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[Cefixime in urinary tract infections. (Specific studies and literature review)].

Cefixime, a new oral cephalosporin, is more active against enterobacteriaceae than the conventional oral cephalosporins. About 20% of the drug is excreted by the kidneys as active drug. Therefore, the treatment of urinary tract infection (UTI) by cefixime may be a good alternative. In two smaller uncontrolled and four larger, controlled (amoxicillin, co-trimoxazole) "western" studies as well as in eight Japanese studies the good efficacy of cefixime in uncomplicated UTI could be demonstrated. Because of its antibacterial spectrum in this kind of infection the therapy with cefixime can be initiated already prior to sensitivity testing. Concerning the treatment of acute pyelonephritis only few cases are reported. Good results, except in the case of Proteus mirabilis infection, could be achieved. In the treatment of complicated UTI our own controlled (norfloxacin) and 13 uncontrolled Japanese studies showed cefixime to be an effective antibiotic if infections are caused by sensitive strains. Since in complicated UTI also gram-positive and nonfermenting pathogens resistant to cefixime can be found, treatment should not be initiated without sensitivity testing. Concerning treatment of UTI in children only few, but promising, results are reported. The tolerance of cefixime was similar to that of the comparative drugs. The once daily dose (400 mg), however, showed a higher incidence of gastrointestinal adverse effects than a twice daily dose (200 mg). Therefore, the daily dose should be administered in two divided doses. In summary, cefixime proved to be a good alternative in the treatment of UTI.

Anti-Infective Agents, Urinary↗

Treatment of uncomplicated gonococcal urethritis by double-dosing of 200 mg cefixime at a 6-h interval.

The efficacy of antimicrobial regimens for the treatment of uncomplicated gonococcal urethritis depends partially upon the period of time (therapeutic time) during which the drug concentration in the blood after the concentration peak is greater than four times the minimum inhibitory concentration for 90% of clinical isolates of Neisseria gonorrhoeae (MIC(90)). A therapeutic time of at least 10 h is suggested as an important determinant for elimination of 95% or more of the infection. In this study, therapeutic times for a single 400-mg dose of cefixime at various MIC(90)s were calculated, and pharmacokinetic profiles of double-dosing of 200 mg cefixime at various intervals were simulated. Subsequently, a dosing interval of 6 h was tested in 6 healthy Japanese men, and then 93 Japanese men with gonococcal urethritis were treated with a regimen of two 200-mg doses of cefixime given at a 6-h interval. For a single dose of 400 mg cefixime, therapeutic times were calculated to be 12.8, 9.1, 5.4, and 1.7 h for MIC(90)s of 0.06, 0.125, 0.25, and 0.5 microg/ml, respectively. In the simulation study of double-dosing of 200 mg cefixime at a 6-h interval, the therapeutic times for the MIC(90)s of < or =0.125 microg/ml were longer than 10 h. Of the 93 patients, 68 were evaluated for microbiological outcome, and N. gonorrhoeae was eradicated in 60 (88.2%). The MIC(90) of cefixime for the 61 isolates tested was 0.125 microg/ml. All strains with MICs of < or =0.06 microg/ml were eradicated, whereas 8 of 16 strains with MICs of > or =0.125 microg/ml persisted after treatment. This regimen would not be effective against infection by strains exhibiting cefixime MIC(90)s of > or =0.125 microg/ml. For such strains, a different regimen with a higher dose of cefixime would be required.

Anti-Bacterial Agents↗

Cefixime compared with amoxicillin for treatment of acute otitis media.

