cefepime and Hematologic-Diseases

The aim of this study was to evaluate the usefulness of carbapenems as initial treatment for febrile neutropenia (FN), and in patients unresponsive to this initial therapy, to evaluate the efficacy of subsequent treatment with aminoglycosides (AGs) or ciprofloxacin (CPFX). FN patients were randomized to receive cefepime (CFPM, control), panipenem/betamiprom (PAPM/BP), or meropenem (MEPM). Defervescence, an outcome endpoint, was evaluated 3 days later. Patients with minimal response were given CPFX or AGs, and their responses were reevaluated on day 7. A total of 255 patients were included. The efficacies of CFPM, PAPM/BP, and MEPM were comparable. In patients unresponsive to this initial therapy, the efficacy of subsequent CPFX and AGs treatments was also similar. There was no significant between-arm difference in cumulative efficacy on days 14 and 30. Adverse reactions were infrequent and mild. In conclusion, PAPM/BP and MEPM are as useful as CFPM as initial therapy for FN, and AGs are as efficacious as CPFX in patients unresponsive to the initial therapy.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Carbapenems; Cefepime; Cephalosporins; Female; Fever; Hematologic Diseases; Humans; Male; Meropenem; Neutropenia; Prospective Studies; Thienamycins; Treatment Outcome; Young Adult

We previously reported that monotherapy with carbapenem or cefepime exhibited efficacy equivalent to cefepime plus an aminoglycoside as initial therapy for febrile neutropenia (FN), achieving an adequate response in two-thirds of the patients. However, only one-third of the remaining poor responders to monotherapy became afebrile after an aminoglycoside was added to the initial carbapenem or cefepime. The present study was designed to evaluate the benefit of intravenous ciprofloxacin for neutropenic patients with fever who were refractory to initial therapy given for the first 3 days. Patients with FN--as defined by an axillary temperature >or=37.5 degrees C and a neutrophil count <1,000/microL-who had no response to initial therapy with carbapenem or cefepime for 72 hours were to receive additional ciprofloxacin 600 mg/day. They were otherwise managed according to the Japanese guidelines for FN. An adequate response was defined as a decline of temperature to <37.5 degrees C within 7 days after initiation of ciprofloxacin treatment. Thirty-one patients with FN (seventeen male and fourteen female; mean age 53.1 +/- 14.8 years) were entered in the study. The initial antibiotics were cefepime (2 - 4 g/day) in twenty and carbapenem (1 - 2 g/day) in eleven. Three patients were excluded from analysis, leaving 28 patients for evaluation of efficacy. The response rate was 16/31 patients (51.6%),with four patients judged non-assessable due to adverse effects, protocol violation or early change to other agents. Adverse events occurred in seventeen patients, but all were mild and reversible. Only three patients had adverse events (skin rash, hepatic dysfunction and elevation of alkaline phosphatase in one patient, respectively) considered related to ciprofloxacin. These findings indicate that addition of intravenous ciprofloxacin is effective against FN refractory to initial antibiotic therapy and has acceptable toxicity.

Topics: Adult; Aged; Algorithms; Carbapenems; Cefepime; Cephalosporins; Ciprofloxacin; Female; Fever; Hematologic Diseases; Humans; Male; Middle Aged; Neutropenia; Remission Induction; Salvage Therapy; Treatment Failure; 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

Prompt empiric antibiotic therapy is of critical importance for patients with neutropenic fever. However, a major concern with important clinical consequences is the emergence of bacterial resistance to antibiotics. After using ceftazidime with a glycopeptide as initial empiric therapy for neutropenic fever, we were confronted with a 75% reduced susceptibility rate to ceftazidime of inducible Enterobacteriaceae collected in 1994. The initial empiric therapy was therefore replaced in May 1995 by a combination of cefepime with amikacin, with addition of a glycopeptide after 48 h if necessary. After this change, we observed a significant decrease in reduced susceptibility of inducible Enterobacteriaceae, not only to ceftazidime, but also to amikacin, cotrimoxazole and ciprofloxacin. There was also a decrease in reduced susceptibility of non-inducible Enterobacteriaceae, such as Klebsiella spp, to ceftazidime. The reduction of resistance may be related at least in part to the combined use of cefepime together with an aminoglycoside. This study shows that it is possible to reverse bacterial resistance by modifying the antibiotic regimen used.

