Effect of erythromycin treatment delay on therapeutic outcome of experimental acute otitis media caused by Streptococcus pneumoniae

Martínez-Marín, Carmina; Huelves, Lorena; Prado, Gema del; García-Cía, José I.; Cenjor, Carlos; Ponte, Carmen; Granizo, Juan José; Soriano, Francisco

doi:10.1093/jac/dki322

Cited by 6 publications

(3 citation statements)

References 10 publications

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“…We have previously shown a favorable pharmacokinetic profile in both serum and ME fluid after early administration of 5 mg/kg erythromycin. However, the half-life in the ME fluid is shorter with delayed administration, which correlates with the poorer outcome of AOM treated with delayed administration of erythromycin, an observation also previously published (13). Animals treated with erythromycin and the high dose of ibuprofen, administered in early or delayed form, had lower bacterial counts in the ME fluid than those receiving the antibiotic alone, although the difference was not statistically significant.…”

Section: Discussionsupporting

confidence: 58%

Impact of Ibuprofen Therapy in the Outcome of Experimental Pneumococcal Acute Otitis Media Treated With Amoxicillin or Erythromycin

et al. 2006

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ABSTRACT:The impact of ibuprofen combined with amoxicillin or erythromycin for therapy of penicillin-resistant pneumococcal acute otitis media (AOM) was evaluated in a gerbil model. Ibuprofen (at 2.5 or 7.5 mg/kg, orally) and/or amoxicillin or erythromycin (5 mg/kg each, s.c.) were administered at 5 h (early therapy, as singledose regimen) or at 18 h (delayed therapy, five doses) postinoculation (PI). Each antibiotic alone and combined with ibuprofen was more effective administered as early regimen than as delayed treatment when evaluating the presence of otorrhea, otoscopic aspect, culturepositive and bacterial counts in middle ear (ME) samples, and loss of body weight. There was a trend for a better bacteriological outcome in animals receiving amoxicillin or erythromycin and ibuprofen, especially with the high dose. Such a dose of ibuprofen, associated with each antibiotic regimen, also preserved the animal well-being, avoiding a great weight loss in comparison to those receiving the antibiotic alone but a statistically significant difference was only observed for animals receiving delayed therapy with erythromycin and high-dose ibuprofen. In conclusion, ibuprofen combined with antibiotics seemed to improve the outcome of this experimental pneumococcal AOM. A OM is one of the most frequently diagnosed infectious diseases and the most common reason for antibiotic prescriptions written for children in many countries (1). Most experts recommend empirical antimicrobial treatment of AOM in children to eradicate the pathogen and the use of an anti-inflammatory or analgesic drug such as ibuprofen or acetaminophen to relieve the symptoms (2,3). Acetaminophen acts as a weak inhibitor of the synthesis of prostaglandins inhibiting cyclooxygenase (COX)-2-dependent pathways (4). In contrast, ibuprofen inhibits both COX-1 and COX-2 having more potent analgesic and anti-inflammatory effects (5). We previously demonstrated using an experimental AOM model caused by Streptococcus pneumoniae that acetaminophen combined with amoxicillin/clavulanic acid or erythromycin had neither a synergistic nor an antagonistic effect on the antipneumococcal activity (6). Therefore, use of acetaminophen to alleviate ear pain and decrease body temperature (3) may be advocated alone or combined with an antibiotic in the management of AOM. We selected ibuprofen, a potent antiinflammatory drug, to determine its effect when combined with antimicrobial treatment on the outcome of penicillinresistant pneumococcal AOM in a gerbil model. METHODS Bacteria.A strain of S. pneumoniae serotype 23 F [minimum inhibitory concentration (MIC) for benzylpenicillin ϭ 2 g/mL] isolated from a bacteremic patient was used.Pharmacological compounds. Ibuprofen sodium salt and erythromycin (Sigma Chemical Co., St. Louis, MO) and amoxicillin trihydrate (GlaxoSmithKline, Worthing, UK) were used for in vitro studies. For in vivo (therapeutic) use, Junifen, an ibuprofen suspension (Boots Healthcare International, Nottingham, UK), was used diluted with sterile distilled water ...