Cefixime was compared with amoxicillin for treatment of acute otitis media in a randomized trial. Results of tympanocentesis on day 3 to 5 of therapy were used as the major outcome. Total daily doses were 8 mg/kg of cefixime and 40 mg/kg of amoxicillin. One hundred twenty-six patients were randomly assigned to receive treatment; 64 cultures grew pathogens. Pathogens were eradicated from the middle ear after 3 to 5 days of therapy in 27 (79.4%) of 34 children given amoxicillin and 26 (86.7%) of 30 children given cefixime (p = 0.47). When Streptococcus pneumoniae cases were analyzed, bacteriologic cure occurred in 14 (93.3%) of 15 children given amoxicillin and 12 (75%) of 16 given cefixime (p = 0.333). When cases of Haemophilus influenzae infection were analyzed, significantly more cures occurred with cefixime (10/10, 100%) than amoxicillin (8/13, 62%) (p = 0.046). Pathogens associated with failure of amoxicillin therapy were H. influenzae (five cases, two beta-lactamase-positive), S. pneumoniae (one case), and Moraxella catarrhalis (one case, beta-lactamase-positive). The four failures with cefixime therapy were all in patients infected with S. pneumoniae. Rates of rash, diarrhea, and vomiting were the same in both groups and did not necessitate stopping therapy. We conclude the following: (1) Cefixime and amoxicillin were equivalent in overall clinical and bacteriologic efficacy for otitis media. (2) Cefixime was more efficacious than amoxicillin in treating H. influenzae otitis media and should be preferred when H. influenzae is the suspected etiologic agent. (3) Side effects of both drugs were mild and equivalent.

Acute Disease↗

Treatment of uncomplicated gonorrhea with single doses of 200 mg cefixime.

BACKGROUND: Single-dose cefixime 400 mg orally is effective in the treatment of uncomplicated gonorrhea. However, lower doses of cefixime have not been studied, and the minimum effective single-dose regimen may risk selecting resistant strains of Neisseria gonorrhoeae. Therefore, we studied the efficacy of a lower dose of cefixime. OBJECTIVE: To assess the efficacy of 200 mg cefixime in the treatment of uncomplicated gonorrhea. METHODS: One hundred twenty-five patients (106 men, 19 women) with presumptive gonorrhea were treated with single doses of cefixime 200 mg orally in an open non-comparative study. Follow-up visits were scheduled for four to seven days after treatment. RESULTS: Genital and rectal gonorrhea were eradicated in 93 (95%, CI95 90.5-99.2%) of 98 patients who were culture-positive at enrollment and returned for follow-up. Treatment was effective in 78 (95%) of 82 men with urethral infection and 15 (94%) of 16 women with anogenital infection. Two of three pharyngeal infections also were eradicated. Persistent infection was not associated with resistance to cefixime, penicillin, or tetracycline. CONCLUSIONS: Cefixime 200 mg in a single dose has substantial efficacy in the treatment of uncomplicated gonorrhea, enhancing confidence that use of 400 mg cefixime for gonorrhea has a low risk of selecting gonococci with clinically significant antibiotic resistance. However, the 200 mg dose should not be used for routine treatment.

Adolescent↗

Clinical pharmacology of cefixime in unweaned calves.

Cefixime is a unique third-generation oral cephalosporin. Its in vitro activity and pharmacokinetic properties have been studied to assess its potential for use in the therapy of newborn calf infections due to gram-negative bacteria. The minimum inhibitory concentrations of cefixime for 90% (MIC90) of field isolates of Escherichia coli, Salmonella and Pasteurella were 0.10-0.40 micrograms/mL. The serum disposition kinetics of cefixime following intravenous and oral administration was evaluated. The elimination half-life of cefixime after intravenous and oral administration was 3.5-4.0 h, the steady-state volume of distribution was 0.34 L/kg and approximately 90% of the drug was bound to serum proteins. Oral absorption was comparatively slow and bioavailability values for single 5 mg/kg doses were 20.2% after the administration of 200 mg of cefixime in capsules, 28.3% after dosing an aqueous solution of cefixime and 35.7% after fasted calves received the solution of cefixime. Mean serum drug concentrations 12 h after the cefixime solution was administered orally (5 mg/kg) were 1.05 micrograms/mL for the milk-fed calves and 1.76 micrograms/mL for the fasted calves. Computations showed that mean free drug concentrations equal to the MIC50 of the drug for gram-negative pathogens associated with newborn calf infections can be maintained in tissues by multiple treatments at 5 mg/kg every 12 h or 10 mg/kg every 24 h.

