Divergent Mechanisms for Passive Pneumococcal Resistance to beta-Lactam Antibiotics in the Presence of Haemophilus influenzae

作者：Weimer Kristin E D; Juneau Richard A; Murrah Kyle A; Pang Bing; Armbruster Chelsie E; Richardson Stephen H; Swords W Edward^*

来源：Journal of Infectious Diseases, 2011, 203(4): 549-555.

DOI：10.1093/infdis/jiq087

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 beta-lactamase-producing strain of nontypeable Haemophilus influenzae (NTHi 86-028NP) and an isogenic mutant deficient in beta-lactamase production (NTHi 86-028NP bla) to define the roles of biofilm formation and beta-lactamase production in antibiotic resistance. Coinfection studies were done with Streptococcus pneumoniae to determine if NTHi provides passive protection by means of beta-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 beta-lactamase and formation of biofilm communities.

• 出版日期2011-2-15