cefepime and Fever-of-Unknown-Origin

Cefepime is increasingly used as empiric treatment for fever in the setting of neutropenia. We present a patient with acute-on-chronic renal disease who received cefepime at the appropriate dose for his glomerular filtration rate but developed cefepime-associated encephalopathy. Here, we review neurologic toxicities of cefepime and present suggestions for work-up and management.

Topics: Adolescent; Anti-Bacterial Agents; Cefepime; Cephalosporins; Fever of Unknown Origin; Humans; Male; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Renal Insufficiency

On the basis of meta-analyses, concern has been raised regarding a possible signal of increased mortality associated with the use of cefepime versus other beta-lactam antibiotics. To further investigate this possible signal, we accessed findings and data from published and unpublished cefepime clinical trials.. We performed meta-analyses using trial- and patient-level data from comparative trials. Trial-level analyses were performed using summary data from all patients in the trials, and patient-level analyses were performed on trials for which patient-level data were available. Thirty-day, all-cause mortality was analyzed using the Mantel-Haenszel adjusted risk difference (ARD) method.. The trial-level meta-analysis was based on 88 trials (9467 cefepime patients and 8288 comparator patients). The 30-day, all-cause mortality rates were 6.21% (588/9467) for the cefepime patients and 6.00% (497/8288) for comparator patients (ARD per 1000 population, 5.38; 95% confidence interval [CI], -1.53 to 12.28). In the patient-level analysis (35 trials, 5058 cefepime patients, and 3976 comparator patients), 30-day, all-cause mortality rates were 5.63% (285/5058) for cefepime patients and 5.68% (226/3976) for comparator patients (ARD per 1000 population, 4.83; 95% CI, -4.72 to 14.38). A sensitivity analysis based solely on the 24 febrile neutropenia trials did not show a statistically significant increase in mortality with cefepime use (ARD per 1000 population, 9.67; 95% CI, -2.87 to 22.21).. In both trial-level and patient-level meta-analyses, we did not identify a statistically significant increase in mortality among cefepime-treated patients, compared with those treated with other antibacterials.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Cefepime; Cephalosporins; Child; Child, Preschool; Clinical Trials as Topic; Female; Fever of Unknown Origin; Humans; Infant; Infant, Newborn; Male; Middle Aged; Neutropenia; Pneumonia, Bacterial; Skin Diseases, Bacterial; Survival Analysis; Urinary Tract Infections; Young Adult

Patients with fever and granulocytopenia are at risk of developing severe infection. We performed a prospective, randomized trial to evaluate the efficacy of low-dose cefepime plus amikacin (C-A) compared to low-dose piperacillin/tazobactam plus amikacin (PT-A). Patients received cefepime (2 g/12 h) plus amikacin (15 mg/kg/day) or piperacillin/tazobactam (4 g/500 mg/8 h) plus amikacin. A total of 317 episodes of febrile granulocytopenia in 190 patients were studied (152 in the C-A group, 165 in the PT-A group). A microbiologically documented infection was present in 53 (35%) episodes in the C-A group and 41 (25%) episodes in the PT-A group (p = ns); a clinically documented infection was observed in 39 (26%) and 47 (28%) episodes, respectively. Toxicity was observed in 6 (4%) episodes in the C-A group and in 5 (3%) episodes in the PT-A group. The antibiotic success rate (no change or addition of antibiotics) was recorded in 89 (59%) and 105 (64%) cases, respectively (p = ns). Mortality related to infection was similar in each arm (3.9% vs. 3.6%). Combination therapy of low-dose beta-lactam with an aminoglycoside achieves very good response rates and low rates of toxicity. It might be an attractive option in an environment of increasing resistance among gram-negative bacteria.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amikacin; Anti-Bacterial Agents; Cefepime; Cephalosporins; Female; Fever of Unknown Origin; Humans; Incidence; Male; Middle Aged; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Poisoning; Prospective Studies; Treatment Outcome; Young Adult

After changing empiric treatment of febrile neutropenia from meropenem to cefepime, the effect on Clostridium difficile infection (CDI) was investigated. The change was assessed using an autoregressive model. A significant increase in CDI rates occurred following the introduction of cefepime. There may be an association between increased cefepime usage and CDI.

Topics: Anti-Bacterial Agents; Cefepime; Cephalosporins; Clostridioides difficile; Clostridium Infections; Fever of Unknown Origin; Hematologic Neoplasms; Humans; Neutropenia; Retrospective Studies

Cefepime hydrochloride is approved for pneumonia, empirical therapy for febrile neutropenia, uncomplicated and complicated urinary tract infections, uncomplicated skin and skin structure infections and complicated intra-abdominal infections. A recent meta-analysis by Yahav et al. (Lancet Infect Dis 2007; 7: 338-48) concluded that cefepime was associated with a statistically significant increase in mortality (risk ratio 1.26, 95% confidence interval 1.08-1.49) when compared with other antibiotics. The US FDA decided to re-evaluate the meta-analysis data in collaboration with the drug sponsor. Two years later the FDA Alert summarized that 'data do not indicate a higher rate of death in cefepime-treated patients. Cefepime remains an appropriate therapy for its approved indications.' However, a thorough evaluation of the 52-page FDA report still shows that safety remains an unresolved issue. A Bayesian re-appraisal of the findings by the FDA and by Yahav et al. indicates that there is a 90.9% (by FDA trial-level meta-analysis), 80.8% (by FDA patient-level meta-analysis) and 99.2% (by Yahav et al. meta-analysis) probability that cefepime raises mortality in neutropenic fever patients, which translates into the following numbers needed to harm (NNH), i.e. to cause one extra death with the use of cefepime: FDA trial-level meta-analysis, NNH = 109; FDA patient-level meta-analysis, NNH = 76; Yahav et al. meta-analysis, NNH = 54. A similar harmful probability was observed with skin structure infections but not with pneumonias, intra-abdominal infections and urinary tract infections. In conclusion, cefepime should be avoided in patients with neutropenic fever or with skin structure infections.

Topics: Anti-Bacterial Agents; Bacterial Infections; Cefepime; Cephalosporins; Fever of Unknown Origin; Humans; Incidence; Neutropenia; Skin Diseases, Bacterial; Statistics as Topic; United States

Topics: Amikacin; Anti-Bacterial Agents; Cefepime; Cephalosporins; Drug Resistance, Bacterial; Drug Therapy, Combination; Fever of Unknown Origin; Humans; Neutropenia

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