7432-s and Bacterial-Infections

Respiratory infections in children may occur as a consequence of resistant bacterial pathogens. Streptococcus pneumoniae organisms resistant to penicillin, trimethoprim/sulfamethoxazole and macrolides are increasingly prevalent. Amoxicillin- and macrolide-resistant Haemophilus influenzae and Moraxella (Branhamella) catarrhalis are also more commonly seen. Traditional agents such as amoxicillin and trimethoprim/sulfamethoxazole remain acceptable choices for most children with respiratory infections because currently most patients are not infected by resistant pathogens and there is a high spontaneous cure rate associated with these infections.. To analyze the criteria for the selection of extended spectrum antimicrobials as empiric therapy for respiratory infections.. When an extended spectrum antimicrobial is appropriate for empiric therapy, selection should be based on: (1) efficacy; (2) adverse event profile; and (3) compliance-enhancing features (dosing with meals, once or twice daily administration, good palatability in suspension, shortened course of therapy and affordability). A new agent, ceftibuten, has recently joined other extended spectrum cephalosporins and newer macrolides (clarithromycin and azithromycin) as a choice to be considered for empiric therapy for respiratory infections. These antimicrobials are differentiated from each other and traditional agents by differences in activity in vitro against penicillin-resistant pneumococci, relative beta-lactamase stability against Gram-negative bacteria and pharmacodynamic properties. When resistant organisms are isolated or suspected in community-acquired respiratory infections, cautious use of newer antibiotics may have to be considered.

Topics: Anti-Bacterial Agents; Bacterial Infections; beta-Lactamases; Ceftibuten; Cephalosporins; Child; Child, Preschool; Drug Resistance, Microbial; Drug Therapy; Empiricism; Humans; Patient Compliance; Penicillin Resistance; Respiratory Tract Infections; Taste

To discuss the pharmacokinetics, spectrum of activity, clinical trials, and adverse effects of cefprozil, cefpodoxime proxetil, loracarbef, cefixime, and ceftibuten, an investigational cephalosporin.. Literature was identified by a MEDLINE search from 1986 to January 1995.. 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 were evaluated with respect to in vitro activity, study design, clinical and microbiologic outcomes, and adverse drug reactions.. 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.. 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.

Topics: Bacterial Infections; Cefixime; Cefotaxime; Cefpodoxime Proxetil; Cefprozil; Ceftibuten; Ceftizoxime; Cephalosporins; Humans; Microbial Sensitivity Tests; Prodrugs; Randomized Controlled Trials as Topic

Ceftibuten suspension was administered to 1312 pediatric patients in clinical trials at a dosage of 9 mg/kg once daily, with a maximal daily dose of 400 mg. Adverse experiences were collected by voluntary reports by physicians from direct observations, parental and/or patient complaints in 1152 patients. In 160 patients gastrointestinal adverse experiences were elicited at each visit in addition to voluntary reports. Patients had a mean age of 4.9 years, the male: female ratio was 1:1 and 72% were white. Fifty-five percent (719 of 1312) of patients were treated in otitis media studies, 33% (438 of 1312) were treated in a pharyngitis study and 12% (155 of 1312) were treated in other studies. Adverse experiences occurred in 10% (138 of 1312) of all patients receiving ceftibuten suspension. The most common voluntarily reported treatment-related adverse events were diarrhea 3% (34 of 1152) and vomiting 2% (22 of 1152). For elicited adverse events related to treatment, the most common were also diarrhea 9% (14 of 160) and vomiting 3% (5 of 160). There were no deaths and only 0.9% (12 of 1312) patients discontinued treatment because of adverse events. Abnormal laboratory values related to therapy were uncommon and no patient discontinued treatment because of abnormal laboratory values. No cases of Stevens-Johnson syndrome, toxic epidermal necrolysis, serum sickness-like reactions or pseudomembranous colitis have been observed with ceftibuten suspension in research studies to date.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Bacterial Infections; Ceftibuten; Cephalosporins; Child; Child, Preschool; Clinical Trials as Topic; Drug Evaluation; Female; Humans; Infant; Male; Suspensions; Treatment Outcome

