title: Haemophilus influenzae infection of human respiratory mucosa in low concentrations of antibiotics.
abstract: 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.
authors.affiliation: Host Defence Unit, Royal Brompton National Heart and Lung Institute, London, England.
authors.forename: K W
authors.initials: KW
authors.lastname: Tsang
authors.forename: A
authors.initials: A
authors.lastname: Rutman
authors.forename: K
authors.initials: K
authors.lastname: Kanthakumar
authors.forename: J
authors.initials: J
authors.lastname: Belcher
authors.forename: V
authors.initials: V
authors.lastname: Lund
authors.forename: D E
authors.initials: DE
authors.lastname: Roberts
authors.forename: R C
authors.initials: RC
authors.lastname: Read
authors.forename: P J
authors.initials: PJ
authors.lastname: Cole
authors.forename: R
authors.initials: R
authors.lastname: Wilson
mesh_terms: D000234:Adenoids / Q000187:drug effects* / Q000382:microbiology / Q000648:ultrastructure; D000658:Amoxicillin / Q000008:administration & dosage; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D002511:Cephalosporins / Q000008:administration & dosage; D002675:Child, Preschool; D002939:Ciprofloxacin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006192:Haemophilus Infections / Q000188:drug therapy / Q000382:microbiology* / Q000473:pathology; D006193:Haemophilus influenzae / Q000187:drug effects* / Q000302:isolation & purification / Q000472:pathogenicity; D006801:Humans; D008826:Microbial Sensitivity Tests; D008854:Microscopy, Electron; D009079:Mucociliary Clearance / Q000187:drug effects; D009092:Mucous Membrane / Q000187:drug effects / Q000382:microbiology / Q000648:ultrastructure; D009924:Organ Culture Techniques; D012141:Respiratory Tract Infections / Q000188:drug therapy / Q000382:microbiology* / Q000473:pathology
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; C054920:loracarbef; D002939:Ciprofloxacin; D000658:Amoxicillin