cefepime and Leukemia

The empirical treatment of febrile, neutropenic patients with cancer requires antibacterial regimens active against both gram-positive and gram-negative pathogens. This study was performed to demonstrate the noninferiority of monotherapy with piperacillin-tazobactam, compared with cefepime.. We conducted a randomized-controlled, open-label, multicenter clinical trial among high-risk patients from 34 university-affiliated tertiary care medical centers in the United States, Canada, and Australia who were undergoing treatment for leukemia or hematopoietic stem cell transplantation and were hospitalized for empirical treatment of febrile neutropenic episodes. Patients received piperacillin-tazobactam (4.5 g every 6 h) or cefepime (2 g every 8 h) intravenously. The primary outcome was success (defined by defervescence without treatment modification) at 72 h of treatment, end of treatment, and test of cure in the modified intent-to-treat analysis. Secondary outcomes included time to defervescence, microbiological efficacy, the additional use of glycopeptide antibiotics, emergence of resistant bacteria, and safety.. For 528 subjects (265 received piperacillin-tazobactam and 263 received cefepime), success rates were 57.7% and 48.3%, respectively (P = .04) at the 72-h time point, 39.6% and 31.6% (P = .06) at end of treatment, and 26.8% and 20.5% (P = .11) at the test-of-cure visit. The analyses demonstrated noninferiority for piperacillin-tazobactam at all time points (P< or = .0001). Treatment with piperacillin-tazobactam was independently associated with treatment success in multivariate analysis (odds ratio, 1.65; 95% confidence interval, 1.04-2.64; P = .035). Both regimens were well tolerated.. This study demonstrates the noninferiority and safety of piperacillin-tazobactam monotherapy, compared with cefepime, for the empirical treatment of high-risk febrile neutropenic patients with cancer.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cefepime; Cephalosporins; Female; Fever; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Leukemia; Male; Middle Aged; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Treatment Outcome

A multicenter open randomized trial was conducted to compare cefepime monotherapy with cefepime/amikacin combination (dual) therapy in treating febrile neutropenic patients with hematologic disorders. Among the 189 evaluable patients, 5.8% had microbiologically and 10.6% had clinically documented infections. Excellent response was seen in 32.6% and 45.7% of monotherapy and dual therapy recipients, respectively, at day 3 (P=.065). At day 3, patients with neutrophil counts of <500/ mu L receiving dual therapy had a better response than did those receiving monotherapy (45% vs. 27.6%; P=.024). The same was true for patients with leukemia. Adverse events were minimal, and early death was observed in 7 patients in the dual therapy group and 5 patients in the monotherapy group. Overall, cefepime monotherapy is as effective as dual therapy for the initial treatment of febrile neutropenic patients. Further study is warranted for patients with severe neutropenia and leukemia who may benefit from dual therapy.

Topics: Amikacin; Antineoplastic Agents; Bacteremia; Cefepime; Cephalosporins; Drug Therapy, Combination; Female; Fever; Hematologic Diseases; Humans; Immunocompromised Host; Japan; Leukemia; Male; Neutropenia; Opportunistic Infections

1998, a consensus meeting was held in Miyazaki, Japan, to develop an approach to management of febrile neutropenia (FN). The K-HOT study group decided to examine whether this proposal was applicable to clinical practice in a multicenter study. Patients who developed fever with neutrophil counts <1,000/microL were randomized to receive either a single antibiotic, cefepime or one of the carbapenems, or a combination of cefepime and an aminoglycoside. Patients who became afebrile within the first 3 days were continued on the same treatment. Patients who remained febrile were switched to a combination regimen if they were randomized to receive a single agent, and patients on combination medication were changed from cefepime to another cephalosporin. A total of 165 patients were entered into the trial. One hundred fifty-three patients were evaluable for response. The average age was 52 years, and 70% of the patients had acute leukemia. Severe neutropenia, defined as <100/microL at the time of FN, was seen in 62% of the patients on entry and during the course of treatment 71% of patients experienced neutrophil counts of <100/microL. Microbiologically documented infection was seen in 6.5% for monotherapy, and 10.5% for a combination treatment, and fever of unknown origin occurred in 75.3% and 59.2% of the patients in each regimen, respectively. Excellent to good response was seen in two-thirds of the patients in all treatment groups. Adverse events were minimal, and three early deaths were observed at days 9, 16, and 16 among patients treated with a single antibiotic and three in the combination regimen group at days 14, 15, and 20. These results indicate that cefepime or a carbapenem alone is as effective as a combination of cefepime and an aminoglycoside for treating FN.

