cefepime and Fever

Several beta-lactams are recommended as single agents for the treatment of febrile neutropenia.. To compare the effectiveness of different anti-pseudomonal beta-lactams as single agents in the treatment of febrile neutropenia. To compare the development of bacterial resistance, bacterial and fungal superinfections during or following treatment with the different beta-lactams.. We searched the Cochane Register of Controlled Trials (CENTRAL), Issue 3, 2010. MEDLINE, EMBASE, LILACS, FDA drug applications, conference proceedings and ongoing clinical trial databases up to August 2010. References of included studies were scanned.. Randomised controlled trials (RCTs) comparing an antipseudomonal beta-lactam to another antipseudomonal beta-lactam antibiotic, both given alone or with the addition of the same glycopeptide to both study arms, for the initial treatment of fever and neutropenia among cancer patients.. Two review authors applied inclusion criteria and extracted the data independently. Missing data were sought. Risk ratios (RR) were calculated with 95% confidence intervals (CI), and pooled using the fixed effect model. The primary outcome was all-cause mortality. Risk of bias was assessed using a domain-based evaluation and its effect of results was assessed through sensitivity analyses.. Forty-four trials were included. The antibiotics assessed were cefepime, ceftazidime, piperacillin-tazobactam, imipenem and meropenem. Adequate allocation concealment and generation were reported in about half of the trials and only two trials were double-blinded. The risk for all-cause mortality was significantly higher with cefepime compared to other beta-lactams (RR 1.39, 95% CI 1.04 to 1.86, 21 trials, 3471 participants), without heterogeneity and with higher RRs in trials at low risk for bias. There were no differences in secondary outcomes but for a non-significantly higher rate of bacterial superinfections with cefepime. Mortality was significantly lower with piperacillin-tazobactam compared to other antibiotics (RR 0.56, 95% CI 0.34 to 0.92, 8 trials, 1314 participants), without heterogeneity. Carbapenems resulted in similar all-cause mortality and a lower rate of clinical failure and antibiotic modifications as compared to other antibiotics, but a higher rate of diarrhea caused by Clostridium difficile.. Current evidence supports the use of piperacillin-tazobactam in locations where antibiotic resistance profiles do not mandate empirical use of carbapenems. Carbapenems result in a higher rate of antibiotic-associated and Clostridium difficile-associated diarrhea. There is a high level of evidence that all-cause mortality is higher with cefepime compared to other beta-lactams and it should not be used as monotherapy for patients with febrile neutropenia.

Topics: Anti-Bacterial Agents; beta-Lactams; Cefepime; Ceftazidime; Cephalosporins; Fever; Humans; Imipenem; Meropenem; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Pseudomonas Infections; Randomized Controlled Trials as Topic; Thienamycins

Early, empirical broad-spectrum antibiotic treatment is the established practice for febrile neutropenia. Several beta-lactams are accepted for monotherapy. We asked whether patients' outcomes are influenced by the chosen beta-lactam.. Systematic review and meta-analysis of randomized controlled trials comparing anti-pseudomonal beta-lactams administered as empirical monotherapy for febrile neutropenia, with or without vancomycin. The search included The Cochrane Library, PubMed, Embase, Lilacs databases, bibliography, conference proceedings, trial registries and FDA new drug approvals. Two reviewers independently applied selection criteria, performed quality assessment and extracted the data. Trials assessing the same beta-lactam were pooled using the fixed effect model. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated. The primary outcome assessed was all-cause mortality.. Thirty-three trials fulfilled inclusion criteria. Cefepime was associated with higher all-cause mortality at 30 days than other beta-lactams (RR 1.44, 95% CI 1.06-1.94, 3123 participants). Carbapenems were associated with fewer treatment modifications, including addition of glycopeptides, than ceftazidime or other comparators. Adverse events were significantly more frequent with carbapenems, specifically pseudomembranous colitis (RR 1.94, 95% CI 1.24-3.04, 2025 participants). All-cause mortality was unaltered. Piperacillin/tazobactam was compared only with cefepime and carbapenems, in six trials. No significant differences were demonstrated with paucity of data for all-cause mortality.. The use of cefepime for febrile neutropenia is associated with increased mortality and should be carefully considered pending further analysis. Empirical use of carbapenems entails fewer treatment modifications, but an increased rate of pseudomembranous colitis. Ceftazidime, piperacillin/tazobactam, imipenem/cilastatin and meropenem appear to be suitable agents for monotherapy.

Topics: Anti-Bacterial Agents; beta-Lactamase Inhibitors; Carbapenems; Cefepime; Cephalosporins; Enzyme Inhibitors; Fever; Humans; Neutropenia; Penicillanic Acid; Penicillins; Quality Assurance, Health Care; Randomized Controlled Trials as Topic; Tazobactam; Treatment Outcome

Topics: Anti-Bacterial Agents; Bacterial Infections; Cefepime; Cephalosporins; Clinical Trials as Topic; Fever; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Neutropenia; Pseudomonas aeruginosa; Sensitivity and Specificity

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Candida; Cefepime; Cephalosporins; Cross Infection; Fever; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Middle Aged; Pneumonia; Treatment Outcome

In view of the recent trend toward monotherapy in the treatment of bacterial infection, we evaluate the clinical efficacy and safety of cefepime vs. ceftazidime for the empiric treatment of febrile episodes in neutropenic pediatric cancer patients.. In a single site, open label study, 104 neutropenic pediatric cancer patients [96% with absolute neutrophil count (ANC) of <500 neutrophils/mm3] with a median age of 6 years were randomized (1:1) to receive either intravenous cefepime or ceftazidime (50 mg/kg/dose every 8 h; < or = 6 g/day) for empiric treatment of fever (temperature >38.0 degrees C occurring at least twice in 24 h, or single >38.5 degrees C). Febrile episodes were classified as either microbiologically or clinically documented infection or fever of unknown origin. Therapy continued until the ANC was > or = 1,000 neutrophils/mm3 or there was an increasing ANC in low risk patients (maximum duration of treatment, 8 weeks). The primary efficacy endpoints assessed were clinical and microbiologic response to assigned drug therapy. Secondary outcome measures were rate of early discontinuation of study drug and use of concomitant antibiotic therapy to modify initial study drug regimen.. Of 68 patients who could be evaluated for efficacy, 74% (26 of 35) of cefepime-treated patients and 70% (23 of 33) of ceftazidime-treated patients responded to treatment. The small number of study patients precluded statistical analysis of results. In a modified intent-to-treat analysis, 59% of the patients treated with cefepime and 47% of ceftazidime-treated patients responded to therapy. Cefepime patients developed fewer new infections than ceftazidime patients (9% vs. 21%, respectively) and early discontinuation of study drug therapy occurred slightly more often in the ceftazidime group. Further, the use of concomitant systemic antimicrobial therapy (mostly vancomycin) occurred less often in the cefepime-treated patients, as compared with the ceftazidime group [35% [17 of 49] vs. 44% (24 of 55), respectively]. No deaths or serious adverse events were considered to be related to study therapy. The most frequent adverse event was rash that was moderate in severity, and it occurred equally in both groups.. Cefepime appears to be safe and effective compared with ceftazidime for initial empiric therapy of febrile episodes in neutropenic pediatric cancer patients.

Topics: Adolescent; Adult; Bacterial Infections; Cefepime; Ceftazidime; Cephalosporins; Child; Child, Preschool; Fever; Humans; Infant; Neoplasms; Neutropenia; Safety; Treatment Outcome

Topics: Adult; Cefepime; Cephalosporins; Child; Fever; Gentamicins; Humans; Neutropenia; Penicillins; Piperacillin

Monotherapy with ceftazidime, cefepime, imipenem or meropenem for the empiric treatment of febrile neutropenia appears as effective as the combination therapy involving aminoglycosides. However, empiric therapy with a combination of a beta-lactam plus an aminoglycoside is a reasonable decision under circumstances where Gram negative sepsis is very likely. Monotherapy is usually associated with a modest rate of response in infections caused by Gram positive organisms. In about 30% of the patients, a glycopeptide will be added at some point, because the response to the initial therapy is not considered optimal.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Cefepime; Ceftazidime; Cephalosporins; Drug Therapy, Combination; Fever; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Imipenem; Meropenem; Neutropenia; Sepsis; Thienamycins

To evaluate clinically the efficacy and safety in northern India of cefepime monotherapy versus piperacillin-tazobactam in patients of paediatric age group with febrile neutropenia.. Children aged ≤18 years admitted febrile with chemotherapy-induced neutropenia were randomised into two groups comprising 20 cases in each group viz. CEF (receiving cefepime only) and PIP-TAZO (receiving piperacillin-tazobactam). Based on clinical and laboratory tests, patients were classified into: microbiologically documented infections (MDI); clinically documented infections (CDI); and unexplained fever (UF). They were assessed for clinical signs and symptoms as well as laboratory parameters at the time of enrolment and subsequently on days 3 and 7.. Incidence of MDI, CDI and UF were 22.5%, 47.5% and 30%, respectively. The mean duration of neutropenia (in days) was 5.45 ± 2.1 in the PIP-TAZO group and 5.5 ± 1.5 in the CEF group (P = 0.305). The success rate defined as clearing infection effectively and improvement of neutropenia was comparable (P = 0.705). There was a mortality rate of 20% in the PIP-TAZO group as compared to 10% in the CEF group.. We conclude that cefepime monotherapy and piperacillin-tazobactam are equally efficacious and safe in treating patients with febrile neutropenia. Empirical monotherapy with cefepime would prevent an unnecessary extra economic burden as well as avoiding the serious adverse or toxic effects of multi-drug regimes, especially in low- and middle-income countries.

Topics: Adolescent; Anti-Bacterial Agents; Bacterial Infections; Cefepime; Cephalosporins; Child; Child, Preschool; Drug Therapy, Combination; Febrile Neutropenia; Female; Fever; Humans; India; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Tertiary Care Centers; Treatment Outcome

There exists few pediatric data on the safety and efficacy of prophylactic antibiotics during chemotherapy-induced agranulocytosis.. We prospectively studied the incidence of infection-related fever in 38 children, aged 2-16 years, with acute myeloid leukemia (AML) over 121 chemotherapy treatment cycles. A prophylactic group (n = 18) was given either vancomycin/cefepime (400 mg/m(2), q12 h/50 mg/kg, q12 h) or piperacillin/tazobactam (110 mg/kg, q12 h). Control patients (n = 20) received no preventive antibiotics.. The prophylactic group (59 treatment cycles) experienced fever less frequently than the control group (0.4 vs. 0.9 events; p < 0.001), had a longer interval between agranulocytosis and fever (6.4 vs. 3.8 days; p = 0.007), had a shorter duration of hospitalization (21.5 vs. 28.5 days; p < 0.001), and had a lower rate of lung infection (38.8 vs. 80.0%; p < 0.001). One patient taking vancomycin experienced a skin rash and 3 patients taking piperacillin/tazobactam had diarrhea; these side effects subsided after antibiotics were discontinued.. In children with AML, prophylactic antibiotics during the period of chemotherapy-induced agranulocytosis can effectively reduce the incidence of infectious fever and can shorten the average length of hospital stay, improving treatment success and quality of life.