Ceftibuten is a new, orally administered cephalosporin with exceptional beta-lactamase stability and potency against commonly isolated Gram-negative pathogens. More than 90% of recent Enterobacteriaceae clinical isolates were inhibited by < or = 8 micrograms/ml of ceftibuten. In only five enteric species (Citrobacter freundii, Enterobacter aerogenes, Enterobacter cloacae, Morganella morganii, Serratia marcescens) were more than 15% of strains resistant (minimal inhibitory concentrations (MIC, with percent of strains inhibited in subscript numbers) > 16 micrograms/ml) to ceftibuten. Enteritis-producing bacteria such as Salmonella, Shigella, Escherichia coli and Yersinia were very ceftibuten-susceptible (MIC50 < or = 0.13 microgram/ml). Fastidious Gram-negative species causing respiratory tract or genital infections had very low ceftibuten MICs, including beta-lactamase-positive Haemophilus influenzae (MIC90 0.06 to 2 micrograms/ml), Moraxella catarrhalis (MIC90 0.25 to 4 micrograms/ml), and Neisseria gonorrhoeae (MIC90 0.015 to 0.5 microgram/ml). Beta-hemolytic streptococci and penicillin-susceptible pneumococci were also inhibited by ceftibuten. Staphylococci, enterococci, Pseudomonas species and Gram-negative anaerobic bacteria were generally resistant to ceftibuten. Ceftibuten has demonstrated bactericidal activity against susceptible pathogens, has high affinity for several lethal penicillin-binding proteins and possesses stability to common plasmid- or chromosomal-mediated beta-lactamases, including those enzymes that hydrolyze parenteral third generation cephalosporins. The microbiologic features for ceftibuten indicate its clinical potential as chemotherapy for community-acquired respiratory tract infections.

Topics: Bacteria; Bacterial Infections; Ceftibuten; Cephalosporins; Humans; Microbial Sensitivity Tests; Sensitivity and Specificity; Structure-Activity Relationship

Ceftibuten, a new orally absorbed cephalosporin with a novel side chain, has broad in vitro activity against most of the important respiratory pathogens including Streptococcus pneumoniae and both beta-lactamase-negative and beta-lactamase-positive Haemophilus influenzae and Moraxella (Branhamella) catarrhalis. Furthermore it has high activity against Enterobacteriaceae, which contain classic TEM-1 beta-lactamases and those containing the new extended spectrum beta-lactamases, which hydrolyze parenteral third generation cephalosporins. Studies have shown that ceftibuten has a postantibiotic effect comparable to that of other beta-lactams against S. pneumoniae, H. influenzae and M. catarrhalis. Blood levels achieved after a single 400-mg dose given once daily or 9 mg/kg/day taken once daily for children yield blood levels and postantibiotic inhibition for the majority of a dosing period. The in vitro and pharmacokinetic data can be correlated to provide reasonable dosing programs for the new oral cephalosporins.

Topics: Bacteria; Bacterial Infections; beta-Lactamases; Ceftibuten; Cephalosporins; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Microbial Sensitivity Tests; Respiratory Tract Infections

The bioavailability and pharmacokinetics of ceftibuten administered as an oral suspension were characterized by several studies in young healthy male adults (19 to 39 years old) and children ranging in age from 6 months to 17 years. Ceftibuten suspension was found to be bioequivalent and thus interchangeable with a standard 400-mg capsule. As with the capsule formulation, food slightly (< 20%) affected the rate and extent of absorption of the suspension. The recommended dose of 9.0 mg/kg was found to produce comparable plasma concentrations in children of all ages (6 months to 17 years). The range of mean values of maximum plasma concentrations (Cmax) was 12 to 16 micrograms/ml at the 9.0-mg/kg dose level. Doses of 4.5, 9.0 and 13.5 mg/kg produced Cmax and area under the plasma concentration-time curve values that were dose-proportional. The half-life (t1/2) was essentially independent of age and dose, ranging from 2 to 3 hours. The apparent clearance (Cl/F), uncorrected for the fraction of drug absorbed (F), is independent of dose but appears to increase with a decrease in age. This also occurs to a lesser degree with the volume of distribution (Vd/F), uncorrected for F. Current evidence suggests that this is more likely to be caused primarily by a decrease in F than an increase in Cl. Ceftibuten rapidly and extensively reaches the middle ear fluid in children with acute otitis media. Within 4 hours concentrations in middle ear fluid are similar to plasma concentrations and can be measured for 12 hours. The ratio of area under the concentration time curve for middle ear fluid relative to plasma was about 70%.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Adolescent; Adult; Age Factors; Bacterial Infections; Biological Availability; Ceftibuten; Cephalosporins; Child; Child, Preschool; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Infant; Male; Suspensions

Topics: Administration, Oral; Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Bacterial Infections; Cefixime; Cefotaxime; Cefpodoxime Proxetil; Cefprozil; Ceftibuten; Ceftizoxime; Cefuroxime; Cephalosporins; Child; Clarithromycin; Fluoroquinolones; Humans

