ly-163892 and Respiratory-Tract-Infections

The efficacy and safety of the antibiotic loracarbef have been demonstrated in a series of 22 clinical trials involving over 9,000 patients. The data compiled from these trials indicate that loracarbef is well tolerated by the majority of patients, including children and elderly patients. Most adverse events in patients receiving loracarbef were mild and transient in nature; only 1.5% of patients discontinued therapy because of drug-related adverse events. The frequency of adverse events associated with this agent compares favorably with that reported for the other antibiotics in these trials. The most commonly reported adverse reaction in the loracarbef study group was diarrhea, but this condition occurred less frequently in patients who received loracarbef than in those treated with the comparative agents. Other gastrointestinal events, such as nausea and vomiting, were reported infrequently. Headache was the second most common adverse event reported and occurred at a slightly higher frequency in the loracarbef-treated group than in patients receiving comparative antibiotics. No clinically significant alterations in laboratory parameters or gastrointestinal flora were observed following loracarbef administration. The compiled data indicate that loracarbef is a safe therapeutic option for the treatment of a wide spectrum of bacterial infections.

Topics: Adult; Adverse Drug Reaction Reporting Systems; Aged; Cephalosporins; Child; Diarrhea; Headache; Humans; Incidence; Intestines; Respiratory Tract Infections; Skin Diseases, Infectious; Urinary Tract Infections

Acute bronchitis, an illness frequently encountered by primary-care physicians, is an inflammation of the tracheobronchial tree that results from a respiratory tract infection. It is characterized by persistent cough and sputum production and is occasionally accompanied by fever and/or chest pain. Acute bronchitis may have a viral or bacterial origin and is often treated with antibiotics. Four clinical trials were conducted to compare high and low doses of loracarbef, a new oral beta-lactam antibiotic, with three agents commonly used to treat acute bronchitis: amoxicillin/clavulanate, cefaclor, and amoxicillin. Results of these studies indicated that loracarbef, 400 and 200 mg twice daily, had clinical and bacteriologic efficacy against the common respiratory pathogens Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella (Branhamella) catarrhalis that was comparable with that of the comparative agents. Loracarbef was as well tolerated as cefaclor and amoxicillin; moreover, it produced a significantly lower incidence of diarrhea than did amoxicillin/clavulanate. Loracarbef may be considered a safe and effective alternative agent for the treatment of patients with acute bronchitis.

Topics: Acute Disease; Bronchitis; Cephalosporins; Clinical Trials as Topic; Drug Resistance, Microbial; Europe; Gastrointestinal Diseases; Humans; Respiratory Tract Infections; United States

We report here the first case of severe immune thrombocytopenia induced by a second-generation cephalosporin antibiotic, Loracarbef. A 56-year old white female developed acute severe thrombocytopenia associated with acute respiratory symptoms following administration of Loracarbef. She responded to Loracarbef withdrawal and systemic corticosteroid administration. Loracarbef-dependent platelet-reactive antibodies were demonstrable in her serum by flow cytometry.

Topics: Autoantibodies; Blood Platelets; Cephalosporins; Female; Flow Cytometry; Humans; Methylprednisolone; Middle Aged; Purpura, Thrombocytopenic, Idiopathic; Respiratory Tract Infections

The susceptibility of Canadian isolates of three respiratory tract pathogens (Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae) to several antimicrobial agents were tested by two different methods. Beta-lactamase was produced by 68/211 (32.2%) of H. influenzae isolates and 64/75 (85.3%) of M. catarrhalis isolates. For S. pneumoniae, 19/156 (12.2%) isolates were resistant to penicillin (MIC > or = 0.12 mg/L) and two isolates had MICs of 1.5 mg/L. For some combinations of agents and organisms, different methods gave different values for the proportion of isolates susceptible. Regardless of methodology, for H. influenzae, the most active antimicrobials based on proportion of strains susceptible were ciprofloxacin (100%) and cefpodoxime (98.5-100%). For M. catarrhalis, the most active agents were azithromycin, cefaclor, cefixime, cefpodoxime, cefuroxime, ciprofloxacin, clarithromycin and loracarbef (100% each); the least active was ampicillin. Against penicillin-sensitive and -resistant pneumococci, the activity was not significantly different for azithromycin and clarithromycin (93.4-100%) and ciprofloxacin (MIC90 2.0 and 1.5 mg/L, respectively) but was different for cefuroxime (99.3% and 31.6%, respectively), cefaclor (MIC90 0.75 and > or = 256 mg/L, respectively), cefpodoxime (MIC90 0.047 and 1.5 mg/L, respectively) and loracarbef (MIC90 0.75 and > or = 256 mg/L, respectively). This study indicates the increasing incidence, in Canada, of beta-lactamase resistance in H. influenzae and M. catarrhalis and penicillin resistance in S. pneumoniae.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Cephalosporins; Ciprofloxacin; Haemophilus influenzae; Microbial Sensitivity Tests; Moraxella catarrhalis; Penicillin Resistance; Respiratory Tract Infections; Streptococcus pneumoniae

