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Vol. 31. Issue. 3.May 2011
Pages 0-378
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Intraperitoneal daptomycin
Administración intraperitoneal de daptomicina
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L.. García-Lópeza, L.. Gómez Sayagoa, M.J.. Fernández-Reyes Luisb
a Servicio de Farmacia, Hospital General de Segovia,
b Servicio de Nefrolog??a, Hospital General de Segovia,
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To the Editor,

Peritonitis is one of the main causes of morbidity in patients undergoing peritoneal dialysis (PD). Although the usual treatments with vancomycin, aminoglycosides or semi-synthetic penicillins recommended in treatment guidelines for peritonitis1 are efficient in most cases, situations such as colonisation by methicillin-resistant microorganisms with some degree of resistance to vancomycin are common. These treatments are ineffective in these cases.

The proliferation of multi-resistant gram-positive pathogens has led to the antibiotic daptomycin being brought back and its clinical development has started again. It was approved by the United States Food and Drug Administration (FDA) in 2003 for the treatment of endocarditis caused by gram-positive pathogens, and skin and white-tissue infections.

A case study has been published of peritonitis which was not linked to the peritoneal catheter that was treated with intravenous daptomycin. This study analysed the concentration of daptomycin reached in the peritoneal fluid after intravenous administration. It was found to be 5mg/ml (minimum inhibitory concentration [MIC]=4mg/ml).2 Therefore, the concentrations in the intraperitoneal fluid as a result of intraperitoneal administration of the antibiotic would be less close to the microorganism MIC for daptomycin.

The clinical experience published to date is limited to two cases. Intraperitoneal daptomycin was used in these cases to treat peritonitis caused by vancomycin-resistant gram-positive bacteria.3 This treatment succeeded in these cases where conventional therapies had previously failed. The intraperitoneal administration of daptomycin was well tolerated in these patients and they had no peritoneal irritation or negative effects associated with the administration of drugs through this route.

Furthermore, daptomycin is a drug that is currently used to treat catheter-related bacteriaemias4 due to its efficacy in controlling biofilm growth, and that is why it may be considered useful in the treatment of biofilm on intraperitoneal catheters.

We report here the clinical case of a 61-year-old man who had been diagnosed with advanced chronic kidney disease (CKD) secondary to diabetic nephropathy since 2001. He started PD in December 2006. The patient has had three episodes of peritonitis since February 2008 that led us to consider removing the catheter in October 2009 due to suspected biofilm.

In May 2010 he had a new episode of peritonitis and was started on intraperitoneal empiric treatment with vancomycin following normal dosage guidelines (a shock dosage of 2g followed by 2g/3 days and a shock dosage of 100mg of tobramycin and 50mg/24h). The presence of Staphylococcus epidermidis and Streptococcus viridans which were only sensitive to carbapenems was found four days later when the culture results were received. We, therefore, continued with the intraperitoneal treatment with vancomycin at a dose of 2g a week (3 weeks), and tobramycin was changed for 1g of imipenem/24h for 14 days.

He had a new relapse in June 2010 and S. epidermidis with intermediate sensitivity to vancomycin (MIC=2) was isolated. Treatment with vancomycin was started according to protocol, with a positive clinical response, although after this relapse, it was suspected that the peritoneal catheter had been colonised by S. epidermidis biofilm. An application was made for the compassionate use of intraperitoneal daptomycin on the basis of the previous experience of two clinical cases published. Treatment with vancomycin was maintained until daptomycin was authorised.

We used the following treatment plan with daptomycin:

A shock dosage of 200mg (in a 2l PD1 solution), followed by 40mg in each change of the intraperitoneal fluid (four times a day) for 10 days. After finishing this treatment plan, the catheter was then put in an antibiotic lock with 350mg in 7ml for 12h once a week for one month. The patient responded positively to this treatment and has had no relapses or new episodes of peritonitis.

Bibliography
[1]
1.??Furgeson SB,??Teiltelbaum I. New treatment options and protocols for peritoneal dialysis-related peritonitis. Contrib Nephrol 2009;163:169-76. [Pubmed]
[2]
Burklein D, Heyn J, Kirchhoff C, Ozimek A, Traunmuller F, Joukhadar C, et al. Analysis of plasma and peritoneal fluid concentrations of daptomycin in a patient with Enterococcus faecium peritonitis. Int J Antimicrob Agents 2008;32(4):369-71. [Pubmed]
[3]
Huem SC, Hall I, Topal J, Mahnenmith R, Brewster U, Abu-alfa A. Successful use of intraperitoneal daptomicyn in the treatment of vancomycin-resistant enterococcus peritonitis. Am J Kidney Dis 2009;54(3):538-41. [Pubmed]
[4]
Raad I, Hanna H, Jiang Y, Dvorak T, Reitzel R, Chaiban G, et al. Comparative activities of daptomycin, linezolid and tigecycline against catheter-related methicilin-resistant Staphylococcus bacteremic isolates embedded in biofilm. Antimicrob Agents Chemother 2007;51:1656-60. [Pubmed]
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