Topics: Adult; Aged; Animals; Bacterial Infections; Ceftibuten; Cephalosporins; Female; Humans; Male; Mice; Mice, Inbred Strains; Microbial Sensitivity Tests; Respiratory Tract Infections; Urinary Tract Infections

117 patients suffering for bacterial exacerbation of chronic bronchitis were treated with ceftibuten, a new orally administered cephalosporin, at the dosage of 400 mg once a day for 7.9 days (range 5-14). The results, referring to 105 evaluable patients, underlyne ceftibutent's efficacy (good clinical results in 96.1% of 102 treated patients) and safety; before and after treatment values of spirometric tests were notable in terms of improvement of lung functions.

Topics: Aged; Bacterial Infections; Bronchitis; Ceftibuten; Cephalosporins; Chronic Disease; Female; Humans; Male; Middle Aged

A randomized, controlled, single blind clinical trial was conducted in children with acute otitis media to evaluate the safety and efficacy of a 10-day course of therapy with ceftibuten 9 mg/kg taken as a single daily dose, up to a maximum daily dose of 400 mg, compared with cefaclor 40 mg/kg/day in three divided doses, up to a maximum of 1 g/day. Patients were evaluated any time from 1 to 3 days after completion of therapy (posttreatment follow-up). A total of 154 patients (106 ceftibuten, 48 cefaclor) were evaluable for efficacy. Clinical success as determined by resolution (cure) or improvement of signs and symptoms of infection were seen in 89 and 88% of patients treated with ceftibuten and cefaclor, respectively, at the posttreatment follow-up visit. At the extended follow-up visit (any time from 2 to 4 weeks after completion of therapy), clinical success was sustained in 88 and 82% of the ceftibuten-treated and cefaclor-treated patients, respectively. A total of 391 patients (264 ceftibuten, 127 cefaclor) were included in the safety analysis. Treatment-related adverse experiences occurred in 8% of ceftibuten-treated patients and 14% of cefaclor-treated patients. All were mild or moderate and the majority were gastrointestinal. There were no deaths or serious adverse events. The results of this study suggest that ceftibuten is an effective and well-tolerated alternative to other antibiotic therapies for the treatment of children with acute otitis media.

Topics: Acute Disease; Adolescent; Bacterial Infections; Cefaclor; Ceftibuten; Cephalosporins; Child; Child, Preschool; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Infant; Male; Otitis Media with Effusion; Prospective Studies; Single-Blind Method; Treatment Outcome

The efficacy and safety of a once-daily oral regimen of 400 mg ceftibuten was compared with oral co-amoxiclav 500 mg three times daily in a multicentre, single-blind study. In patients with a bacteriologically confirmed infection, a successful clinical outcome was reported in 25 of 25 patients treated with ceftibuten and 10 of 10 patients treated with co-amoxiclav. In a further group of 88 patients, most of whom had been excluded from the primary efficacy evaluation because no pathogen was isolated pretreatment, overall successful clinical outcomes of 87% and 88% were reported for ceftibuten and co-amoxiclav, respectively. The duration of treatment and the time to resolution of the signs and symptoms of sinusitis were not significantly different in the two treatment groups. The incidence of adverse events was higher in the co-amoxiclav-treated patients (31% versus 15% in the ceftibuten group) as was the incidence of severe events (10% for co-amoxiclav-treated patients versus < 1% in the ceftibuten group). In summary, once-daily ceftibuten can be considered a safe and effective treatment for acute bacterial sinusitis.

Topics: Acute Disease; Adult; Aged; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Bacterial Infections; Ceftibuten; Cephalosporins; Clavulanic Acids; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Single-Blind Method; Sinusitis

Topics: Acute Disease; Bacterial Infections; Ceftibuten; Cephalosporins; Chronic Disease; Clavulanic Acid; Drug Resistance, Multiple; Humans; Mometasone Furoate; Penicillanic Acid; Pregnadienediols; Sinusitis; Treatment Outcome

The aim of this study was to determine the distribution of uropathogens isolated from outpatients living in South Croatia and the in vitro susceptibility of these organisms to antimicrobial agents. Of 5080 enrolled uropathogen isolates, 82.28% isolates were Gram-negative, the most frequent isolates being Escherichia coli (62.62%), enterococci (10.18%), Proteus mirabilis (5.31%), Streptococcus agalactiae (3.84%), Staphylococcus spp. (3.70%), Pseudomonas spp. (3.46%), Klebsiella spp. (2.38%). The E. coli resistance rate was 42.17% to amoxycillin, 20.59% to trimethoprim-sulphamethoxazole and 6.09% to norfloxacin. Almost all Klebsiella spp. isolates were resistant to amoxycillin and the resistance rate to trimethoprim-sulphamethoxazole was over 20%, and 14.15% to the fluoroquinolones. A high methicillin-resistance rate was found among S. aureus (61.22%) and coagulase negative staphylococci (41.48).

