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PubMed2005

Activity of cefepime and carbapenems in experimental pneumonia caused by porin-deficient Klebsiella pneumoniae producing FOX-5 beta-lactamase.

The in-vivo activities of cefepime, imipenem and meropenem against the porin-deficient strain Klebsiella pneumoniae C2 and its derivative K. pneumoniae C2(pMG252) coding for the AmpC-type beta-lactamase FOX-5 were determined. Bactericidal activities were determined with the kill-curve method. A pneumonia model in guinea-pigs was developed, and Cmax, t(1/2) and DeltaT/MIC were calculated for the three agents tested. Animals were treated for 72 h with sterile saline (control group) or with cefepime, imipenem or meropenem (240 mg/kg/day, intramuscularly, three times daily). Bacterial counts in lungs (log10 CFU/g tissue) were determined by serial dilution. MICs (mg/L) of cefepime, imipenem and meropenem against K. pneumoniae C2/K. pneumoniae C2(pMG252), determined by macrodilution, were: 0.5/4, 0.5/0.5 and 0.25/0.5, respectively. Bacterial counts in the lungs of animals infected with K. pneumoniae C2 and treated with antimicrobial agents were always lower than in the control group (cefepime, 4.4 +/- 0.5; imipenem, 4.6 +/- 0.4; meropenem, 4.7 +/- 0.5; control group, 5.6 +/- 0.8; p <0.01). No significant differences were observed among the groups receiving therapy (p >0.05). Bacterial lung clearance was higher in treated animals than in control animals following infection with K. pneumoniae C2(pMG252) (cefepime, 4.5 +/- 0.4; imipenem, 4.0 +/- 0.3; meropenem, 4.6 +/- 0.4; control group, 6.1 +/- 0.6; p <0.01), with imipenem producing better clearance than either cefepime or meropenem (p <0.05). Thus, in the guinea-pig pneumonia model, cefepime, imipenem and meropenem were each effective against the porin-deficient K. pneumoniae strain C2 and its derivative expressing the plasmid-mediated AmpC type beta-lactamase FOX-5.

Animals↗

PubMed1991

In vitro activities of cefepime alone and with amikacin against aminoglycoside-resistant gram-negative bacteria.

The in vitro activity of cefepime was compared with those of ceftazidime, cefotaxime, and cefpirome against aminoglycoside-resistant gram-negative bacteria. Cefepime was the most active cephalosporin, with a MIC for 90% of strains tested for all non-Pseudomonas aeruginosa species of less than or equal to 4 micrograms/ml. No cefepime resistance was encountered among members of the family Enterobacteriaceae. Of the 40 aminoglycoside-resistant P. aeruginosa isolates, 15% were resistant to cefepime, compared with 18% for ceftazidime, 30% for cefpirome, and 35% for cefotaxime. Synergism between cefepime and amikacin was observed and occurred most frequently in P. aeruginosa strains resistant to cefepime but susceptible to amikacin. In no case did cefepime and amikacin exhibit antagonism against P. aeruginosa.

Amikacin↗

PubMed2001

Pharmacokinetics of cefepime during continuous renal replacement therapy in critically ill patients.

The pharmacokinetics of cefepime were studied in 12 adult patients in intensive care units during continuous venovenous hemofiltration (CVVH) or continuous venovenous hemodiafiltration (CVVHDF) with a Multiflow60 AN69HF 0.60-m(2) polyacrylonitrile hollow-fiber membrane (Hospal Industrie, Meyzieu, France). Patients (mean age, 52.0 +/- 13.0 years [standard deviation]; mean weight, 96.7 +/- 18.4 kg) received 1 or 2 g of cefepime every 12 or 24 h (total daily doses of 1 to 4 g/day) by intravenous infusion over 15 to 30 min. Pre- and postmembrane blood (serum) samples and corresponding ultrafiltrate or dialysate samples were collected 1, 2, 4, 8, and 12 or 24 h (depending on dosing interval) after completion of the drug infusion. Drug concentrations were measured using validated high-performance liquid chromatography methods. Mean systemic clearance (CL(S)) and elimination half-life (t(1/2)) of cefepime were 35.9 +/- 6.0 ml/min and 12.9 +/- 2.6 h during CVVH versus 46.8 +/- 12.4 ml/min and 8.6 +/- 1.4 h during CVVHDF, respectively. Cefepime clearance was substantially increased during both CVVH and CVVHDF, with membrane clearance representing 40 and 59% of CL(S), respectively. The results of this study confirm that continuous renal replacement therapy contributes substantially to total CL(S) of cefepime and that CVVHDF appears to remove cefepime more efficiently than CVVH. Cefepime doses of 2 g/day (either 2 g once daily or 1 g twice daily) appear to achieve concentrations adequate to treat most common gram-negative pathogens (MIC <or= 8 microg/ml) during CVVH or CVVHDF.

