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PubMed1987

In vitro activity of a new broad spectrum, beta-lactamase-stable oral cephalosporin, cefixime.

Cefixime is a new orally absorbed iminomethoxy, aminothiazolyl cephalosporin. It inhibits the majority, 90%, of Streptococcus pneumoniae, Streptococcus pyogenes, Branhamella catarrhalis, Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Neisseria gonorrhoeae at concentrations less than or equal to 0.25 micrograms/ml. It inhibits 90% of the other members of the Enterobacteriaceae at concentrations less than 1 microgram/ml, with the exception of some strains of Enterobacter spp., Citrobacter freundii and Morganella morganii, Cefixime does not inhibit enterococci, Listeria, Pseudomonas aeruginosa, Acinetobacter, Bacteroides spp. or staphylococci. In general, cefixime has in vitro activity superior to cephalexin, cephradine, cefadroxil and cefaclor against all bacteria with the exception of staphylococci. Cefixime is not destroyed by most of the common plasmid and chromosomal beta-lactamases and its activity is not reduced by serum, blood or urine. Cefixime overall has excellent in vitro activity against the commonly encountered respiratory and urinary tract pathogens.

Bacteria↗
PubMed1987

Pharmacokinetic profile of cefixime in man.

Cefixime is an orally absorbed third generation cephalosporin with a broad spectrum of activity against Gram-positive and Gram-negative bacteria and is highly resistant to beta-lactamase degradation. In general serum and urinary concentrations of cefixime achieved after recommended daily doses are well above the minimal inhibitory concentrations at 90% for indicated microorganisms. The pharmacokinetics of cefixime were determined in adult and pediatric subjects. In general the half-life of the drug is about 3 to 4 hours and is not dependent on dose. The drug is not extensively bound to serum proteins; the free fraction is about 31% and is concentration-independent. The absolute bioavailability, based on comparisons of area under the serum concentration-time curve values after 200-mg intravenous, 200-mg oral solution, and 200- and 400-mg capsule doses, ranged from 40 to 52%, showing a comparable bioavailability for cefixime at single 200- and 400-mg oral doses. In a dose proportionality study, over an oral dose range of 200 to 2000 mg, peak serum concentration (Cmax) and area under the concentration-time values increased linearly but were not directly proportional with dose. Upon multiple dosing for 2 weeks on a 400-mg daily or 200-mg twice a day regimen, serum concentrations and urinary recovery of unchanged drug were similar for each group, and there was no drug accumulation. Peak serum concentration and area under the concentration-time curve values after a 400-mg dose were almost double those after a 200-mg dose. All formulations of cefixime were bioequivalent to an oral reference solution at doses of 200 and 400 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Once daily cefixime compared with twice daily trimethoprim/sulfamethoxazole for treatment of urinary tract infection in infants and children.

We conducted a randomized prospective multicenter study to compare the safety and efficacy of once daily oral cefixime (8 mg/kg) to twice daily oral trimethoprim/sulfamethoxazole (TMP/SMX) (8/40 mg/kg/day) for the treatment of acute urinary tract infection in children ages 6 months to 13 years. Seventy-six patients (38 in each group) were studied. Thirty-seven percent were younger than 3 years of age. Escherichia coli was the most common isolate in both groups (85%). Eighty-five percent of all Gram-negative organisms were susceptible to TMP/SMX and all were susceptible to cefixime. Seventy-two percent of all patients were febrile at the time of diagnosis. Both groups were treated for 7 to 10 days. Peripheral white blood cell counts, erythrocyte sedimentation rate, body temperature and urinalysis returned to normal at the same rate in both groups. No failures were observed and relapse occurred in 3 cases within the 4 weeks after treatment (2 in the cefixime group and one in the TMP/SMX group). Side effects were observed in 14% of the cefixime group and 16% of the TMP/SMX group and were all mild enough not to necessitate discontinuation of therapy. We conclude that the efficacy and safety of cefixime administered once daily compared favorably with TMP/SMX administered twice daily for acute uncomplicated urinary tract infection.

Administration, Oral↗
PubMed1995

Comparison of the efficacy, safety and cost of cefixime, ceftriaxone and aztreonam in the treatment of multidrug-resistant Salmonella typhi septicemia in children.

