The Effect of Levofloxacin Prophylaxis on Epidemiology and Microbial Resistance Profiles of Sterile Site Infections in Acute Leukemia Patients.

Background: Neutropenia is the most common predisposing factor that increases the susceptibility of cancer patients (pts) to infection. The use of fluoroquinolones (FQs) as prophylaxis during chemotherapy-induced neutropenia has been shown to decrease the frequency of gram-negative (GN) infections (Cullen et al. NEJM 2005) with the benefit of reduced infection-related mortality in neutropenic pts with cancer (Bucaneve et al. NEJM 2005) and was instituted as part of our institution-wide standard clinical practice in January 2006. The widespread use of FQs for prophylaxis of pts with neutropenia and hematologic malignancies raises concerns about the evolving resistance of organisms.

Methods: This retrospective observational study compared acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) pts, ages 18 and older who were admitted to the hematology service and received levofloxacin prophylaxis (LEVP) within 60 days of admission with those who were admitted but did not receive LEVP during the period of chemotherapy-induced neutropenia. Pts had to have a positive sterile site culture up to 96 hours prior to admission excluding Staphylococcus coagulase negative, Propionibacterium, Corynebacterium, and other common colonizing organisms. Analysis also compared the rates of Methicillin-resistant Staphylococcus aureus (MRSA) infections, positive Vancomycin-resistant Enterococci (VRE) swabs, and positive Clostridium difficile cultures and evaluated them for a correlation LEVP.

Results: A total of 213 pts were evaluated between September 2004 and May 2007. Ninety-four pts received LEVP and 119 did not. Patient characteristics were similar between groups. There was a shift from almost equal incidence of gram-positive (GP) and GN cultures in the group without prophylaxis (51% vs 49%, respectively) to a predominance of GP cultures with LEVP (68% vs 32%, respectively). There was a significant decrease in the number of sterile site cultures of GN organisms (n = 94 vs 37, respectively), while cultures of GP organisms remained similar (n = 98 vs. 77, respectively). GN organisms in sterile site cultures occurred less often in the LEVP group, however; the incidence of resistance to levofloxacin in GN was higher (32% vs 15%), particularly the susceptibility profiles of Pseudomonas sp., Escherichia coli, and Stenotrophomonas maltophilia. Both groups had equal cultures of Staphylococcus aureus, but the group receiving LEVP had a greater incidence of MRSA (55% vs 30%). Rates of positive VRE swabs declined and had no apparent correlation with the use of levofloxacin as prophylaxis. There were more documented positive Clostridium difficile cultures in the pts receiving LEVP (29% vs 22%, respectively), but rates of Clostridium difficile have shown a constant increase throughout the institution; therefore, LEVP should not be considered the sole contributing factor to an increased rate of positive cultures.

Conclusions: The epidemiology and microbial susceptibility profile of positive sterile site cultures of acute leukemia pts receiving LEVP during chemotherapy-induced neutropenia differed from those that did not. The LEVP group had a decrease in the absolute number of sterile site cultures, number and percent of GN sterile site cultures. There was an increase in GN organism resistance to levofloxacin and the incidence of several GP organisms increased with the number of GP organisms remaining constant.