Administration, Oral↗

Mechanism of therapeutic effectiveness of cefixime against typhoid fever.

beta-Lactams have been considered ineffective against organisms growing inside mammalian cells because of their poor penetration into cells. However, cefixime has been shown to be clinically effective against typhoid fever. The probable mechanism of therapeutic effectiveness of cefixime against typhoid fever was investigated using Salmonella enterica serovar Typhimurium instead of S. enterica serovar Typhi both in a cellular and in a mouse infection model. Cefixime was able to inhibit the growth of serovar Typhimurium inhabiting monocyte-derived THP-1 cells. Elongation of serovar Typhimurium in THP-1 cells was observed microscopically. Apparent morphological changes of serovar Typhimurium in THP-1 cells were also observed by electron microscopy. The concentration of cefixime inside THP-1 cells was almost half (46 to 48%) of the concentration outside the cells when serovar Typhimurium coexisted in the solution. The length of time after oral dosing (8 mg/kg) that cefixime was present-calculated from levels in serum-at a concentration above the MIC at which 90% of the serovar Typhi organisms inside human cells were inhibited was presumed to be more than 12 h. Cefixime also showed excellent activity in the mouse systemic and oral infection models based on infections caused by serovar Typhimurium. It is concluded that a fair amount of cefixime can enter mammalian cells and inhibit the growth of bacteria inside cells when the bacteria are sensitive enough to cefixime, as are serovars Typhimurium and Typhi.

Animals↗

Double-blind comparison of cefixime and cefaclor in the treatment of acute otitis media in children.

In a double-blind study cefixime, an oral cephalosporin of the third generation, was compared to cefaclor in the treatment of acute otitis media in 397 children aged 6 months to 12 years. Clinical evaluation was carried out at the beginning, at day 10-12 and day 28-35 after the start of the treatment. Specimens for bacterial culture and sensitivity testings were taken from the nasopharynx at the initial visit. Patients were randomized either to cefixime in a dose of 8 mg/kg/day or cefaclor in a dose 40 mg/kg/day in the proportion of 2 cefixime patients to 1 cefaclor patient. Two daily doses were administered for 7 days. At day 10-12, 93.5% in the cefixime group and 90.5% in the cefaclor group (p = 0.08) were clinically cured or improved. At day 28-35 the rate of cured or improved patients had decreased, mostly due to reinfections, to 90.1% in the cefixime group and to 86.6% in the cefaclor group (p = 0.12), respectively. 375 patients (69.9%) had positive bacterial culture in the nasopharynx of at least one strain of Haemophilus influenzae, Streptococcus pneumoniae, Branhamella (Moraxella) catarrhalis or combinations of these 3.73.6% of the B. catarrhalis strains were beta-lactamase producing and 11.4% of the H. influenzae strains, respectively. All isolated bacteria were sensitive to cefixime. Adverse events were reported in 17.9% in the cefixime and 10.6% in the cefaclor group. Most reactions were of moderate or mild nature and mostly affected skin or the gastrointestinal region. No serious adverse experiences occurred. In view of the good clinical results obtained cefixime seems to be at least as effective as cefaclor in the treatment of acute otitis media in children.

Acute Disease↗

Flavonoids with epidermal growth factor-receptor tyrosine kinase inhibitory activity stimulate PEPT1-mediated cefixime uptake into human intestinal epithelial cells.

We have tested 33 flavonoids, occurring ubiquitously in foods of plant origin, for their ability to alter the transport of the beta-lactam antibiotic cefixime via the H+-coupled intestinal peptide transporter PEPT1 in the human intestinal epithelial cell line Caco-2. Of the flavonoids tested, quercetin, genistein, naringin, diosmin, acacetin, and chrysin increased uptake of [14C]cefixime dose dependently by up to 60%. All other flavonoids were either without effect or decreased the absorption of cefixime. Quercetin was shown to increase the Vmax of cefixime influx without changing the apparent Km for transport. However, the expected concomitant increase in intracellular acidification due to PEPT1-mediated cefixime/H+-cotransport was less pronounced in the presence of quercetin. This suggested that pH regulatory systems such as apical Na+/H+-exchange could be activated by quercetin and maintain the proton-motive driving force for cefixime uptake. Since quercetin and genistein have been shown to inhibit epidermal growth factor (EGF)-receptor tyrosine kinases, we applied tyrphostin 25 to prove whether such an inhibition could explain the stimulatory effects seen on cefixime uptake. It was found that tyrphostin 25 simulated the effects of quercetin by increasing cefixime absorption due to maintenance of the transmembrane pH gradient. In conclusion, our studies show that flavonoids with EGF-receptor tyrosine kinase inhibitory activities enhance the intestinal absorption of the beta-lactam antibiotic cefixime in Caco-2 cells by activation of apical Na+/H+-exchange and a concomitant increase of the driving force for PEPT1.