An increase in the incidence of Salmonella typhi strains resistant to chloramphenicol, ampicillin and trimethoprim-sulfamethoxazole causing enteric fever in Egyptian children stimulated the evaluation of alternative drugs. Children with positive blood cultures were treated with cefixime, ceftriaxone or aztreonam, and the efficacy, safety and cost of these regimens were evaluated and compared. Cefixime (7.5 mg/kg) was given orally twice daily to 50 children for 14 days, ceftriaxone (50 to 70 mg/kg) was given im once daily for 5 days to 43 children and aztreonam (50 to 70 mg/kg) was given im every 8 hours for 7 days to 31 children. Children in the 3 groups were comparable with regard to age, sex, duration and severity of illness before admission. All children were cured. A significant difference (P < 0.05) in duration of treatment before becoming afebrile seemed to favor ceftriaxone (3.9 days) over aztreonam (5.5 days) and cefixime (5.3 days). During the 4-week follow-up period relapses occurred in 3 (6%) children in the cefixime group, in 2 (5%) in the ceftriaxone group and in 2 (6%) in the aztreonam group. Safety and efficacy were comparable for all 3 drugs. Ceftriaxone was most cost-effective on an inpatient basis, because of a more rapid clinical cure, and cefixime was the most cost-effective on an outpatient basis, because of drug cost.

Adolescent↗
PubMed1996

Pharmacokinetics of cefixime in children with urinary tract infections after a single oral dose.

The pharmacokinetics of cefixime, a third-generation broad-spectrum cephalosporin, were determined following administration of a 8 mg/kg single oral dose of cefixime suspension to six children with urinary tract infections, ages from 6 to 13 years and weights from 17 to 60 kg. Blood samples for determination of plasma cefixime concentrations were obtained for up to 12 hr and complete urine collections were obtained for urinary excretion of unchanged parent drug for up to 24 hr after administration. Plasma and urine concentrations of cefixime were determined using a reversed phase HPLC assay and pertinent pharmacokinetic parameters were estimated by model-independent standard methods. Mean peak plasma concentration was 4.04 micrograms/ml and was reached after 3.2 hr. The mean area under the plasma concentration-time curve was 33.07 micrograms.hr/ml and the mean elimination half-life was 3.91 hr. The mean apparent total clearance was 4.74 ml/min./kg and about 15% of the dose administered was recovered unchanged in urine. In conclusion, the estimated pharmacokinetic values of cefixime were comparable to those observed in healthy adult subjects based on equivalent mg/ kg doses. Plasma and urine concentrations of the drug were well above the reported minimal plasma and urinary concentrations for most common urinary tract pathogens for up to 12 and 24 hr after administration, respectively.

Adolescent↗
PubMed2006

Amino acid substitutions in mosaic penicillin-binding protein 2 associated with reduced susceptibility to cefixime in clinical isolates of Neisseria gonorrhoeae.

The molecular mechanisms of reduced susceptibility to cefixime in clinical isolates of Neisseria gonorrhoeae, particularly amino acid substitutions in mosaic penicillin-binding protein 2 (PBP2), were examined. The complete sequence of ponA, penA, and por genes, encoding, respectively, PBP1, PBP2, and porin, were determined for 58 strains isolated in 2002 from Japan. Replacement of leucine 421 by proline in PBP1 and the mosaic-like structure of PBP2 were detected in 48 strains (82.8%) and 28 strains (48.3%), respectively. The presence of mosaic PBP2 was the main cause of the elevated cefixime MIC (4- to 64-fold). In order to identify the mutations responsible for the reduced susceptibility to cefixime in isolates with mosaic PBP2, penA genes with various mutations were transferred to a susceptible strain by genetic transformation. The susceptibility of partial recombinants and site-directed mutants revealed that the replacement of glycine 545 by serine (G545S) was the primary mutation, which led to a two- to fourfold increase in resistance to cephems. Replacement of isoleucine 312 by methionine (I312M) and valine 316 by threonine (V316T), in the presence of the G545S mutation, reduced susceptibility to cefixime, ceftibuten, and cefpodoxime by an additional fourfold. Therefore, three mutations (G545S, I312M, and V316T) in mosaic PBP2 were identified as the amino acid substitutions responsible for reduced susceptibility to cefixime in N. gonorrhoeae.

