Reduced severity of middle ear infection caused by nontypeable Haemophilus influenzae lacking the hemoglobin/hemoglobin–haptoglobin binding proteins (Hgp) in a chinchilla model of otitis media

ABSTRACT Treatment of acute otitis media (AOM) with azithromycin results in apparent clinical success, but tympanocentesis performed 4 to 6 days after initiation of therapy in children with nontypeable Haemophilus influenzae (NTHI) recovered from initial middle ear cultures demonstrates persistence of infection in more than 50% of episodes. We sought to determine the effect of azithromycin at different doses on the density of middle ear infection due to NTHI to provide additional understanding of this dichotomy between clinical and microbiologic outcome measures in AOM. In a chinchilla model of experimental otitis media (EOM), animals treated with placebo were compared to animals receiving a single daily dose 30 or 120 mg of azithromycin per kg of body weight per day for 5 days. Microbiologic outcome was assessed by obtaining quantitative cultures from the middle ear during a 5-day course and for 1 week following therapy. Azithromycin concentrations were measured to ascertain whether a concentration-dependent effect was present. Azithromycin at 30 and 120 mg/kg/day demonstrated a dose-dependent effect on the quantitative assessment of middle ear infection due to NTHI. A 30-mg/kg dose of azithromycin daily resulted in levels in serum and areas under the serum concentration-time curve at 24 h comparable to published data obtained with children given azithromycin at 5 to 10 mg/kg in multiday regimens. Increased doses of azithromycin (120 mg/kg) achieved 2.5- to 4-fold-higher levels in serum and 3- to 6-fold-higher total levels and levels in extracellular middle ear fluid as well as more rapid reduction in bacterial density and a greater proportion of middle ears with complete sterilization than either placebo or the 30-mg/kg/day regimen.

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Nasopharyngeal Colonization with Nontypeable Haemophilus influenzae in Chinchillas

Infection and Immunity ◽

10.1128/iai.66.5.1973-1980.1998 ◽

1998 ◽

Vol 66 (5) ◽

pp. 1973-1980 ◽

Cited By ~ 11

Author(s):

Yan-ping Yang ◽

Sheena M. Loosmore ◽

Brian J. Underdown ◽

Michel H. Klein

Keyword(s):

Haemophilus Influenzae ◽

Otitis Media ◽

Middle Ear ◽

Candidate Vaccine ◽

Nontypeable Haemophilus Influenzae ◽

Nasopharyngeal Colonization ◽

Ear Infection ◽

Middle Ear Infection ◽

Significant Difference ◽

Vaccine Antigens

ABSTRACT Colonization of the nasopharynx by a middle ear pathogen is the first step in the development of otitis media in humans. The establishment of an animal model of nasopharyngeal colonization would therefore be of great utility in assessing the potential protective ability of candidate vaccine antigens (especially adhesins) against otitis media. A chinchilla nasopharyngeal colonization model for nontypeable Haemophilus influenzae (NTHI) was developed with antibiotic-resistant strains. This model does not require coinfection with a virus. There was no significant difference in the efficiency of NTHI colonization between adult (1- to 2-year-old) and young (2- to 3-month-old) animals. However, the incidence of middle ear infection following nasopharyngeal colonization was significantly higher in young animals (83 to 89%) than in adult chinchillas (10 to 30%). Chinchillas that had recovered either from a previous middle ear infection caused by NTHI or from an infection by intranasal inoculation with NTHI were completely protected against nasopharyngeal colonization with a homologous strain and were found to be the best positive controls in protection studies. Systemic immunization of chinchillas with inactivated whole-cell preparations significantly protected animals not only against homologous NTHI colonization but also partially against heterologous NTHI infection. In all protected animals, significant serum anti-P6 and anti-HMW antibody responses were observed. The outer membrane P6 and high-molecular-weight (HMW) proteins appear to be promising candidate vaccine antigens to prevent nasopharyngeal colonization and middle ear infection caused by NTHI.

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NOD2/RICK-Dependent β-Defensin 2 Regulation Is Protective for Nontypeable Haemophilus influenzae-Induced Middle Ear Infection

PLoS ONE ◽

10.1371/journal.pone.0090933 ◽

2014 ◽

Vol 9 (3) ◽

pp. e90933 ◽

Cited By ~ 12

Author(s):

Jeong-Im Woo ◽

Sejo Oh ◽

Paul Webster ◽

Yoo Jin Lee ◽

David J. Lim ◽

...