Adult↗

PubMed2002

In vitro activities of quinupristin-dalfopristin and cefepime, alone and in combination with various antimicrobials, against multidrug-resistant staphylococci and enterococci in an in vitro pharmacodynamic model.

Use of combinations of antimicrobials that together achieve synergistic activities against targeted microorganisms is one potential strategy for overcoming bacterial resistance. As the incidence of infections caused by multidrug-resistant staphylococci and enterococci increases, the importance of devising additional synergistic drug combinations for these bacteria is magnified. We evaluated a number of antimicrobial combinations, with a focus on quinupristin-dalfopristin (Q-D), cefepime, and linezolid, using a previously described in vitro pharmacodynamic model. The combination of Q-D with either linezolid or vancomycin, as well as the combination of cefepime-vancomycin, resulted in enhanced killing (> or =2-log(10) increase in killing versus the most-active single agent) against methicillin-resistant Staphylococcus aureus (MRSA) 494. An improved effect (<2 log(10) kill increase in kill) against MRSA 494 was noted for cefepime plus either Q-D or linezolid, as well as linezolid-vancomycin. Similar relationships were observed for a methicillin-susceptible S. aureus isolate (isolate 1199). Against methicillin-resistant S. epidermidis R444, enhanced killing was achieved with the combination of cefepime-linezolid, while improvement was noted for vancomycin with either cefepime or linezolid. The combination of cefepime and vancomycin also achieved enhanced killing against a glycopeptide-intermediate-susceptible S. aureus isolate (isolate 992). The combination of linezolid and doxycycline achieved an enhanced effect against vancomycin-resistant Enterococcus faecalis (VREFc) and E. faecium. Q-D plus ampicillin or linezolid resulted in similar enhancement of activity against the VREFc isolate. The results of this study suggest a number of novel antimicrobial combinations that may be useful against staphylococci and enterococci. Combination regimens including cefepime, Q-D, and/or linezolid warrant further investigation for the treatment of refractive infections due to multidrug-resistant gram-positive pathogens.

Anti-Bacterial Agents↗

PubMed2003

Diffusion of cefepime into cancellous and cortical bone tissue.

The degree of penetration of an antibiotic into the infection site is an important factor in its therapeutic efficacy, particularly in bone and joint infections. In the present study, we examined the bone tissue penetration of cefepime at a dose of 2 g, and the results were correlated to microbiological data to estimate the clinical efficacy of cefepime in bone infections. In this open-label, single-arm, noncomparative study, subjects of similar age, body weight, height and creatinine clearance who were undergoing elective total hip replacement received a single, parenteral 2 g dose of cefepime. Plasma samples were collected simultaneously with bone tissue samples 1.5 hours later, on average, and analyzed by a validated high performance liquid chromatography assay. Ten patients (7 women and 3 men; mean age, 78 years; mean body weight, 57 Kg; mean creatinine clearance, 56 mL/min) were enrolled. The mean +/- SD plasma concentration of cefepime at the time of bone removal was 72.9 +/- 24.4 microg/mL. The mean +/- SD cefepime concentrations were 73.5 +/- 16.2 microg/mL in cancellous bone tissue and 67.7 +/- 17.0 microg/mL in cortical bone tissue. The mean +/- SD ratios of cefepime concentration in bone and plasma (bone/plasma) were 1.06 +/- 0.23 for cancellous bone tissue and 0.87 +/- 0.37 for cortical bone tissue. Cefepime exhibits an excellent diffusion into bone tissue, with concentrations achieved in both cancellous and cortical bone tissue greater than the minimum concentrations required to inhibit the growth of 90% of strains (MIC90) of most of the susceptible pathogens commonly involved in bone infections.