Amino Acid Sequence↗
PubMed1986

Pharmacokinetics of cefixime (CL 284,635; FK 027) in healthy subjects and patients with renal insufficiency.

The pharmacokinetics of the extended-half-life, broad-spectrum oral cephalosporin cefixime (CL 284,635; FK 027) were studied in 7 healthy volunteers and 35 patients with various degrees of renal insufficiency, including patients undergoing continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis. Apparent total body, renal, and apparent nondialysis-nonrenal clearances and protein binding declined and elimination half-life increased with decreasing creatinine clearance. All of these alterations became statistically significant as the creatinine clearance fell below 20 ml/min per 1.73 m2. Cefixime concentrations in urine exceeded the MICs for most urinary tract pathogens for up to 24 h postdose, even in patients with severe renal insufficiency. CAPD removed an insignificant fraction of cefixime body burden over the 72-h study period (1.57 +/- 0.60% [mean +/- the standard error of the mean]). Area under the curve data suggested that hemodialysis similarly removed an insignificant fraction of the cefixime body burden. Volume of distribution at steady state was not altered significantly by renal insufficiency. It is recommended that standard doses of cefixime be administered at extended intervals, especially in patients with creatinine clearances less than 20 ml/min per 1.73 m2. In addition, supplemental doses are not necessary during CAPD and at the end of hemodialysis.

Adult↗
PubMed1986

Penetration of cefixime into fibrin clots and in vivo efficacy against Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus.

The experimental model of infected fibrin clots in rabbits was used to study the penetration and in vivo activity of cefixime against Klebsiella pneumoniae, Escherichia coli, and Staphylococcus aureus. The respective MICs of cefixime against these strains were 0.25, 2, and 8 micrograms/ml. The clots were infected with 10(6) to 10(8) CFU/g. Groups of four animals for each strain received an intravenous injection of 100 mg of cefixime per kg over 30 min. High peak levels were observed in serum (146.5 micrograms/ml) and clots (15.8 micrograms/g), and the antibiotic was still detectable in the clots (0.6 micrograms/g) 24 h after administration. The respective serum and clot elimination half-lives were 0.7 and 5.0 h. The mean serum protein binding was 23.8 +/- 3.8%. Cefixime was highly bactericidal against K. pneumoniae and E. coli and reduced, over a 24-h period, their respective colony counts by 7.8 log10 and 6.2 log10 CFU/g of fibrin. It was less effective against S. aureus but still reduced the bacterial counts by 2.8 log10 CFU/g of fibrin. The present results demonstrate that cefixime, a new broad-spectrum oral cephalosporin, has a long tissue half-life which ensured, at the dose given here, good in vivo bactericidal activity against both gram-positive and gram-negative bacteria up to 24 h after administration of the antibiotic.

Animals↗
PubMed1993

Biliary excretion of cefixime: assessment in patients provided with T-tube drainage.

The biliary excretion profile of cefixime was studied in 10 patients provided with T-tube drainage of the common bile duct after cholecystectomy. Following a single 200-mg oral dose, the peak concentration of cefixime in bile reached 56.9 +/- 70 mg/liter, approximately 20 times as high as the peak concentration in serum, 2.3 +/- 0.85 mg/liter. Cefixime levels in bile proved relatively sustained, since a concentration of 4.3 +/- 3.7 mg/liter was still found 20 h after dosing. The cumulative amount of cefixime recovered in the 24-h bile drainage averaged 10.0 +/- 12.3 mg, which is 5% of the administered dose and positions this beta-lactam antibiotic among the most highly bile-excreted cephalosporins. The presented results show that a single 200-mg oral dose of cefixime provided drug levels in bile consistently higher than the MICs for the most frequently recovered members of the family Enterobacteriaceae in biliary tract infections and maintained these levels for over 20 h after dosing. Accordingly, this cephalosporin deserves further clinical trials to assess its usefulness in both prophylaxis and treatment of biliary tract infections.

Administration, Oral↗
PubMed1995

Cefixime penetration in human renal parenchyma.

