Characterization of bacterial infections in allogeneic hematopoietic stem cell transplant recipients who received prophylactic levofloxacin with either penicillin or doxycycline

Abstract

Objective: To describe the effect of a combination prophylactic regimen of levofloxacin, a synthetic chemotherapeutic antibiotic of the fluoroquinolone drug class, with either penicillin or doxycycline on the changing epidemiology of bacterial infections and antimicrobial resistance patterns of isolated organisms in the allogeneic hematopoietic stem cell transplant (HSCT) patient population.

Patients and methods: We conducted a single-center, retrospective cohort study of all allogeneic HSCT recipients from January 1, 2003, through August 31, 2008, who received prophylactic levofloxacin in combination with penicillin (or with doxycycline in penicillin-allergic patients) from allogeneic stem cell infusion until neutrophil engraftment.

Results: Of the 258 patients who underwent allogeneic HSCT during the study period, 231 received levofloxacin prophylaxis, 76 (33%) of whom developed an infection within 3 months after transplant. Over time, the ratio of gram-positive to gram-negative (GN) infections decreased from 2.11 in 2004, the first year that GN organisms were isolated, to 1.11 in 2008 (P=.20). Emergence of fluoroquinolone-resistant GN bacteria was observed (P=.02), whereas resistance to extended-spectrum beta-lactams did not change over time. Combined vancomycin-resistant enterococci colonization and infection rates increased during the study period (P=.04). Clostridium difficile colitis was uncommon.

Conclusion: Levofloxacin with penicillin or doxycycline prophylaxis may contribute to the emergence of resistant GN infections in allogeneic HSCT recipients over time. Our findings provide additional support for the current standard of practice of administering empiric monotherapy with an antipseudomonal beta-lactam if these patients develop fever or are suspected to have an infection.

FIGURE 1.

Study design. Flow diagram of patient screening and eligibility. HSCT = hematopoietic stem cell transplant.

FIGURE 2.

Epidemiology of infection. Percentage of isolates caused by gram-positive and gram-negative organisms per year (P=.20; exact Wilcoxon signed rank test).

FIGURE 3.

Epidemiology of infection-causing Enterococcus spp. There were no Enterococcus spp. isolates in 2006. Amp = ampicillin; R = resistant; S = susceptible; Vanco = vancomycin.

FIGURE 4.

Gram-negative resistance to fluoroquinolones (P=.02; exact Wilcoxon signed rank test) and aminoglycosides (P=.26; exact Wilcoxon signed rank test).

FIGURE 5.

Resistance of Pseudomonas, Klebsiella, and Enterobacter spp. and Escherichia coli to fluoroquinolones and aminoglycosides (P=.05 for both classes of drugs; exact Wilcoxon signed rank test).