Aged↗

PubMed1999

Stability of cefepime in peritoneal dialysis solution.

OBJECTIVE: To determine the stability of cefepime in peritoneal dialysis solution. DESIGN: Cefepime HCl was added to premade bags of Delflex peritoneal dialysis solution with 1.5% dextrose to produce a cefepime concentration of approximately 100 microg/mL. Peritoneal dialysis solution bags were stored at 4, 25, and 37 degrees C to simulate refrigeration, room temperature, and body temperature, respectively. Samples were drawn at scheduled times up to 336, 168, and 48 hours, respectively, after the addition of cefepime HCl. Cefepime concentrations were measured by HPLC. SETTING: This study was performed at a university-affiliated tertiary care hospital. OUTCOME MEASURE: If the mean concentration of the samples at a given time and condition was >90% of the initial concentration, cefepime was considered stable at that time and condition. RESULTS: The mean HPLC results for samples drawn at each time and condition were all >90%. CONCLUSIONS: Cefepime is stable in peritoneal dialysis solution with dextrose 1.5% for 14 days refrigerated, seven days at room temperature, and 48 hours at 37 degrees C.

Cefepime↗

PubMedDate not supplied

Ocular penetration of cefepime following systemic administration in humans.

OBJECTIVE: To investigate the penetration of cefepime (a fourth generation cephalosporin) into the aqueous humor after single-dose intravenous administration in humans. PATIENTS AND METHODS: Before receiving cataract surgery, 30 patients received randomly 1 g (group 1, 15 patients) and 2 g (group 2, 15 patients) single intravenous injection of cefepime before surgery. Samples of aqueous humor and serum were obtained at 0.5, 1, 2, 4, and 12 hours after injection. Three patients were sampled each time for 1 g and 2 g of cefepime. Samples were assayed for cefepime concentrations with high performance liquid chromatography (HPLC). RESULTS: All the patients had detectable cefepime in their aqueous humor and serum measurable by HPLC. A mean peak aqueous humor level was 5.16 +/- 0.88 microg/mL in group 1 and 5.87 +/- 1.64 microg/mL in group 2 at 0.5 hour after injection. The mean level of cefepime in aqueous humor decreased after 0.5-hour measurements in both groups and was measured as 0.82 +/- 0.21 microg/mL in group 1 and 2.04 +/- 0.30 microg/mL in group 2 at 12 hours after injection. CONCLUSION: Aqueous humor levels of cefepime after single IV injection were above the minimum inhibitory concentration (MIC90) for most ocular pathogens, but the duration of exposure to an antibiotic was not sufficient for therapeutic effect.

Absorption↗

PubMed2002

Safety and efficacy of cefepime versus ceftazidime in the treatment of severe infections.

An open-label, randomized study was conducted to evaluate the safety and efficacy of cefepime versus ceftazidime in the treatment of severe bacterial infections, including septicemia, urinary tract infection, bacterial bronchitis, bacterial pneumonia, and intraabdominal infection. Fifty-two patients with severe infections were eligible and prospectively randomized to receive cefepime (26 patients) or ceftazidime (26 patients) during a 15-month period. Forty-two patients were evaluable (24 in the cefepime group and 18 in the ceftazidime group). Most (86%) of the patients had urinary tract infections and the most commonly isolated pathogen was Escherichia coli (79%). Satisfactory clinical response rates of 71% and 61%, and bacteriological eradication rates of 87.5% and 89% were achieved for the cefepime and ceftazidime groups, respectively. Two patients treated with cefepime died, one from superinfection and one from suspected paraneoplastic syndrome. Cultures of the blood obtained at entry into the study were positive in 19 (45%) of the 42 evaluable cases. In the cefepime group, a patient with Salmonella paratyphi A septicemia was cured, which has not been previously reported. Adverse effects attributable to therapy were minimal in both groups of patients, and none required discontinuation or dose reduction. In conclusion, these results suggest that cefepime is as efficacious and well tolerated as ceftazidime in the treatment of severe bacterial infections, such as septicemia, urinary tract infection, bacterial bronchitis, bacterial pneumonia, and intraabdominal infection.