Keyword(s):

Haemophilus Influenzae ◽

Middle Ear ◽

Nontypeable Haemophilus Influenzae ◽

Ear Infection ◽

Middle Ear Infection

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Middle Ear Infection (Otitis Media)

The Pediatric Infectious Disease Journal ◽

10.1097/00006454-199012000-00027 ◽

1990 ◽

Vol 9 (12) ◽

pp. 936

Author(s):

S. Michael Marcy ◽

Michael E. Pichichero ◽

Richard H. Schwartz

Keyword(s):

Otitis Media ◽

Middle Ear ◽

Ear Infection ◽

Middle Ear Infection

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Luc Abscess: A Rare Complication of a Common Pediatric Ear Infection

Malaysian Journal of Paediatrics and Child Health ◽

10.51407/mjpch.v27i1.127 ◽

2021 ◽

Vol 27 (1) ◽

pp. 20-24

Author(s):

Nurfadhilah Aisyah Murad ◽

Zalilah Musa ◽

Kharudin Abdullah ◽

Irfan Mohamad

Keyword(s):

Inflammatory Response ◽

Bacterial Infection ◽

Otitis Media ◽

Middle Ear ◽

Rare Complication ◽

Bone Involvement ◽

Ear Infection ◽

Temporal Muscle ◽

Middle Ear Infection ◽

The Difference

Middle ear infection occurs when fluid accumulate in middle ear as a result of inflammatory response to viral or bacterial infection. Infections may spread from the middle ear, resulting in a subperiosteal collection beneath the temporal muscle. Luc abscess is a rare complication of otitis media. The difference of this complication with other extracranial abscesses relating to otitis media is, it may not be associated with mastoid bone involvement. Therefore, it is defined as benign complication of otitis media. Here, we report a case of 10-month-old baby boy diagnosed with Luc abscess with mastoid involvement.

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Biofilm Biology and Vaccine Strategies for Otitis Media Due to Nontypeable Haemophilus influenzae

Journal of Pediatric Infectious Diseases ◽

10.1055/s-0038-1660818 ◽

2018 ◽

Vol 14 (02) ◽

pp. 069-078 ◽

Cited By ~ 6

Author(s):

Laura Novotny ◽

Kenneth Brockman ◽

Elaine Mokrzan ◽

Joseph Jurcisek ◽

Lauren Bakaletz

Keyword(s):

Haemophilus Influenzae ◽

Otitis Media ◽

Middle Ear ◽

Causative Agent ◽

Upper Respiratory Tract ◽

Nontypeable Haemophilus Influenzae ◽

Physical Defenses ◽

Upper Respiratory ◽

Recurrent Nature ◽

Gain Access

AbstractOtitis media (OM) is one of the most common diseases of childhood, and nontypeable Haemophilus influenzae (NTHI) is the predominant causative agent of chronic and recurrent OM, as well as OM for which treatment has failed. Moreover, NTHI is now as important a causative agent of acute OM as the pneumococcus. NTHI colonizes the human nasopharynx asymptomatically. However, upon perturbation of the innate and physical defenses of the airway by upper respiratory tract viral infection, NTHI can replicate, ascend the Eustachian tube, gain access to the normally sterile middle ear space, and cause disease. Bacterial biofilms within the middle ear, including those formed by NTHI, contribute to the chronic and recurrent nature of this disease. These multicomponent structures are highly resistant to clearance by host defenses and elimination by traditional antimicrobial therapies. Herein, we review several strategies utilized by NTHI to persist within the human host and interventions currently under investigation to prevent and/or resolve NTHI-induced diseases of the middle ear and uppermost airway.

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Vocal Cord Paralysis and Dysphagia as Sequelae of Gradenigo Syndrome

Philippine Journal of Otolaryngology Head and Neck Surgery ◽

10.32412/pjohns.v28i1.495 ◽

2018 ◽

Vol 28 (1) ◽

pp. 15-18

Author(s):

Mary Ann V. Macasaet ◽

Emmanuel Tadeus S. Cruz

Keyword(s):