Caco-2 Cells↗

[Effect of sub-inhibitory concentrations of cefixime on the morphology, hemagglutination and adhesiveness of urinary strains of Escherichia coli].

The treatment of urinary tract infections is one of the indications of cefixime, a new oral cephem. The aim of the present work was to study the in vitro effect of cefixime sub- and infra-MICs on the morphology, haemagglutination and adhesiveness to epithelial cells of three uropathogenic Escherichia coli strains pretreated with sub-MICs (1/2 to 1/64 the MIC) of cefixime during growth phase (37 degrees C for 18 h). This treatment led to morphological alterations of the bacteria with filament formation. The E. coli strains showed different haemagglutination profiles (MS; MS-MR; MR). In the presence of cefixime sub-MICs (1/2 to 1/32 the MIC), MR E. coli showed a markedly altered capacity for haemagglutination (using guinea pig, human P1 and p erythrocytes). Adhesiveness was studied with human buccal cells for MS adhesins and human urothelial cells for MR adhesins. A significant decrease of adherence (70-90 per cent) was observed after pretreatment of E. coli strains with cefixime (up to 1/32 the MIC). Compared with other antibiotics active against E. coli, such as nalidixic acid, norfloxacin and ampicillin, the effect of 1/8 the MIC of cefixime on adhesiveness, was more pronounced. These results demonstrate that sub-MICs of cefixime induce a marked reduction in adhesiveness of E. coli. This property might potentiate the effectiveness of cefixime in the treatment of urinary tract infections due to E. coli.

Animals↗

H+ gradient-dependent and carrier-mediated transport of cefixime, a new cephalosporin antibiotic, across brush-border membrane vesicles from rat small intestine.

The characteristics of the transport of cefixime, a new p.o. cephalosporin, antibiotic, were studied by using brush-border membrane vesicles from the rat small intestine. The initial rate of uptake of cefixime was not affected by the presence of an inward gradient of either Na+ or other monovalent cations. With an intravesicular pHi of 7.5, optimal cefixime uptake occurred at an extravesicular pHo of 5.0, with about 6-fold acceleration compared with that in the absence of an inward proton gradient (pHi = pHo = 7.5). A protonophore, carbonyl-cyanide-4-trifluoromethoxy-phenylhydrazone, abolished the stimulating effect of low pHo. In the presence of a sufficient inward proton gradient (pHi = 7.5, pHo = 5.0), cefixime uptake showed an overshoot phenomenon and apparent saturation kinetics expressed by the Michaelis-Menten equation with the maximum rate of 2.67 +/- 0.06 nmol/30 sec/mg of protein and a Michaelis constant of 0.83 +/- 0.04 mM. Cefixime uptake was inhibited competitively by glycyl-L-proline and stimulated by the countertransport effect of this dipeptide. The other peptides also inhibited cefixime uptake significantly. A valinomycin-induced inside-negative K+-diffusion potential had a dramatic reducing effect on the uptake of dianionic cefixime. All the data obtained in this study demonstrate that cefixime transport across the brush-border membrane vesicles is carrier-mediated, independent of Na+ and dependent on a H+ gradient via the peptide transport systems.

Amino Acids↗

Increased intestinal absorption of cefixime by nifedipine in the rat intestinal perfusion model: evidence for a neural regulation.

