Effect of Antibiotic Treatment Delay on Therapeutic Outcome of Experimental Acute Otitis Media Caused by
            <i>Streptococcus pneumoniae</i>
            Strains with Different Susceptibilities to Amoxicillin

Parra, Araceli; Ponte, Carmen; Cenjor, Carlos; Martinez-Marin, Carmen; Soriano, Francisco

doi:10.1128/aac.48.3.860-866.2004

Cited by 8 publications

(6 citation statements)

References 26 publications

(32 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These data can explain, in part, the better outcome achieved when the antibiotic was administered early compared to delayed despite giving five doses. These results are also consistent with previous data showing decreased amoxicillin effectiveness when administered 21 h PI compared to early administration (12). It is interesting to point out that most parameters of efficacy (presence of otorrhea, number of ME culturepositive samples, bacterial counts, and body weight) were more favorable in animals treated early with single doses of amoxicillin and ibuprofen, especially when the latter was used at high dose, although these differences were not statistically significant when compared to those receiving the antibiotic alone.…”

Section: Discussionsupporting

confidence: 82%

“…This result may be explained by its favorable pharmacokinetics in both serum (10,11) and ME fluid (12) after an early administration of 5 mg/kg amoxicillin. The amoxicillin ME fluid concentration and half-life have been found to be less advantageous when administration of the antibiotic was delayed (12). These data can explain, in part, the better outcome achieved when the antibiotic was administered early compared to delayed despite giving five doses.…”

Section: Discussionsupporting

confidence: 48%

See 1 more Smart Citation

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

et al. 2006

Self Cite

View full text Add to dashboard Cite

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 ...

show abstract

Section: Discussionsupporting

confidence: 82%

Section: Discussionsupporting

confidence: 48%

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

et al. 2006

Self Cite

View full text Add to dashboard Cite

show abstract

“…Study designs for in vitro and animal studies are all described in Table 1 10 – 32 and Table 2 33 – 36 …”

Section: Resultsmentioning

confidence: 99%

“…Study designs for in vitro and animal studies are all described in Table 1 10-32 and Table 2. [33][34][35][36] Among those studies provided in Table 1, 8 studies were produced by a shared set of researchers, [12][13][14][15][16][17][18][19] with most of these studies generated from within the same research facility in the Netherlands. In most cases, in vitro studies used organisms obtained from clinical samples for biofilm development.…”

Section: Study Qualitymentioning

confidence: 99%

Eradicating Chronic Ear, Nose, and Throat Infections

Smith

Buchinsky

Post

2011

Otolaryngol.--head neck surg.

View full text Add to dashboard Cite

show abstract

“…The results of experiments performed in order to evaluate the effect that early or delayed treatment may have on antibiotic efficacy indicate that early treatment is associated with a better outcome than delayed treatment, as observed in other experimental infection models (20) as well as in humans (15).…”

Section: Discussionmentioning

confidence: 99%

Pulmonary Damage and Bacterial Load in Assessment of the Efficacy of Simulated Human Treatment-Like Amoxicillin (2,000 Milligrams) Therapy of Experimental Pneumococcal Pneumonia Caused by Strains for Which Amoxicillin MICs Differ

Gracia

Martínez-Marín

Huelves

et al. 2005

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

An experimental rat pneumonia model using two amoxicillin-susceptible (MICs, <0.015 and 2 g/ml) and two non-amoxicillin-susceptible (MIC, 4 g/ml) Streptococcus pneumoniae strains was developed for testing the efficacy of amoxicillin administered to simulate human serum kinetics after treatment with amoxicillinclavulanate (2,000 and 125 mg, respectively, twice a day, for 2.5 days). The end points for efficacy were reductions in bacterial loads in the lungs and reductions in levels of pulmonary damage. For the amoxicillinsusceptible strains (serotypes 23F and 14), a decrease greater than 4.5 log 10 CFU/pair of lungs was obtained, and the time for which the serum antibiotic concentration (SAC) was higher than the MIC (T SAC>MIC ) was greater than 60% of the dosing interval. Acute pneumonia is the most frequent cause of death from infectious diseases in developed countries (16). Streptococcus pneumoniae is the leading cause of community-acquired pneumonia (2). Despite the availability of potent antimicrobial agents, pneumococcal pneumonia has a very high mortality, reaching 38% in some areas (3,19). In addition, the appearance of pneumococcal strains with decreased susceptibility to ␤-lactams and other antibiotics has caused concern because in some areas as many as 35% of pneumococcal pneumonias are caused by non-penicillin-susceptible organisms (3). In spite of this, ␤-lactams are widely and successfully used for respiratory tract infections caused by S. pneumoniae strains, even nonpenicillin-susceptible strains. However, there has been little experience with the treatment of pneumococcal pneumonia caused by strains for which amoxicillin MICs are higher than 2 g/ml, because the probability of pathogens with such a reduced susceptibility profile is too low (11) and this warrants the use of animal models for testing efficacy. To cover pneumococcal strains for which amoxicillin MICs are 4 g/ml for approximately 50% of the dosing interval with a twice-a-day (b.i.d.) regimen, a new sustained-release amoxicillin-clavulanate formulation has been developed (12). This antibiotic treatment has shown clinical efficacy in community-acquired pneumonia (8,11,22), but there was a small number of patients infected with pneumococci for which amoxicillin MICs were high.The aim of this study was to compare the efficacies of amoxicillin in an experimental model of pneumonias caused by four pneumococcal strains with different amoxicillin susceptibilities. The antibiotic was administered so as to attain an amoxicillin pharmacokinetic profile similar to that obtained in humans after administration of the new sustained-release amoxicillinclavulanic acid formulation of 2,000 and 125 mg, respectively, b.i.d. A secondary aim was to evaluate the effect of the time from inoculation to treatment initiation on antibiotic efficacy. MATERIALS AND METHODSBacteria. Four strains of S. pneumoniae with different in vitro susceptibilities to amoxicillin were selected based on their similar virulence in experimental animals. Strain AR30118 (serotype 23F)...

show abstract

Effect of Antibiotic Treatment Delay on Therapeutic Outcome of Experimental Acute Otitis Media Caused by Streptococcus pneumoniae Strains with Different Susceptibilities to Amoxicillin

Cited by 8 publications

References 26 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

Eradicating Chronic Ear, Nose, and Throat Infections

Pulmonary Damage and Bacterial Load in Assessment of the Efficacy of Simulated Human Treatment-Like Amoxicillin (2,000 Milligrams) Therapy of Experimental Pneumococcal Pneumonia Caused by Strains for Which Amoxicillin MICs Differ

Contact Info

Product

Resources

About