The online version of this article (doi:10.1186/1476-9255-7-22) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
MS carried out the experimental protocol and collected all the data. ST and GI contributed in the design of the protocol, performed the statistical analysis, were involved in the drafting of the manuscript and carried out the revisions of the final version. MT and AT participated in the design of the study, carried out the analytical procedures and were involved in the drafting of the methodology of the manuscript. IL and AP participated in the design and the validation of the empyemic rabbit model. DB designed the experimental protocol and gave the final approval for the submission of this manuscript.
All authors read and approved the final manuscript.
This study was supported by a grant from Experimental Research Center ELPEN A. E. Farma, Athens, Greece.
To determine the extent of linezolid and ertapenem penetration into the empyemic fluid using a rabbit model of empyema.
An empyema was created via the intrapleural injection of Escherichia coli bacteria (ATCC 35218) into the pleural space of New Zealand white rabbits. After an empyema was verified by thoracocentesis, 24 hours post inoculation, linezolid (10 mg/kg) and ertapenem (60 mg/kg) were administered intravenously into 10 and 8 infected empyemic rabbits, respectively. Antibiotic levels were determined in samples of pleural fluid and blood serum, collected serially at 1, 2, 4, 6 and 8 hours, after administration each of the two antibiotics.
Linezolid as well as ertapenem penetrate well into the empyemic pleural fluid, exhibiting a slower onset and decline compared to the corresponding blood serum levels. Equilibration between blood serum and pleural fluid compartments seems to occur at 1.5 hours for both linezolid and ertapenem, with peak pleural fluid levels (Cmaxpf of 2.02 ± 0.73 «mu»g/ml and Cmaxpf of 3.74 ± 1.39 «mu»g/ml, correspondingly) occurring 2 hours post antibiotics administration and decreasing very slowly thereafter. The serum concentrations for both antibiotics were significantly lower from the corresponding pleural fluid ones during the 8 hours collecting data, with the exception of samples collected at the 1st hour (Cmaxserum of 2.1 ± 1.2 «mu»g/ml for linezolid and Cmaxserum of 6.26 ± 2.98 «mu»g/ml for ertapenem).
Pleural fluid levels of both antibiotics are inhibitory for common specified pathogens causing empyema.
Bouros D: Parapneumonic Pleural Effusions and Empyema. Pleural Disease. Edited by: Bouros D. 2004, New York, Marcel Dekker CrossRef
Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, Dowell SF, File TM, Musher DM, Niederman MS, Torres A, Whitney CG, Infectious Diseases Society of America; Infectious Diseases Society of America/American Thoracic Society: Consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007, 44 (Suppl 2): S27-72. 10.1086/511159. PubMedCrossRef
Sasse SA: Parapneumonic effusions and empyema. Curr Opin Pulm Med. 1996, 2: 520-526.
Strange C, Sahn SA: Management of parapneumonic pleural effusions and empyema. Infect Dis Clin North Am. 1991, 5: 539-559. PubMed
Bouros D, Plataki M, Antoniou KM: Parapneumonic effusion and empyema: best therapeutic approach. Monaldi Arch Chest Dis. 2001, 56: 144-8. PubMed
Liapakis IE, Kottakis I, Light RW, Bouros D: Pharmacokinetics and pharmacodynamics in the pleural space. Pleural Diseases. Edited by: Bouros D. 2004, New York, Marcel Dekker, 999-1008. CrossRef
Bouros D, Schiza S, Siafakas N: Utility of fibrinolytic agents for draining intrapleural infections. Semin Respir Infect. 1999, 14: 39-47. PubMed
Sahn SA, Potts DE: Turpentine pleurisy in rabbits: a model of pleural fluid acidosis and low pleural fluid glucose. Am Rev Respir Dis. 1978, 118: 893-901. PubMed
Peng GW, Stryd RP, Murata S, Igarashi M, Chiba K, Aoyama H, Aoyama M, Zenki T, Oza N: Determination of linezolid in plasma by reversed-phase high performance liquid chromatography. Journal of Pharm Biomed Anal. 1999, 20 (1-2): 65-73. 10.1016/S0731-7085(98)00310-0. CrossRef
Soltani M, MacGowan A, Lovering A: Assay of ertapenem in human serum by high performance liquid chromatography. Int J Antimicrobial Agents. 27 (2006): 165-167.
