Ciprofloxacin versus colistin prophylaxis during neutropenia in acute myeloid leukemia: two parallel patient cohorts treated in a single center

Abstract

P atients undergoing intensive chemotherapy for acute myeloid leukemia are at high risk for bacterial infections during therapyrelated neutropenia. However, the use of specific antibiotic regimens for prophylaxis in afebrile neutropenic acute myeloid leukemia patients is controversial. We report a retrospective evaluation of 172 acute myeloid leukemia patients who received 322 courses of myelosuppressive chemotherapy and had an expected duration of neutropenia of more than seven days. The patients were allocated to antibiotic prophylaxis groups and treated with colistin or ciprofloxacin through 2 different hematologic services at our hospital, as available. The infection rate was reduced from 88.6% to 74.2% through antibiotic prophylaxis (vs. without prophylaxis; P=0.04). A comparison of both antibiotic drugs revealed a trend towards fewer infections associated with ciprofloxacin prophylaxis (69.2% vs. 79.5% in the colistin group; P=0.07), as determined by univariate analysis. This result was confirmed through multivariate analysis (OR: 0.475, 95%CI: 0.236-0.958; P=0.041). The prophylactic agents did not differ with regard to the microbiological findings (P=0.6, not significant). Of note, the use of ciprofloxacin was significantly associated with an increased rate of infections with pathogens that are resistant to the antibiotic used for prophylaxis (79.5% vs. 9.5% in the colistin group; P<0.0001). The risk factors for higher infection rates were the presence of a central venous catheter (P<0.0001), mucositis grade III/IV (P=0.0039), and induction/relapse courses (vs. consolidation; P<0.0001). In conclusion, ciprofloxacin prophylaxis appears to be of particular benefit during induction and relapse chemotherapy for acute myeloid leukemia. To prevent and control drug resistance, it may be safely replaced by colistin during consolidation cycles of acute myeloid leukemia therapy. ABSTRACT Ferrata Storti Foundation

Bacterial Blood Stream Infections Negatively Impact on Outcome of Patients Treated With Allogeneic Stem Cell Transplantation: 6 Years Single-Centre Experience

“…This policy, indeed, may reduce the mortality of Gram negative bacteria, but other propylaxis are under investigation. Recently, Pohlen and Colleagues, reported on a study comparing ciprofloxacin versus colistin prophylaxis in AML patients during neutropenia 28. Although this was not a randomized trial, ciprofloxacin prophylaxis was confirmed highly effective in reducing the incidence of infections (69% vs 79% for colistin; p=0,07), but was confirmed to be associated with fluoroquinolone resistance, as expected.…”

Efficacy of Colistin Therapy in Patients with Hematological Malignancies: What if There is Colistin Resistance?

“…Patients with hematological malignancies are more susceptible to infections due to immunosuppression, neutropenia, long-term hospitalization, invasive procedures, bone marrow depression, and mucosal barrier impairment (1). Infections are a leading cause of morbidity and mortality in individuals with hematological malignancies who have received intensive treatment (2,3). Antibiotics may be overused or misused, resulting in the development of antibiotic-resistant bacteria (4,5).…”

“…Kidney toxicity is reported to occur in a range of 0 to 50% of people. However, there is a limitation of data on colistin therapy and stem cell transplantation in patients with hematological malignancies (1,3). Although the use of colistin in empirical treatment reduces mortality in eligible patients, the drug's usage is limited because to potential adverse effects, pharmacological interactions, and the rapid development of resistance in gram-negative bacteria.…”

Modification of the antibiotic, colistin, with dextrin causes enhanced cytotoxicity and triggers apoptosis in myeloid leukemia

“…15 Thus, several LSD1/KDM1A inhibitors, including GSK2879552 and tranylcypromine, are currently in clinical trials for cancer treatment, 16 including AML, as a combination therapy. 17 Given the efficacy of colistin as a prophylactic treatment of neutropenia in AML, 18 polymyxin antibiotics have the potential to simultaneously act as antibacterial and anticancer agents. However, dose-limiting neuro-and nephrotoxicity prevent their routine use, 19 which may be overcome by polymer conjugation, as we have shown in our previous work, where dextrin-colistin conjugates reduced toxicity in vitro and in vivo , and extended plasma half-life.…”