An Animal Model of Acute Otitis Media Consequent to β-Lactamase-Producing Nontypable Haemophilus Influenzae

1982 ◽  
Vol 90 (6) ◽  
pp. 831-836 ◽  
Author(s):  
William J. Doyle ◽  
John S. Supance ◽  
Gabriel Marshak ◽  
Erdem I. Cantekin ◽  
Charles D. Bluestone ◽  
...  

A chinchilla model of acute otitis media with effusion consequent to β-lactamase-producing nontypable Haemophilus influenzae was developed using the method of direct inoculation of 145 colony-forming units (CFU) or 252 CFU of β-lactamase—producing nontypable H influenzae into the right superior bullae of 40 chinchillas. The course of the disease was documented longitudinally by otomicroscopy, tympanometry, and periodic culturing of the middle ears. Onset of the disease occurred in 100% of the animals between two and six days postinoculation and resolution was complete in all ears by day 36. Results of rechallenge with the same organism support the combined effect of a local and weaker systemic middle ear protective mechanism rendering resistance to reinfection with a homologous organism in the chinchilla.

1982 ◽  
Vol 91 (3) ◽  
pp. 256-260 ◽  
Author(s):  
John S. Supance ◽  
Gabriel Marshak ◽  
William J. Doyle ◽  
Erdem I. Cantekin

A chinchilla animal model was used to determine the effects of early antibiotic treatment with ampicillin on the local and systemic protective mechanisms during pneumococcal acute otitis media with effusion (AOME). The right bullae of 74 chinchillas were inoculated with 170 colony-forming units (CFU) of Streptococcus pneumoniae type 7F, and animals were randomly assigned to 1 of 2 groups; early (24 hours postinoculation) and late (12 days postinoculation) initiation of ampicillin treatment. During the first challenge, 52 chinchillas died within a I-month period, apparently from suppurative complications of AOME. Following the resolution of AOME in their right ears, all surviving animals were challenged for the second time by bilateral bullar inoculations using 130 CFU of the same organism. All 10 animals in the early ampicillin treatment group developed severe bilateral AOME, whereas only 3 of the 12 animals in the late ampicillin treatment group developed a recurrence of AOME in the right ear. Significantly, 8 of the 12 animals in this group developed severe left AOME. These findings suggest the presence of a local middle ear defense system and support the results of previous similar studies in which S pneumoniae types 3 and 6A were used. The results of the present study also suggest that in the chinchilla the early administration of a systemic antibiotic (ampicillin) interferes with this defense mechanism.


2003 ◽  
Vol 71 (6) ◽  
pp. 3454-3462 ◽  
Author(s):  
Kevin M. Mason ◽  
Robert S. Munson ◽  
Lauren O. Bakaletz

ABSTRACT The gram-negative bacterium nontypeable Haemophilus influenzae (NTHI) is the predominant pathogen in chronic otitis media with effusion and, with Streptococcus pneumoniae and Moraxella catarrhalis, is a causative agent of acute otitis media. To identify potential virulence determinants, bacterial gene expression was monitored by differential fluorescence induction during early disease progression in one specific anatomical niche of a chinchilla model of NTHI-induced otitis media. Genomic DNA fragments from NTHI strain 86-028NP were cloned upstream of the promoterless gfpmut3 gene. NTHI strain 86-028NP served as the host for the promoter trap library. Pools of 2,000 transformants were inoculated into the left and right middle ear cavities of chinchillas. Middle ear effusions were recovered by epitympanic tap at 24 and 48 h, and clones containing promoter elements that were induced in vivo and producing green fluorescent protein were isolated by two-color fluorescence-activated cell sorting. Insert DNA was sequenced and compared to the complete genome sequence of H. influenzae strain Rd. In a screen of 16,000 clones, we have isolated 44 clones that contain unique gene fragments encoding biosynthetic enzymes, metabolic and regulatory proteins, and hypothetical proteins of unknown function. An additional eight clones contain gene fragments unique to our NTHI isolate. Using quantitative reverse transcription-PCR, we have confirmed that 26 clones demonstrated increased gene expression in vivo relative to expression in vitro. These data provide insight into the response of NTHI bacteria as they sense and respond to the middle ear microenvironment during early events of otitis media.