Vocal Cord ◽

Otitis Media ◽

Middle Ear ◽

Vocal Cord Paralysis ◽

Petrous Apex ◽

Suppurative Otitis Media ◽

Ear Infection ◽

Nerve Paralysis ◽

Middle Ear Infection ◽

Petrous Apicitis

Objectives: To present a case of vocal cord paralysis and dysphagia developing in Gradenigo syndrome and to discuss its clinical presentation, differential diagnosis and therapeutic approach. Methods: Design: Case Report Setting: Tertiary Government Hospital Patient: One Results: A 54-year-old lady was admitted with a six month history of left-sided otorrhea, cheek and jaw pain, three months otalgia, and recent-onset hoarseness, dysphagia and diplopia on a background of mastoidectomy at age 6. Otoscopy revealed granulation tissue and chlolesteatoma occupying the left external auditory canal. There was left vocal cord paralysis with pooling of saliva in the pyriform sinus, left lateral gaze paralysis, and left facial nerve paralysis. CT scan revealed sclerosis of the left petrous apex and leptomeningeal enhancement on the left temporal lobe. Chronic suppurative otitis media with cholesteatoma and Gradenigo syndrome was diagnosed, and canal wall down mastoidectomy was performed Postoperatively, the otalgia and pain over the left jaw diminished in intensity while hoarseness and left lateral gaze palsy remained. Conclusion: Gradenigo syndrome is known for its triad of retro-orbital pain, lateral gaze paralysis, and chronic middle ear infection due to petrous apicitis. Although rare, vocal cord paralysis and dysphagia may develop when infection traverses and encroaches on the jugular foramen where cranial nerves IX, X, and XI are lodged. Knowledge of the syndrome should not be limited or confined to the classic triad. Practicing ear specialists should be vigilant and cognizant of the clinical manifestations and sequelae of chronic middle ear infection. Prompt surgical intervention is crucial while resolution of the disease may vary for different individuals. Keywords: Chronic otitis media, Gradenigo syndrome, vocal cord paralysis, petrous apicitis

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Viral Co-Infection Does Not Reduce the Efficacy of Vaccination against Non-Typeable Haemophilus influenzae Middle Ear Infection in a Rat Model

ORL ◽

10.1159/000055718 ◽

2001 ◽

Vol 63 (2) ◽

pp. 96-101 ◽

Cited By ~ 2

Author(s):

Ryka Moore ◽

Brett A. Lidbury ◽

Allan W. Cripps ◽

Jennelle M. Kyd

Keyword(s):

Haemophilus Influenzae ◽

Middle Ear ◽

Rat Model ◽

Ear Infection ◽

Middle Ear Infection

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Middle Ear Infection (Otitis Media)

Instructions for Sports Medicine Patients ◽

10.1016/b978-1-4160-5650-8.00287-9 ◽

2012 ◽

pp. 661

Author(s):

Marc R. Safran ◽

James Zachazewski ◽

David A. Stone

Keyword(s):

Otitis Media ◽

Middle Ear ◽

Ear Infection ◽

Middle Ear Infection

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A Mutation in the sap Operon Attenuates Survival of Nontypeable Haemophilus influenzae in a Chinchilla Model of Otitis Media

Infection and Immunity ◽

10.1128/iai.73.1.599-608.2005 ◽

2005 ◽

Vol 73 (1) ◽

pp. 599-608 ◽

Cited By ~ 60

Author(s):

Kevin M. Mason ◽

Robert S. Munson ◽

Lauren O. Bakaletz

Keyword(s):

Haemophilus Influenzae ◽

Antimicrobial Peptides ◽

Otitis Media ◽

Middle Ear ◽

Parent Strain ◽

Upper Airway ◽

Nontypeable Haemophilus Influenzae ◽

Nthi Strain ◽

Passage Number ◽

Low Passage

ABSTRACT Bacteria have evolved strategies to resist killing by antimicrobial peptides (APs), important effectors of innate immunity. The sap (sensitivity to antimicrobial peptides) operon confers resistance to AP-mediated killing of Salmonella. We have recently shown that sapA gene expression is upregulated in the middle ear in a chinchilla model of nontypeable Haemophilus influenzae (NTHI)-induced otitis media. Based on these findings, we constructed an NTHI strain containing a Lux reporter plasmid driven by the sapA promoter and demonstrated early yet transient expression of the sap operon within sites of the chinchilla upper airway upon infection. We hypothesized that the sap operon products mediate NTHI resistance to APs. In order to test this hypothesis, we constructed a nonpolar mutation in the sapA gene of NTHI strain 86-028NP, a low-passage-number clinical isolate. The sapA mutant was approximately eightfold more sensitive than the parent strain to killing by recombinant chinchilla β-defensin 1. We then assessed the ability of this mutant to both colonize and cause otitis media in chinchillas. The sapA mutant was significantly attenuated compared to the parent strain in its ability to survive in both the nasopharynx and the middle ear of the chinchilla. In addition, the mutant was impaired in its ability to compete with the parent strain in a dual-strain challenge model of infection. Our results indicate that the products of the sap operon are important for resisting the activity of APs and may regulate, in part, the balance between normal carriage and disease caused by NTHI.

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