In Vivo Efficacies of Amoxicillin and Cefuroxime against Penicillin-Resistant Streptococcus pneumoniae in a Gerbil Model of Acute Otitis Media

Abstract

The comparative efficacies of amoxicillin and cefuroxime against acute otitis media caused by a penicillin-resistant (MIC, 2 μg/ml) Streptococcus pneumoniae strain were assessed in a gerbil model by challenging each ear with 107 bacteria through transbullar instillation. Each antibiotic was tested at two doses (5 and 20 mg/kg of body weight) administered at 2, 10, and 18 h postinoculation. Samples were obtained from the middle ear (ME) on days 3 and 7 postinoculation for determination of bacterial counts. Only amoxicillin, at both doses, was able to significantly halt the weight loss in animals, reducing both the number of culture-positive animals and the bacterial concentration in ME samples versus the values for untreated animals. Comparison of the efficacies between the antibiotics, determined by their ability to achieve culture-negative ME specimens, showed that amoxicillin at 5 mg/kg was significantly more active than cefuroxime at the same dose. The use of higher doses of either amoxicillin or cefuroxime did not produce significantly better results than those obtained with the lower dose but caused a greater inflammatory response. The more favorable results obtained with amoxicillin compared with those obtained with cefuroxime could be related to the antimicrobial susceptibility of the pneumococcal strain (MICs and minimum bactericidal concentrations of 1 and 1 μg/ml and 4 and 4 μg/ml for amoxicillin and cefuroxime, respectively) as well as to the better pharmacokinetic parameters obtained with amoxicillin.

Antibiotic therapy of community respiratory tract infections: strategies for optimal outcomes and minimized resistance emergence

“…Thus, in gerbil otitis media, amoxicillin was significantly more effective than cefuroxime against a penicillin-resistant strain (MIC 2 mg/L). 61 Similar observations apply to fluoroquinolones. In the rat pneumonia model, grepafloxacin and gemifloxacin were significantly more effective against pneumococci than either levofloxacin or ciprofloxacin (P Ͻ 0.01).…”

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

“…AOM is related to infection by organisms with high pathogenic potential, such as S. pneumoniae, in humans [16,24,25] and in experimental models [26,27]. In contrast, OME seems to be related to infection by less pathogenic organisms, such as nonserotypeable H. influenzae strains, mainly from biotype II, as has been confirmed in humans [24,28] and experimental models [19].…”

“…influenzae inoculum developed AOM, whereas challenge with H. influenzae culture alone caused OME in 86.7% of the animals. In an earlier study [26], we obtained AOM after inoculating a pure culture of the same S. pneumoniae strain used in the present work. This confirms that both conditions (AOM and OME) may depend on the organism involved.…”

Community-acquired pneumonia: new management strategies for evolving pathogens and antimicrobial susceptibilities

“…The best example of this is amoxicillin [23,24]. By using higher doses of amoxicillin it is possible to overcome 'non-susceptible' strains of pneumococci in middle ear fluids [24][25][26].…”