Fluoroquinolone prophylaxis during the early period of neutropenia is a standard of care after autologous peripheral blood stem cell transplantation (PBSCT). The widespread use of fluoroquinolones has increased colonization with fluoroquinolone-resistant enterobacteriaceae (FRE). Hence, patients who present for PBSCT with FRE colonization may not be protected from blood-stream infections (BSI) with the same organisms allowing severe sepsis to develop until appropriate antibiotic adjustments. We conducted a prospective study to detect FRE colonization in a restricted population of subjects with multiple myeloma undergoing autologous PBSCT.

We enrolled 124 subjects conditioned with melphalan 200 mg/m2. Peri-rectal swabs were collected to test for FRE at three time points: pre-transplant, at hospital discharge, and 12-16 weeks post-PBSCT. Post-transplant care was per standard of care and the presence of FRE colonization was not known by the transplant staff caring for the subjects.

Of 124 subjects enrolled, 117 were evaluable; 7 were removed for failure to collect adequate PBSC, loss of consent, change in conditioning regimen, or inadequate sample collection. Pre-transplant samples were collected at a median of -5 days (interquartile range (IQR): -7 to -3) before transplantation. Four subjects had a delay to transplantation of >28 days after sample collection for management of complications at the discretion of the treating physician. FRE colonization was detected in 23 of 117 subjects (19.7%). Isolates were identified as Escherichia coli (n=14), Klebsiella species (n= 6), or both (n=3); 15 of the isolates (12 subjects) also demonstrated extended spectrum beta-lactamase (ESBL) production. At hospital discharge (median day 13, IQR: 12-14 days), a slightly higher proportion of subjects tested positive (29/99, 29.3%), though the difference was not significant (p=0.10). At discharge time point, isolates were Escherichia coli (n=14), Klebsiella species (n=11), or both (n=4). Notably, 15 of the subjects demonstrating FRE colonization at discharge did not test positive pre-transplant; FRE colonization was not detected at discharge for 6 subjects who tested positive pre-transplant. A second post-transplant (12-16 weeks post-PBSCT) sample was collected for 92 subjects at 48-120 days (median, 101.5 days) with isolates identified as Escherichia coli (n=14), Klebsiella species (n=11), or both (n=3). Including all time points, a total of 49 of 117 subjects (41.9%) tested positive for FRE colonization.

Fever (>38.3 ℃) occurred in 27 subjects; blood cultures and/or antibiotic modification were made for an additional 10 subjects. Enterobacteriaceae species were detected in blood cultures for 3 subjects and S mitis for 1. The Enterobacteriaceae were all fluoroquinolone resistant or intermediate sensitivity. One additional subject developed fluoroquinolone-resistant ESBL E coli urinary tract infection without BSI. Diarrhea was common, but only 3 subjects tested positive for toxin-producing Clostridium difficile.

All patients achieved neutrophil engraftment and resolution of regimen-related toxicities. No deaths occurred during the initial 12 weeks post-transplantation.

These data demonstrate that FRE colonization is common in this population, with about 20% of patients colonized pre-transplant. Although the clinical relevance of colonization is not fully defined. FRE organisms caused BSI in 3 subjects. The small number of BSI observed is likely a benefit of the short period of neutropenia and mild mucositis characteristic of this patient population undergoing autologous PBSCT after single-dose melphalan conditioning. These results may not be generalizable to other populations, such as those undergoing leukemia remission induction or allogeneic transplantation, where the degree of mucosal damage and the duration of neutropenia are greater.

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2025
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