We examined the effects of 0.25 and 0.5 minimal inhibitory concentrations (MIC) of amoxicillin, loracarbef, and ciprofloxacin on the interaction of a clinical isolate of nontypable Haemophilus influenzae (NTHi) with human adenoid organ culture. Adenoid tissue was embedded in agar so that only the mucosal surface was exposed. Minimum essential medium containing NTHi with or without antibiotics was added to the organ culture and incubated with 5% CO2 at 37 degrees C for 24 h. The organ cultures (n = 6) were assessed for several parameters by light microscopy (LM) and transmission electron microscopy (TEM). Bacterial viable counts after 24 h were not significantly different in all organ cultures. Compared with uninfected controls at 24 h, infection with NTHi caused significant (p < 0.05) damage to epithelium as assessed by LM: reduced ciliary beat frequency (CBF), disruption of epithelium integrity, and reduced number of ciliated sites. TEM showed extrusion of cells from the epithelial surface, loss of cilia from ciliated cells, cytoplasmic blebbing, and mitochondrial damage. In the presence of 0.25 and 0.5 MIC of all three antibiotics, the mucosal damage was significantly less (p < 0.05). We conclude that in the presence of sub-MIC levels of amoxicillin, loracarbef, and ciprofloxacin, NTHi infection causes less functional (CBF) and structural damage.

Topics: Adenoids; Amoxicillin; Anti-Bacterial Agents; Cephalosporins; Child, Preschool; Ciprofloxacin; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Haemophilus Infections; Haemophilus influenzae; Humans; Microbial Sensitivity Tests; Microscopy, Electron; Mucociliary Clearance; Mucous Membrane; Organ Culture Techniques; Respiratory Tract Infections

The antibiotic susceptibility of Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes and Streptococcus pneumoniae was investigated in five different geographical areas of Sweden in 1990 and compared with results from similar investigations performed in 1983 and 1986. Tests on 100 isolates per species and laboratory were performed by the disk diffusion method, and 10% of the strains plus all resistant ones were sent to the central laboratory for determination of MICs of ampicillin, phenoxymethylpenicillin, cefaclor, loracarbef, erythromycin, tetracycline and trimethoprim/sulfamethoxazole. Beta-lactamase production was found in 7% of H. influenzae and 71% of M. catarrhalis, and reduced susceptibility to penicillin in 3% of S. pneumoniae. Low frequencies (1-3%) of tetracycline resistance were found in H. influenzae and in the 2 streptococcal species, in which also less than 1% of the strains were resistant to erythromycin. Resistance to trimethoprim/sulfamethoxazole occurred in 7% (range 3-14%) of H. influenzae and in 3% of S. pneumoniae. Cefaclor was active against all streptococci except against S. pneumoniae with reduced susceptibility to penicillin. It was active against beta-lactamase negative strains of M. catarrhalis but had, according to the SIR-system, intermediate activity against H. influenzae. Loracarbef was twice as active as cefaclor against H. influenzae but equally active against the 3 other species tested.

Topics: Cephalosporins; Drug Resistance, Microbial; Follow-Up Studies; Haemophilus influenzae; Humans; Moraxella catarrhalis; Respiratory Tract Infections; Streptococcus pneumoniae; Streptococcus pyogenes; Sweden

Topics: Adult; Cephalosporins; Child; Clinical Trials as Topic; Costs and Cost Analysis; Humans; Microbial Sensitivity Tests; Respiratory Tract Infections; Skin Diseases, Infectious; Urinary Tract Infections

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