Adolescent↗

PubMed2006

[Efficacies of ceftazidime and cefepime in rats with experimental pneumonia caused by extended-spectrum beta-lactamase-producing strain of Klebsiella pneumonia].

OBJECTIVE: To investigate the in vivo activities of ceftazidime and cefepime with susceptibility in vitro in rats with experimental pneumonia caused by extended-spectrum beta-lactamase-producing strain of Klebsiella pneumonia. METHODS: With intratracheal instillation method, 3 Klebsiella pneumonia strains isolated from this hospital were used to produce 3 groups of experimental model of pneumonia in rats. All the 3 strains showed resistant to cefotaxime and susceptible to piperacillin-tazobactam in vitro. To ceftazidime and cefepime, strain 1 was both susceptible. Strain 2 was susceptible to ceftazidime and resistant to cefepime. Strain 3 was resistant to ceftazidime and susceptible to cefepime. The three groups of rats were randomly assigned to one of the following five groups: one control group and four treatment groups. The efficacies were evaluated 96 hours later by the survival rate and the viable bacterial counts of the lungs (lg CFU/g). RESULTS: Group 1: piperacillin-tazobactam, ceftazidime and cefepime significantly improved the survival rate (75.0%, 76.9%, 80.0%) and reduced the bacterial counts [(10.8 +/- 2.8), (11.1 +/- 3.2), (11.0 +/- 3.7) lg CFU/g] compared with cefotaxime and the control group [36.0%, 32.0%; (15.7 +/- 5.6), (16.0 +/- 5.5) lg CFU/g; P < 0.05]. Group 2: piperacillin-tazobactam, ceftazidime significantly improved the survival rate (79.2%, 73.1%) and reduced the bacterial counts [(10.7 +/- 2.3), (11.0 +/- 2.7) lg CFU/g] compared with cefotaxime and the control groups [42.3%, 33.3%; (15.5 +/- 5.4), (15.8 +/- 4.6) lg CFU/g; P < 0.05]. Group 3: the survival rate in piperacillin-tazobactam and cefepime groups (80.8%, 75.0%) were significantly higher and the bacterial counts in piperacillin-tazobactam [(10.4 +/- 2.4) lg CFU/g] were significantly lower compared with the cefotaxime and the control groups [37.5%, 34.6%; (14.2 +/- 5.6), (15.3 +/- 4.9) lg CFU/g; P < 0.05]. CONCLUSION: Cefepime and ceftazidime can reduce the mortality and the number of viable bacteria in rat pneumonia caused by some ESBL-producing Klebsiella pneumonia strains susceptible to either of them and their efficacies were similar to piperacillin-tazobactam.

Animals↗

PubMed1991

Dose-proportional pharmacokinetics of cefepime in rats.

Cefepime (BMY-28142) is a new parenteral cephalosporin antibiotic with excellent activity against a broad-spectrum of clinically important pathogens resistant to other new cephalosporins. A single bolus dose of 10, 20 or 40 mg/kg cefepime was given i.v. to male and female Sprague-Dawley rats from which blood and urine samples were collected. For statistical reasons, pharmacokinetic parameters (AUC, Kel) were derived by fitting an exponential curve to the plasma concentrations; subsequently, contrasts were made between the different doses for AUC and Kel and, in addition, plasma concentrations observed after the first sampling time (Cmax). Cmax and AUC appeared to be linearly related to the administered dose in both males and females. The dose increased in the ratio 1:2:4 and mean Cmax in male and female rats increased in the ratio 1:2.3:4.1 and 1:2.3:4.4 respectively; similarly, AUC increased in the ratio 1:2.2:4.3 and 1:2.0:4.2 respectively. Deviations from linearity and proportionality were not significant (P0.05). The systemic clearance of cefepime in rats was 2.3 ml/min. The volume of distribution was about 60 ml and cefepime appears to be selectively distributed into the extracellular water. Plasma concentrations declined monoexponentially with a mean half-life of 15-20 min which did not significantly change with increasing doses. The renal clearance of cefepime was 1.8 ml/min and approximately 80% of the dose was excreted in the urine unchanged; renal excretion of cefepime is the major route of elimination in rats. The elimination and distribution characteristics of cefepime in rats were similar to those observed in man.