Topics: Amoxicillin; Anti-Bacterial Agents; Bacterial Infections; Ceftibuten; Cephalosporins; Clavulanic Acid; Croatia; Drug Resistance, Bacterial; Escherichia coli; Gram-Negative Bacteria; Humans; Nitrofurantoin; Norfloxacin; Sulfamethoxazole; Trimethoprim; Urinary Tract Infections

Topics: Administration, Topical; Bacterial Infections; Ceftibuten; Cephalosporins; Drug Therapy, Combination; Humans; Mometasone Furoate; Pregnadienediols; Sinusitis

In a multicentric study at several leading hospitals of this country, microbiological assessment was carried out in 500 specimens from patients suffering from respiratory tract infections (RTIs; both upper and lower) for a period of 6 months from January, 1999 to June, 1999. The antibiotic sensitivity study was done in 201 isolates from 500 different specimens of throat swab, postpharyngeal swab, sinusitis drainage fluid, sputum, broncho-alveolar lavage (BL), etc. Ceftibuten, an orally active third generation cephalosporin showed encouraging results when compared with seven other selected antibiotics used for RTI. The majority of the patients with acute or chronic RTIs showed an excellent in vitro response to ceftibuten in the analysis of the isolates. Seventy to ninety per cent of the isolated respiratory pathogens were found to be sensitive to ceftibuten in vitro; which offers a promising alternative to other antibiotics included in this study.

Topics: Administration, Oral; Bacteria; Bacterial Infections; Ceftibuten; Cephalosporins; Humans; India; Microbial Sensitivity Tests; Respiratory Tract Infections

The postantibiotic effect (PAE) of ceftibuten, a novel beta-lactamase-stable cephem, was determined for Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. The ceftibuten PAE after a 2-hour exposure to 2 micrograms/ml (4 x minimum inhibitory concentration) for S. pyogenes was 2.7 to > 10 hours. The PAE for S. pneumoniae after a 2-hour exposure to 15 micrograms/ml, concentrations that are achieved in man after usual therapeutic doses, was 1.1 to 3.4 hours and the PAE for H. influenzae was 1 to 1.1 hours. M. catarrhalis had a PAE of 1.5 to 1.8 hours after exposure to 15 micrograms/ml of ceftibuten. The ceftibuten PAE was not affected by serum. The ceftibuten PAE was prolonged by exposure to a sub-minimum inhibitory concentration concentration of ceftibuten as would occur in the clinical situation. The PAE of ceftibuten was not affected by the copresence of erythromycin as would occur when treating infections in which atypical organisms are suspected. There was no correlation between bacterial reduction in colony-forming units and the duration of PAE. A level of 6 micrograms/ml of ceftibuten had a similar bacterial killing activity compared with a 6-hour exposure to 15 micrograms/ml of ceftibuten against S. pneumoniae, H. influenzae and M. catarrhalis. This study suggests that ceftibuten can be administered orally, once daily in an adult dose of 400 mg or a pediatric dose of 9 mg/kg, to treat respiratory infections caused by the most common pathogens.

Topics: Bacterial Infections; Ceftibuten; Cephalosporins; Haemophilus influenzae; Humans; Microbial Sensitivity Tests; Moraxella catarrhalis; Respiratory Tract Infections; Streptococcus pneumoniae; Streptococcus pyogenes

