||||||||||||||
3A | BAL | 1 day | 253 | 32 | 32 | 16 | 4 | 1 | 2 | IPM/TN (day 1) | — | discharge from intensive care unit | ||
3B | BAL | 11 days | 253 | 32 | 16 | 8 | 4 | 1 | 2 | IPM (day 11); CAZ/CS (day 13) | DEL | lasR: 138_148delCTACGAGAACG | LasR: Tyr47fs | |
INS | algB: 853_854insCCGCGACCAA | AlgB: Trp288fs | ||||||||||||
3C | BAL | 35 days | 253 | 32 | 32 | 8 | 4 | ≥16 | 2 | FEP (day 37) | DEL | lasR: 138_148delCTACGAGAACG | LasR: Tyr47fs | |
INS | algB: 853_854insCCGCGACCAA | AlgB: Trp288fs | ||||||||||||
DEL | oprD: 16_132del117-bp | OprD: loss of 39 AA | ||||||||||||
SNP | mpl: 314 T > G | Mpl: Val105Gly | ||||||||||||
Patient 4 ( strain PA-VAP-4 ) | ||||||||||||||
4A | BAL | 21 days | 2042 | 32 | 32 | 16 | 2 | 1 | ≤0.25 | FEP/LVX (day 22) | — | discharge from intensive care unit | ||
4B | BAL | 46 days | 2042 | ≥128 | ≥128 | 64 | 8 | 1 | 1 | IPM (day 46) | SNP | lasR: 676 G >A | LasR: Val226Ile | |
DEL | rhlA, rhlB, and rhlR: 175_1 del 2186-bp | loss of RhlR & RhlB RhlA: Phe59fs | ||||||||||||
INS | mexR: 80_81insT | MexR: Glu27fs | ||||||||||||
4C | blood culture | 48 days | 2042 | 32 | 16 | 8 | 2 | 1 | ≤0.25 | — |
aAN, amikacin; CAZ, ceftazidime; CIP, ciprofloxacin; CS, colistin; FEP, cefepime; IPM, imipenem; LVX, levofloxacin; PIP, piperacillin; TCC, ticarcillin-clavulanate; TIC, ticarcillin; TN, tobramycin.
bDEL, deletion; INS, insertion; SNP, Single Nucleotide Polymorphism.
c,*STOP codon; AA, amino acids; fs, frameshift mutation.