In healthy volunteers, the simultaneous administration of nifedipine and cefixime has been shown to increase the oral absorption of the antibiotic. To investigate the pharmacological basis of this interaction, we used an in situ intestinal perfusion technique in the rat. pH 5.5 yielded optimum cefixime absorption, which was greater in segments from the duodenojejunum than in those from the jejunoileum. Cefixime absorption was similar when perfused at 0.5 and 1.0 mg/ml, suggesting transport saturation at the lower concentration. Cefixime arterial and portal blood concentrations after an intestinal perfusion of 0.5 mg/ml cefixime were significantly increased by a previous 15-min intestinal perfusion of 0.05 mg/ml nifedipine. Nifedipine did not significantly alter intestinal blood flow. At the end of the cefixime perfusion, intestinal blood flow was higher in the nifedipine group than in the control group (0.44 +/- 0.12 vs. 0.26 +/- 0.09 ml.min-1.g of intestine wt-1, respectively), although the difference did not reach statistical significance. The absorption kinetics of salicylic acid, which is strictly absorbed by passive diffusion, were unaffected by nifedipine. After 15 and 50 min of recirculation, residual salicylate levels fell from 85.1 +/- 5.6% to 57.1 +/- 2.8% with nifedipine compared with 87.4 +/- 1.4% to 52.8 +/- 1.6% without nifedipine. Thus, the improvement in cefixime absorption by nifedipine was not secondary to increased local blood flows or to induced passive diffusion mechanisms. Nifedipine did not affect intestinal motility. The action of nifedipine appears to indirect, involving a neural regulation, because any increase in cefixime absorption was prevented by tetrodotoxin and hexamethonium administration.

Animals↗

Clinical Comparison of Cefuroxime Axetil with Cefixime in the Treatment of Acute Bronchitis.

Acute bronchitis is the ninth most common outpatient illness seen by physicians in the United States. Oral antibiotic treatment is usually directed empirically against the most common bacterial pathogens associated with acute bronchitis, such as Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Although cefuroxime axetil and cefixime are both approved in the United States for treatment of acute bronchitis, currently they have not undergone direct clinical comparison for this indication. This randomized, investigator-blind, multicenter study was designed to compare the efficacy and safety of 250 mg cefuroxime axetil administered twice daily with that of 400 mg cefixime administered once daily in the treatment of acute bronchitis. Outpatients had to be greater-than-or-equal12 years of age and have signs and symptoms of acute bronchitis to be eligible for this study. Patients were randomly assigned to receive 10 days of oral treatment with either 250 mg cefuroxime axetil taken twice daily or 400 mg cefixime taken once daily. Patients were assessed for both clinical and bacteriologic responses once during treatment (3--5 days) and twice after treatment (1--3 days and 14 days). Bacteriologic assessments were based on sputum specimen cultures obtained pretreatment and posttreatment when possible. Of 465 patients with acute bronchitis who were enrolled in the study, 227 received cefuroxime axetil and 238 received cefixime. Organisms were isolated from the pretreatment sputum specimens in 172 of the 465 (37%) patients, with the primary pathogens being Haemophilus influenzae, Streptococcus pneumoniae, Morazella catarrhalis, and Staphylococcus aureus (30%, 14%, 14%, and 14% of isolates, respectively). A satisfactory clinical outcome (cure or improvement) was achieved in 88% (130 of 148) and 91% (152 of 167) of the clinically evaluable patients who had received cefuroxime axetil or cefixime, respectively (p = 0.36). Regarding the eradication of bacterial pathogens, a satisfactory outcome (cure or presumed cure) was obtained in 89% (47 of 53) and 91% (41 of 45) of bacteriologically evaluated patients who had received cefuroxime axetil or cefixime, respectively (p = 0.75). Treatment with cefixime was associated with a significantly higher incidence of drug-related gastrointestinal adverse events than was treatment with cefuroxime axetil (18% versus 10%, respectively; p = 0.01). This difference primarily reflects a higher incidence of drug-related diarrhea (15% versus 5%, p = 0.001). These results indicated the cefuroxime axetil taken twice daily is as effective as cefixime taken once daily in the treatment of acute bronchitis and that cefuroxime axetil produces fewer gastrointestinal adverse events, particularly diarrhea.

Journal Article↗

[Cefixime treatment in different bacterial infections in the ENT region].

The clinical efficacy and tolerance of cefixime were evaluated in an open uncontrolled clinical trial including 37 patients suffering from ENT-infections. The MIC90 values of this new oral cephalosporin against gram-negative pathogens are less than 1 mg/l. The antibacterial activity of cefixime against gram-negative pathogens is stronger than that of other oral cephalosporins. Cefixime was administered for five to twelve days twice daily in a dose of 200 mg. In one patient the treatment with cefixime was discontinued after five days due to perioral dermatitis. In 33 of 36 patients cure or distinct improvement was observed after cefixime treatment, showing a clinical success rate of 91.7%. Causative organisms were isolated in 17 of 37 patients (47.2%). After the cefixime therapy the causative organisms were eradicated in 13 of 17 patients (76.5%). The tolerance of cefixime is comparable with that of other oral cephalosporins.

