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

Abstract

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 ...

Systematic review and meta-analysis of the effects of antipyretic medications on mortality in Streptococcus pneumoniae infections

“…In mice treated with sodium salicylate, Spanuolo et al 40–42 noted a reduction in the median lethal inoculum (LD 50 )—bacterial dose required to kill 50%—as well as numbers of granulocytes found in peritoneal exudate compared with placebo treated controls. However, in contrast, two experimental models of S pneumoniae acute otitis media found fewer inflammatory changes37 and lower bacterial cell counts36 in the middle ears of chinchillas and gerbals treated with a combination of ibuprofen and antibiotic versus antibiotic therapy alone. One further experimental animal model of S pneumoniae acute otitis media investigated combinations of paracetamol and/or antibiotics and reported no significant difference in bacterial cell counts between the groups 38…”

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“…Murine studies found that nonselective NSAIDs can increase GAS infections of injured muscles and exacerbate established infections [104,105]. On the other hand, the use of ibuprofen in a gerbil study of penicillinresistant pneumococcal acute otitis media found ibuprofen combined with antibiotic therapy improved outcomes [106].…”

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