Background: CEFEPIME was used as empirical treatment in ventilator-associated pneumonia (VAP) induced by gram-negative and gram-positive bacteria. This study aimed to determine the antimicrobial susceptibility pattern of CEFEPIME against microorganism causing VAP in Mazandaran, North of Iran.Methods: This study was performed on VAP patients diagnosed with clinical pulmonary infection score (CPIS) scores in ICU of two hospitals. For each patient suspected of having VAP, quantitative culture of endotracheal aspiration (QEA) was performed and MIC was determined by micro dilution test. Data were collected and analyzed.Results: Thirty- five cases of enterobacteriaceae were isolated orderly including E coli 13, P. aeruginosa 11, Enterobacter 7 and K. pneumonia 4 cases. All the isolated E. coli, Enterobacter and Klebsiella, 54.5% of P. aeruginosa isolated were fully resistant to CEFEPIME.Conclusion: The results of this study show that CEFEPIME is not a reasonable choice for empirical treatment of nosocomial pneumonia and VAP.

CEFEPIME is a fourth-generation cephalosporin which is approved in Europe and in the USA. Food and Drug Administration (FDA) approves CEFEPIME in the treatment of febrile neutropenia. CEFEPIME is active against gram-negative microorganisms such as Escherichia coli, Haemophilus influenzae, Enterobacter, Klebsiella, Morganella, Neisseria, Serratia, and Proteus species. CEFEPIME is also active against gram-positive microorganisms such as Streptococcus pneumoniae, Streptococcus agalactiae, and Staphylococcus aureus. CEFEPIME binds to plasma proteins ≤ 20%, and it is excreted unchanged in the urine. CEFEPIME distributes widely in body tissues and fluids such as cerebrospinal fluid, bile, bronchial secretions, ascites fluid, and middle ear. In neonates, the half-life of CEFEPIME ranges from 3. 59+0. 61 and 5. 09+1. 80 hours, and in adults it is 2. 1 (range, 1. 3 to 2. 4 hours). The rank order of the top 10 pediatric pathogens was analyzed and the comparative antimicrobial potency of broad-spectrum parenteral cephalosporins was exterminated. The rank order of the top 10 pediatric pathogens was Streptococcus pneumoniae (15. 5%) > Haemophilus influenzae (14. 6%) > Staphylococcus aureus (13. 8%) > Moraxella catarrhalis = coagulase-negative staphylococci (8. 0%) > Escherichia coli (7. 8%) > Pseudomonas aeruginosa (5. 2%) > Klebsiella spp. (4. 8%) > Enterococcus spp. (4. 7%) > beta-hemolytic streptococci (4. 4%). CEFEPIME is the most active antibiotic among β-lactams. CEFEPIME is active against Enterobacter species (MIC90), 2 μ g/ml; 99. 3% susceptible, whereas the susceptibility rates of other broad-spectrum β-lactams (ceftriaxone, ceftazidime and piperacillin-tazobactam), were significantly lower (78. 4 to 81. 5). CEFEPIME remains a very potent alternative for the treatment of contemporary pediatric infections. The aim of the present study was to review the clinical pharmacology of CEFEPIME in infants and children.

Pharmacokinetics of CEFEPIME was studied following single dose intravenous and intramuscular administration at the dose of 20 mg/kg of body weight in sheep. Drug concentration in serum was determined using high performance liquid chromatography (HPLC). Following single dose intravenous administration, the drug was rapidly distributed (t1/2a: 0.20±0.02 h) and eliminated (t1/2b: 2.54±0.12 h) from the body. The area under curve (AUC0-¥) was 135.50±5.63 mg h/mL. The drug was cleared at the rate of 2.48±0.09 mL/min/kg with mean residence time (MRT) of 2.84±0.13 h. Following IM administration, the drug was rapidly absorbed (Cmax: 26.34±1.44 mg/mL; tmax: 0.75 h) and slowly eliminated (t1/2b: 5.17±0.44 h) from body. The volume of distribution at steady state (Vdss), area under curve (AUC), total body clearance (ClB) and mean residence time (MRT) were 1.11±0.10 L/kg, 140.90±8.67 mg h/mL, 0.15±0.01 mL/min/kg and 6.89±1.0 h, respectively. The bioavailability of CEFEPIME following intramuscular administration was 103±8.0%.

Background: The rapid emergence of antibiotic resistance, especially broad-spectrum antibiotics, resulted in the avid use of new potent antibiotics. Ceftriaxone and ceftazidime, two third-generation cephalosporin, are usually used to manage complicated and uncomplicated infections. The use of CEFEPIME in resistant infections is increasing gradually, which put this potent antibiotic at risk of resistance.Patients and methods: During an 18-month period, a total of 220 gram-negative bacteria including Pseudomonas spp, Serratia spp, Acinetobacter spp, Proteus spp, E-coli and Klebsiella spp. have been isolated by standard microbiological methods from nosocomial surgical site, abscess, blood stream and urinary tract infections. MIC of antibiotics on isolated bacteria was determined by gradient concentration method.Results: Totally, 29.4%, 19.5% and 23.3% of isolated bacteria with MIC£8μg/ml were sensitive to CEFEPIME, ceftriaxone and ceftazidime, respectively. High level resistance with MIC³256mg/ml to CEFEPIME, ceftriaxone and ceftazidime was also observed in 47.1%, 70.8% and 62.5% of cases, respectively (p<0.05). High level resistance to CEFEPIME were more commonly observed for pseudomonas (73.1%) and Klebsiella spp. (73.5%), respectively (p<0.05). Conclusion: According to CLSI criteria, 47.1% of isolated bacteria in this study showed high level of resistance (MIC³256mg/ml) to CEFEPIME. Therefore application of CEFEPIME, as a drug of choice, for gram-negative organisms is not reasonable. Our result demonstrated that this potent antibiotic should not be used as a choice for empiric antibiotic therapy, in the cases of nosocomial infections caused by gram-negative organisms.