tebipenem and Haemophilus-Infections

Topics: Acute Disease; Ampicillin; Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenems; Cephalosporins; Child, Preschool; Drug Resistance, Multiple, Bacterial; Fluoroquinolones; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Japan; Microbial Sensitivity Tests; Multilocus Sequence Typing; Naphthyridines; Otitis Media; Pneumococcal Vaccines; Quinolones; Streptococcus pneumoniae; Vaccines, Conjugate

Tebipenem pivoxil, an oral carbapenem antibiotic for pediatric use, exhibits excellent clinical effects on acute otitis media (AOM). The present study was conducted to assess the pharmacokinetic profile of tebipenem in middle ear effusion and to examine the clinical efficacy of tebipenem pivoxil by calculating the values of the pharmacokinetic-pharmacodynamic parameters (AUC/MIC, C max/MIC, and T > MIC) of tebipenem at the site of action. Twenty-three pediatric outpatients diagnosed with AOM were enrolled. Ear discharge or nasopharyngeal swabs collected before the onset of oral administration were used to conduct bacteriological examinations, and subjects were then treated by twice-a-day oral administration of tebipenem pivoxil 6 mg/kg. The clinical isolates of Streptococcus pneumoniae and Haemophilus influenzae were obtained from 10 and 19 pediatric patients (8 overlapped), respectively. On day 2 of administration, blood and middle ear effusion were collected from 20 pediatric patients to measure plasma and middle ear concentrations of tebipenem. Consequently, the C max and the AUC0-∞ in plasma were 5.3 ± 1.6 μg/ml (mean ± SD) and 7.9 ± 0.2 μg h/ml, respectively. The C max in middle ear effusion of tebipenem was 1.2 ± 0.1 μg/ml, exceeding its MIC for these pathogens. The ratio of AUC0-∞ in middle ear effusion to AUC0-∞ in plasma was 0.36, showing the good transfer of tebipenem into the effusion; this result corroborated the known high rate of clinical efficacy of tebipenem pivoxil for patients with AOM and the low incidence of recurrence in them as manifested by the healing rate of 94.1 % (16/17).

Topics: Anti-Bacterial Agents; Carbapenems; Child, Preschool; Cohort Studies; Exudates and Transudates; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Male; Otitis Media with Effusion; Pneumococcal Infections; Streptococcus pneumoniae; Treatment Outcome

Morphological changes in penicillin-resistant Streptococcus pneumoniae (PRSP) and beta-lactamase-nonproducing, ampicillin-resistant Haemophilus influenzae (BLNAR) after exposure to oral antibacterial agents could be observed over time under a phase-contrast microscope. Morphological changes in BLNAR were also observed using a scanning electron microscope. The organisms used in this study were ME19F strain identified as genotypic(g) gPRSP (serotype: 19F) and JPH002 strain identified as gBLNAR (serotype: b). The antibacterial agents used were amoxicillin (AMPC), cefditoren (CDTR), tebipenem (TBPM), and tosufloxacin (TFLX). The concentration of each antibacterial agent to which the bacteria were exposed was set at the blood level one hour after Cmax when administered to children at the usual dose. Bacteriolysis of gPRSP cells started after exposure of only 20minutes to TBPM, and 90% of the cells were lysed within 2 hours. A high bactericidal action of TBPM on gPRSP was supported by these findings. When gBLNAR was exposed to AMPC and TBPM, lysis from spheroplasts and cells with vacuoles were sometimes observed. In contrast, after gBLNAR was exposed to CDTR, lysis occurred after marked filamentation in the cells, but after exposure to TFLX, cells deduced to be killed after mild filamentation without lysis. Time-dependent morphological changes that reflect the differences in bactericidal activity and PBP affinity among beta-lactams provide beneficial information to select antibacterial agents.

Topics: Amoxicillin; Ampicillin Resistance; Anti-Bacterial Agents; Bacteriolysis; beta-Lactamases; Carbapenems; Cephalosporins; Child; Dose-Response Relationship, Drug; Fluoroquinolones; Haemophilus Infections; Haemophilus influenzae; Humans; Microscopy, Phase-Contrast; Naphthyridines; Penicillin Resistance; Pneumococcal Infections; Streptococcus pneumoniae; Time Factors

We assessed the clinical efficacy of tebipenem pivoxil (TBPM-PI) in 30 children with pneumonia who, despite having received oral administration of beta-lactam antibiotics at the standard dose for at least 3 days, had no relief of symptoms and showed an abnormal shadow on the chest X-ray and elevated serum CRP levels of 3.0 mg/dl or more between December 2009 and November 2010. TBPM-PI was administered at a single dose of 4 mg/kg twice a day for 3 days. The children ranged in age from 8 months to 5 years. The serum CRP level ranged from 3.05 to 12.9 mg/dl. In 28 of the 30 children, either Streptococcus pneumoniae or Haemophilus influenzae or both were detected. Of the 28 children, 7 carried penicillin resistant S. pneumoniae; 9 carried beta-lactamase nonproducing ampicillin resistant H. influenzae; and 3 carried both. In all children, defervescence was observed within 48 hours of the start of TBPM-PI administration, and the severity of coughing/wheezing reduced significantly by the 3rd to 5th day. Thus, TBPM-PI was determined to be effective. Diarrhea or loose stool was observed as an adverse reaction in 4 children (13.3%).

Topics: Administration, Oral; Amdinocillin Pivoxil; Anti-Bacterial Agents; beta-Lactams; Carbapenems; Child, Preschool; Drug Administration Schedule; Drug Combinations; Drug Resistance, Bacterial; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Male; Pneumonia, Bacterial; Streptococcal Infections; Streptococcus pneumoniae; Treatment Failure; Treatment Outcome