Role of<i>Streptococcus pneumoniae</i>and<i>Haemophilus influenzae</i>in the Development of Acute Otitis Media and Otitis Media with Effusion in a Gerbil Model

Soriano, Francisco; Parra, Araceli; Cenjor, Carlos; Nieto, Eva; Garcı́a-Calvo, Gloria; Giménez, Marı́a José; Aguilar, Lorenzo; Ponte, Carmen

doi:10.1086/315237

Cited by 15 publications

(14 citation statements)

References 31 publications

(32 reference statements)

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“…The inhibitory quotient, calculated taking into account the ME concentrations (antibiotic concentration in MEF/MIC) was Ͼ1.6, thus indicating that the antibiotic concentration in the infectious foci was higher than the MIC of the offending penicillin-resistant, erythromycin-sensitive pneumococcus. In this study, as has been demonstrated previously (23), the main pharmacodynamic parameter predicting antibiotic efficacy in otitis media is the MEF inhibitory quotient. Clinical and bacteriologic success was obtained when the antibiotic concentration in the MEF exceeded the MIC of the pathogen, which may, to some extent, be independent of serum levels (23,24).…”

Section: Discussionsupporting

confidence: 62%

“…In this study, as has been demonstrated previously (23), the main pharmacodynamic parameter predicting antibiotic efficacy in otitis media is the MEF inhibitory quotient. Clinical and bacteriologic success was obtained when the antibiotic concentration in the MEF exceeded the MIC of the pathogen, which may, to some extent, be independent of serum levels (23,24).…”

Section: Discussionsupporting

confidence: 62%

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Does Acetaminophen Interfere in the Antibiotic Treatment of Acute Otitis Media Caused by a Penicillin-Resistant Pneumococcus Strain? A Gerbil Model

et al. 2003

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The possible interference of acetaminophen, combined with antibiotics, in the treatment of acute otitis media (AOM) caused by a penicillin-resistant (minimal inhibitory concentration [MIC], 2 g/mL), amoxicillin/clavulanic acid-and erythromycin-sensitive pneumococcus was evaluated in a gerbil model. Animals were challenged with 5 ϫ 10 6 bacteria in each ear through transbullar instillation. Acetaminophen was administered s.c. at 50 mg/kg 30 min before each antibiotic dose. Amoxicillin/clavulanic acid and erythromycin (2.5 and 10 mg/ kg) were administered s.c. at 2, 10, and 18 h after inoculation. Samples were obtained from the middle ear (ME) on day 2 after inoculation for bacterial count. The overall results showed no difference between animals that received acetaminophen, with or without antibiotics, and those that did not receive acetaminophen. The antibiotic concentrations in the ME were practically identical in both groups of animals, so acetaminophen did not interfere with the pharmacokinetics of antibiotics in the ME. However, both antibiotics significantly reduced the number of culture-positive and the bacterial concentration in ME samples when compared with antibiotic-untreated animals. Both antibiotics, whether combined with acetaminophen or not, lowered the number of AOM to Ͻ25%, but Ͼ75% of animals presented otitis media with effusion, and no differences were shown between groups. A high rate of bacterial eradication from the ME correlated with antibiotic serum concentrations being over the MIC of the infecting organism for only Ͼ15% of the dose interval and with an ME concentration exceeding the MIC by a factor of 1.7. In this experimental model, acetaminophen had neither a synergistic nor an antagonistic effect on the antibiotics tested. Abbreviations AOM, acute otitis media BHIE, brain-heart infusion broth enriched with 5% horse serum C 15 min, concentration at 15 min after antibiotic administration CFU, colony-forming units MBC, minimal bactericidal concentration ME, middle ear MEF, middle ear fluid without washing MEWF, middle ear washing fluid MIC, minimal inhibitory concentration MIC 50 , minimal concentration inhibiting 50% of the strains tested MIC 90 , minimal concentration inhibiting 90% of the strains tested OME, otitis media with effusion Acute otitis media (AOM) is one of the most frequently diagnosed infectious diseases of childhood, and the number of office visits for this pathology is increasing in many countries (1). One of the most common approaches to treating AOM in children is to administer an antibiotic to eradicate the pathogen, as well as an anti-inflammatory or analgesic drug such as acetaminophen (2, 3). Anti-inflammatory activity is mainly exerted through the inhibition of COX-1 and COX-2 isoenzymes that catalyze the rate-limiting step of prostaglandin synthesis (4). Recent data suggest that the little antiinflammatory activity of acetaminophen is due to its activity against COX-3 (that shows Ͻ20% activity of COX-1 and COX-2 and is present at approximately 25% of the level ...