1992 ◽  
Vol 107 (4) ◽  
pp. 511-515 ◽  
Author(s):  
Patrick J. Antonelli ◽  
Steven K. Juhn ◽  
Marcos V. Goycoolea ◽  
G. Scott Giebink

Previous experiments have shown that Pseudomonas aeruginosa may infect the middle ears of chinchillas by way of the eustachian tube and that chinchillas with acute otitis media (AOM) are more susceptible to pseudomonas infection than animals without AOM. The purpose of this experiment was to examine the effects of otitis media with effusion (OME), induced by means of eustachian tube obstruction, on middle ear susceptibility to nasal inoculation of P. aeruginosa. Chinchilla eustachian tubes were obstructed with silicone rubber sponge bilaterally; OME developed in eight animals (11 ears)—three bilaterally and five unilaterally—and persisted for 6 months. Ten chinchillas with normal eustachian tube function served as controls. All animals were nasally inoculated with 5 times 104 colony-forming units of P. aeruginosa. Pseudomonas otitis media developed in eight of 11 OME ears with effusion, none of five ears without OME, and four of 20 control ears (X2 = 11.782, p = 0.003). Therefore, P. aeruginosa can infect the middle ear by way of the eustachian tube. Tubal dysfunction may lead to the development of chronic suppurative otitis media by increasing tubotympanic susceptibility to opportunistic pathogens.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Amanda Jane Leach ◽  
Edward Kim Mulholland ◽  
Mathuram Santosham ◽  
Paul John Torzillo ◽  
Peter McIntyre ◽  
...  

Abstract Background Aboriginal children living in Australian remote communities are at high risk of early and persistent otitis media, hearing loss, and social disadvantage. Streptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi) are the primary pathogens. We compared otitis media outcomes in infants randomised to either a combination of Synflorix™ (PHiD-CV10, with protein D of NTHi) and Prevenar13™ (PCV13, with 3, 6A, and 19A), with recommended schedules for each vaccine alone. We previously reported superior broader overall immunogenicity of the combination schedule at 7 months, and early superiority of PHiD-CV10 compared to PCV13 at 4 months. Methods In an open-label superiority trial, we randomised (1:1:1) Aboriginal infants at 28 to 38 days of age, to either Prevenar13™ (P) at 2–4-6 months (_PPP), Synflorix™ (S) at 2–4-6 months (_SSS), or Synflorix™ at 1–2-4 months plus Prevenar13™ at 6 months (SSSP). Ears were assessed using tympanometry at 1 and 2 months, combined with otoscopy at 4, 6, and 7 months. A worst ear diagnosis was made for each child visit according to a severity hierarchy of normal, otitis media with effusion (OME), acute otitis media without perforation (AOMwoP), AOM with perforation (AOMwiP), and chronic suppurative otitis media (CSOM). Results Between September 2011 and September 2017, 425 infants were allocated to _PPP(143), _SSS(141) or SSSP(141). Ear assessments were successful in 96% scheduled visits. At 7 months prevalence of any OM was 91, 86, and 90% in the _PPP, _SSS, and SSSP groups, respectively. There were no significant differences in prevalence of any form of otitis media between vaccine groups at any age. Combined group prevalence of any OM was 43, 57, 82, 87, and 89% at 1, 2, 4, 6, and 7 months of age, respectively. Of 388 infants with ear assessments at 4, 6 and 7 months, 277 (71.4%) had OM that met criteria for specialist referral; rAOM, pOME, or CSOM. Conclusions Despite superior broader overall immunogenicity of the combination schedule at 7 months, and early superiority of PHiD-CV10 compared to PCV13 at 4 months, there were no significant differences in prevalence of otitis media nor healthy ears throughout the first months of life. Trial registration ACTRN12610000544077 registered 06/07/2010 and ClinicalTrials.govNCT01174849 registered 04/08/2010.


1989 ◽  
Vol 103 (4) ◽  
pp. 369-371 ◽  
Author(s):  
C. Diamond ◽  
P. R. Sisson ◽  
A. M. Kearns ◽  
H. R. Ingham

AbstractSamples of middle ear effusions from 102 children with serous and mucoid otitis media were cultured for mycoplasmas and bacteria. No sample yielded mycoplasmas but bacteria were cultured from 48 (47 per cent). Organisms commonly regarded as pathogens were present in 25 samples (Haemophilus influenzae 17, Streptococcus pneumoniae four, other streptococci four). The only sample from which anaerobic bacteria were isolated was from a patient with cholesteatoma.


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