The diffusion of cefixime, a new orally active expanded-spectrum cephalosporin, was studied in 12 patients undergoing nephrectomy after receiving 200-mg oral doses every 12 h for 2 days. The patients were divided into two groups according to the time of perioperative sampling after the last dose: 4 h (group 1) and 12 h (group 2). Preoperative blood samples were taken just before administration of the last dose of cefixime. Simultaneous blood and tissue samples were collected perioperatively at 4 h (time to peak level) and 12 h (residual level). The intrarenal concentrations of cefixime were measured by an isocratic reversed-phase high-pressure liquid chromatographic (HPLC) assay. Concentrations in serum were determined by both microbiological and HPLC assays. The mean peak levels in serum were 3.41 +/- 0.43 micrograms/ml (group 1), and the residual levels averaged 1.54 +/- 1.17 micrograms/ml (group 2). The diffusion in renal parenchyma was not significantly different in the cortexes and medullas of both groups of patients: 5.7 to 6.4 micrograms/g in group 1 and 4.6 to 4.7 micrograms/g in group 2. The decrease in cefixime concentrations was slower in tissue than in serum; the ratios of concentrations in tissue to those in serum were 3.5 to 3.6 and 1.7 to 1.9 at 4 and 12 h, respectively. The intrarenal concentrations of cefixime remained higher than the MIC for the most susceptible gram-negative bacteria during the time interval between the administration of two doses.

Administration, Oral↗
PubMed1997

Differential intracellular efficacies of ciprofloxacin and cefixime against Neisseria gonorrhoeae in human fallopian tube organ culture.

This study compared the abilities of ciprofloxacin and cefixime to kill intracellular Neisseria gonorrhoeae in a human fallopian tube organ culture assay. When invasion was inhibited by cytochalasin D, 0.996% of the tissue-associated gonococci survived ciprofloxacin exposure compared to 1.70% of gonococci exposed to cefixime (95% confidence interval for the ratio of the means, 0.267 to 1.30), indicating that the two antibiotics did not significantly differ in the ability to kill extracellular attached organisms. In the absence of cytochalasin D, 1.63% survived ciprofloxacin exposure while 9.76% survived cefixime treatment (95% confidence interval for the ratio of the means, 0.067 to 0.418). These results suggest that ciprofloxacin penetrated epithelial cells and killed intracellular gonococci better than did cefixime. Thus, at concentrations achievable in serum, ciprofloxacin was more effective in total gonococcal killing than cefixime in this human fallopian tube organ culture model.

Anti-Infective Agents↗
PubMed1998

Cefixime in the treatment of respiratory and urinary tract infections.

Cefixime is quickly establishing in Western countries as a potent broad-spectrum antibiotic with a variety of indications. A multinational, nonrandomized study in Central and Eastern Europe has confirmed the excellent efficacy of cefixime in both children and adults. In 45 children with acute sinusitis and 50 with acute otitis media, once-daily cefixime in oral suspension resulted in clinical cure or improvement in 45 (100%) and 48 (96%) patients, respectively. In 60 adult patients with acute exacerbations of chronic bronchitis and 12 with pneumonia, cefixime 400 mg resulted in cure or improvement in 59 (98%) and 12 (100%) patients, respectively. Similarly, excellent efficacy was found in adults with urinary tract infections (UTI), with cure in 80 (94%) patients, improvement in 4 (5%), and failure in 1 (1%). Very good efficacy of cefixime was also demonstrated microbiologically, with eradication in 35 of 36 isolates from children, including all Streptococcus pneumoniae isolates, 40 of 45 isolates from patients with respiratory tract infections, and 64 of 71 isolates from patients with UTI.

Adult↗
PubMed1988

Activity of cefixime (FK 027) for resistant gram-negative bacilli.

