title: Divergent mechanisms for passive pneumococcal resistance to β-lactam antibiotics in the presence of Haemophilus influenzae.
abstract: BACKGROUND
  Otitis media, for which antibiotic treatment failure is increasingly common, is a leading pediatric public health problem.
  
  
  METHODS
  In vitro and in vivo studies using the chinchilla model of otitis media were performed using a β-lactamase-producing strain of nontypeable Haemophilus influenzae (NTHi 86-028NP) and an isogenic mutant deficient in β-lactamase production (NTHi 86-028NP bla) to define the roles of biofilm formation and β-lactamase production in antibiotic resistance. Coinfection studies were done with Streptococcus pneumoniae to determine if NTHi provides passive protection by means of β-lactamase production, biofilm formation, or both.
  
  
  RESULTS
  NTHi 86-028NP bla was resistant to amoxicillin killing in biofilm studies in vitro; however, it was cleared by amoxicillin treatment in vivo, whereas NTHi 86-028NP was unaffected in either system. NTHi 86-028NP protected pneumococcus in vivo in both the effusion fluid and bullar homogenate. NTHi 86-028NP bla and pneumococcus were both recovered from the surface-associated bacteria of amoxicillin-treated animals; only NTHi 86-028NP bla was recovered from effusion.
  
  
  CONCLUSIONS
  Based on these studies, we conclude that NTHi provides passive protection for S. pneumoniae in vivo through 2 distinct mechanisms: production of β-lactamase and formation of biofilm communities.
authors.affiliation: Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Kristin E D
authors.initials: KE
authors.lastname: Weimer
authors.forename: Richard A
authors.initials: RA
authors.lastname: Juneau
authors.forename: Kyle A
authors.initials: KA
authors.lastname: Murrah
authors.forename: Bing
authors.initials: B
authors.lastname: Pang
authors.forename: Chelsie E
authors.initials: CE
authors.lastname: Armbruster
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Richardson
authors.forename: W Edward
authors.initials: WE
authors.lastname: Swords
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018441:Biofilms / Q000254:growth & development; D002682:Chinchilla; D004195:Disease Models, Animal; D006192:Haemophilus Infections / Q000150:complications / Q000382:microbiology; D006193:Haemophilus influenzae / Q000378:metabolism* / Q000502:physiology; D050296:Microbial Viability; D010033:Otitis Media / Q000188:drug therapy / Q000382:microbiology; D011008:Pneumococcal Infections / Q000150:complications / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000254:growth & development; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000096:biosynthesis*; D047090:beta-Lactams / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D001618:beta-Lactamases