Therapeutic efficacy of cefadroxil and cephalexin for pneumonia in a rat test model

Chisholm, D. R.; Deregis, R. G.; Behr, Douglas

doi:10.1128/aac.30.1.105

Cited by 7 publications

(6 citation statements)

References 7 publications

(3 reference statements)

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“…15,22 Data from animal studies suggest that lung tissue concentrations are important predictors for the outcome of treatment of experimental pneumonia. [23][24][25] In this study, in all ELF and lung tissue samples ertapenem was clearly demonstrable. The highest ELF CLINICAL STUDIES concentrations were achieved 1 hour after infusion (4.06 ± 6.64 mg/L), and the highest mean level of ELF penetration was 9.40% 5 hours after infusion.…”

Section: Discussionsupporting

confidence: 55%

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Penetration of Ertapenem Into Different Pulmonary Compartments of Patients Undergoing Lung Surgery

Burkhardt

Majcher-Peszynska

Börner

et al. 2005

The Journal of Clinical Pharma

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Ertapenem is approved for the treatment of community-acquired pneumonia (CAP), but its in vivo penetration into lung tissue (LT), epithelial lining fluid (ELF), and alveolar cells (AC) is unknown. Fifteen patients undergoing thoracotomy were treated with 1 g intravenously for perioperative prophylaxis. Bronchoalveolar lavage was performed 1, 3, and 5 hours after ertapenem infusion. Normal LT was sampled at the time of lung extraction. Blood was collected before and at different time points up to 24 hours after infusion. Mean concentrations of ertapenem in plasma, ELF, and AC were at 1.0 hour, 63.1, 4.06, 0.004 mg/L; at 3.0 hours, 39.7, 2.59, 0.003 mg/L; and at 5.0 hours, 27.2, 2.83, 0.007 mg/L. Mean (range) concentration in LT was 7.60 (2.5-19.4) mg/kg tissue 1.5 to 4.5 hours after infusion. In plasma, ertapenem exhibited a Cmax of 94.7 +/- 23.3 mg/L and an AUC(0-last) of 501.1 +/- 266.3 mg x h/L. These results, combined with the reported (MIC)90 of most CAP bacteria, support the previously observed clinical efficacy of ertapenem in the treatment of CAP.

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Section: Discussionsupporting

confidence: 55%

“…The significance of antibiotic concentrations in lung tissue has still not been fully assessed with respect to the clinical efficacy of the drug 15,22 . Data from animal studies suggest that lung tissue concentrations are important predictors for the outcome of treatment of experimental pneumonia 23–25 …”

Section: Discussionmentioning

confidence: 99%

Penetration of Ertapenem Into Different Pulmonary Compartments of Patients Undergoing Lung Surgery

Burkhardt

Majcher-Peszynska

Börner

et al. 2005

The Journal of Clinical Pharma

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“…39 As has been shown previously, it is a very effective substrate for transport by PEPT2 in renal brush border membrane vesicles. 40 In addition to its use as an antibiotic, it is also effective in reducing antigen induced bronchial hyperresponsiveness.…”

Section: Discussionmentioning

confidence: 87%

Distribution and function of the peptide transporter PEPT2 in normal and cystic fibrosis human lung

Groneberg

Eynott²,

Döring³

et al. 2002

Thorax

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Background: Aerosol administration of peptide based drugs has an important role in the treatment of various pulmonary and systemic diseases. The characterisation of pulmonary peptide transport pathways can lead to new strategies in aerosol drug treatment. Methods: Immunohistochemistry and ex vivo uptake studies were established to assess the distribution and activity of the β-lactam transporting high affinity proton coupled peptide transporter PEPT2 in normal and cystic fibrosis human airway tissue. Results: PEPT2 immunoreactivity in normal human airways was localised to cells of the tracheal and bronchial epithelium and the endothelium of small vessels. In peripheral lung immunoreactivity was restricted to type II pneumocytes. In sections of cystic fibrosis lung a similar pattern of distribution was obtained with signals localised to endothelial cells, airway epithelium, and type II pneumocytes. Functional ex vivo uptake studies with fresh lung specimens led to an uptake of the fluorophore conjugated dipeptide derivative D-Ala-L-Lys-AMCA into bronchial epithelial cells and type II pneumocytes. This uptake was competitively inhibited by dipeptides and cephalosporins but not ACE inhibitors, indicating a substrate specificity as described for PEPT2. Conclusions: These findings provide evidence for the expression and function of the peptide transporter PEPT2 in the normal and cystic fibrosis human respiratory tract and suggest that PEPT2 is likely to play a role in the transport of pulmonary peptides and peptidomimetics.

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“…Recent animal data suggest that pharmacokinetic parameters of the drug in lung tissue could be important in the outcome of the treatment of experimental pneumonia. In the treatment of lung infection in rats, the better cure rates obtained with cefadroxil compared to cefalexin may be due to the higher drug concentration and greater area under the lung tissue concentration-time curve of cefadroxil compared to those of cefalexin (6). In mouse experimental pneumonia, survival rates and lung clearance of the pathogen are greater when the animals are treated with temafloxacin than when they are treated with ofloxacin or ciprofloxacin (2).…”

mentioning

confidence: 99%

Penetration of Meropenem in Lung, Bronchial Mucosa, and Pleural Tissues

Byl¹,

Jacobs²,

Roucloux³

et al. 1999

Antimicrob Agents Chemother

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Therapeutic efficacy of cefadroxil and cephalexin for pneumonia in a rat test model

Cited by 7 publications

References 7 publications

Penetration of Ertapenem Into Different Pulmonary Compartments of Patients Undergoing Lung Surgery

Penetration of Ertapenem Into Different Pulmonary Compartments of Patients Undergoing Lung Surgery

Distribution and function of the peptide transporter PEPT2 in normal and cystic fibrosis human lung

Penetration of Meropenem in Lung, Bronchial Mucosa, and Pleural Tissues

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