Topics: Adolescent; Agranulocytosis; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Cefepime; Cephalosporins; Child; Child, Preschool; Female; Fever; Humans; Infection Control; Length of Stay; Leukemia, Myeloid, Acute; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Vancomycin

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

Ciprofloxacin (CPFX) is a potential alternative in patients with febrile neutropenia (FN) because of its activity against Gram-negative organisms. We conducted a non-inferiority, open-label, randomized controlled trial comparing intravenous CPFX and cefepime (CFPM) for FN patients with hematological malignancies.. Patients aged from 15 to 79 years with an absolute neutrophil count of <0.500 × 10(9/)l were eligible, and were randomized to receive 300 mg of CPFX or 2g of CFPM every 12h. Initial treatment efficacy, overall response, and early toxicity were evaluated.. Fifty-one episodes were included in this trial, and 49 episodes (CPFX vs. CFPM: 24 vs. 25) were evaluated. Treatment efficacy at day 7 was significantly higher in the CFPM group (successful clinical response: nine with CPFX and 19 with CFPM; p=0.007). The response was better in high-risk patients with neutrophil counts of ≤ 0.100 × 10(9/)l (p=0.003). The overall response during the study period was similar between the CPFX and CFPM groups (p=0.64). Adverse events were minimal, and all patients could continue the treatment.. We could not prove the non-inferiority of CPFX in comparison with CFPM for the initial treatment of FN. CFPM remains the standard treatment of choice for FN.

Topics: Adolescent; Adult; Aged; Algorithms; Anti-Bacterial Agents; Cefepime; Cephalosporins; Ciprofloxacin; Female; Fever; Hematologic Neoplasms; Humans; Male; Middle Aged; Neutropenia; Treatment Outcome; Young Adult

Our unit adopted the single administration of cefepime as the initial treatment for febrile episodes in neutropenic patients with hematological malignancies. However, recently, cefepime-resistant gram-negative bacteremia, including those with extended-spectrum β-lactamase (ESBL)-producers, was frequently observed in these patients. Therefore, we instituted a rotation of primary antibiotics for febrile neutropenic patients in an attempt to control antibiotic resistance.. This prospective trial was performed from August 2008 through March 2011 at our unit. After a pre-intervention period, in which cefepime was used as the initial agent for febrile neutropenia, 4 primary antibiotics, namely, piperacillin-tazobactam, ciprofloxacin, meropenem, and cefepime, were rotated at 1-month intervals over 20 months. Blood and surveillance cultures were conducted for febrile episodes, in order to assess the etiology, the resistance pattern (particularly to cefepime), and the prognosis.. In this trial, 219 patients were registered. A 65.9% reduction in the use of cefepime occurred after the antibiotic rotation. In the surveillance stool cultures, the detection rate of cefepime-resistant gram-negative isolates, of which ESBL-producers were predominant, declined significantly after the intervention (8.5 vs 0.9 episodes per 1000 patient days before and after intervention respectively, P<0.01). Interestingly, ESBL-related bacteremia was not detected after the initiation of the trial (1.7 vs 0.0 episodes per 1000 patient days before and after intervention respectively, P<0.01). Infection-related mortality was comparable between the 2 periods.. We implemented a monthly rotation of primary antibiotics for febrile neutropenic patients. An antibiotic heterogeneity strategy, mainly performed as a cycling regimen, would be useful for controlling antimicrobial resistance among patients treated for febrile neutropenia.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; Cefepime; Cephalosporins; Ciprofloxacin; Drug Administration Schedule; Female; Fever; Gram-Negative Bacterial Infections; Hematologic Neoplasms; Humans; Male; Meropenem; Middle Aged; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Thienamycins

To check the effectiveness of ticarcillin clavulanate versus cefepime as monotherapy in febrile neutropenia in lymphoma patients and also to check tolerability profile of both drugs.. We randomly assigned 107 neutropenic patients to receive either cefepime or ticarcillin/clavulanate. The clinical efficacy and tolerability profile of both drugs were compared using either cefepime or ticarcillin clavulanate (TC) as an empirical treatment for management of febrile neutropenia in lymphoma patients only with same characteristics at time of presentation.. A significant difference in efficacy of the two treatment arms was noted. A successful outcome was reported with 28 (51%) out of 55 in cefepime arm compared to 16 (42%) out of 52 patients in ticarcillin/clavulanate group (p = 0.35; 95% Confidence). The distribution of time for defervesence was estimated for each treatment group and a trend to a shorter time for defervesence was found in the CEFEPIME group (48.4 hour for cefepime, 58.28 hour for TC group; p = 0.018). For microbiologically documented infections, the successful eradication rate was 49% (6 of 14 patients) for TC group as compared to 83% (10 of 12 patients) for cefepime group. This difference was statistically significant for microbiologically documented infections. Twenty seven (52%) patients of TC group and 19 (35%) of cefepime group required modifications of antibiotic regimen. The most frequent modifications consisted of the addition of either an amino glycoside (amikacin) or glycopeptides (vancomycin).. CEFEPIME regimen was more effective than TC regimen, with a consistent trend toward a better outcome associated with cefepime compared to Ticarcillin/clavulanate.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Antineoplastic Agents; Bacterial Infections; Cefepime; Cephalosporins; Child; Child, Preschool; Clavulanic Acid; Drug Therapy, Combination; Female; Fever; Humans; Infant; Infant, Newborn; Lymphoma; Male; Middle Aged; Neutropenia; Prospective Studies; Ticarcillin; Treatment Outcome; Young Adult

Fever often occurs along with chemotherapy-induced neutropenia. This condition is referred to as febrile neutropenia (FN). Excellent guidelines for FN treatment have recently been published; however, there has so far been insufficient research concerning FN associated with solid tumors, especially in Japan. A multi-institution prospective study of cefepime for the treatment of FN in lung cancer patients was conducted. The objective of this study was to determine the efficacy and safety of cefepime for FN in lung cancer patients. Cefepime (2 g x 2/day) was administered to patients with FN after treatment for lung cancer. The therapeutic response rate, the effect of the drug on pathogen populations, and the incidence of adverse effects were statistically analyzed. Twenty-one patients with FN were registered for this study. One case was excluded because of protocol violation; therefore, a total of 20 cases were analyzed. Three days after the administration of cefepime, improvement was evident in 15 cases. The response rate was 75%, 95% CI: 53.1-88.8. After 7 days, 17 patients experienced improvement in their condition (85%, 95% CI: 64.0-94.8). Carbapenem was eventually substituted for cefepime in three cases, and all cases finally displayed improvement. There was no mortality. Pathogens for FN were detected in three cases and they disappeared in one case. Four patients experienced adverse side effects, including skin eruption, serum bilirubin elevation, neutrophil depletion, and anterior chest pain. There were no severe adverse events. In this study, cefepime demonstrated a high degree of clinical efficacy and safety in the treatment of FN. Empiric monotherapy using cefepime is a recommended regimen for FN in patients with lung cancer in Japan.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Antineoplastic Agents; Blood; Cefepime; Cephalosporins; Female; Fever; Humans; Lung Neoplasms; Male; Middle Aged; Neutropenia; Sputum

This is a prospective, randomized, and open-label clinical trial that examines the efficiency and safety of PIP/TAZO monotherapy in comparison to cefepime (CEF), for the empirical treatment of pediatric cancer patients with neutropenia and fever.. One hundred thirty-one consecutive febrile episodes in 70 neutropenic pediatric cancer patients received randomized treatment either with piperacillin/tazobactam (PIP/TAZO) 80 mg/kg piperacillin/10 mg/kg tazobactam every 6 hr or CEF 50 mg/kg every 8 hr. Clinical response was determined at completion of therapy. Duration of fever, neutropenia, hospitalization, the need for modification of the therapy, and mortality rates were compared between the two groups.. One hundred twenty-seven episodes in 69 patients (35 females, 34 males) with a median age of 4.2 years were assessed for efficiency (65 PIP/TAZO, 62 CEF). The frequency of success without modification of treatment was nearly identical for both PIP/TAZO (60.0%) and CEF (61.3%) (P > 0.05). The overall response rate, with or without modification of assigned treatment, was 96.9% for PIP/TAZO and 98.4% for CEP (P > 0.05). Infection-related mortality at the end of the febrile episode was 2.4%. Duration of fever and hospitalization were not different between the treatment groups. No major side effects were observed in neither of the groups.. PIP/TAZO treatment was as effective and safe as CEF monotherapy as an initial empirical regimen in pediatric cancer patients with fever and neutropenia.

Topics: Adolescent; Anti-Bacterial Agents; Cefepime; Cephalosporins; Child; Child, Preschool; Female; Fever; Humans; Infant; Male; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies

The pharmacokinetic behavior of cefepime was studied in healthy and febrile cross-bred calves after single intravenous administration (10 mg/kg). The fever was induced with E. coli lipopolysaccharide (1 microg/kg, IV). The drug concentration in plasma was detected by microbiological assay method using E. coli (MTCC 739) test organism. Pharmacokinetic analysis of disposition data indicated that intravenous administration data were best described by 2 compartment open model. At 1 min the concentration of cefepime in healthy and febrile animals were 55.3 +/- 0.54 microg/ml and 50.0 +/- 0.48 microg/ml, respectively and drug was detected up to 12 h. The elimination half-life of cefepime was increased from 1.26 +/- 0.01 h in healthy animals to 1.62 +/- 0.09 h in febrile animals. Drug distribution was altered by fever as febrile animals showed volume of distribution (0.27 +/- 0.02 L/kg) higher than normal animal (0.19 +/- 0.01 L/kg). Total body clearances in healthy and febrile animals were 104.4 +/- 2.70 and 114.2 +/- 1.20 ml/kg/h, respectively. To maintain minimum therapeutic concentration of 1 mug/ml, a satisfactory dosage regimen of cefepime in healthy and febrile cross-bred calves would be 15.5 mg/kg and 8.2 mg/kg body weight, respectively, to be repeated at 8 h intervals. The T>MIC values (8 h) of cefepime suggested that this agent is clinically effective in the treatment of various infections.

Topics: Animals; Anti-Bacterial Agents; Area Under Curve; Cattle; Cattle Diseases; Cefepime; Cephalosporins; Escherichia coli; Fever; Half-Life; Lipopolysaccharides; Male; Time Factors

To compare the efficacy and safety of panipenem/betamipron with cefepime as empirical monotherapy for adult cancer patients with febrile neutropenia, a randomized, open-label, comparative trial was performed.. All enrolled patients were randomly assigned to receive either panipenem or cefepime. All febrile episodes were classified as microbiologically defined infection (MDI), clinically defined infection (CDI) or unexplained fever (UF). Clinical responses to antibiotic therapy were defined as success, initial response but regimen modified or failure.. A total of 116 patients were enrolled: 55 patients in the panipenem group and 61 patients in the cefepime group. Demographic and clinical characteristics were similar in the two groups (P > 0.05). In the final evaluation, the success rate for the panipenem group (89.1%) was similar to that of the cefepime group (91.8%) (non-inferiority, P = 0.002, 95% confidence interval: -13.48%, 10.35%). Of the 18 bacterial isolates, nine (50%) were gram-positive and nine (50%) were gram-negative. The prevalence of adverse events in the panipenem group (23.6%) were similar to those in the cefepime group (23.0%) (P = 0.93). All of the adverse events were well tolerated and transient.. Although larger studies are necessary, panipenem appeared to be as effective and safe as cefepime for empirical monotherapy in the treatment of adult cancer patients with febrile neutropenia.