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Section: Discussionsupporting

confidence: 62%

Section: Discussionsupporting

confidence: 62%

Does Acetaminophen Interfere in the Antibiotic Treatment of Acute Otitis Media Caused by a Penicillin-Resistant Pneumococcus Strain? A Gerbil Model

et al. 2003

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“…The amplification of samples that are culture negative has been reported in previous publications and has been attributed to one or more of the following: (i) the superior sensitivity of PCR methods over that of culture, (ii) amplification of viridans group streptococcus-related sequences, (iii) detection of bacterial DNA from dead organisms, or (iv) contamination (15,16,27). The fact that we detected S. pneumoniae in MEF specimens that were culture positive only for H. influenzae is not surprising; other investigators have reported that up to approximately 24% of MEF samples from patients result in mixed S. pneumoniae-H. influenzae culture isolations (4,9,31). Thus, another plausible explanation for these S. pneumoniae culturenegative, PCR-positive MEF specimens is dual infection not revealed by culture, for even though S. pneumoniae was undetectable by culture, its presence and/or the presence of its DNA cannot be ruled out.…”

Section: Discussionmentioning

confidence: 60%

Evaluation and Improvement of Real-Time PCR Assays Targeting lytA , ply , and psaA Genes for Detection of Pneumococcal DNA

Carvalho¹,

Tondella²,

McCaustland³

et al. 2007

J Clin Microbiol

489

485

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The accurate diagnosis of pneumococcal disease has frequently been hampered not only by the difficulties in obtaining isolates of the organism from patient specimens but also by the misidentification of pneumococcuslike viridans group streptococci (P-LVS) as Streptococcus pneumoniae. This is especially critical when the specimen comes from the respiratory tract. In this study, three novel real-time PCR assays designed for the detection of specific sequence regions of the lytA, ply, and psaA genes were developed (lytA-CDC, ply-CDC, and psaA, respectively). These assays showed high sensitivity (<10 copies for lytA-CDC and ply-CDC and an approximately twofold less sensitivity for psaA). Two additional real-time PCR assays for lytA and ply described previously for pneumococcal DNA detection were also evaluated. A panel of isolates consisting of 67 S. pneumoniae isolates (44 different serotypes and 3 nonencapsulated S. pneumoniae isolates from conjunctivitis outbreaks) and 104 nonpneumococcal isolates was used. The 67 S. pneumoniae isolates were reactive in all five assays. The new real-time detection assays targeting the lytA and psaA genes were the most specific for the detection of isolates confirmed to be S. pneumoniae, with lytA-CDC showing the greatest specificity. Both ply PCRs were positive for all isolates of S. pseudopneumoniae, along with 13 other isolates of other P-LVS isolates confirmed to be non-S. pneumoniae by DNA-DNA reassociation. Thus, the use of the ply gene for the detection of pneumococci can lead to false-positive reactions in the presence of P-LVS. The five assays were applied to 15 culture-positive cerebrospinal fluid specimens with 100% sensitivity; and serum and ear fluid specimens were also evaluated. Both the lytA-CDC and psaA assays, particularly the lytA-CDC assay, have improved specificities compared with those of currently available assays and should therefore be considered the assays of choice for the detection of pneumococcal DNA, particularly when upper respiratory P-LVS might be present in the clinical specimen.

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“…For these reasons, we have studied the effect of delayed antibiotic administration on the course of experimental AOM caused by both penicillinsensitive and -resistant S. pneumoniae strains. This model has been very useful for evaluating antibiotic treatment either for AOM or for otitis media with effusion (OME) (1,2,4,21,23,25). Most of these experimental models have shown that many organisms inoculated into the middle ear (ME) are cleared by antibiotics active in vitro, but in most published studies the antibiotics were administered very early.…”

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confidence: 99%

“…Eight-to 9-week-old adult female Mongolian gerbils (Meriones unguiculatus) weighing 49 Ϯ 5 g each were purchased from the Centre dЈÉlevage R. Janvier (Le Genest, St.-Isle, France) and managed as previously described (25). The study was performed in accordance with prevailing regulations regarding the care and use of laboratory animals in the European Community and approved by our ethical committee for animal experimentation.…”

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confidence: 99%

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

Parra¹,

Ponte²,

Cenjor

et al. 2004

Antimicrob Agents Chemother

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Role ofStreptococcus pneumoniaeandHaemophilus influenzaein the Development of Acute Otitis Media and Otitis Media with Effusion in a Gerbil Model

Cited by 15 publications

References 31 publications

Does Acetaminophen Interfere in the Antibiotic Treatment of Acute Otitis Media Caused by a Penicillin-Resistant Pneumococcus Strain? A Gerbil Model

Does Acetaminophen Interfere in the Antibiotic Treatment of Acute Otitis Media Caused by a Penicillin-Resistant Pneumococcus Strain? A Gerbil Model

Evaluation and Improvement of Real-Time PCR Assays Targeting lytA , ply , and psaA Genes for Detection of Pneumococcal DNA

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

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