cefepime and Skin-Diseases--Bacterial

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 To further investigate this possible signal, we accessed findings and data from published and unpublished cefepime clinical trials..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

In phase 3 clinical trials for ceftobiprole treatment of complicated skin and skin structure infections, 1,219 gram-positive and 276 gram-negative aerobic baseline pathogens were identified. Ceftobiprole inhibited all staphylococcal isolates, including methicillin-resistant strains, at MICs of

Topics: Anti-Bacterial Agents; Cephalosporins; Enterobacteriaceae; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Skin Diseases, Bacterial; Staphylococcus

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

The purpose of this study was to compare in a randomized, open-label clinical study, the efficacy and safety of cefepime (1 g every 12 hours) with that of ceftazidime (1 g every 8 hours) in patients with serious skin and skin-structure infections. Of 298 patients enrolled in the study, 130 with serious skin and skin-structure infections were evaluable. Demographics and underlying medical conditions were comparable in both groups. The most common infections were cellulitis, abscesses, ulcers, and postoperative wound infections. The most common pathogens isolated were Staphylococcus aureus, group A streptococci, Enterobacteriaceae, and Pseudomonas aeruginosa. Duration of therapy in the 93 patients treated with cefepime was 3-18 days and in the 37 ceftazidime-treated patients was 4-16 days. Pathogen bacteriologic response rates were high: 92% (124 of 135) of pathogens were eradicated by cefepime and 95% (55 of 58) by ceftazidime. Clinical response rates were satisfactory in 88% (82 of 93) of cefepime-treated patients and in 89% (33 of 37) of ceftazidime-treated patients. Adverse events occurred with similar frequency in both groups. Events probably related to study drugs affected 3% (6 of 198) of patients treated with cefepime and 4% (4 of 100) of ceftazidime-treated patients. Cefepime, a new parenteral cephalosporin administered every 12 hours, is an extremely well tolerated and effective alternative to ceftazidime given every 8 hours for the treatment of serious skin and skin-structure infections.

Topics: Bacteria; Cefepime; Ceftazidime; Cephalosporins; Female; Humans; Infusions, Intravenous; Male; Microbial Sensitivity Tests; Middle Aged; Skin Diseases; Skin Diseases, Bacterial

Antibiotics not only support to alleviate the infections but also facilitate to avert the multiplication of microbes. Due to the irrational use of antibiotics, the resistance of antibiotics has been augmented which results may increase in morbidity and mortality with the span of time. World renowned regulatory bodies like Food and Drug Administration (FDA), Center of Disease Control and Prevention (CDC), and World Health Organization (WHO) vigorously advocate the surveillance of the resistance of antibiotics. During the present study by Kirby-Bauer disk diffusion method 141 clinical isolates of Staphylococcus aureus (n=47, 33.34%), Escherichia coli (n=54, 38.3%), Proteus species (n=26, 18.4%), and Klebsiella pneumoniae (n=14, 9.92%) are evaluated against cefepime and cefpirome which comes of fourth generation cephalosporin. It has been found that cefpirome has better bactericidal activity than cefepime against E. coli and K. pneumoniae while cefepime has been possessed better antibacterial activity against S. aureus and Proteus species which were isolated from respiratory tract infections, blood stream infection, intra-abdominal and urinary tract infections, and skin and soft tissue infections. K. pneumoniae, E. coli, Proteus species, and S. aureus were 34.8%, 26.3%, 11.3%, and 37.7% resistance against cefepime respectively. S. aureus, E. coli, K. pneumoniae, Proteus species has shown 41.4%, 21.7%, 17.6%, and 8.9% resistance against cefpirome correspondingly.

Topics: Anti-Bacterial Agents; Bacteremia; Cefepime; Cefpirome; Cephalosporins; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Humans; In Vitro Techniques; Intraabdominal Infections; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Pakistan; Proteus; Proteus Infections; Respiratory Tract Infections; Skin Diseases, Bacterial; Soft Tissue Infections; Staphylococcal Infections; Staphylococcus aureus; Urinary Tract Infections

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

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