Topics: Anti-Bacterial Agents; Bacterial Infections; Cefepime; Cephalosporins; Drug Therapy, Combination; Female; Fever; Humans; Male; Middle Aged; Neoplasms; Neutropenia; Prospective Studies; Survival Rate; Thienamycins; Treatment Outcome

Cefepime is a fourth-generation cephalosporin with a broad antimicrobial spectrum and good activity against both gram-positive and gram-negative organisms. We present the case of a 61-year-old man who developed an immediate urticarial reaction after receiving a single dose of cefepime. Skin tests were positive to cefepime and negative to the other beta-lactam antibiotics. Controlled administration of amoxicillin-clavulanic acid and ceftazidime was well tolerated by the patient. To the best of our knowledge, this is the first report of selective hypersensitivity to cefepime demonstrated by skin and challenge tests. Complete allergological studies, including challenge tests with other beta-lactam antibiotics that produce a negative result in skin tests, should be considered in these patients.

Topics: Anti-Bacterial Agents; Cefepime; Cephalosporins; Fever; Humans; Hypersensitivity, Immediate; Immunoglobulin E; Male; Middle Aged; Skin Tests

We performed a randomized comparison of pre-emptive and empiric antibiotic therapy for adult patients undergoing allogeneic or autologous stem cell transplantation. One hundred and fifty-three patients were randomized to receive cefepime either pre-emptively on the day that neutropenia (ANC<1.0 x 10(9) cells/l) developed irrespective of the presence of fever, or at onset of fever and neutropenia (empiric). Although there was no difference between the two arms in the proportion of patients developing fever or in the median number of days of fever, the time to onset of fever was a mean of 1 day longer in each patient on the pre-emptive arm (log rank P<0.001). The number of patients with bloodstream infections was significantly reduced in those receiving pre-emptive therapy (16/75) compared to the empiric arm (31/76) (P<0.01) but this did not translate into an appreciable clinical benefit as measured by days of hospitalization, time to engraftment, use of additional antimicrobial agents or mortality at 30 days. This study does not support the use of pre-emptive intravenous antibiotic therapy in adult stem cell transplant recipients.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Bacterial Infections; Cefepime; Cephalosporins; Female; Fever; Hematopoietic Stem Cell Transplantation; Humans; Male; Neutropenia; Time Factors; Transplantation, Autologous; Transplantation, Homologous; Treatment Outcome

We evaluated the efficacy of cefepime in association with amikacin in the initial empirical therapy of febrile neutropenic children.. The study was an open-labelled, non-randomised prospective trial to assess the efficacy and safety of this association, from January 2003 to December 2003. Children and adolescents were treated for a haematological malignancy or a primary, refractory or relapsed solid tumour, and presented with febrile neutropenia. Patients received cefepime (50 mg per kg per dose every 8 hours for children weighing less than or equal to 40 kg; and 2 g every 8 hours for those weighing more than 40 kg) plus a single daily dose of amikacin at 15 mg per kg per day, up to a maximum 250 mg. If fever persisted, a second-line therapy with carbapenem was administered. Amphotericin B was added at 96 hours if fever and neutropenia persisted.. 103 episodes of fever and neutropenia were evaluated in 54 patients. 18.4 percent of the episodes were microbiologically-documented infections, 24.3 percent were clinically documented, and 57.3 percent were episodes with unexplained fever. 54.4 percent of the episodes responded to cefepime plus amikacin without a need for treatment modification. A higher success rate (74.6 percent) was observed in episodes with unexplained fever. In all cases of persistent fever, the antibiotics were changed to carbapenem within 72 hours and all patients survived. One patient died because of culture-negative septic shock within 24 hours of admission. A mild gastrointestinal intolerance occurred in three patients.. This study suggests that cefepime plus amikacin presents a satisfactory efficacy and a good tolerance as an initial empirical therapy for febrile neutropenic children.

Topics: Adolescent; Adult; Amikacin; Anti-Bacterial Agents; Cefepime; Cephalosporins; Child; Child, Preschool; Drug Therapy, Combination; Female; Fever; Humans; Infant; Male; Neoplasms; Neutropenia; Remission Induction

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

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

Empirical therapy for children with febrile neutropenia has traditionally consisted of combination antibiotics, usually a beta-lactam and an aminoglycoside. However, recent trends and international guidelines have now made monotherapy a feasible option in the management of this group of patients. We prospectively evaluated the efficacy and safety of cefepime monotherapy in our population of paediatric cancer patients with febrile neutropenia.. An audit was performed on children aged 16 years and younger presenting with fever and neutropenia who were managed with empirical single-agent cefepime. The patients were analysed for clinical outcome, documented infections and side-effects of the study drug. Success was defined as clinical improvement without treatment modification. Death or any change to the empirical antibiotic was considered as failure.. In this study 79 children (median age 5.2 years) with 133 episodes of febrile neutropenia were prospectively studied between August 2004 and August 2005. A microbiologically documented infection was seen in 26 episodes. The success rate of cefepime monotherapy was 60%. The rate of survival through neutropenia (with or without modification) was 98%. No significant adverse effects were seen.. Cefepime monotherapy is a safe and feasible option for treatment of childhood cancer patients with febrile neutropenia.

Topics: Adolescent; Anti-Bacterial Agents; Cefepime; Cephalosporins; Child; Child, Preschool; Female; Fever; Humans; Infant; Malaysia; Male; Neoplasms; Neutropenia; Prospective Studies; Treatment Outcome; Vancomycin

This randomized clinical trial evaluated the efficacy and safety of monotherapy with cefepime for patients with solid tumors treated with high dose chemotherapy (HDC) and peripheral blood stem cell support (PBSCS) with febrile neutropenia.. Patients with solid tumors treated with HDC and PBSCS, that developed fever and neutropenia (absolute neutrophil count < 500 cells/microL) were eligible, and randomly assigned to receive ceftazidime plus amikacin or cefepime.. Fifty-one episodes were randomized, and all were evaluable (27 received ceftazidime plus amikacin arm, and 24 cefepime). Major efficacy endpoints did not show significant differences, with success rates of 44.4% and 54.2% (p = 0.481) for the combination arm and the monotherapy arm, respectively. The proportion of patients that became afebrile in the first 24 hours was significantly higher in the cefepime group (41.7% vs 11.1%, respectively; p = 0.012). However, due to its premature closure and small sample size, this study lacks the adequate power to definitely address this question.. Cefepime monotherapy appeared to have an equivalent efficacy and safety as empiric treatment in febrile neutropenia episodes in a highrisk population compared with ceftazidime and amikacin. Nevertheless, this study is not adequately powered to answer this question. Given the small number of patients randomized and the single-center nature of this study, these results must be cautiously interpreted.

Topics: Adult; Amikacin; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Cefepime; Ceftazidime; Cephalosporins; Drug Therapy, Combination; Female; Fever; Humans; Male; Middle Aged; Neoplasms; Neutropenia; Stem Cell Transplantation; Treatment Outcome

Topics: Adolescent; Anti-Bacterial Agents; Bacteremia; Cefepime; Cephalosporins; Child; Child, Preschool; Empiricism; Female; Fever; Granulocyte Colony-Stimulating Factor; Humans; Infant; Lymphoma, Non-Hodgkin; Male; Meropenem; Neoplasms; Neutropenia; Therapeutic Equivalency; Thienamycins; 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

A prospective, open label, randomized, multicentre study was conducted, comparing the efficacy and safety of cefepime with that of imipenem-cilastatin for the management of febrile neutropenia in patients with haematological malignancies. Furthermore, the safety of early discontinuation of antibiotic therapy in patients with fever of undetermined origin (FUO) was assessed. A total of 180 patients with 207 febrile episodes were randomized at start of fever (105 episodes for cefepime and 102 episodes for imipenem). The 2 groups were comparable in terms of age, gender, underlying malignancy, prior transplantation, and presence of central venous catheters. All patients were neutropenic at inclusion with median absolute neutrophil count (ANC) 0.1 x 10(9)/l(range 0-1 x 10(9)/l), and ANC < or = 0.1 x 10(9)/l in 77% of included patients. The mean duration of neutropenia, with ANC < 0.5 x 10(9)/l was 6.2 d. Febrile episodes were classified as microbiologically documented infection (47%), FUO (43%), or clinically documented infection (10%). At final evaluation 1-2 weeks after completion of antibiotic therapy, monotherapy success rates were 40% and 51% in the cefepime and imipenem-cilastatin groups respectively (p = 0.33). The 4-week overall mortality rate was 5%. Three (2%) of the cefepime treated patients and 4 (3%) of the imipenem-cilastatin treated patients died as a result of infection. Adverse events directly related to antibiotic treatment were uncommon and did not differ between groups. Early discontinuation of antibiotic therapy in 31 patients with FUO 48 h after defervescence was not associated with an increased rate of fever relapse or mortality compared with a subgroup of 29 patients where therapy was continued.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cefepime; Cephalosporins; Cilastatin; Cilastatin, Imipenem Drug Combination; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Fever; Follow-Up Studies; Hematologic Neoplasms; Humans; Imipenem; Male; Middle Aged; Neutropenia; Probability; Prospective Studies; Risk Assessment; Single-Blind Method; Survival Analysis; Sweden; Treatment Outcome

An open labeled randomized trial comparing the efficacy and cost of empirically applied cefepime (C) as monotherapy versus combination therapy consisting of ticarcillin and clavulanate potassium and aztreonam (T/A) was performed in febrile neutropenic patients following high-dose chemotherapy (HDC) +/- radiation, with or without peripheral blood stem cell support. Over a 28-month period, 126 patients were screened and included in the study. Using afebrile status following 3 days of therapy as a primary endpoint, both regimens produced comparable clinical response rates (C = 55% vs. T/A = 61%). Also, the use of vancomycin for resistant gram-positive infections and alteration of gram-negative infection coverage was similar in both groups (C = 40% vs. T/A = 47% and C = 29% vs. T/A = 24%). Both treatment groups had similar needs for empirical antifungal therapy (C = 25% vs. T/A = 22%). There was a postrandomization difference between the two groups in that the "C" group had a significantly higher number of allogeneic transplants and non-stem-cell-supported patients, whereas the "T/A" group had a significantly greater number of autologous peripheral blood stem cell patients (p < 0.0001). Despite this difference, the C group had a significantly lower cost ratio than the T/A group (p = 0.016). In conclusion, we have shown that C treatment of febrile neutropenic patients following HDC results in similar efficacy and lower cost when compared to T/A, despite the inclusion of higher risk patients in the C group.