Cefixime is an orally absorbable cephalosporin with an extended spectrum of in vitro activity for gram-negative bacteria especially members of the Enterobacteriaceae. Gram-negative rod isolates collected over a three month period were tested against cefixime. Greater than 99% of Escherichia coli isolates was susceptible to cefixime including those resistant to ampicillin. Similarly isolates of Klebsiella, Proteus and Providencia were also exquisitely susceptible to cefixime as were 91% of Enterobacter cloacae and 71% of Enterobacter aerogenes. Killing kinetics of cefixime did not differ from that of the intravenously administered third-generation cephalosporin, cefotaxime. The addition of magnesium and calcium divalent cations or the lowering of the pH to 5.0 did not affect the action of this antibiotic. The extended spectrum of this oral antibiotic may be useful in treatment of urinary tract and skin and soft tissue infections caused by the more resistant gram-negative rods.

Ampicillin Resistance↗
PubMed1992

In vitro activity of a new broad-spectrum, beta-lactamase-stable oral cephalosporin, cefixime, in comparison with other drugs, against Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis and Streptococcus pneumoniae.

Cefixime, a new orally absorbed iminomethoxyaminothiazolyl cephalosporin, was tested against some microorganisms involved in upper and lower respiratory tract infections such as Haemophilus (influenzae and parainfluenzae), Moraxella catarrhalis and Streptococcus pneumoniae, isolated in the period from November 1990 to April 1991. Its activity was compared to nine other antimicrobial agents: erythromycin, trimethoprim-sulfamethoxazole, ampicillin, amoxicillin-clavulanate, cefaclor, ceftazidime, ceftriaxone, cefotaxime and ofloxacin. Cefixime inhibits 90% of S. pneumoniae, H. influenzae and H. parainfluenzae, both beta-lactamase producers (BLP) or not (NBLP) at concentrations of less than 0.25 mg/l. It inhibits 90% of M. catarrhalis (BLP and NBLP) at concentrations of less than 1 mg/l. In general, cefixime has a superior in vitro activity with respect to cefaclor and the other cephalosporins as well as erythromycin and amoxicillin (the last one in BLP strains). In the evaluation of the antibacterial activity of beta-lactam against Haemophilus and M. catarrhalis, the authors observed different indications in the guidelines for ampicillin. Cefixime is not destroyed by the plasmid-mediated beta-lactamase produced by Haemophilus sp. and M. catarrhalis (TEM and ROB in Haemophilus strains and BRO in M. catarrhalis). In view of its excellent in vitro activity against the commonly encountered respiratory tract pathogens, cefixime is indicated in the therapy of these infections.

Administration, Oral↗
PubMed2005

Tissue penetration of cefpodoxime and cefixime in healthy subjects.

Microdialysis is a technique that allows the measurement of free antibiotic concentrations in different tissues, which are responsible for the antibacterial activity at the infection site. In an open, randomized, 2-way crossover study in healthy volunteers, the muscle penetration of orally administered cefpodoxime (400 mg) and cefixime (400 mg) was compared using microdialysis. The results show that the total plasma concentration-time profiles of each antibiotic were similar; the area under the curve for cefpodoxime was 22.4 +/- 8.7 versus 25.6 +/- 8.5 mg/L*h for cefixime. However, tissue penetration was twice as high for cefpodoxime (area under the curve 15.4 +/- 5.1 mg/L*h) as for cefixime (area under the curve 7.3 mg/L*h). This degree of tissue distribution is consistent with their protein binding of 21% for cefpodoxime and 65% for cefixime. After equilibration, the unbound tissue concentrations of both antibiotics were similar to their unbound plasma concentrations. Pharmacokinetic modeling was applied to describe the pharmacokinetic profiles in plasma and muscle. The study demonstrates that cefpodoxime shows greater tissue penetration than cefixime.

Anti-Bacterial Agents↗
PubMed1990

Cefixime.

Cefixime is a new orally active third-generation cephalosporin with a broad spectrum of activity against a variety of both gram-positive and -negative bacteria including many beta-lactamase-producing strains of streptococci, Haemophilus influenzae, Neisseria gonorrhoeae, and the majority of the Enterobacteriaceae. Activity of cefixime against Staphylococcus aureus, enterococci, Listeria monocytogenes, and Pseudomonas spp. is poor. The relatively long elimination half-life of cefixime (approximately 3.0 h) has made possible once- to twice-daily administration with the potential added benefit of improved patient compliance. Clinical trials indicate that cefixime is at least as effective as standard agents in the treatment of genitourinary and upper respiratory tract infections. The incidence of resistant organisms reported during clinical trials with cefixime was low. Adverse reactions observed during clinical trials were relatively uncommon and generally mild and transient in nature. The most significant adverse reactions reported were diarrhea and stool changes occurring in up to 20 percent of patients.