Adolescent↗

A randomized, double-blind study comparing cefixime and trimethoprim-sulfamethoxazole in the treatment of childhood shigellosis.

We compared the clinical and bacteriologic response of 5-day treatment with cefixime, 8 mg/kg per day, with the response to trimethoprim-sulfamethoxazole (TMP-SMX), 10-50 mg/kg per day, the currently recommended therapy. Of the assessable children with acute, culture-proven shigellosis, 38 received cefixime and 39 received TMP-SMX. Pretreatment data on the two study groups were similar. In the first group, all isolates were susceptible to cefixime; in the TMP-SMX group, 32 isolates were resistant and 7 were susceptible to TMP-SMX. Clinical response (day 5) showed cure, improvement, and failure in 89%, 8%, and 3%, respectively, of the cefixime group, and in 25%, 44%, and 31%, respectively, of the TMP-SMX-resistant group (p < 0.001). Bacteriologic cure (day 3) occurred in 78% and 23% of the cefixime and TMP-SMX-resistant groups, respectively (p < 0.001). Clinical or bacteriologic relapse (day 12) was infrequent in both groups. The response to treatment of the cefixime and the TMP-SMX-susceptible groups was similar. No significant side effects were noted. We conclude that cefixime is superior to TMP-SMX in the treatment of suspected shigellosis in areas with a high rate of resistance to TMP-SMX.

Adolescent↗

Cost-effectiveness decision analysis of intramuscular ceftriaxone versus oral cefixime in adolescents with gonococcal cervicitis.

STUDY OBJECTIVE: We compared the cost-effectiveness of two single-dose treatment strategies for adolescents with uncomplicated Neisseria gonorrhoeae cervicitis. METHODS: We used a cost-effectiveness decision- analysis model to compare the two methods: the standard, ceftriaxone 125 mg given by IM injection; and an alternative, cefixime 400 mg given orally. The effect of the costs associated with the risk of accidental needlestick during IM administration was also evaluated. Key baseline assumptions (with ranges, when tested) were from the literature or costs to our hospital. These included ceftriaxone, $8.60 per dose; cefixime, $4.67 per dose; ceftriaxone efficacy, 98% (range, 94.9% to 100%); cefixime efficacy, 97% (94.1% to 100%); and a 15% probability of pelvic inflammatory disease (PID) related to failed treatment. We included costs for PID necessitating hospitalization, disseminated gonococcal infection, infertility, and ectopic pregnancy. Assumptions related to accidental needlestick included the rate of needlesticks with the disposable syringe, 6.9 per 100,000 injections (range, 0 to 69); cost of accidental needlestick to hospital; risk of HIV seroconversion after needlestick exposure to HIV-infected blood, .36% (range, 0% to .86%); rate of HIV infection in 15- to 19-year-olds attending sexually transmitted diseases clinics, .4% (range, 0 to 5); and lifetime treatment costs for a person with HIV. RESULTS: At baseline values the model favored ceftriaxone ($45 per patient) or cefixime ($59 per patient). However, over the range of efficacy of both drugs, two-way sensitivity analysis revealed no consistent cost advantage for either drug. The model was also insensitive to the economic effects associated with the risk of accidental needlestick during IM injection. CONCLUSION: over the range of efficacy by the 95% confidence intervals of both drugs, our analysis demonstrated no clear cost advantage for either. The economic effects of accidental needlestick do not change this conclusion. Compared with the IM alternative, oral cefixime is painless to the patient and simpler for the practitioner to administer. Oral cefixime also eliminates the psychologic effects associated with needlesticks in health care workers. For these reasons, we favor the use of oral cefixime for uncomplicated gonococcal cervicitis in adolescents.

Administration, Oral↗

Randomized, open label, multicenter trial of cefixime compared with amoxicillin for treatment of acute otitis media with effusion.