Topics: Adult; Aged; Anti-Bacterial Agents; Antineoplastic Agents; Aztreonam; Cefepime; Cephalosporins; Clavulanic Acid; Costs and Cost Analysis; Drug Therapy, Combination; Female; Fever; Humans; Immunocompromised Host; Male; Middle Aged; Neoplasms; Neutropenia; Opportunistic Infections; Peripheral Blood Stem Cell Transplantation; Ticarcillin

The objective of the current study was to compare the efficacy and safety of imipenem and cefepime in the treatment of adult patients with cancer who had fever and neutropenia requiring hospitalization according to Infectious Disease Society of America criteria.. In the current prospective randomized clinical trial at a university-affiliated tertiary cancer center, adult patients with cancer who had fever (> or = 38.3 degrees C or > or = 38.0 degrees C for > 2 hours) and neutropenia (< or = 500/mm(3) or < 1000/mm(3) but declining) requiring hospitalization were randomized to receive either cefepime or imipenem. Vancomycin or amikacin was added on suspicion of gram-positive or gram-negative bacterial infection, respectively.. Patients who received an imipenem regimen or a cefepime regimen were comparable in terms of age, gender, underlying malignancy, prior transplantation, degree and trend of neutropenia, and presence of central venous catheters (P > or = 0.3). An intent-to-treat analysis showed a 68% response rate to the imipenem regimen, compared with a 75% response rate to the cefepime regimen (P = 0.2). The rates of antibiotic-related adverse events and superinfections also were comparable (P = 0.6). There was no difference in response among patients who received imipenem or cefepime alone compared with patients who also received vancomycin or amikacin (P = 1.0). Leukemia was the only independent risk factor associated with a poor outcome (odds ratio, 4.6; 95% confidence interval, 1.9-10.7; P < 0.0001).. Imipenem and cefepime had similar efficacy and safety profiles in the treatment of adult cancer patients with fever and neutropenia who required hospitalization. The addition of either vancomycin or amikacin may not be necessary.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amikacin; Anti-Bacterial Agents; Bacterial Infections; Catheterization, Central Venous; Cefepime; Cephalosporins; Female; Fever; Hospitalization; Humans; Imipenem; Male; Middle Aged; Neoplasms; Neutropenia; Practice Guidelines as Topic; Prospective Studies; Risk Factors; Vancomycin

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

Currently, monotherapy is considered a valid alternative to the combination antibiotic treatments used for initial, empirical management of febrile neutropenia. The advent of new cephalosporins warrants assessment. The aim of this study was to prospectively evaluate the effectiveness of cefepime monotherapy in the treatment of cancer patients with febrile granulocytopenia (< 1000 leukocytes/muL and/or < 500 neutrophils/muL). A prospective, multicenter, nonrandomized trial was conducted. Initial treatment consisted of iv cefepime, 2 g every 8 h. If the patient was still febrile after 72 h, amikacin, vancomycin/teicoplanin, and amphotericin B were added sequentially. Response was evaluated according to EORTC criteria. One hundred twenty episodes were analyzed in 81 males and 39 females (median age, 52 yr; range, 15-83). The median leukocyte count at the time of diagnosis was 781 microL(-1) (range, 100-2600) and the median neutrophil count was 173 microL(-1) (range 0-500). The median duration of neutropenia (< 1000 neutrophils/microL) was 4.8 d (range, 3-20). Fifty-two episodes (44%) were confirmed microbiologically (42 presented as bacteremia), 31 with Gram-positive bacteria and 21 with Gram-negative bacteria, 47 (39.3%) were confirmed clinically, 16 (13.3%) were considered as probable infections, and 5 (4.2%) as doubtful infections. Protocol success was achieved in 110 episodes (91.7%), 8 (6.6%) were treatment failures, and 2 (1.7%) were not evaluable. Ninety-nine episodes (83.3%) were controlled with cefepime monotherapy, with 19 other episodes requiring additional antibiotics: amikacin in 7 (5.8%), amikacin + vancomycin/teicoplanin in 12 (10.1%). Three patients (2,5%) died during an episode of neutropenic fever. Cefepime is effective as an initial, empirical treatment of febrile neutropenia. The early addition of amikacin and/or vancomycin resolves most of the monotherapy failures, which seem somewhat lower than with other monotherapies.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amikacin; Anti-Bacterial Agents; Antineoplastic Agents; Bacterial Infections; Cefepime; Cephalosporins; Drug Therapy, Combination; Female; Fever; Humans; Male; Middle Aged; Multicenter Studies as Topic; Neoplasms; Neutropenia; Teicoplanin; Treatment Outcome; Vancomycin

A prospective, randomized, controlled monocentric trial was performed to evaluate the efficacy and safety of once daily ceftriaxone 2 g plus gentamicin 5 mg/kg in comparison to cefepime 2 g t.i.d. plus gentamicin 5 mg/kg q.d. in the treatment of neutropenic fever. In case of fever (oral temperature > or =38.5 degrees C on one occasion or > or =38.0 degrees C twice within 24 h) and a granulocytopenia (neutrophil count below 500 or below 1000/microl when expected to fall below 500 within 72 h), patients with hematological malignancies or solid tumors were assigned to ceftriaxone or cefepime, each with gentamicin. The primary endpoint was defined as defervescence on day 4-6 followed by at least 7 afebrile days. Secondary endpoints were overall response, defined as defervescence on day 28 and toxicity. Two hundred eleven episodes were included. Fever of unknown origin (FUO) accounted for 124 episodes (58.8%), microbiologically defined infection (MDI) for 39 (18.5%), clinically defined infection (CDI) for 25 (11.8%), and both clinically and microbiologically defined infection (CMDI) for 19 episodes (9%). On an intent-to-treat basis 207 episodes were evaluable for the primary endpoint. Ceftriaxone plus gentamicin and cefepime plus gentamicin were successful in 49.5% and 51%, respectively. Overall response was achieved on study day 28 in 92.5% and 91%, respectively. Diarrhea was more frequent with ceftriaxone/gentamicin (6.5% vs 17%), while nausea/vomiting was less (12.1% vs 5%). Once-daily ceftriaxone plus gentamicin was not inferior to cefepime t.i.d. plus gentamicin q.d. in the empirical treatment of neutropenic fever.

Topics: Anti-Bacterial Agents; Cefepime; Ceftriaxone; Cephalosporins; Drug Therapy, Combination; Fever; Gentamicins; Humans; Neutropenia; Prospective Studies; Treatment Outcome

Monotherapy with cefepime or ceftazidime is an effective alternative to combination therapy for the treatment of febrile neutropenic adult cancer patients. We compared the efficacy and safety of cefepime and ceftazidime as empiric monotherapy of febrile neutropenia in children with cancer.. A prospective, open label, randomized, comparative study in pediatric cancer patients was conducted at Chang Gung Children's Hospital from January 1, 2000, to April 15, 2001. Patients with fever and neutropenia (absolute neutrophil count of < or = 500/mm3) were randomized to receive either intravenous cefepime or ceftazidime (50 mg/kg/dose as two or three doses daily). Febrile episodes were classified as microbiologically documented infection, clinically documented infection or unexplained fever. Clinical response to therapy was classified as success and failure.. Ninety-five pediatric cancer patients with 120 febrile neutropenic episodes were randomized to receive empiric treatment with cefepime or ceftazidime. After 72 h of treatment, 82.8% (48 of 58) of the eligible patients in the cefepime group continued with unmodified therapy, compared with 87.9% (51 of 58) in the ceftazidime group. The neutrophil count was <100/mm3 at randomization for 76% of the patients in the cefepime group and 83% of those in the ceftazidime group; the median durations of neutropenia (<500/mm3) were 8.5 and 6.5 days, respectively. Of the 96 evaluable episodes the overall success rate with unmodified empiric therapy until the end of the treatment course in the cefepime group was comparable with that in the ceftazidime group (69% vs. 71%, P = 0.95). The response rate after glycopeptides were added to the regimens was 79.2% for the cefepime group and 77.1% for the ceftazidime group. The bacterial eradication rate was 33% for the cefepime group and 20% for the ceftazidime group (P = 0.85), and the rates of new infections were 10.4% vs. 4.2% (P = 0.67), respectively. Both study drugs were well-tolerated. Three (6.4%) patients in the cefepime group and 2 (4.3%) patients in the ceftazidime group died.. Cefepime appeared to be as effective and safe as ceftazidime for empiric treatment of febrile episodes in neutropenic pediatric cancer patients.

Topics: Adolescent; Bacterial Infections; Cefepime; Ceftazidime; Cephalosporins; Child; Child, Preschool; Female; Fever; Humans; Infant; Male; Neoplasms; Neutropenia; Treatment Outcome

Standard therapy for suspected infections in patients with profound neutropenia is the combination of a beta-lactam antibiotic plus an aminoglycoside. Cefepime's broad-spectrum activity makes it an option for initial empirical therapy in neutropenic patients. The aim of this study is to evaluate the efficacy and safety of cefepime plus amikacin compared with piperacillin-tazobactam plus amikacin for initial empirical treatment of fever in adult haematology patients with severe neutropenia.. In this prospective multicentre trial, 969 patients with 984 febrile neutropenic episodes were randomized to receive iv amikacin (20 mg/kg every 24 h) combined with either cefepime (2 g every 8 h) or piperacillin-tazobactam (4 g/500 mg every 6 h). Clinical response was determined at 72 h and at completion of therapy.. Eight hundred and sixty-seven episodes were assessable for efficacy (432 cefepime, 435 piperacillin-tazobactam). The frequency of success without modification of the empirical therapy was nearly identical for cefepime plus amikacin (49%) compared with piperacillin-tazobactam plus amikacin (51%). Similar rates of success were found for microbiologically documented infection: 40% versus 39%, respectively. Antibiotic modification was necessary in 49% of cefepime and 44% of piperacillin-tazobactam patients. The overall response rate, with or without modification of the assigned treatment, was 94% in both groups. Drug-related adverse events were reported in 10% of cefepime plus amikacin versus 11% of piperacillin-tazobactam plus amikacin patients. Mortality due to infection occurred in a total of 10 patients (two cefepime, eight piperacillin-tazobactam).. The empirical regimen of cefepime plus amikacin is equivalent to piperacillin-tazobactam plus amikacin in febrile adult haematology patients with severe neutropenia.. cefepime, piperacillin-tazobactam, amikacin, empirical antibiotic therapy, febrile neutropenia, haematological malignancy

Topics: Adult; Amikacin; Anti-Bacterial Agents; Cefepime; Cephalosporins; Drug Therapy, Combination; Female; Fever; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Male; Neutropenia; Penicillanic Acid; Piperacillin; Tazobactam; Treatment Outcome

With the availability of new broad-spectrum antibiotics, initial therapy with a single agent has become an alternative to classic combinations, especially beta-lactam antibiotics plus aminoglycosides, in the management of febrile neutropenic cancer patients.. Since January 1994, monotherapy has been used for empiric initial treatment at our center. The aim of this prospective randomized study is to compare the efficacy of cefepime (CFP), a new fourth-generation cephalosporin, and ceftazidime (CFZ) as empirical monotherapy of febrile neutropenic patients with solid tumors. From January 1998 to November 1998, 63 episodes of fever and neutropenia occurring in 33 children with solid tumors including lymphomas, were randomized to receive treatment with either CFP or CFZ. The patients were analyzed for leukocyte count and absolute neutrophil count (ANC) at entry, days in fever, neutropenia and hospitalization, and side effects of drugs. Success with or without modifications of the initial antibiotic was defined as survival through neutropenia; failure was death due to infection.. In our study group, with a median age of 7 [(1/12)-14] years, CFP was administered in 32, and CFZ in 31 episodes. An infection was documented microbiologically in eight episodes (25%) in the CFP arm and in nine episodes (29%) in the CFZ arm. The success rate with initial empiric monotherapy was 62.5% in the CFP arm and 61.3% in the CFZ arm respectively (P > 0.05). The total success rate (success with or without modification) was 100% in both arms. No major adverse effects were observed in either groups.. CFP is as effective and safe as CFZ for the empirical treatment of febrile episodes in neutropenic patients with solid tumors.

