Fluoroquinolones (FQs) are routinely used as antimicrobial prophylaxis in leukemia patients receiving chemotherapy to prevent Pseudomonas aeruginosa infections. Patients who are intolerant to FQs may receive cefpodoxime (CPD) or other agents. How FQ use affects the resistance profile and epidemiology of breakthrough P. aeruginosa infections is unknown. To determine this, we performed a whole-genome sequencing (WGS)-driven epidemiologic study of leukemia patients with P. aeruginosa bloodstream infections.
All adult (age > 17 years) inpatients with leukemia and a first episode of monomicrobial P. aeruginosa bloodstream infection were included. Clinical data were extracted from the electronic medical record. Isolates were sequenced using an Illumina NextSeq and phylogenomics was performed using an in-house analysis pipeline consisting of Bowtie2, SAMtools and bcftools.
110 patients were included and most had a diagnosis of acute myeloid leukemia (n = 66). Twenty (18%) patients received FQ prophylaxis, 56 (54%) received CPD, and the remaining 34 (31%) received other agents. 9 (8%) isolates were multidrug-resistant (MDR). MDR was more common in those receiving FQ prophylaxis (20% vs 6%, P = 0.06). 76 sequence types (STs) were represented with ST235 (n = 8) being most common followed by ST244 (n = 7). ST235 strains were genetically distinct, but closely related (>10 but < 250 SNPs) in comparison to other STs. 2 ST244 strains were genetically identical despite being isolated 4 months apart, suggesting horizontal transmission. MDR was more common among ST235 isolates compared with other STs (38% vs 6%, P = 0.02). ST235 strains were more common in patients receiving FQ vs other prophylaxis (20% vs 4%, P = 0.04). 1 ST244 isolate harbored a VIM-2 β-lactamase. In 20 FQ-resistant isolates, 80% had mutations in either parC (S87L) or gyrA (T83I) and 50% had both. FQ-resistance mutations were more common in FQ recipients (50% vs 8%, P < 0.01).
Most P. aeruginosa infections occurred in non-FQ recipients, while MDR P. aeruginosa infections were more common in FQ recipients. These data suggest that decisions on empiric treatment of patients with P. aeruginosa bacteremia must take antimicrobial prophylaxis history into account.
Samuel L. Aitken, PharmD, Melinta Therapeutoics: Grant/Research Support, Research Grant; Merck, Sharpe, and Dohme: Advisory Board; Shionogi: Advisory Board.