Cefixime, a new third generation cephalosporin antibiotic for oral use, was evaluated for safety and efficacy in the treatment of children with acute otitis media with effusion. Fifteen United States clinical investigators participated in the multicenter clinical trial. One hundred twenty children were randomly assigned to a 10-day course of either cefixime, 8 mg/kg, given daily (qd) (60 patients) or amoxicillin, 40 mg/kg/day, administered in three divided doses (60 patients). Tympanocentesis was performed on each patient before therapy was initiated. Pathogens were isolated from a middle ear aspirate in 88% of the cases. Of the specimens from which pathogens were cultured, 33% yielded Haemophilus sp., 41% Streptococcus pneumoniae and 6% Branhamella catarrhalis. Of the 120 patients, 64 (30 cefixime and 34 amoxicillin) were evaluable for assessment of efficacy. Favorable clinical responses (cure or improvement) were obtained in 93% of cefixime-treated patients and in 94% of amoxicillin-treated patients. Overall, bacteriologic eradication rates (as determined by clinical criteria) were 94 and 95%, respectively. Clinical failure or relapse was documented in 2 of 30 (7%) patients treated with cefixime and in 2 of 34 (6%) patients treated with amoxicillin. Gastrointestinal disturbance and rash were significantly more common in children treated with cefixime (22 and 15%, respectively) than in those taking amoxicillin (8 and 2%, respectively), but in only one case was it necessary to discontinue medication because of these adverse effects (rash). Results of this study demonstrate that cefixime given once daily is as safe and effective as amoxicillin in the treatment of acute otitis media with effusion in children and has the possible advantage of less frequent dosing.

Acute Disease↗

[Effects of cefixime and cefaclor on pharyngeal flora in children].

Influences of cefixime and cefaclor, oral antibiotics, were studied in 50 children (age range, 11 months to 13 years) with pharyngitis. Daily doses of cefixime were 6 to 10 mg/kg in 25 children and those of cefaclor were 40 to 50 mg/kg in 25 children. Pharyngeal swabs were taken before and after 3 to 7 days of the antibiotic treatment. Pathogenic organisms, such as Streptococcus pyogenes, Haemophilus influenzae and Streptococcus pneumoniae, were isolated in 14 children before and in 1 child after cefixime use. But these bacteria were isolated in 15 children before and in 9 children, and 3 strains of H. influenzae and 3 strains of S. pneumoniae were newly isolated after cefaclor use. An isolation rate of Gram-negative bacilli, such as Acinetobacter spp., were increased after use of cefixime. In both antibiotics, isolation rates of yeasts were slightly increased. An isolation rate of alpha-hemolytic streptococci was increased from 16% to 48% by cefixime treatment and from 24% to 52% by cefaclor treatment. The MIC50 of cefixime and cefaclor against alpha-hemolytic streptococci isolated after treatment was higher than that isolated before. Effects of cefixime and cefaclor was less extensive than that of ampicillin in previous reports.

Adolescent↗

In vitro activity of cefixime (CL284635) and other antimicrobial agents against Haemophilus isolates from pediatric patients.

In vitro activity of cefixime, an experimental oral third-generation cephalosporin and 7 other antimicrobials (ampicillin, augmentin, trimethoprim/sulfamethaxazole, cefamandole, cefotaxime, cefuroxime, and cefaclor) were determined for 150 isolates of Haemophilus obtained from pediatric patients. All (109) non-typeable H. influenzae isolates were sensitive to cefixime and cefotaxime. All (18) isolates of H. parainfluenzae were sensitive to cefotaxime, cefuroxime, cefamandole, cefaclor, and augmentin; 17/18 isolates were sensitive to cefixime. All (23) isolates of H. influenzae-b were sensitive to cefixime, cefotaxime, cefamandole, cefuroxime, cefaclor, and augmentin. Only 10/23 were sensitive to tri/sulfa. 137 of 150 (91.3%) isolates had MBCs equivalent to their MICs for cefixime, compared to 149/150 (99.3%) isolates for cefotaxime. Approximately 95% (143/150) of isolates tested had MICs of less than or equal to 0.06 microgram/ml for cefixime. These data demonstrate that in vitro cefixime has good activity against Haemophilus isolates and it is very similar to the activity of cefotaxime.

Anti-Bacterial Agents↗