The duration of time that serum drug levels remain above the MIC (time above the MIC) for the pathogen has been shown to be the most significant parameter determining the efficacies of beta-lactam antibiotics. In the described study, we investigated the optimal time above the MIC of ceftibuten and cefaclor using a nonneutropenic mouse model of intra-abdominal infections caused by Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Streptococcus pneumoniae. The abilities of the drugs to protect mice against the organisms were determined in mouse protection tests, and the doses were fractionated to produce various dosing regimens with different times above the MIC. All drug-organism combinations showed a significant correlation (r > 0.9) between drug efficacy and the time above the MIC. Also, with ceftibuten treatment, the different dosing regimens that produced equal times above the MIC resulted in the same efficacy, whereas with cefaclor, an apparent dose-dependent effect was observed. These results showed that for a 100% recovery from K. pneumoniae and E. coli infections, the optimal times above the MIC with ceftibuten treatment were 2.2 and 1.6 h, respectively. Relatively high doses of both antibiotics were required to ensure recovery from S. pneumoniae infections. In vitro time-kill studies demonstrated that cefaclor exhibits a marked inoculum effect against the pathogens, and there was a concentration-dependent killing at a large inoculum size. On the other hand, ceftibuten showed no inoculum effect. It is suggested that optimization of both dose and time above the MIC appears to be necessary for the treatment of S. aureus infections with cefaclor, and this may apply to other beta-lactams tht exhibit marked inoculum effects.

Topics: Abdomen; Animals; Bacterial Infections; Cefaclor; Ceftibuten; Cephalosporins; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Half-Life; Mice; Time Factors

In a multicentre, international study of 187 adult patients with bacterial pneumonia or bronchiectasis, the safety and efficacy of a regimen of 200 mg ceftibuten administered twice-daily was compared with cefaclor given in a dosage of 500 mg three times a day. Of the 94 evaluable patients, 66 received ceftibuten and 28 received cefaclor. The overall bacteriological response was similar in the two treatment groups with elimination of the original pathogen in 91% and 89% of the patients receiving ceftibuten and cefaclor, respectively. The overall clinical response mirrored the bacteriological results with a successful clinical outcome in 92% of ceftibuten-treated patients compared with 93% in patients receiving cefaclor. Adverse experiences were, in general, few and mild, being reported in 8% and 17% of patients receiving ceftibuten and cefaclor, respectively.

Topics: Adolescent; Adult; Aged; Bacteria; Bacterial Infections; Bronchiectasis; Cefaclor; Ceftibuten; Cephalosporins; Female; Humans; Male; Middle Aged; Pneumonia

Efficacies of ceftibuten (CETB, 7432-S, 200 mg/capsule) in urinary tract infections (UTI) were studied. The results of the study are summarized as described below. 1. CETB was administered to 15 complicated chronic cases of UTI using a dose level of 400 mg per day. The efficacy rates determined according to the criteria prescribed by the UTI committee and according to physicians' judgements were 81.8% and 92.3%, respectively. Bacteriological efficacy rates were 100% against Gram-negative rods and 87.5% against Gram-positive cocci. 2. Only 1 case of adverse reaction, slight dizziness, was noted. 3. CETB appears to be the most useful agent of the new oral cephems against strains of Serratia marcescens which are resistant to new quinolones.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Bacterial Infections; Capsules; Ceftibuten; Cephalosporins; Drug Resistance, Microbial; Female; Humans; Male; Middle Aged; Serratia marcescens; Urinary Tract Infections

The in-vitro activity of ceftibuten was compared with cefuroxime and cefadroxil against 475 clinically-significant, epidemiologically-distinct isolates of Gram-negative bacilli: 170 from blood, 212 from urine and 93 from a supplementary collection of multiply-resistant strains known to have resistance plasmids, to have caused sporadic or epidemic nosocomial infection, or both. Ceftibuten MICs ranged from 0.003 to greater than 32 mg/l, with a modal MIC of 0.01 mg/l: 95% of all isolates had ceftibuten MIC values of less than or equal to 8 mg/l, the sensitivity breakpoint suggested by the manufacturer. Ninety per cent of isolates had MICs of less than or equal to 1 mg/l and 49% had MICs of less than or equal to 0.03 mg/l. All isolates of Klebsiella, Serratia, Proteus and Providencia spp., and Morganella morganii had MIC values of 8 mg/l or less. Only two of 124 isolates of Escherichia coli tested, and only one of 23 Citrobacter spp., had MICs of greater than 8 mg/l (16, 16 and greater than 32 mg/l respectively). Resistance MIC greater than 16 mg/l) was more frequent among Enterobacter and Acinetobacter spp. Thirteen of 52 Enterobacter spp., and seven of 18 Acinetobacter calcoaceticus had MICs of at least 32 mg/l. MIC ranges, modal MICs and MIC90s indicated that ceftibuten was, with the exception of only two strains, consistently more active in-vitro than cefuroxime, which was in turn more active than cefadroxil.

Topics: Bacterial Infections; Cefadroxil; Ceftibuten; Cefuroxime; Cephalosporins; Drug Resistance, Microbial; Gram-Negative Bacteria; Humans; Microbial Sensitivity Tests