Animals↗

PubMed1993

A comparative study of the in-vitro activity of cefepime and other cephalosporins.

Cefepime is a new cephalosporin antibiotic which is highly active against both Gram-positive and Gram-negative organisms. The purpose of this study was to establish the in-vitro activity of cefepime and three other cephalosporins against recent clinical isolates from patients at the General Hospital Kuala Lumpur. A total of 334 strains comprising Enterobacteriaceae, non-fermentative Gram-negative bacilli and Staphylococcus aureus were tested for their sensitivity to cefepime, cefotaxime, ceftriaxone and ceftazidime. Minimum inhibitory concentrations of the antibiotics were established using an agar dilution method. With the exception of some strains of Flavobacterium meningosepticum, Xanthomonas maltophilia and other non-fermentative Gram-negative bacilli, cefepime was found to be active against a wide range of Gram-negative organisms. Cefepime was as or more active than the other cephalosporins against Acinetobacter, Enterobacteriaceae and methicillin-sensitive Staphylococcus aureus. Strains of Klebsiella and Salmonella that were resistant to the third generation cephalosporins were sensitive to cefepime. Cefepime could be a valuable alternative for the treatment of nosocomial infections due to multiply resistant organisms.

Cefepime↗

PubMed1998

Antimicrobial activity and spectrum investigation of eight broad-spectrum beta-lactam drugs: a 1997 surveillance trial in 102 medical centers in the United States. Cefepime Study Group.

Because antimicrobial agents become less effective after the emergence of resistance mechanisms in clinically prevalent pathogens, physicians must utilize local, regional, and national antimicrobial susceptibility surveillance data to assist in choices of appropriate agents. An investigation of the spectrum and potency of eight broad-spectrum beta-lactam drugs (cefepime, cefotaxime, ceftazidime, ceftriaxone, imipenem, piperacillin with or without tazobactam, and ticarcillin/clavulanic acid) was performed using a common protocol and method (Etest; AB BIODISK, Solna, Sweden) in 102 clinical microbiology laboratories in the United States. A total of 9777 strains of Gram-negative bacilli were tested from late 1996 through April 1997. Quality assurance measures using three control strains observed quality control failures in 13 laboratories (usually ticarcillin/clavulanic acid or piperacillin), but only 2% of results required deletion. A total of 33.4% of Enterobacter spp. (1977 strains) were either resistant or intermediately susceptible to ceftazidime. Only imipenem (99.6% susceptible) and cefepime (99.1%) remained highly active against strains of Enterobacter, as well as Citrobacter freundii, indole-positive Proteae, and Serratia spp. Ceftazidime-resistant Escherichia coli and Klebsiella pneumoniae were detected at rates of 10.3% and 23.8%, respectively. Although these were participant-selected strains, only imipenem and cefepime had broad-spectrum coverage (> or = 97.1%) against these extended-spectrum beta-lactamase phenotypes. A dominant number of these extended-spectrum beta-lactamase phenotypes were reported from medical centers in the Northeast, but a nationwide distribution was observed. Among the nonenteric Gram-negative bacilli (4057 strains), the rank order of susceptibility (percent inhibited at published breakpoint concentrations) was: imipenem (86.1%) > piperacillin/tazobactam (80.1%) > cefepime (77.1%) > ceftazidime = piperacillin (74.9%) > ticarcillin/clavulanic acid (61.6%) > cefotaxime (18.2%) > ceftriaxone (12.9%). The cephalosporins, cefepime and ceftazidime, had rates of resistance for the 3005 Pseudomonas aeruginosa isolates of 10.1% and 14.4%, respectively. For all Gram-negative strains tested, only two contemporary beta-lactam antimicrobials exhibited > 90% inhibition of strains, imipenem at 93.6% and cefepime at 90.2%. These drugs were superior to the other tested compounds (48.8-84.3%). Ticarcillin/clavulanic acid had the narrowest spectrum of activity (48.8% of isolates susceptible). These results indicate that carbapenems and a new fourth-generation cephalosporin, cefepime, possess usable in vitro potencies against current clinical strains of Gram-negative bacilli, many of which harbored resistance to other antimicrobial agents.

