ly-163892 and Bacterial-Infections

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

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: Aztreonam; Bacterial Infections; Cephalosporins; Humans; Imipenem; Microbial Sensitivity Tests

To discuss the in vitro activity, pharmacokinetics, clinical efficacy, adverse effects, and relative merits of loracarbef, a new orally administered carbacephem antibiotic.. Pertinent literature was identified by a review of selected journals and a MEDLINE search. Additional information was provided by the manufacturer of loracarbef.. All studies that have evaluated the clinical efficacy of loracarbef were included. In vitro studies were included if they used similar methodologies. Additional information was incorporated regarding the chemistry, pharmacokinetics, and adverse effects of loracarbef.. Loracarbef has antibacterial activity against most community-acquired respiratory tract, skin and skin structure, and urinary tract pathogens. The drug is well absorbed after oral administration and plasma concentrations achieved in patients are greater than the in vitro minimum inhibitory concentrations for most of the above bacteria. Although the majority of the clinical studies with loracarbef have methodologic deficiencies, loracarbef therapy has demonstrated similar efficacy in the treatment of upper respiratory tract (except otitis media), lower respiratory tract, skin and skin-structure, and urinary tract infections compared with accepted antibiotics. Potential advantages of the new carbacephem may be improved patient compliance with its less frequent dosing schedule (once or twice a day, depending on the infection), and a low incidence of adverse effects.. Preliminary data indicate that loracarbef may be an alternative agent for the treatment of a variety of community-acquired infections. Additional clinical experience and rigorously controlled comparative clinical trials are necessary to enable practitioners to fully define the therapeutic role of loracarbef.

Topics: Administration, Oral; Bacterial Infections; Cephalosporins; Drug Interactions; Humans; Microbial Sensitivity Tests

The treatment of bacterial pneumonia requires an agent with activity against a wide range of bacterial pathogens, including pathogens that produce beta-lactamase. Loracarbef, a member of the carbacephem class of antibiotics, was tested in a series of clinical trials for its efficacy and safety in the treatment of lobar and bronchial bacterial pneumonia. Successful clinical responses were achieved in 97.6% of the evaluable patients receiving 400 mg twice daily of loracarbef. This compared favorably with the respective response rates of 92.3% for patients receiving 500 mg three times a day of amoxicillin/clavulanate and 95.0% for patients receiving 500 mg three times a day of amoxicillin for the same illnesses. Proven or presumed elimination of the pretherapy pathogen was found in 89% of the patients receiving loracarbef, 92.3% of the amoxicillin/clavulanate-treated patients, and 70.0% of those receiving amoxicillin. Loracarbef was also well tolerated, although nausea and vomiting were associated with the use of all three agents. Nevertheless, treatment with loracarbef resulted in the lowest rate of discontinuation of therapy due to drug-related adverse events. Thus, these clinical trials support the conclusion that loracarbef is a safe and effective treatment for bacterial pneumonia.

Topics: Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Bacterial Infections; Cephalosporins; Clavulanic Acids; Drug Therapy, Combination; Humans; Nausea; Pneumonia; Randomized Controlled Trials as Topic; Vomiting

To compare the efficacy and safety of five-day cefdinir treatment with seven-day loracarbef treatment in patients with acute exacerbations of chronic bronchitis, 586 patients were enrolled in a multicentre, randomised, double-blind trial. Patients received either five days of treatment with cefdinir (n = 291) at 300 mg twice daily or seven days of treatment with loracarbef (n = 295) at 400 mg twice daily. Microbiological assessments were done on sputum specimens obtained at admission and at the two post-therapy visits, if available. The clinical cure rates were 86% (138/160) and 85% (141/166) for the evaluable patients treated with cefdinir and loracarbef, respectively. Respiratory tract pathogens were isolated from 457 (78%) of 586 admission sputum specimens, with the predominant pathogens being Haemophilus parainfluenzae, H. influenzae, Moraxella catarrhalis and Staphylococcus aureus. The microbiological eradication rates at the test-of-cure visit were 88% (193/219 pathogens) and 90% (227/251 pathogens) for the evaluable patients treated with cefdinir and loracarbef, respectively. Adverse event rates while on treatment were 30% and 21% for cefdinir- and loracarbef-treated patients, respectively. These results indicate that a five-day regimen of cefdinir is effective and safe for the treatment of patients with acute exacerbations of chronic bronchitis.

Topics: Adolescent; Adult; Aged; Anti-Infective Agents; Bacterial Infections; Bronchitis; Cefdinir; Cephalosporins; Chronic Disease; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Prospective Studies; Sputum; Treatment Outcome

Topics: Administration, Oral; Analysis of Variance; Area Under Curve; Bacterial Infections; Biological Availability; Cephalosporins; Child; Child, Preschool; Female; Humans; Male; Suspensions; Tablets

Loracarbef (LY 163892), a beta-lactam antibiotic (carbacephem), was compared with amoxicillin/clavulanate potassium in a 10-day, single-blind, randomized parallel trial in the treatment of acute bacterial maxillary sinusitis. Based on posttherapy aspirate and culture, there was a 95.2% bacteriologic cure rate in patients receiving loracarbef (400 mg twice daily) and an 86.7% cure rate in patients receiving amoxicillin/clavulanate (500/125 mg three times daily) (p = 0.359). Loracarbef was comparable in efficacy to amoxicillin/clavulanate with a more desirable safety profile.