Topics: Adolescent; Antineoplastic Agents; Bacterial Infections; Candidiasis; Cefepime; Ceftazidime; Cephalosporins; Child; Child, Preschool; Female; Fever; Humans; Infant; Male; Neoplasms; Neutropenia; Statistics, Nonparametric

In view of the recent trend toward monotherapy in the treatment of bacterial infection, we evaluate the clinical efficacy and safety of cefepime vs. ceftazidime for the empiric treatment of febrile episodes in neutropenic pediatric cancer patients.. In a single site, open label study, 104 neutropenic pediatric cancer patients [96% with absolute neutrophil count (ANC) of <500 neutrophils/mm3] with a median age of 6 years were randomized (1:1) to receive either intravenous cefepime or ceftazidime (50 mg/kg/dose every 8 h; < or = 6 g/day) for empiric treatment of fever (temperature >38.0 degrees C occurring at least twice in 24 h, or single >38.5 degrees C). Febrile episodes were classified as either microbiologically or clinically documented infection or fever of unknown origin. Therapy continued until the ANC was > or = 1,000 neutrophils/mm3 or there was an increasing ANC in low risk patients (maximum duration of treatment, 8 weeks). The primary efficacy endpoints assessed were clinical and microbiologic response to assigned drug therapy. Secondary outcome measures were rate of early discontinuation of study drug and use of concomitant antibiotic therapy to modify initial study drug regimen.. Of 68 patients who could be evaluated for efficacy, 74% (26 of 35) of cefepime-treated patients and 70% (23 of 33) of ceftazidime-treated patients responded to treatment. The small number of study patients precluded statistical analysis of results. In a modified intent-to-treat analysis, 59% of the patients treated with cefepime and 47% of ceftazidime-treated patients responded to therapy. Cefepime patients developed fewer new infections than ceftazidime patients (9% vs. 21%, respectively) and early discontinuation of study drug therapy occurred slightly more often in the ceftazidime group. Further, the use of concomitant systemic antimicrobial therapy (mostly vancomycin) occurred less often in the cefepime-treated patients, as compared with the ceftazidime group [35% [17 of 49] vs. 44% (24 of 55), respectively]. No deaths or serious adverse events were considered to be related to study therapy. The most frequent adverse event was rash that was moderate in severity, and it occurred equally in both groups.. Cefepime appears to be safe and effective compared with ceftazidime for initial empiric therapy of febrile episodes in neutropenic pediatric cancer patients.

Topics: Adolescent; Adult; Bacterial Infections; Cefepime; Ceftazidime; Cephalosporins; Child; Child, Preschool; Fever; Humans; Infant; Neoplasms; Neutropenia; Safety; Treatment Outcome

Infection remains the major cause of morbidity and mortality in immunocompromised children with malignancy. In addition, the economic impact of antibiotic treatment should always be evaluated, especially in developing countries. In our center between January 1998 and January 1999, 73 children with hematological malignancies [acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML)]; 9 children with solid tumors (rhabdomyosarcoma, neuroblastoma) had 87 febrile neutropenic episodes (related to chemotherapy). These children were randomized prospectively into three treatment groups. The first group (n: 28) received cefepime plus netilmicin, while the second group (n: 29) was treated with ceftazidime plus amikacin and the third (n: 30) with meropenem as monotherapy. The aim of the study was to compare the success rates and cost of fourth generation cephalosporin plus aminoglycoside and monotherapy of meropenem with ceftazidime plus amikacin, which is the standard therapy for febrile neutropenia. Microbiologically documented infections were 29.9%, clinically documented infections were 9.2% and 60.9% of the febrile neutropenic episodes were considered to be FUO. Gram-positive microorganisms were the most commonly isolated agents from blood cultures [MRSA (Methicillin Resistant Staphylococcus aureus) in 6 patients and MSSA (Methicillin Sensitive Staphylococcus aureus) in 4 patients]. The success rates were 78.5%, 79.3% and 73.3 % for the 1st, 2nd and 3rd groups respectively. In 4 patients (4.5%) fever responded only to amphotericin-B therapy. There was no statistically significant difference between the three treatment regimens with respect to efficacy, safety and tolerance (chi2 test, p>0.05), but while the third and fourth generation cephalosporins + aminoglycosides were comparable for cost, the monotherapy regimen was the most expensive. The main determining factors for the choice of treatment of febrile neutropenic children, especially in a developing country, are cost, presence of indwelling catheter and the bacterial flora of the unit, as well as efficacy.

Topics: Adolescent; Adult; Amikacin; Cefepime; Cephalosporins; Child; Child, Preschool; Cost-Benefit Analysis; Drug Therapy, Combination; Female; Fever; Humans; Infant; Male; Meropenem; Neoplasms; Netilmicin; Neutropenia; Prospective Studies; Thienamycins; Turkey

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

To compare the efficacies of cefepime and ceftazidime as empiric therapy during the management of fever in cancer patients with chemotherapy-induced neutropenia.. A prospective, double-blind, randomized study of cefepime 2 g every eight hours and ceftazidime 2 g every eight hours was performed in 276 adult neutropenic (absolute neutrophil count < 500/mm3) cancer patients with fever.. Median duration of neutropenia was five days. Sixty-one percent (n = 188) of the patients were evaluable. Treatment was successful in 57% (58/101) of cefepime-treated patients and 60% (52/87) of ceftazidime-treated patients (95% CI -18 to 12; p = 0.77). Bacteremic clearance occurred in 71% (12/17) of cefepime-treated patients and 40% (6/15) of ceftazidime-treated patients (p = 0.3). Both drugs were well tolerated.. Cefepime appears to be as effective as ceftazidime in the initial treatment of febrile episodes in adult cancer patients with chemotherapy-associated neutropenia of modest duration.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacterial Infections; Cefepime; Ceftazidime; Cephalosporins; Double-Blind Method; Female; Fever; Humans; Male; Middle Aged; Mycoses; Neoplasms; Neutropenia; Prospective Studies; Treatment Failure; Treatment Outcome

The purpose of this phase II trial was to evaluate the efficacy and safety of cefepime monotherapy in patients with neutropenia expected to last more than 7 days. Sixty-nine patients with neutropenia (<0.5 x 10(9)/1) were randomized during 94 episodes of fever to receive either cefepime monotherapy (n=76) or combination therapy with trimethoprim/sulfamethoxazole plus amikacin (TMP/SMZ plus AMI, n=18). A successful response to cefepime was seen in 31/76 (41%) episodes, with 10/36 (28%) in microbiologically documented infections, 3/4 (75%) in clinically documented infections and 18/36 (50%) in fever of unknown origin. No patient in either treatment group died due to the presenting infection. One patient in the cefepime group discontinued treatment due to a rash. Susceptibility testing of blood isolates by E-test strip showed low MIC values to cefepime for most isolates. It is concluded that cefepime monotherapy appeared both safe and effective as empirical therapy in patients with febrile neutropenia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cefepime; Cephalosporins; Female; Fever; Gram-Positive Bacterial Infections; Hematologic Neoplasms; Humans; Male; Middle Aged; Neutropenia

Cefepime, a fourth-generation cephalosporin, was used in the treatment of 11 febrile episodes in 8 patients with profound neutropenia. The patients were neutropenic because of high-dose chemotherapy with stem-cell rescue or second-line salvage chemotherapy for malignant lymphomas (5 patients) or solid tumors (3 patients). The median duration of grade-IV neutropenia (according to the WHO classification) was 11 days (7 to 14). Cefepime was used as the monotherapy in a dose of 2 g thrice daily. Disappearance of the infection signs was recorded in 8 episodes (73 per cent). In 3 episodes (23 per cent) cefepime was replaced by another drug. The tolerability of cefepime was good and no adverse events were observed with the exception of 1 event of an allergic reaction.

Topics: Adolescent; Adult; Bacterial Infections; Cefepime; Cephalosporins; Female; Fever; Humans; Male; Middle Aged; Neutropenia; Time Factors; Treatment Outcome

The objective of the presented prospective, randomized study was to compare the efficacy of empirical antimicrobial monotherapy with piperacillin/tazobactam (PIP/TAZ) to cefepime (CEFP) for treatment of infections in neutropenic patients. From a total of 102 febrile episodes 100 were evaluable. The most frequent microorganisms were gram-negative, documented in 22% vs. 24% of the febrile episodes (gram-positives 18% vs. 16%, fungi 2% vs. 4%). The response rate was similar with 22/51 (43%) of episodes treated with PIP/TAZ vs. 19/49 (39%) with CEFP. Of the different infection types classified at the end of the febrile episodes, patients with fever of unknown origin (FUO) and primary bacteremias showed the best initial responses with 25/44 (57%) and 11/22 (50%). Lower initial response rates were found in pneumonias with totally 3/13 (23%) and other clinically documented infections with 2/21 (10%), without any difference between both groups. Gram positive infections showed a higher response with PIP/TAZ than with CEFP (4/9 vs. 0/8), gram negative responded less frequently (3/11 vs. 7/13). The median time until persistent defervescence was equal in both groups (2.5 vs. 2 days), likewise the response rates after the different steps of therapy modifications (change to imipenem or ceftazidim, or addition of gentamycin, vancomycin or amphotericin B). Totally, 96% of febrile episodes responded in both therapy arms. Overall, we found no significant differences in efficacy between the two therapeutic regimens. In conclusion, PIP/TAZ as well as CEFP might be a sufficient initial therapy for febrile neutropenia, but further randomized trials with larger patient numbers are necessary.

Topics: Anti-Infective Agents; Cefepime; Cephalosporins; Drug Therapy, Combination; Fever; Humans; Neutropenia; Penicillanic Acid; Pilot Projects; Piperacillin; Prognosis; Prospective Studies; Tazobactam

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

This open, comparative, randomized, multicentre equivalence study compared cefepime 2 g bd and imipenem-cilastatin 1 g tds (50 mg/kg/day) as empirical monotherapy for febrile episodes in a homogeneous cohort of cancer patients with short duration neutropenia following chemotherapy for solid tumour, lymphoma or myeloma. The study was conducted in 17 French anti-cancer centres in 1995 and 1996. Response to monotherapy was assessed 7 days after treatment and was based on resolution of fever and signs and symptoms, eradication of pathogens, absence of new infection, relapse, and death of infectious origin, without addition of other antibiotics. Patients were treated for a minimum of 4 days. Of the 400 episodes randomized, 344 (86%) were evaluable for efficacy. Patient characteristics were comparable between treatment groups. Success of monotherapy was observed in 79% of episodes with cefepime and 72% with imipenem-cilastatin (equivalence, P <0.0001). The response rate for microbiologically documented infections was 66% with cefepime and 61% with imipenem-cilastatin (bacteraemic episodes: 63% for cefepime; 44% for imipenem-cilastatin). A second antibiotic (usually a glycopeptide) was added in 20% and 21% of the cases, respectively. Overall, the response to therapy, with or without an additional antibiotic, was 95% (cefepime) and 90% (imipenem-cilastatin). Survival was similar in both groups (95% and 98%, respectively). Cefepime treatment was better tolerated, with 9% of the patients experiencing related intercurrent events compared with 19% in the imipenem-cilastatin group (P = 0.003). Nausea/vomiting was significantly more frequent in the imipenem-cilastatin group (15%) than in the cefepime group (5%; P = 0.001). Cefepime monotherapy was as effective as, and better tolerated than, imipenem-cilastatin in the empirical treatment of fever during short duration neutropenia.