Topics: Adult; Algorithms; Aminoglycosides; Anti-Bacterial Agents; Carbapenems; Cefepime; Cephalosporins; Drug Administration Schedule; Drug Therapy, Combination; Female; Fever; Humans; Leukemia; Lymphoma; Male; Neutropenia

A total of 208 adult patients with cancer and febrile neutropenia from 5 medical institutions were randomized to receive either cefepime (2 g b.i.d.) or ceftazidime (2 g t.i.d.) in combination with amikacin (15 mg/kg/o.d.). Ninety-seven patients in the ceftazidime (CEZ) group and 98 in the cefepime group (CEF) were evaluable for efficacy. In 68 patients (35%), infection could be documented. The average duration of antibiotic therapy was 11 and 12 d and response rates to the empirical regimen were 36 and 30% for the CEZ and CEF groups, respectively (p > 0.05). The average time of defervescence in responders was 3 d for both groups. Modification of the initial regimen with antivirals and/or azole antifungals raised the number of responders to 44% and 35%, respectively (p > 0.05). Vancomycin was additionally given to 29 patients in the CEZ group and to 27 patients in the CEF group. Twenty-six patients in each group received empirical amphotericin B. Mild, reversible study drug-related side-effects were observed in 12 patients (12%) in the CEZ group and 13 patients (13%) in the CEF group (p > 0.05). Cefepime in combination with amikacin seems to be as effective, safe and tolerable as ceftazidime + amikacin in patients with high-risk neutropenia and fever.

Topics: Adolescent; Adult; Amikacin; Anti-Bacterial Agents; Cefepime; Ceftazidime; Cephalosporins; Drug Therapy, Combination; Fever; Humans; Leukemia; Lymphoma, Non-Hodgkin; Neutropenia; Prospective Studies; Risk Factors; Treatment Outcome

Fluoroquinolone prophylaxis is indicated to prevent neutropenic fever in patients with acute leukemia. However, fluoroquinolone use has been associated with development of multi-drug-resistant Pseudomonas aeruginosa and extended spectrum β-lactamase producing gram-negative bacilli. Due to a presumed risk of multi-drug resistance associated with fluoroquinolone prophylaxis, patients admitted to our hospital with neutropenic fever receive empiric carbapenem therapy until cultures are negative for 72 h or identification of an organism. Our study seeks to identify the incidence of multi-drug-resistant organism colonization and bacteremia among patients who receive fluoroquinolone prophylaxis and to evaluate duration of empiric carbapenem therapy. A retrospective review of adult patients with acute leukemia receiving a fluoroquinolone as outpatient infection prophylaxis, admitted to our tertiary cancer center for treatment of neutropenic fever was completed. Surveillance and blood cultures were reviewed for antibiotic resistance. Duration of empiric carbapenem therapy was reviewed. One hundred patients and 177 admissions for neutropenic fever were included. Six patients harbored a piperacillin-tazobactam-resistant organism found during routine surveillance. Among these patients, two bacteremias were identified, one of which was a piperacillin-tazobactam-resistant organism. Five bacteremias were identified among 83 patients with negative surveillance cultures. Among the bloodstream infections, five organisms isolated were fluoroquinolone resistant. No cefepime-resistant organism was isolated on surveillance or bloodstream cultures. Adherence to the institution guideline of narrowing antibiotics after 72 h of negative cultures occurred in only 13% of neutropenic fever cases. The average duration of carbapenem therapy in 177 neutropenic fever episodes was 4.4 days. Our findings show that among our patient population, there is a low risk of bacteremia with a piperacillin-tazobactam-resistant or cefepime-resistant organism. However, prompt de-escalation of carbapenem therapy needs to be reiterated within hospital practice.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Cefepime; Cephalosporins; Drug Resistance, Bacterial; Female; Fluoroquinolones; Humans; Leukemia; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Post-Exposure Prophylaxis; Random Allocation; Retrospective Studies; Risk Factors; Young Adult

In a prospective observational study of 133 neutropenic episodes, interleukin (IL)-8 serum levels > 2000 pg/mL at the onset of fever had a sensitivity of 53% and a specificity of 97% as a predictor of gram-negative bacteremia (GNB; positive predictive value, 73%; negative predictive value, 94%). The rates of early death differed significantly between patients with high and those with low IL-8 levels (3/11 vs. 1/122; P< .01). Serum IL-8 levels at the onset of fever define a low-risk subgroup of patients who can safely be treated with monotherapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacteremia; Cefepime; Cephalosporins; Drug Therapy, Combination; Fever; Gentamicins; Gram-Negative Bacterial Infections; Humans; Interleukin-8; Leukemia; Lymphoma; Male; Middle Aged; Netilmicin; Neutropenia; Predictive Value of Tests; Prospective Studies