Anti-Bacterial Agents↗

PubMed2007

Meropenem -valproic acid interaction in patients with cefepime-associated status epilepticus.

PURPOSE: Two case reports of rapid decreases in valproic acid levels after initiation of meropenem in patients who developed new-onset seizure activity during treatment with cefepime are presented. SUMMARY: A 60-year-old Caucasian woman with myelodysplasia was transferred to the medical intensive care unit (MICU) on day 11 of her hospitalization. Cefepime was given as empiric therapy for febrile neutropenia. Pulmonary invasive aspergillosis was diagnosed. On day 16 of hospitalization, epileptic activity was confirmed. Valproic acid was initiated. Cefepime was discontinued and meropenem was initiated for treatment of cefepime-resistant pneumonia. Serum valproic acid levels decreased to subtherapeutic levels within 24 hours. Meropenem was discontinued and ceftazidime was started on day 22; serum valproic acid levels gradually increased but never reached therapeutic levels again. The patient died of intractable invasive aspergillosis on day 33. A 54-year-old Caucasian man with myelodysplasia was admitted to the MICU for nonconvulsive status epilepticus. Ten days before admission, cefepime had been started empirically for the treatment of neutropenic fever. One day before MICU admission, valproic acid was initiated as treatment for status epilepticus. The next day, serum valproic acid levels were therapeutic; cefepime was switched to meropenem. Serum valproic acid levels decreased within 24 hours and phenytoin was added. On day 4, the patient's serum valproic acid levels decreased further and meropenem was discontinued. Although the valproic acid dosage was increased, valproic acid levels did not return to the therapeutic range. The patient died on day 11. CONCLUSION: Following cefepime therapy, a clinically important interaction between meropenem and valproic acid occurred in two critically ill patients with new-onset status epilepticus.

Anti-Bacterial Agents↗

PubMed2003

Treatment of febrile neutropenic patients with cancer who require hospitalization: a prospective randomized study comparing imipenem and cefepime.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Adolescent↗

PubMed1990

Safety, tolerance, and pharmacokinetics of cefepime administered intramuscularly to healthy subjects.

Steady state pharmacokinetics, absolute bioavailability, and dose proportionality of cefepime were evaluated in healthy male subjects after single (250, 500, 1000, or 2000 mg) and multiple (1000 mg every 12 hours for 10 days) intramuscular injections. Safety and tolerance were also monitored. High performance liquid chromatography/UV methodology was used to determine cefepime concentrations in plasma and urine. Key pharmacokinetic parameters were determined using noncompartmental methods. Cefepime was absorbed rapidly; mean peak times were 1.0-1.6 hours. Pharmacokinetics were linear over the 250-mg to 2000-mg dose range, with mean total body clearance ranging from 125 to 141 mL/min. The peak plasma concentration and area under the curve increased in a dose-proportional manner. The apparent elimination half-life (2 hours) did not appear to be influenced by dose or by duration of dosing. No accumulation of cefepime was observed during the multiple-dose study. More than 80% of the administered dose was excreted in the urine as unchanged cefepime, and absolute bioavailability after intramuscular dose was 100%. Cefepime was well tolerated. Most subjects experienced none to mild pain and only minimum discomfort at the site of injection.

Adult↗

PubMed2006

Pharmacodynamic profiling of cefepime in plasma and cerebrospinal fluid of hospitalized patients with external ventriculostomies.

