ly-163892 and Haemophilus-Infections

A double blind, randomized clinical trial involving 214 children, ages 6 months to 12 years, compared the safety and effectiveness of the new carbacephem loracarbef and the cephalosporin cefaclor for the treatment of skin and skin structure infections. The two agents were given primarily as oral suspensions. Dosages were 15 mg/kg/day in two divided doses for loracarbef and 20 mg/kg/day in three divided doses for cefaclor. Assessment 72 hours after completion of the 7-day course of treatment indicated a favorable clinical response plus eradication of the pretherapy pathogen in 97.3% of the 74 loracarbef-treated patients eligible for evaluation and 92.3% of 78 evaluable cefaclor-treated patients. Favorable response rates at a second posttreatment visit 10 to 14 days after the end of therapy were 95.6% in 68 evaluable loracarbef-treated patients and 86.2% in 65 treated with cefaclor. The incidence of adverse reactions, including gastrointestinal effects, was low in both groups. No statistical difference in clinical or bacteriologic efficacy or safety was detected between patients treated with loracarbef and cefaclor.

Topics: Cefaclor; Cephalosporins; Child; Child, Preschool; Double-Blind Method; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Male; Skin Diseases, Infectious; Staphylococcal Skin Infections; Staphylococcus aureus; Streptococcal Infections; Streptococcus pyogenes

The aim of the current five-center collaborative study was to reassess the interpretive criteria for cefaclor, loracarbef, cefprozil and cefixime previously adopted or proposed by the National Committee for Clinical Laboratory Standards (NCCLS) for disk diffusion susceptibility tests with Haemophilus influenzae on Haemophilus Test Medium (HTM) agar. MICs and zones of inhibition were determined using NCCLS methods, HTM and two collections of strains of Haemophilus influenzae. One group of strains consisted of 118 stock organisms taken largely from various recent U.S. antibiotic resistance surveillance studies. The emphasis in this selected group of organisms was on strains that were beta-lactamase negative but ampicillin resistant (BLNAR) by some other mechanism. The second collection of test organisms consisted of 50 recent clinical isolates of Haemophilus influenzae obtained from each of the five participating study centers. This group was considered representative of the type of Haemophilus influenzae currently recovered from clinical sources in the USA. Frequency distribution assessment and error-rate bounded analysis of scattergram comparisons of MICs and zone sizes were used to develop the following zone diameters interpretive for disk diffusion susceptibility tests with Haemophilus influenzae on HTM agar: cefaclor, > or = 20 mm (susceptible, S) and < or = 16 mm (resistant, R); loracarbef, > or = 19 mm (S) and < or = 15 mm (R); and cefprozil, > 18 mm (S) and < 14 mm (R). The respective MIC correlates for all three antimicrobial agents were < or = 8 micrograms/ml (S) and 32 micrograms/ml (R).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Cefaclor; Cefixime; Cefotaxime; Cefprozil; Cephalosporins; Culture Media; Haemophilus Infections; Haemophilus influenzae; Humans; Microbial Sensitivity Tests; Quality Control

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

Data on susceptibility of Haemophilus influenzae are scanty in Italy. We compared the activity of loracarbef (Ly 163892), a new carbacephem, with that of 4 other agents against 265 strains of H. influenzae (46 type b, 219 nontypable) isolated from adults and children at Istituti Clinici di Perfezionamento of Milano, between 1/1/84 and 1/1/89, and also from 7 children at pediatric departments in Lombardy during 1988. In adults 72 strains were all isolated from sputum of patients with pneumonia or chronic bronchitis; in children 199 strains were isolated from conjunctiva (53% of the patients had also a concomitant respiratory infection), 24 from middle ear, 18 from sputum and 32 from blood or cerebrospinal fluid. Minimal inhibiting concentrations (MIC) were determined by the broth microdilution technique. The incidence of resistance of H. influenzae to ampicillin was 3.8%; the lowest percentage of resistance was found for loracarbef (0%) and the highest for erythromycin (94% for strains isolated from children and 97% for strains isolated from adults).

Topics: Adult; Ampicillin; Anti-Bacterial Agents; Cephalosporins; Child; Dose-Response Relationship, Drug; Drug Resistance, Bacterial; Erythromycin; Haemophilus Infections; Haemophilus influenzae; Humans; Microbial Sensitivity Tests; Penicillins

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