Comparison of adverse effects associated with antibiotics use in febrile neutropenic patients

Medical records of patients > 18 years of age, who were hospitalized in the Hematology Department of Celal Bayar University Faculty of Medicine between January 2005 and December 2011, and diagnosed with and treated for febrile neutropenia, were retrospectively evaluated. The diagnosis of febrile neutropenia was based on the detection of neutropenia by peripheral blood smear or an absolute neutrophil count of < 500/mm3 with an accompanying fever (a single oral body temperature of 38.3°C or a body temperature of 38°C lasting for more than 1 hour) that was not associated with blood products or cytotoxic therapy. A total of 127 neutropenic fever episodes noted in 71 patients were evaluated. Of the fever episodes, 75 were noted in men and 52 were noted in women. The primary disease was acute leukemia in 94 (74%) episodes, and it was acute myeloid leukemia in 70, acute lymphoblastic leukemia in 20, plasma cell leukemia in 2, acute eosinophilic leukemia in 2, Hodgkin's lymphoma in 3, non-Hodgkin's lymphoma in 8, agranulocytosis in 3, hairy cell leukemia in 3, chronic lymphocytic leukemia in 3, blastic phase chronic myeloid leukemia in 6, myelodysplastic syndrome in 5, primary myelofibrosis in 1 and multiple myeloma in 1 episode. In this study, while the rate of change in drug combination for any reason was 27.3% in the imipenem + ciprofloxacin / amikacin (ICA) group, it was 60% in the P/T + ciprofloxacin/amikacin (PTCA) group; the difference between the groups was significant (p=0.006). The rate of drug change due to side effects was significantly higher in the PTCA group than the ICA group (p=0.03). The rate of reducing fever within 72 hours was significantly higher for imipenem combinations than P/T combinations (p=0.05).The rate of side effects was 19.3% for imipenem combinations while it was 30% for P/T combinations (p=0.29). The primary disease being relapsed / refractory in two patients receiving imipenem combinations, who had central nervous system side effects, brings the question into mind that are these side effects more common in patients with end-stage disease? There is need for larger studies to find an answer to this question. The number of days with fever was 5.4 days in the ICA group and 7.6 days in the PTCA group (p=0.34). The rate of grade 3?4 mucocytis was 9.2% in the ICA group and it was 5.3% in the PTCA group. However, the difference did not reach statistical significance. The mean duration of antibiotic use was 24.75 days in the ICA group and it was 27.82 days in the PTCA group. The difference did not reach statistical significance (p=0.5). The frequency of side effects was 28.8% in amikacin combination and it was 10.6% in ciprofloxacin combination (p=0.02). Gram-positive bacteria were the most common isolates. Consistent with the literature, coagulase-negative staphylococci were the most common pathogen isolated (36.5%), followed by E. coli (13%), Klebsiella spp. (9.7%), and Enterococcus faecalis (8.9%). E. coli were isolated in 16 episodes. The ratio of resistance to the number of antibiograms was 0/6, 6/8, 7/13, 0/15 for amikacin, P/T, ciprofloxacin and imipenem, respectively. Klebsiella spp. were isolated in 12 episodes. The ratio of resistance to the number of antibiograms was 1/12, 5/12, 6/12, 4/12 for amikacin, P/T, ciprofloxacin, and imipenem, respectively. Acinetobacter spp. were isolated in 11 episodes. The ratio of resistance to the number of antibiograms was 5/11, 6/11, 9/11, 7/11 for amikacin, P/T, ciprofloxacin, and imipenem, respectively. P/T resistance was more common, and the ICA group being more successful than the PTCA group was attributed to this finding. We are in the opinion that every center should select empiric antimicrobial therapy based on their antibiotic resistance pattern. We observed that antibiotic susceptibility tests that were performed for bacteria isolated from cultures in our hospital were not adequate.In conclusion, in the treatment of neutropenic fever, every hospital should determine an empiric antimicrobial therapy regimen that is convenient with its microbial flora in accordance with the guidelines. We found that imipenem combinations were more effective as an empiric antimicrobial therapy in our hospital. In accordance with the literature, we found no significant difference between combination therapy and monotherapy in terms of efficacy. Side effects were more common in patients receiving amikacin.