Topics: Antineoplastic Agents; Cefepime; Cephalosporins; Cilastatin; Drug Therapy, Combination; Fever; Humans; Imipenem; Neoplasms; Neutropenia; Risk Factors; Survival Analysis

We conducted a randomized multicenter study to compare the efficacy and safety of two antibiotic regimens (cefepime [2 g b.i.d.] plus amikacin or ceftazidime [2 g t.i.d.] plus amikacin) as first-line therapy for fever in patients with hematologic malignancies and neutropenia. A total of 353 patients were randomized according to a 2:1 (cefepime:ceftazidime) ratio. Two hundred-twelve patients in the cefepime group and 107 in the ceftazidime group (90% of all patients) were evaluable for efficacy. The polymorphonuclear neutrophil count was < 100/mm3 on enrollment for 70% of the patients. The mean duration of neutropenia was 26 days. The efficacy in both study arms was comparable, although a trend in favor of cefepime was seen in terms of therapeutic success (response rate, 27% vs. 21% for the ceftazidime group). The overall response rate after glycopeptides were added to the regimens was 60% for the cefepime group and 51% for the ceftazidime group; the bacterial eradication rates were 81% vs. 76%, respectively, and the rates of new bacterial infections were 14% vs. 18%, respectively. We conclude that the combination cefepime/amikacin is at least as effective as the reference regimen of ceftazidime/amikacin in this setting.

Topics: Amikacin; Anti-Bacterial Agents; Bacteremia; Bacterial Infections; Cefepime; Ceftazidime; Cephalosporins; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Fever; Gastrointestinal Diseases; Gram-Negative Bacteria; Gram-Positive Bacteria; Hematologic Neoplasms; Humans; Male; Neutropenia; Skin Diseases, Bacterial; Soft Tissue Infections; Urinary Tract Infections

An open-label randomized trial comparing the efficacy and safety of cefepime versus piperacillin plus gentamicin (P+G) given intravenously for the treatment of febrile episodes in neutropenic patients with underlying malignancy was conducted at two oncology centers. Over a 30-month period 111 patients were enrolled and 99 patients were found to be suitable for evaluation. At the 72-h time of evaluation, cefepime monotherapy and P+G combination therapy produced comparable clinical response rates (78% for both). P+G and cefepime produced comparable response rates in microbiologically documented (78 versus 71%), clinically documented (100 versus 100%), and possible (75 versus 79%) infections. The P+G and cefepime treatments achieved comparable microbiological eradication of gram-negative (100 versus 71%) (P = 0.09) and gram-positive (44 versus 70%) (P = 0.37) organisms. There were no statistically significant differences in the rates of superinfection between the groups; however, more superinfections of fungal origin were noted in the P+G group. Cefepime was demonstrated to be an effective and safe treatment for febrile episodes in neutropenic patients with malignancies, and its lack of nephrotoxicity compared to P+G was noteworthy. Cefepime appears to be a candidate for monotherapy in febrile neutropenic cancer patients.

Topics: Adult; Bacterial Infections; Cefepime; Cephalosporins; Drug Therapy, Combination; Female; Fever; Gentamicins; Humans; Male; Middle Aged; Neoplasms; Neutropenia; Piperacillin

Choice of antibiotic therapy for the management of infection in the neutropenic patient continues to challenge the clinician. The shift toward gram-positive organisms and the continuing need to provide gram-negative coverage demands the use of an agent or agents that provide coverage for the spectrum of potential infecting organisms. Cefepime is an extended-spectrum fourth-generation cephalosporin that has good activity against gram-positive and gram-negative organisms; in addition, it resists degradation by Bush group 1 beta-lactamases. These properties make this agent a promising candidate for empiric therapy with febrile neutropenic patients. Data presented in this article are from febrile neutropenic cancer patients enrolled into two randomized, prospective, nonblinded comparative U.S. clinical trials. Patients were randomized to receive cefepime (2 g thrice daily) or a comparator regimen of either ceftazidime (2 g thrice daily) or piperacillin + gentamicin (3 g every 4 hours + 1.5 mg/kg every 8 hours). When indicated, vancomycin was added to the regimen. A total of 109 febrile episodes were treated with cefepime and 107 episodes were treated with the comparator regimens. Neutropenia (< or = 500 PMNs/mm3) persisted for > or = 10 days in >40% of episodes and severe neutropenia (< or = 100 PMNs/mm3) in >25%. More than 40% of the total number of episodes were documented bacterial infections. These characteristics did not differ among treatment groups. Duration of therapy was similar in both groups (median: cefepime, 9 days; comparators, 11 days). In >40% of episodes, patients received study therapy without addition of other antibacterials (cefepime, 46%; comparators, 41%). Vancomycin was added in almost half of all the episodes (cefepime, 45%; comparators, 53%). Patients became afebrile by the fourth day of study therapy in approximately 60% of episodes (cefepime, 58%; comparators, 60%). In approximately 75% of the episodes, patients had a satisfactory response at the end of therapy (cefepime, 74%; comparators, 76%); and following approximately 90% of episodes, patients survived for >30 days (cefepime, 90%; comparators, 92%). Eradication rates were similar for all pathogens for cefepime and comparator agents. There were similar numbers of superinfecting organisms in each treatment arm; most involved gram-positive organisms. These multiple measures of efficacy suggest that initial empiric cefepime monotherapy is comparable to the pooled experience with st

Topics: Anti-Bacterial Agents; Cefepime; Ceftazidime; Cephalosporins; Drug Therapy, Combination; Female; Fever; Gentamicins; Humans; Male; Middle Aged; Neoplasms; Neutropenia; Penicillins; Piperacillin; Prospective Studies; Superinfection; Vancomycin

In a pilot study, we evaluated the efficacy and the safety of cefepime, a new cephalosporin with extended-spectrum activity against both Gram-positive and Gram-negative bacteria, as empirical monotherapy for 108 febrile episodes in 84 granulocytopenic cancer patients. Cefepime (2 g tds) was given for a minimum of 7 days or until resolution of infection. Of the 108 episodes, 91 were evaluable. Microbiologically documented infections occurred in 25 patients (27%) (18 Gram-positive, 7 Gram-negative), of whom 18 had bacteraemia. Infection was clinically documented in 47 patients (52%) and fever was unexplained in 19 (21%). Overall, 71% (65/91) of the infections resolved. Response rates were 86% (6/7) for Gram-negative infections, 44% (8/18) for Gram-positive infections (57% for cefepime-susceptible Gram-positive bacteria), 77% (36/47) for clinically documented infections and 79% (15/19) for unexplained fevers. Of the 26 patients (29%) whose primary infections did not improve with cefepime monotherapy, 23 responded after the addition of other antibiotics. Sixteen patients (18%) developed secondary infections of which 13 were microbiologically documented; Gram-positive bacteria were isolated from seven patients, Gram-negative bacteria from two, fungi from three and a virus from one. Adverse effects were mild and did not require premature discontinuation of therapy except for one patient who developed an immediate allergic reaction after the first dose of cefepime from which he recovered fully. The survival rate after resolution of granulocytopenia was 96%; three patients died of primary bacterial infection and one from secondary disseminated candidiasis. In this pilot study, cefepime monotherapy appeared safe and effective as empirical therapy for fever in cancer patients with granulocytopenia. Whether cefepime is superior to other advanced-generation cephalosporins for the treatment of Gram-positive infections will require evaluation in a larger comparative study.

Topics: Adolescent; Adult; Aged; Agranulocytosis; Bacterial Infections; Cefepime; Cephalosporins; Female; Fever; Humans; Leukocyte Count; Male; Middle Aged; Neoplasms; Pilot Projects; Prospective Studies

Generally national guidelines for febrile neutropenia recommend treatment with cefepime 2 g every 8 h. Due to beta-lactam's time dependent killing effects, it is hypothesized smaller doses given more frequently might be non-inferior. The objective of this study is to retrospectively evaluate the efficacy of cefepime 1 g every 6 h versus 2 g every 8 h in cancer patients with febrile neutropenia.. This retrospective, single-center, cohort study included patients with a diagnosis of febrile neutropenia treated with cefepime during an inpatient encounter. Patients were grouped based on receipt of cefepime 2 g every 8 h (high dose cohort) versus cefepime 1 g every 6 h (low dose cohort). The primary outcome compared the time to defervescence after cefepime initiation between the two dosing strategies. A subgroup analysis of the primary endpoint was conducted in patients who received both cefepime and vancomycin.. Ninety-seven patients were included in the high dose cohort, and seventy-six patients were included in the low dose cohort. Baseline characteristics were similar between cohorts with the exception of race. The time to defervescence between the high dose cohort and low dose cohort were comparable between groups (49.2 vs. 46.7 h). The time to defervescence in subgroup analysis of patients who received empiric vancomycin and cefepime was 65.7 versus 59.7.. Patients who received cefepime 1 g every 6 h were found to have similar trends in achieving time to defervescence compared to 2 g every 8 h.

Topics: Anti-Bacterial Agents; Cefepime; Cephalosporins; Cohort Studies; Febrile Neutropenia; Fever; Humans; Retrospective Studies; Vancomycin

Febrile neutropenia has a significant clinical and economic impact on cancer patients. This study evaluates the cost-effectiveness of different current empiric antibiotic treatments.. A decision analytic model was constructed to compare the use of cefepime, meropenem, imipenem/cilastatin, and piperacillin/tazobactam for treatment of high-risk patients. The analysis was performed from the perspective of U.S.-based hospitals. The time horizon was defined to be a single febrile neutropenia episode. Cost-effectiveness was determined by calculating costs and deaths averted. Cost-effectiveness acceptability curves for various willingness-to-pay thresholds (WTP), were used to address the uncertainty in cost-effectiveness.. The base-case analysis results showed that treatments were equally effective but differed mainly in their cost. In increasing order: treatment with imipenem/cilastatin cost $52,647, cefepime $57,270, piperacillin/tazobactam $57,277, and meropenem $63,778. In the probabilistic analysis, mean costs were $52,554 (CI: $52,242-$52,866) for imipenem/cilastatin, $57,272 (CI: $56,951-$57,593) for cefepime, $57,294 (CI: $56,978-$57,611) for piperacillin/tazobactam, and $63,690 (CI: $63,370-$64,009) for meropenem. Furthermore, with a WTP set at $0 to $50,000, imipenem/cilastatin was cost-effective in 66.2% to 66.3% of simulations compared to all other high-risk options.. Imipenem/cilastatin is a cost-effective strategy and results in considerable health care cost-savings at various WTP thresholds. Cost-effectiveness analyses can be used to differentiate the treatments of febrile neutropenia in high-risk patients.