Oramas-Shirey MP, Buchanan LV, Dileto-Fang CL, Dailey CF, Ford CW, Batts DH, Gibson JK: Efficacy of linezolid in a staphylococcal endocarditis rabbit model. J of Antimicr Chemother. 2001, 47: 349-352. 10.1093/jac/47.3.349. CrossRef
Dinleyici EC, Yarar C, Dinleyici M, Yakut A: Successful treatment with linezolid of meningitis complicated with subdural empyema in a 6-month-old boy. J of Trop Pediatrics. 2007, 53 (6): 431-433. 10.1093/tropej/fmm058. CrossRef
Majumbar AK, Musson DG, Birk KL, Kitchen CJ, Holland S, McCrea J, Mistry G, Hesney M, Xi L, Li SX, Haesen R, Blum RA, Lins RL, Greenberg H, Waldman S, Deutsch P, Rogers JD: Pharmacokinetics of ertapenem in healthy young volunteers. Antimicrob Agents Chemother. 2002, 46: 3506-11. 10.1128/AAC.46.11.3506-3511.2002. CrossRef
Roy S, Higareda I, Angel-Muller E, Ismail M, Hague C, Adeyi B, Woods GL, Teppler H: Ertapenem once a day versus piperacillin-tazobactam every 6 hours for treatment of acute pelvic infections: A prospective, multicenter, randomized, double-blind study. Infect Dis Obstet Gynecol. 2003, 11 (1): 27-37. 10.1155/S1064744903000048. PubMedPubMedCentralCrossRef
Ortiz-Ruiz G, Caballero-Lopez J, Friedland IR, Woods GL, Carides A, Protocol 018 Ertapenem Community-Acquired Pneumonia Study Group: A study evaluating the efficacy, safety, and tolerability of ertapenem versus ceftriaxone for the treatment of community-acquired pneumonia in adults. Clin infect Dis. 2002, 34: 1076-1083. 10.1086/339543. PubMedCrossRef
Cottagnoud P, Pfister M, Cottagnoud M, Acosta F, Tauber MG: Activities of ertapenem, a New Long-Acting Carbapenem, against Penicillin-Sensitive or -Resistant Pneumococci in Experimental Menigitis. Antimicrobial Agents and Chemotherapy. 2003, 47 (6): 1943-1947. 10.1128/AAC.47.6.1943-1947.2003. PubMedPubMedCentralCrossRef
Makino J, Kanke M, Nakashima E, Kamata M, Ozawa S, Maruyama H, Masuhara K, Kobayashi T: Pharmacokinetic study of penetration of meropenem into pleural effusion in patients with pleurisy. Jpn J Antibiot. 2002, 55 (1): 77-88. PubMed
Fraschini F, Nebuloni R, Cortelazzi R, Falchi M: Antibiotics and mucous membrane: pharmacokinetic aspects. J Chemother. 1991, 3 (suppl 1): 182-9. PubMed
Wooddnutt G, Berry V, Mizen L: Effect of protein binding on penetration of β-lactams into rabbit peripheral lymph. Antimicrob Agents Chemother. 1995, 39: 2678-83. CrossRef
Sakuma T, Kubo H, Tanita T, Koike K, Fujimura S: Penetration of intravenous antibiotics from the lung into the pleural space after pulmonary resection. Thorac Cardiovasc Surg. 1994, 107: 955-957.
Jacqueline C, Caillon J, Grossi O, Le Mabecque V, Miegeville AF, Bugnon D, Batard E, Potel G: In vitro and in vivo assessment of linezolid combined with ertapenem: a highly synergistic combination against methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 2006, 50 (7): 2547-9. 10.1128/AAC.01501-05. PubMedPubMedCentralCrossRef
- Pharmacokinetics of Linezolid and Ertapenem in experimental parapneumonic pleural effusion
- BioMed Central
Neu im Fachgebiet Innere Medizin
Meistgelesene Bücher aus der Inneren Medizin
Sommerakademie-Visual, Mail Icon II