Population pharmacokinetic (PK) modeling and Monte Carlo simulation (MCS) were used to describe the pharmacodynamic profile of cefepime in the both plasma and cerebrospinal fluid (CSF). Plasma and CSF cefepime data were obtained from a PK study of 7 hospitalized patients with external ventricular drains. Concentration-time profiles in plasma and CSF were modeled using a 3-compartment model with zero-order infusion and first-order elimination and transfer. Estimates of the PK parameters were identified in the Big Non Parametric Adaptive Grid with adaptive gamma (BigNPAG) program of Leary, Jelliffe, Schumitzky, and Van Guilder. MCS (10,000 subjects) was performed to estimate the probability of attaining the targets of free plasma concentration (20% protein binding) and total drug CSF concentration of 50-100% T>minimal inhibitory concentration (MIC) for MICs 0.06-8 mg/L for cefepime 2 g, iv, every 8 h (0.5-h infusion); cefepime 2 g, iv, every 12 h (0.5-h infusion); and cefepime 2 g (0.5-h infusion) once and 250 mg/h continuous infusion. After the Bayesian step, the observed-predicted regression and r(2) for plasma and CNS were as follows: plasma, observed=0.984 x predicted+2.570, r(2)=0.944; CSF, observed=0.785 x predicted+0.868, r(2)=0.821. The median penetration of cefepime as measured by AUC(CSF)/AUC(plasma) was 7.8%. In the MCS, the target attainment rates in plasma for 60-70% fT>MIC were high at each MIC value between 0.03 and 8 microg/mL for each regimen examined. In CSF, none of the regimens achieved 50-100% T>MIC for>80% of patients for MICs>0.5 mg/L.

Adult↗

PubMed2006

Stability of cefepime and metronidazole prepared for simplified administration as a single product.

The stabilities of cefepime and metronidazole were determined after preparation of a single admixture product in view of its potential use as a simple and cost-effective therapeutic alternative for infections caused by many aerobic and anaerobic pathogens. The stability of cefepime 1000 or 2000 mg mixed with metronidazole 500 or 1500 mg was evaluated via high-performance liquid chromatography after storage for up to 336 h at 4 or 23 degrees C. Cefepime was stable in all 4 degrees C samples for up to 336 h, retaining > or =95% of initial concentrations. Samples of cefepime 1000 and 2000 mg mixed with metronidazole 500 mg were stable at 23 degrees C for up to 48 h, whereas those mixed with metronidazole 1500 mg and cefepime controls were stable at 23 degrees C for up to 72 h. Metronidazole was stable in all samples for up to 336 h, retaining > or =94% of initial concentrations. These data suggest that therapeutic use of cefepime and metronidazole as a single intravenous admixture product is feasible and practical.

Anti-Bacterial Agents↗

PubMed2006

Bactericidal activity of cefepime and ceftriaxone tested against Streptococcus pneumoniae.

The bactericidal activities of cefepime and ceftriaxone were assessed by testing a contemporary collection of 50 Streptococcus pneumoniae strains. Minimum inhibitory and bactericidal concentrations (MIC and MBC, respectively) of cefepime and ceftriaxone were determined, and time-kill studies were performed on 14 selected strains (10 penicillin-resistant, 2-intermediate, and 2-susceptible). Cefepime and ceftriaxone showed essentially identical potency (MIC50, 1 microg/mL and MIC90, 2 microg/mL, for both compounds) and MBC values (MBC50, 1 microg/mL for both). MBC/MIC ratios were < or = 4 for cefepime and < or = 8 for ceftriaxone on 48 (96.0%) strains, and 2 strains (4.0%) displayed MBC/MIC ratios > or = 32 (tolerance) to the 2 cephalosporins. Time-kill curves corroborated the MBC/MIC studies. Cefepime and ceftriaxone bactericidal activity (> or = 3 log10 CFU/mL reduction in inoculum) was demonstrable after 24 h of exposure to 8x MIC for 13 (92.9%) of 14 strains, whereas 1 strain showed approximately 2 log10 CFU/mL reduction. In conclusion, our results indicate that cefepime and ceftriaxone exhibit comparable potency and bactericidal activities when tested against contemporary pneumococcal strains with varying penicillin susceptibility patterns. Both parenteral cephems offer alternative therapeutic choices for the treatment of invasive pneumococcal infections.

Anti-Bacterial Agents↗