Topics: Anti-Bacterial Agents; Cefepime; Cilastatin, Imipenem Drug Combination; Computer Simulation; Cost-Benefit Analysis; Decision Support Techniques; Fever; Health Care Costs; Humans; Meropenem; Neutropenia; Piperacillin, Tazobactam Drug Combination; Treatment Outcome

► Fever ► Generalized rash ► Recent history of calcaneal osteomyelitis.

Topics: beta-Lactams; Cefepime; Drug Hypersensitivity Syndrome; Exanthema; Fever; Humans; Male; Middle Aged; Osteomyelitis; Treatment Outcome

With the emergence of new oral therapies for metastatic melanoma to the market, as well as ongoing pre-marketing trials and special access schemes, it is important to keep up to date with the side effect profiles of these medications. A common side effect associated with the BRAF inhibitor dabrafenib is severe fever symptoms such as pyrexia and rigors/chills; however, treatment options are limited. We report a patient who was debilitated by severe pyrexia and rigors caused by dabrafenib used in combination with trametinib to treat metastatic melanoma, who was treated with low-dose steroids. To our knowledge, the use of prednisolone for the treatment and prevention of further dabrafenib-associated pyrexia is not published; however, it is a low risk and low cost option that was very effective in this case.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cefepime; Cephalosporins; Drug Delivery Systems; Female; Fever; Humans; Imidazoles; Melanoma; Oximes; Pyridones; Pyrimidinones; Severity of Illness Index

Topics: Abscess; Aeromonas hydrophila; Cefepime; Cephalosporins; Ciprofloxacin; Fever; Gram-Negative Bacterial Infections; Humans; Male; Microbial Sensitivity Tests; Sepsis; Skin Diseases, Bacterial; Young Adult

The purpose of this study was to evaluate outcomes such as success of the initial therapy, failure of outpatient treatment, and death in outpatient treatment during intravenous antimicrobial therapy in patients with febrile neutropenia (FN) and hematological malignancies. In addition, clinical and laboratory data and the Multinational Association for Supportive Care of Cancer index (MASCC) were compared with failure of outpatient treatment and death. In a retrospective study, we evaluated FN following chemotherapy events that were treated initially with cefepime, with or without teicoplanin and replaced by levofloxacin after 48 h of defervescence in patients with good general conditions and ANC>500/mm3. Of the 178 FN episodes occurred in 126 patients, we observed success of the initial therapy in 63.5% of the events, failure of outpatient treatment in 20.8%, and death in 6.2%. The success rate of oral levofloxacin after defervescence was 99% (95 out of 96). Using multivariate analysis, significant risks of failure of outpatient treatment were found to be smoking (odds ratio (OR) 3.14, confidence interval (CI) 1.14-8.66; p=0.027) and serum creatinine levels>1.2 mg/dL (OR 7.97, CI 2.19-28.95; p=0.002). With regard to death, the risk found was oxygen saturation by pulse oximetry<95% (OR 5.8, IC 1.50-22.56; p=0.011). Using the MASCC index, 165 events were classified as low risk and 13 as high risk. Failure of outpatient treatment was reported in seven (53.8%) high-risk and 30 (18.2%) low-risk episodes (p=0.006). In addition, death occurred in seven (4.2%) low-risk and four (30.8%) high-risk events (p=0.004). Ours results show that MASCC index was able to identify patients with high risk. In addition, non-smoking, serum creatinine levels≤1.2 mg/dL, and oxygen saturation by pulse oximetry≥95% were protection factors.

Topics: Adult; Anti-Bacterial Agents; Cefepime; Cephalosporins; Fever; Hematologic Neoplasms; Home Infusion Therapy; Humans; Injections, Intravenous; Levofloxacin; Male; Middle Aged; Neutropenia; Ofloxacin; Retrospective Studies; Teicoplanin; Treatment Outcome

Because of the refractory and recurrent nature of febrile neutropenia (FN), definite diagnosis and early empiric treatment with antibiotics are important for FN patients. With this background, guidelines for FN treatment have been published in Japan and overseas, although a treatment method appropriate for clinical practice in Japan has not yet been established. Therefore, we conducted a survey of actual practice, including trends in prescription of antibiotics for FN, in the hope that it would help establish a definitive treatment for FN in Japan. The survey results confirmed that FN patients under care of hematology departments accounted for the largest proportion, followed by pediatrics (hematology), pulmonary medicine, medical oncology, and respiratory surgery, and the proportions of patients diagnosed with FN and those receiving antibiotics in hematology departments are larger than in other departments. Across all departments, cefepime (CFPM) is most frequently used as the initial treatment of choice, accounting for 35.9% of prescriptions, followed by meropenem (MEPM) (24.3%). These drugs are selected because they exhibit high potency and wide coverage against organisms that are presumed to cause FN, and their costs are covered by insurance, while the existence of insurance coverage is the major determining factor for treatment in Japan. Among second-line drugs, MEPM is most frequently used, accounting for 46.3% of prescriptions. The guidelines are commonly used as the basis for treatment, accounting for 52.0% of all departments, especially the guidelines established by the Japan Febrile Neutropenia Study Group. On the other hand, the percentage of departments that have introduced a hospital protocol and clinical path is only 13.0% in total. To provide appropriate treatment for FN patients, insurance coverage and introduction of a hospital protocol and clinical path based on guidelines and evidence are essential. The current situation, in which these are not implemented, is not desirable. The survey results show that the guidelines need to be revised to more closely reflect the actual situation in Japan and hospital protocols and clinical paths need to be introduced.

Topics: Anti-Bacterial Agents; Cefepime; Cephalosporins; Critical Pathways; Evidence-Based Medicine; Fever; Humans; Japan; Meropenem; Neutropenia; Physicians; Practice Guidelines as Topic; Practice Patterns, Physicians'; Surveys and Questionnaires; Thienamycins

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacteremia; Cefepime; Cephalosporins; Enterobacter; Enterobacteriaceae Infections; Female; Fever; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Neutropenia; Treatment Outcome

This study was performed to determine the local etiologic pattern of blood culture isolates and antibiotic resistance in febrile neutropenic patients with hematological malignancies.. A total of 142 blood culture isolates from febrile neutropenic patients admitted to our hematology unit were examined, particularly for the detection of cefepime resistance, because cefepime, a fourth-generation cephalosporin, has been used in our unit as initial therapy for febrile neutropenia.. Among all isolates, 67 (47.2%) were Gram-positive bacteria, the majority of which were fully sensitive to vancomycin. Gram-negative bacteria accounted for 68 (47.9%) of the isolates. Cefepime resistance was seen in 24 (35.3%) of the Gram-negative isolates, and had significantly increased in 2007. The cefepime-resistant isolates primarily consisted of Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Approximately 60% of the cefepime-resistant isolates were extended-spectrum β-lactamase (ESBL)-producing organisms. Molecular analysis showed the predominant emergence of CTX-M types. Most of the cefepime-resistant isolates were resistant to third- and various fourth-generation cephalosporins, while having a high susceptibility to carbapenems, particularly meropenem.. Cefepime resistance was often detected in the blood culture isolates from febrile neutropenic patients. This result suggests that therapeutic strategies for febrile neutropenia should be modified based on the local antibiotic resistance patterns.

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Cefepime; Cephalosporin Resistance; Cephalosporins; Escherichia coli; Escherichia coli Infections; Fever; Genes, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Hematologic Neoplasms; Humans; Klebsiella Infections; Klebsiella pneumoniae; Neutropenia; Pseudomonas aeruginosa; Pseudomonas Infections

The efficacy of conventional doses of piperacillin/ tazobactam (PTZ) plus amikacin (AMK) were compared retrospectively to low doses of cefepime (CEF) plus amikacin in high risk febrile neutropenic patients with an underlying hematologic malignancy, and CEF versus PTZ (without AMK) in low risk individuals with febrile neutropenia and underlying solid tumor malignancies.. Fifty-six high risk hematologic malignancy patients received a combination of PTZ 4.5 grams administered every 8 hours plus AMK 15 mg/kg/day, while 46 received CEF 1 gram administered every 12 hours plus AMK 15 mg/kg/day. In addition, 19 febrile neutropenic individuals with underlying solid malignancies received PTZ 4.5 grams every 8 hours and 25 received CEF 1 gram every 12 hours. All patients were treated in an isolation unit section of a general internal medicine ward.. There was no significant difference between the groups in terms of age, depth of neutropenia, microbiologic result, morbidity, length of hospital stay or mortality.. PTZ and CEF in combination with AMK were equally efficacious in neutropenic patients with hematologic malignancies. In addition, monotherapy with CEF or PTZ proved to be equally efficacious in neutropenic patients with solid tumors. Low dose CEF is safe and allows a reduction of cost and less antibiotic exposure.

Topics: Adult; Aged; Amikacin; Anti-Bacterial Agents; Cefepime; Cephalosporins; Drug Therapy, Combination; Female; Fever; Hematologic Neoplasms; Humans; Male; Middle Aged; Neoplasms; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Risk Factors; Treatment Outcome

Topics: Anti-Bacterial Agents; Back Pain; Cefepime; Cephalosporins; Diagnosis, Differential; Drainage; Epidural Abscess; Fever; Humans; Male; Meropenem; Middle Aged; Myelography; Paresis; Prognosis; Radiography, Abdominal; Shivering; Staphylococcal Infections; Staphylococcus aureus; Thienamycins; Time Factors; Tomography, X-Ray Computed

To compare clinical outcomes of patients receiving an alternative dosage of meropenem with those of patients receiving imipenem-cilastatin or the traditional dosage of meropenem after failure of or intolerance to cefepime for treatment of febrile neutropenia.. Retrospective, single-center cohort study.. 1250-bed urban academic medical center.. One hundred twenty-seven adults with neutropenic fever who received either imipenem-cilastatin or meropenem; imipenem-cilastatin was the preferred carbapenem until September 1, 2006, after which meropenem became the formulary carbapenem.. Of the 127 patients, 40 received imipenem-cilastatin 500 mg every 6 hours between September 1, 2005, and August 31, 2006; 87 patients received meropenem between September 1, 2006, and August 31, 2007: 29 received a traditional dosage of meropenem 1 g every 8 hours, and 58 received an alternative dosage of meropenem 500 mg every 6 hours. Primary outcomes of time to defervescence (median 3 vs 2 vs 3 days), need for additional antibiotics (20% vs 17% vs 14%), and time to receipt of additional antibiotics (median 5 vs 2 vs 1 days) were not significantly different among the imipenem-cilastatin, traditionally dosed meropenem, and alternatively dosed meropenem groups, respectively. In addition, significant differences in secondary outcomes, which were treatment duration (median 10 vs 8 vs 8 days), seizure rate (0% vs 0% vs 0%), in-hospital mortality (5% vs 7% vs 7%), and 30-day mortality (13% vs 7% vs 14%), were not identified among the three groups, respectively.. The alternative meropenem dosage of 500 mg every 6 hours yielded similar patient outcomes, including time to defervescence, need for additional antibiotics, duration of therapy, and mortality, when compared with the traditional meropenem dosage and imipenem-cilastatin in adults with febrile neutropenia. In addition, no adverse effects on clinical outcomes were observed with the alternative dosage of meropenem.

