Penicillin treatment accelerates middle ear inflammation in experimental pneumococcal otitis media

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The pathogenesis of middle ear inflammation caused by Streptococcus pneumoniae was explored in the chinchilla model with different pneumococcal cell wall (CW) preparations, including isolated native CW, M1 muramidase CW (M1-CW) digest, amidase CW digest, and M1 peptidoglycan (M1-PG) digest. Inflammatory cell and lysozyme concentrations in middle ear fluid (MEF) were measured between 6 and 72 h after the middle ears were inoculated with one of the preparations or sterile saline. Middle ear histopathology was measured quantitatively at 72 h. Native CW, M1-CW digest, and amidase-CW digest caused significantly more inflammatory cell influx and lysozyme accumulation in MEF than saline did. M1-PG digest also caused more inflammatory cell influx and lysozyme accumulation in MEF than saline did but caused less inflammation than native CW or either CW digest. Epithelial metaplasia was significantly greater in ears inoculated with native CW than in ears inoculated with the CW or PG digest or with saline. Pneumococcal CW is, therefore, the principal factor that initiates middle ear inflammation in acute pneumococcal otitis media, and CW teichoication seems to be important in initiating this response.

Section: Discussionmentioning

confidence: 74%

Section: Methodsmentioning

confidence: 99%

Role of the bacterial cell wall in middle ear inflammation caused by Streptococcus pneumoniae

Carlsen

Kawana

et al. 1992

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“…Beta-lactam antibiotic treatment accelerated type 3 S. pneumoniae-induced inflammation in the rabbit meningitis model (36) presumably because treatment lysed pneumococci, releasing cell envelope fragments such as cell wall or cytoplasm products such as pneumolysin into the surrounding environment. We observed a similar acceleration of inflammation in the chinchilla otitis media (OM) model using type 3 and 7F S. pneumoniae (19,34). Timing of penicillin treatment with regard to bacterial concentration in MEF was a critical determinant of the middle ear (ME) inflammatory response (34).…”

mentioning

confidence: 66%

Roles of autolysin and pneumolysin in middle ear inflammation caused by a type 3 Streptococcus pneumoniae strain in the chinchilla otitis media model

Sato¹,

Quartey²,

Liebeler³

et al. 1996

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Streptococcus pneumoniae cell wall and pneumolysin are important contributors to pneumococcal pathogenicity in some animal models. To further explore these factors in middle ear inflammation caused by pneumococci, penicillin-induced inflammatory acceleration was studied by using three closely related pneumococcal strains: a wild-type 3 strain (WT3), its pneumolysin-negative derivative (P-1), and its autolysin-negative derivative (A-1). Both middle ears of chinchillas were inoculated with one of the three pneumococcal strains. During the first 12 h, all three strains grew in vivo at the same rate, and all three strains induced similar inflammatory cell responses in middle ear fluid (MEF). Procaine penicillin G was given at 12 h to one-half of the animals in each group, and all treated chinchillas had sterile MEF at 24 h. Penicillin significantly accelerated MEF inflammatory cell influx into WT3-and P-1-infected ears at 18 and 24 h in comparison with the rate for penicillin-treated A-1-infected ears. Inflammatory cell influx was slightly, but not significantly, greater after treatment of WT3 infection than after treatment of P-1 infection. Interleukin (IL)-1␤ and IL-6, but not IL-8, concentrations in MEF at 24 h reflected the penicillin effect on MEF inflammatory cells; however, differences between treatment groups were not significant. Results suggest that pneumococcal otitis media pathogenesis is triggered principally by the inflammatory effects of intact and lytic cell wall products in the middle ear, with at most a modest additional pneumolysin effect. Investigation strategies that limit the release of these products or neutralize them warrant further investigation.

“…Streptococcus pneumoniae is the most prevalent middle ear bacterial pathogen, cultured from approximately 40% of middle ear fluid (MEF) samples from children with acute otitis media (AOM) (2,9) and 7% of MEF samples from children with chronic otitis media with effusion (OME) (2). We have studied the pathophysiology of pneumococcal AOM using the chinchilla otitis media model (18,19,23,28,29) and in the guinea pig model otitis media model induced by Haemophilus influenzae (17,24,25) and Moraxella catarrhalis (27). Inflammatory cells, lysozyme, and oxidative metabolic products have been recognized as being important contributors to acute middle ear inflammation.…”

mentioning

confidence: 99%

Middle Ear Fluid Cytokine and Inflammatory Cell Kinetics in the Chinchilla Otitis Media Model

Sato¹,

Liebeler²,

Quartey³

et al. 1999

Streptococcus pneumoniae is the most frequent microbe causing middle ear infection. The pathophysiology of pneumococcal otitis media has been characterized by measurement of local inflammatory mediators such as inflammatory cells, lysozyme, oxidative metabolic products, and inflammatory cytokines. The role of cytokines in bacterial infection has been elucidated with animal models, and interleukin (IL)-1␤, IL-6, and IL-8 and tumor necrosis factor alpha (TNF-␣) are recognized as being important local mediators in acute inflammation. We characterized middle ear inflammatory responses in the chinchilla otitis media model after injecting a very small number of viable pneumococci into the middle ear, similar to the natural course of infection. Middle ear fluid (MEF) concentrations of IL-1␤, IL-6, IL-8, and TNF-␣ were measured by using anti-human cytokine enzyme-linked immunosorbent assay reagents. IL-1␤ showed the earliest peak, at 6 h after inoculation, whereas IL-6, IL-8, and TNF-␣ concentrations were increasing 72 h after pneumococcal inoculation. IL-6, IL-8, and TNF-␣ but not IL-1␤ concentrations correlated significantly with total inflammatory cell numbers in MEF, and all four cytokines correlated significantly with MEF neutrophil concentration. Several intercytokine correlations were significant. Cytokines, therefore, participate in the early middle ear inflammatory response to S. pneumoniae.