Topics: Adolescent; Adult; Aged; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Bacterial Infections; Cephalosporins; Clavulanic Acids; Decision Trees; Drug Therapy, Combination; Female; Humans; Male; Maxillary Sinusitis; Middle Aged; Severity of Illness Index

The efficacy and safety of loracarbef, a new beta-lactam antibiotic, was compared with that of amoxicillin-clavulanate potassium in the treatment of bacterial acute otitis media with effusion. A double-blind format was utilized to administer 10-day, randomized, parallel treatment regimens to patients who were between 6 months and 12 years of age. The most prevalent causative pathogens found in the two treatment groups were Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella (Branhamella) catarrhalis. The percentages of favorable posttherapy clinical responses in evaluable patients were similar for both drugs: 87.3% (124/142) of the loracarbef group, compared with 91.5% (130/142) of the amoxicillin-clavulanate group, showed favorable responses within 72 hours after treatment. Ten to sixteen days after treatment, 68.1% of the loracarbef group, compared with 76.1% of the amoxicillin-clavulanate group, showed favorable responses. More patients in the amoxicillin-clavulanate group reported treatment-emergent events: 46.1% compared with 35.8% in the loracarbef group (p = 0.023). Diarrhea was the most frequently reported event, occurring in 13.3% of the loracarbef group and in 26.3% of the amoxicillin-clavulanate group (p less than 0.001). Vomiting was reported by 5.8% of the loracarbef group and 10.3% of the amoxicillin-clavulanate group (p = 0.072). Loracarbef is comparable in efficacy to amoxicillin-clavulanate in the treatment of bacterial acute otitis media with effusion and has a more desirable safety profile.

Topics: Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Bacterial Infections; Cephalosporins; Clavulanic Acids; Double-Blind Method; Drug Evaluation; Drug Therapy, Combination; Female; Haemophilus influenzae; Humans; Infant; Male; Moraxella catarrhalis; Otitis Media with Effusion; Streptococcus pneumoniae

Loracarbef (LY163892), a member of the class of beta-lactam antibiotics known as carbacephems, is characterized by a high level of chemical stability and a broad spectrum of antibacterial activity that persists in the presence of beta-lactamase. The efficacy and safety of loracarbef, 200 mg (twice daily), and cefaclor, 250 mg (three times daily) (one patient received 178 mg of cefaclor suspension, three times daily), were compared in a randomized, double-blind, multicenter trial conducted in adults with skin and skin-structure infections due predominantly to Staphylococcus aureus. Examination within 72 hours after the completion of therapy indicated a favorable clinical response in 84 (93.3%) of the 90 loracarbef-treated patients evaluable for efficacy and in 79 (95.2%) of the 83 evaluable patients treated with cefaclor. Pathogens were eradicated in 83 (92.2%) of the patients in the loracarbef group and 74 (89.2%) of those in the cefaclor group. Only four adverse events--headache/migraine, diarrhea, abdominal pain, and nausea--occurred in greater than 2% of the total study population. The overall incidence of adverse events in the 201 loracarbef-treated and 192 cefaclor-treated patients evaluated for safety was 19.9% and 24.5%, respectively. Adverse events that required hospitalization or discontinuation of treatment occurred in four patients in the cefaclor group but in none of those treated with loracarbef. There were no statistically significant differences in the clinical or bacteriologic response or the incidence of side effects between the two treatment groups. These findings indicate that loracarbef given twice daily is comparable in safety and efficacy to cefaclor given three times daily in the treatment of adults with skin and skin-structure infections.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacterial Infections; Cefaclor; Cephalosporins; Child; Double-Blind Method; Gastrointestinal Diseases; Headache; Humans; Incidence; Middle Aged; Skin Diseases, Infectious; Treatment Outcome

The in vitro activity of a new orally administered carbacephem analog of cefaclor, loracarbef (LY163892), was compared with those of cefaclor and several other oral antimicrobial agents against recent clinical isolates of Haemophilus influenzae and Moraxella catarrhalis. Loracarbef was found to be slightly more active than cefaclor against H. influenzae and had activity essentially equivalent to that of cefaclor for M. catarrhalis. Resistance to loracarbef was uncommon and was noted only with rare beta-lactamase-producing strains of H. influenzae. On the basis of these observations, loracarbef may be of utility in the management of localized, non-life-threatening infections caused by H. influenzae and M. catarrhalis.

Topics: Anti-Bacterial Agents; Bacterial Infections; beta-Lactamases; Cephalosporins; Haemophilus Infections; Haemophilus influenzae; Humans; Microbial Sensitivity Tests; Moraxella catarrhalis; Respiratory Tract Infections

KT3777 is a novel carbacephem antibiotic structurally identical to cefaclor (CCL), except that the sulfur atom of position 1 of the cephem nucleus has been replaced by carbon. KT3777 was investigated for in vitro and in vivo antibacterial activities in comparison with CCL, cephalexin (CEX) and amoxicillin. The MIC50 of KT3777 ranged from 0.2 to 3.13 micrograms/ml for clinical isolates of Staphylococcus aureus, Streptococci, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Haemophilus influenzae, and Neisseria gonorrhoeae. KT3777 possessed an antibacterial spectrum and potency similar to that of CCL. However, against E. coli and K. pneumoniae, KT3777 was about twice as active as CCL. KT3777 was more active than CEX against all strains tested. Killing-curve studies demonstrated bactericidal activity of KT3777 at concentrations above the MIC. KT3777 showed good affinity for penicillin-binding proteins 1A, 1Bs, 3 and 4 of E. coli NIHJ JC-2. The protective effect of KT3777 against systemic infections in mice was comparable to that of CCL with a few exceptions and about 3 to 7 times greater than that of CEX. KT3777 also proved effective against localized infections such as acute pneumonia and ascending urinary tract infections in mice.

Topics: Administration, Oral; Animals; Bacterial Infections; Cefaclor; Cephalexin; Cephalosporins; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Male; Mice; Microbial Sensitivity Tests