Bacteria↗
PubMed1996

Comparison of cefprozil, cefpodoxime proxetil, loracarbef, cefixime, and ceftibuten.

OBJECTIVE: To discuss the pharmacokinetics, spectrum of activity, clinical trials, and adverse effects of cefprozil, cefpodoxime proxetil, loracarbef, cefixime, and ceftibuten, an investigational cephalosporin. DATA SOURCES: Literature was identified by a MEDLINE search from 1986 to January 1995. STUDY SELECTION: Randomized, controlled studies were selected for evaluation; however, uncontrolled studies were included when data were limited for indications approved by the Food and Drug Administration. DATA EXTRACTION: Data were evaluated with respect to in vitro activity, study design, clinical and microbiologic outcomes, and adverse drug reactions. DATA SYNTHESIS: Cefprozil, cefpodoxime proxetil, loracarbef, cefixime, and cefributen are active in vitro against organisms frequently involved in community-acquired infections such as Streptococcus pneumoniae, Escherichia coli, beta-lactamase-positive or -negative Haemophilus influenzae, and Moraxella catarrhalis. Except for cefixime and ceflibuten, they all are active against methicillin-susceptible Staphylococcus aureus. Even though there were problems in study design (discussed within the text), clinical data demonstrate that these new oral beta-lactam compounds are as efficacious as conventional therapies for a variety of community-acquired infections. CONCLUSIONS: Cefprozil, cefpodoxime, cefixime, loracarbef, and ceftibuten demonstrate in vitro activity against the major organisms that cause community-acquired infections. Clinical trials confirm that these agents are as effective as traditional therapies for the management of acute otitis media, pharyngitis/tonsillitis, sinusitis, bronchitis, pneumonia, urinary tract infections, and skin and skin-structure infections. In addition, cefixime and cefpodoxime are effective therapies for uncomplicated gonococcal infections. Selection of a specific agent will be influenced by susceptibility data and safety, as well as issues of compliance and cost.

Bacterial Infections↗
PubMed1995

Comparative evaluation of the clinical and microbiological efficacy of co-amoxiclav vs cefixime or ciprofloxacin in bacterial exacerbation of chronic bronchitis.

In an open randomized study 218 outpatients (159 males and 59 females) ranging between 18 and 85 years of age (mean 61.9) suffering from bacterial exacerbation of chronic bronchitis have been randomly treated: 79 with co-amoxiclav (amoxicillin 875 mg+clavulanic acid 125 mg) twice daily, 69 with cefixime (400 mg) once daily, and 70 with ciprofloxacin (500 mg) twice daily for an average period of 10 days. Before treatment start, 234 bacterial strains (105 Gram-positive and 129 Gram-negative) were isolated as the cause of exacerbation; the leading pathogens were Streptococcus pneumoniae and Haemophilus spp. Eradication rates at the end of treatment were 82.2% for the co-amoxiclav group, 77.6% for the cefixime group, and 81.2% for ciprofloxacin group. Clinical success (cure+improvement) was obtained in 90.8% of the cases treated with co-amoxiclav, in 80.9% for the cefixime group and in 85.7% of patients treated with ciprofloxacin. Seven adverse events (8.9%) of which 4 cases of diarrhea and 3 of itching, were recorded in the co-amoxiclav group. Eleven adverse events (14.7%) were recorded in the cefixime group including gastrointestinal disturbances in 6 patients and mild to moderate increase of liver function in 2. Nine adverse events (12.9%) occurred in the ciprofloxacin group, including insomnia in 3 patients, gastrointestinal disturbances in 2, and serious increase of liver function tests in one patient. It can be concluded that there were no statistically significant differences among the three treatment groups. However, co-amoxiclav demonstrated a higher efficacy rate than cefixime and ciprofloxacin and was better tolerated. Therefore, it can be used as a first-choice drug in the treatment of exacerbation of chronic bronchitis.

Adolescent↗