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Section: Discussionsupporting

confidence: 58%

Impact of Ibuprofen Therapy in the Outcome of Experimental Pneumococcal Acute Otitis Media Treated With Amoxicillin or Erythromycin

et al. 2006

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“…Whereas there are multiple rodent models of experimental OM caused by bacteria, the majority of these require direct inoculation of bacteria into the middle ear space [20], [22], [33], [34]. To date, animal models of OM that demonstrate bacterial ascension from the NP into the middle ear space exist only for S. pneumoniae [33] and NTHI [22], not M. catarrhalis .…”

Section: Introductionmentioning

confidence: 99%

“…To date, animal models of OM that demonstrate bacterial ascension from the NP into the middle ear space exist only for S. pneumoniae [33] and NTHI [22], not M. catarrhalis . This is despite the fact that M. catarrhalis is an increasingly important OM pathogen, particularly after the widespread use of the heptavalent pneumococcal conjugate vaccine [35], [36], [37], [38], and nasopharyngeal carriage of this microorganism is more prevalent in some sub-populations, such as Australian Aborigines [19], [39], [40].…”

Section: Introductionmentioning

confidence: 99%

Respiratory Syncytial Virus Promotes Moraxella catarrhalis-Induced Ascending Experimental Otitis Media

et al. 2012

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Otitis media (OM) is a polymicrobial disease wherein prior or concurrent infection with an upper respiratory tract virus plays an essential role, predisposing the middle ear to bacterial invasion. In episodes of acute bacterial OM, respiratory syncytial virus (RSV) is the most commonly isolated virus and thus serves as an important co-pathogen. Of the predominant bacterial agents of OM, the pathogenesis of disease due to Moraxella catarrhalis is the least well understood. Rigorous study of M. catarrhalis in the context of OM has been significantly hindered by lack of an animal model. To bridge this gap, we assessed whether co-infection of chinchillas with M. catarrhalis and RSV would facilitate ascension of M. catarrhalis from the nasopharynx into the middle ear. Chinchillas were challenged intranasally with M. catarrhalis followed 48 hours later by intranasal challenge with RSV. Within 7 days, 100% of nasopharynges were colonized with M. catarrhalis and homogenates of middle ear mucosa were also culture-positive. Moreover, within the middle ear space, the mucosa exhibited hemorrhagic foci, and a small volume of serosanguinous effusion was present in one of six ears. To improve upon this model, and based on epidemiologic data, nontypeable Haemophilus influenzae (NTHI) was included as an additional bacterial co-pathogen via intranasal administration four days before M. catarrhalis challenge. With this latter protocol, M. catarrhalis was cultured from the nasopharynx and middle ear homogenates of a maximum of 88% and 79% animals, respectively, for up to 17 days after intranasal challenge with M. catarrhalis . Additionally, hemorrhagic foci were observed in 79% of middle ears upon sacrifice. Thus, these data demonstrated that co-infection with RSV and NTHI predisposed to M. catarrhalis -induced ascending experimental OM. This model can be used both in studies of pathogenesis as well as to investigate strategies to prevent or treat OM due to M. catarrhalis .

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Modèles animaux de l’otite moyenne aiguë – une mise au point avec des implications pratiques pour la recherche en laboratoire

Davidoss

Varsak

Maria

2018

Annales françaises d'Oto-rhino-laryngologie et de Pathologie Ce

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Effect of erythromycin treatment delay on therapeutic outcome of experimental acute otitis media caused by Streptococcus pneumoniae

Abstract: Bacteriological and clinical efficacies were significantly diminished if antibiotic administration was delayed.

Cited by 6 publications

References 10 publications

Impact of Ibuprofen Therapy in the Outcome of Experimental Pneumococcal Acute Otitis Media Treated With Amoxicillin or Erythromycin

Impact of Ibuprofen Therapy in the Outcome of Experimental Pneumococcal Acute Otitis Media Treated With Amoxicillin or Erythromycin

Respiratory Syncytial Virus Promotes Moraxella catarrhalis-Induced Ascending Experimental Otitis Media

Modèles animaux de l’otite moyenne aiguë – une mise au point avec des implications pratiques pour la recherche en laboratoire

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