Topics: Adult; Amikacin; Cefepime; Ceftazidime; Cephalosporins; Drug Resistance, Microbial; Drug Therapy, Combination; Enterobacteriaceae; Enterobacteriaceae Infections; Fever; Hematologic Diseases; Humans; Microbial Sensitivity Tests; Neutropenia; Teicoplanin; Vancomycin

International guidelines recommend routine microbiological assessment of patients with febrile neutropenia, but do not recommend a change from broad-spectrum antibiotic therapy to pathogen-specific therapy when a clinically relevant organism has been isolated. The aim of the study was to determine the aetiology of febrile neutropenia in adult haematology patients at Auckland City Hospital, to document the changes in treatment made following isolation of a clinically relevant organism and to assess adverse outcomes in any patient who received pathogen-specific therapy after a positive culture result.. The results of all microbiological tests together with antibiotic therapy were recorded from consecutive patients with fever and a neutrophil count <0.5 x 10(9)/L over 1 year beginning in May 2003.. One thousand one hundred and ninety-six specimens were collected from 81 patients during 116 episodes of febrile neutropenia. A pathogen was isolated from blood cultures in 40 episodes: Gram-positive cocci accounted for 46% of isolates and Gram-negative bacilli for 35%. Isolation of a pathogen from blood cultures resulted in a change of treatment in 25 of 40 (62.5%, 95%CI 46-77%) episodes. In 12 of these episodes, antibiotic therapy was optimized to a single pathogen-specific agent. No adverse events or subsequent changes in antibiotic therapy occurred in any of these 12 patients. Isolation of a pathogen from specimens other than blood seldom led to a change in therapy.. Isolation of a pathogen from blood cultures often allows antibiotic therapy to be simplified to a pathogen-specific regimen. Further study of this approach is warranted.

Topics: Anti-Bacterial Agents; Bacteremia; Bacteria; Bacterial Infections; Catheterization; Cefepime; Cephalosporins; Drug Resistance; Equipment Contamination; Fever; Gentamicins; Hematologic Diseases; Hematologic Neoplasms; Hospitals, Urban; Humans; Laboratories, Hospital; Medical Audit; Microbial Sensitivity Tests; Neutropenia; New Zealand; Prospective Studies; Risk Assessment; Species Specificity

Cefepime monotherapy was compared with cefepime-plus-amikacin dual therapy for treatment of febrile neutropenic patients. Response rates were significantly lower for patients receiving monotherapy who had neutrophil counts of <500 cells/mm3 but did not differ significantly between patients receiving dual therapy who had neutrophil counts of > or =500 cells/mm3 or <500 cells/mm3. Dual therapy is recommended for the initial treatment of patients with neutropenia with <500 cells/mm3. Dual therapy was significantly more effective in patients with neutropenia lasting <5 days. The response rates to monotherapy or dual therapy did not differ significantly when neutropenia persisted for > or =6 days, indicating that sustained neutropenia is a risk factor for failure of initial empirical therapy. The rate of response to monotherapy was lower in leukemic patients, whereas the rate of response to dual therapy did not differ between leukemic and nonleukemic groups. The rate of response to either monotherapy or dual therapy did not differ for patients with temperatures of > or =38 degrees C or 37.5 degrees C-38 degrees C. Overall, defervescence occurred in >80% of patients with mild infections, whereas only 32% of those with moderate to severe infection responded by day 3 and 69.8% by day 7.

Topics: Amikacin; Anti-Bacterial Agents; Cefepime; Cephalosporins; Drug Therapy, Combination; Fever; Hematologic Diseases; Humans; Immunocompromised Host; Neutropenia; Opportunistic Infections; Risk Assessment; Sepsis