Topics: Adult; Anti-Bacterial Agents; Cefepime; Cephalosporins; Cilastatin; Cilastatin, Imipenem Drug Combination; Cohort Studies; Dose-Response Relationship, Drug; Drug Combinations; Female; Fever; Hospital Mortality; Humans; Imipenem; Male; Meropenem; Middle Aged; Neutropenia; Retreatment; Seizures; Thienamycins; Time Factors

Topics: Anti-Bacterial Agents; Cefepime; Cephalosporins; Child; Diagnosis, Differential; Drug Therapy, Combination; Female; Fever; Fusobacterium Infections; Fusobacterium necrophorum; Headache; Hip; Humans; Magnetic Resonance Imaging; Meropenem; Thienamycins; Tomography, X-Ray Computed; Vancomycin

The effect of experimentally induced fever on the pharmacokinetics of cefepime administered intravenously at a dose of 75 mg/kg bw was studied in six healthy rabbits. The study was conducted in two consecutive phases, separated by a washout period of 2 weeks. Infection was induced by the intravenous inoculation of 5 x 10(8) cfu of Escherichia coli 24 h before the pharmacokinetic investigation was carried out. Serial blood samples for cefepime concentration determination were obtained for 48 h following drug administration. The concentrations of cefepime in the plasma were determined by a quantitative microbiological assay using an agar-gel diffusion method employing Bacillus subtilis ATCC 6633 as the test organism, with a level of detectability of approximately 0.10 microg/ml. Cefepime plasma concentrations versus time were evaluated by non-compartmental methods using WinNonLin. Cefepime was well tolerated and no serious adverse events were observed. Rectal temperature increased 1 degree C 24 h post injection in infected animals. Highly significant differences in the blood plasma concentrations of cefepime were observed between febrile and healthy animals at all the sampling times. This could explain the greater area under the plasma level-time curve of the drug in febrile compared with healthy animals. The results from pharmacokinetic calculations showed that both the distribution volume at steady state (V (dss)) and body clearance (CL(tot)) were affected in febrile as compared to healthy animals. The mean values of V (dss) and CL(tot) of cefepime in healthy rabbits were 1.168 L/kg and 0.303 L/kg/h, respectively. As compared with healthy animals, the mean estimates of V (dss) (0.917 L/kg) and CL(tot) (0.205 L/kg per h) of cefepime were significantly lower, whereas t (1/2lambda), MRT and AUMC were significantly higher in febrile rabbits. It is concluded that, although experimental infection had an effect on the disposition kinetics of cefepime in healthy and febrile rabbits, this was not sufficiently pronounced to require alteration of the dosage during disease.

Topics: Acute-Phase Reaction; Animals; Anti-Bacterial Agents; Area Under Curve; Cefepime; Cephalosporins; Escherichia coli; Escherichia coli Infections; Fever; Half-Life; Injections, Intravenous; Male; Rabbits

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

This study examined the effect of experimentally induced fever on the pharmacokinetics of cefepime (75 mg/kg BW) administered intramuscularly to six rabbits. The study was carried out in two consecutive phases separated by a two-week washout period. An infection was induced by an intravenous inoculation of 5 x 10(8) colony-forming units of Escherichia coli 24 h before the pharmacokinetic investigation. A quantitative microbiological assay was employed to measure the plasma cefepime concentrations using an agar-gel diffusion method with Bacillus subtilis ATCC 6633 as the test organism. Twenty-four hour after the injection, the rectal temperature in the infected animals increased by 1 degrees C. There was a significant reduction in the elimination halflife by 21.8 % in the febrile rabbits compared to healthy animals. In addition, the infection significantly increased the peak plasma concentrations by 11.9 %, the mean residence time by 19.9 %, the area under the plasmaconcentration-time curve by 53.6 % and the area under the moment curve by 62.3 %. In conclusion, the endotoxin-induced febrile state produced significant changes in the plasma levels as well as some of the pharmacokinetic variables of cefepime in rabbits.

Topics: Animals; Anti-Bacterial Agents; Area Under Curve; Cefepime; Cephalosporins; Endotoxins; Escherichia coli Infections; Fever; Half-Life; Injections, Intramuscular; Male; Rabbits

Febrile neutropenia is one of the most frequent complications in intensively treated hematooncological patients and almost inevitably occurs after high dose therapy and autologous stem cell transplantation. Empiric broad-spectrum antibiotic treatment is indicated in the initial management. Fourth-generation cephalosporins are the option. This retrospective study was initiated to assess efficacy and safety of cefepime as an empiric therapy of febrile neutropenia following high dose therapy and autologous stem cell transplantation.. 319 high dose therapy procedures with autologous stem cell transplantation in 287 patients mostly with hematological malignancies were performed at our department between January 2002 and December 2005. We present analysis of 169 out of 229 febrile episodes in 163 patients (median age 53) being treated with cefepime in the initial empiric treatment of febrile neutropenia. 12 episodes (7.1 %) were clinically documented (pneumonia 9, sinusitis 2, acute cholecystitis 1), 60 (35.5 %) were confirmed microbiologically (presented as bacteremia) and 97 (57.4 %) were fever of unknown origin. 50 isolates (83.4 %) out of 60 microbiologically documented infections were G-positive bacteria, 8 isolates (13.3 %) were G-negative bacteria and 2 (3.3 %) were mixed G-positive and G-negative cultures. According to the MASCC score 14 episodes were assessed as high risk. Effect of cefepime as a single agent was observed in 85 episodes (50.3 %) and in 22 (13.0 %) episodes treated with combination therapy due to susceptibility of isolated pathogen in blood culture. Combination therapy of two antibiotics (cefepime + aminoglycoside or glycopeptide) given for persistent fever was effective in 13 patients (7.7 %). Treatment failure was observed in 48 (28.4 %) episodes, we registered 10 death.. Therapy with cefepime represents an appropriate choice for empiric antibiotic treatment of febrile neutropenia in hematooncological patients. Cefepime demonstrates clinical safety and efficacy and can be used in monotherapy or in combination with other drugs (overall response 72.2 %, as a single agent 50.3 %).

Topics: Adult; Aged; Anti-Bacterial Agents; Antineoplastic Agents; Bacterial Infections; Cefepime; Cephalosporins; Combined Modality Therapy; Female; Fever; Humans; Lymphoma; Male; Middle Aged; Neutropenia; Stem Cell Transplantation

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

Our aim was to evaluate retrospectively the efficacy of a therapeutic strategy with a first line combination based on cefepime-amikacin in febrile neutropenic children treated with chemotherapy.. Sixty-five neutropenic febrile episodes in 43 children treated by the association cefepime-amikacin, were evaluated according to the clinical status, the depth and duration of neutropenia, the underlying disease and the initial treatment.. Thirty-nine (60%) episodes were successfully treated by the association cefepime-amikacin. Among the 26 persisting febrile episodes, adjunction of vancomycin and amphotericin B was effective in 11 (76% of total rate success) and 5 (84% of total rate success) cases respectively. The efficacy of the first line antibiotherapy was not different as regards to the duration and the depth of neutropenia. Otherwise, febrile episodes after chemotherapy against solid tumours were rapidly controlled by the first and second line of the anti-microbial strategy. Children treated for haematological malignancies presented a lower response rate (P = 0.03).. In febrile and neutropenic children treated with chemotherapy, the association cefepime-amikacin appeared to be a safe empirical treatment. In a neutropenic child, the immunodeficiency and possibly the clinical status should be the major factors of the infectious prognosis more than the duration of aplasia.

Topics: Adolescent; Adult; Amikacin; Anti-Bacterial Agents; Antineoplastic Agents; Bacterial Infections; Cefepime; Cephalosporins; Child; Child, Preschool; Drug Therapy, Combination; Fever; Hematologic Neoplasms; Humans; Infant; Neoplasms; Neutropenia; Patient Selection; Prognosis; Retrospective Studies; Time Factors; Treatment Outcome

High-dose etoposide (2 g/m(2)) plus G-CSF is a very effective regimen for peripheral blood progenitor cell (PBPC) mobilization. Unfortunately, neutropenia is common. The infectious complications associated with high-dose etoposide have not been previously described. After noting a high incidence of hospitalizations for neutropenic fever, we began a vigorous prophylactic antibiotic regimen for patients receiving high-dose etoposide plus G-CSF, attempting to reduce infectious complications. Ninety-eight patients underwent etoposide mobilization between December 1997 and June 2000. Three chronological patient groups received: (1) no specific antibiotic prophylaxis (n = 44); (2) vancomycin i.v., cefepime i.v., clarithromycin p.o., and ciprofloxacin p.o. (n = 27); and (3) vancomycin i.v., clarithromycin p.o., and ciprofloxacin p.o. (n = 27). The patients not receiving antibiotic prophylaxis had a 68% incidence of hospitalization for neutropenic fever. In the patients receiving prophylaxis, the incidence was reduced to 26% and 15% respectively, for an overall incidence of 20% (P < 0.001 for comparison between prophylaxed and unprophylaxed groups). We conclude that etoposide mobilization is associated with a significant incidence of neutropenic fever, which can be substantially reduced by a vigorous antimicrobial prophylactic program.

Topics: Ambulatory Care; Antibiotic Prophylaxis; Cefepime; Cephalosporins; Ciprofloxacin; Clarithromycin; Data Collection; Drug Therapy, Combination; Etoposide; Female; Fever; Hematopoietic Stem Cell Mobilization; Humans; Male; Middle Aged; Neutropenia; Opportunistic Infections; Vancomycin

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

We report a case of bacteremia due to Abiotrophia species in a patient with neutropenic fever and cancer who was receiving levofloxacin prophylaxis, followed by empirical therapy with cefepime; the organism was resistant to both antibiotics. We provide susceptibility data on 20 additional bloodstream isolates of Abiotrophia species.

Topics: Anti-Bacterial Agents; Bacteremia; Cefepime; Cephalosporins; Drug Resistance, Microbial; Fever; Gram-Positive Bacterial Infections; Humans; Levofloxacin; Male; Microbial Sensitivity Tests; Middle Aged; Neutropenia; Ofloxacin; Streptococcaceae

We evaluated the impact of applying the Infectious Diseases Society of America guidelines for febrile neutropenic patients in reducing the use of glycopeptides. Forty-five prior episodes of febrile neutropenia were compared to 97 episodes seen after application of the guidelines. Glycopeptide use was reduced from 73% to 43% of episodes (P=.0008), without changes in outcome.

Topics: Adolescent; Adult; Aged; Amikacin; Anti-Bacterial Agents; Brazil; Cefepime; Ceftazidime; Cephalosporins; Child; Drug Therapy, Combination; Female; Fever; Hospitals, Teaching; Humans; Male; Middle Aged; Neutropenia; Oxacillin; Practice Guidelines as Topic; Teicoplanin; Treatment Outcome; Vancomycin

Topics: Adolescent; Amikacin; Anti-Bacterial Agents; Bacteremia; Cefepime; Cephalosporins; Child; Child, Preschool; Drug Therapy, Combination; Escherichia coli Infections; Female; Fever; Fever of Unknown Origin; Humans; Infant; Male; Neoplasms; Neutropenia; Staphylococcal Infections; Streptococcal Infections; Treatment Outcome