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109 ( 57 )具 CASE REPORT典

Successful treatment of pediatric endocarditis andpericarditis due to MRSA with linezolid
TAKASHI MIYAMOTO*, TAKAHIRO TOMOYASU and KAGAMI MIYAJI
The Departments of Cardiothoracic Surgery, Kitasato University School ofMedicine, Kanagawa, Japan(Received for publication December 6, 2010)

The linezolid treatment for methicillin-resistant Staphylococcus aureus (MRSA)
infection was sporadically reported in children. Here we describe a case of a 6 monthold patient underwent mediastinal drainage and artiﬁcial conduit removement causedby MRSA infection. After that, linezolid treatment was started and bacteremia wasresolved after 14 days of treatment. At discharge, he was no febrile, his blood culture
were sterile. We report a case of a patient with MRSA endocarditis treatment withlinezolid.

Introduction
Recent ﬁndings have focused on the possible role of linezolid as a suitable candidate for the treatment of methicillin-resistant Staphylococcus aureus (MRSA). MRSA infections are emerged as themost common cause of postoperative complications. Some investigations suggest that MRSA infections are associated with prolonged hospitalizations increased mortality, mobility and costs. Theraphic options for patients with MRSA infections are limited. Vancomycin has been the standard treatment until recently. However, the potential of vancomycin is ineffective and the development of vancomycin resistant-enterococci (VRE) proliferate has been very rapid with continued use of vancomycin. Linezolid, the ﬁrst member oxazolidinone class of antimicrobial agent, applied for thetreatment of infections caused by MRSA in Japan. We have a case of patient with MRSA endocarditis and pericarditis who was successfully treated with linezolid after glycopeptides treatment failed.

CaseA six months old boy patient underwent mediastinal drainage and artiﬁcial conduit [polytetraﬂuoroethylene (PTFE) graft] removement caused by MRSA infection. A multiple ventricular septal
defect (VSD), coarctation with hypoplastic left ventricle was diagnosed in a 3-month-old boy weigh-110 ( 58 )THE JAPANESE JOURNAL OF ANTIBIOTICS

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ing 5.3 kg. This patient then follows a single ventricle pathway, making them candidates for future
Fontan palliation. First surgical procedure, simultaneous repair of coarctation of the aorta andpulmonary artery banding, was performed through a left thoracotomy at 4 month-old. Secondoperation, Damus-Kaye-Stansel (DKS) anastomosis and right ventricle–pulmonary artery conduit(RV–PA conduit) interposition with a 5 mm polytetraﬂuorethylene (PTFE) graft, was done at 5month-old. The postoperative course was stable condition with respect to surgical mortality, neurologic events and infection. At discharge, his blood cultures were sterile and a transesophagealechocardiogram (TEE) showed no evidence of endocarditis.
One month later the patient returned to our department because of intermittent high fever andanemic conditions. High-grade bacteremia with MRSA was diagnosed because his blood cultures
sets grew a MRSA strains. An antimicrobial regimen of vancomycin was initiated. The patient wasstill bacteremic after several days of treatment and his infectious factors, CRP and WBC, wereincreased. Though both chest X-ray and echocardiography were negative ﬁndings, high-grade bacteremia with MRSA was diagnosed from the blood culture and the computerized tomography (CT)showed a 5 mm abscess at the anastomosis between the PTFE graft and the right ventricle. Therefore, we decide to remove and replacement the PTFE graft with surgical intervention because theinner and outer abscess (Figure 1). The medicine sensitivity inspection of MRSA the fully automaticwhich conforms to the microdirution method which Clinical and Laboratory Standards Institute(CLSI) recommends recently in system MicroScanWalkAway-96 (DADE Behring) measured theMinimum Inhibitory Concentration (MIC) making use of the Pos Combo41J panel (DADEBehring). Furthermore, it measured the MIC of vancomycin (VCM) with the Pos Combo41J panel,Fig. 1.

The intraoperative picture show the abscess around the RV-PA conduit.

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Fig. 2.

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111 ( 59 )Perioperative values of C-reactive protein and WBC counts.

it measured the MIC of linezoid (LZD), making use of nutrient medium Mueller Hinton nutrient
medium (Becton Dickinson) for medicine sensitivity test and Etest “[asuka]”. As for the result, asfor VCM MIC⬍ as for the MIC of 2.0 m g/mL and LZD⬍1.0 m g/mL, was, also both anti-bacterial
medicine showed satisfactory sensitivity.
After that, washing out the intra-mediastinal space with normal saline solution continuously performed for two weeks and 14 daily dose of intravenous vancomycin (VCM) therapy were given.
Trough serum level of VCM measured on three occasions during his effective treatment ranged
from 10.1 to 15.3 m g/ml. However, he remained febrile clinically (⬎38°C) and white blood cellcount and C-reactive protein again rose (Figure 2). The antibiotic regimen was changed to intravenous linezolid (10 mg/kg/day) 8 hourly. Two weeks after initiation of linezolid treatment, hisblood culture was sterile and transthoracic echocardiography (TTE) and CT showed complete disappearance of abscesses. It is known well that the number of blood platelets decreases during linezolidinjection but, the blood platelet is no signiﬁcantly change. At discharge, he became no febrile andthe treatment course was completed uneventfully. During the follow up, no other infectious episodewas observed and he had been in remission for 2 years.

Discussion
Until recently, there were few therapeutic options for the treatment of MRSA infections, intravenous vancomycin remains the standard therapy, but usefulness of vancomycin may limit in thefuture.1) Pediatric MRSA endocarditis has a high mortality and relapse rate when treated with antibi-

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otics alone. Failure of vancomycin to care the infection in these patients could be attributed not onlyto the presence of a non-susceptible bacterial subpopulation but also to the presence of a prostheticdevice. Linezolid has signiﬁcant activity against Gram-positive species and a unique mechanism ofaction, and it lacks cross-resistance with other antimicrobial classed.2) Linezolid inhibit initiation ofprotein synthesis by binding to the 50S ribosomal subunit at a different site than that used by chloramphenicol or clindamycin. Linezolid is a drug with well-recognised activity against MRSA and it
could be a good therapeutic choice when glycopeptides treatment is not feasible.
In a few previous cases, there were successful treatments of MRSA endocarditis with linezolid.3)
To the best our knowledge, however, none of pediatric patients were reported in the literature on thetreatment of MRSA endocarditis with linezolid. Linezolid was well tolerated and safe in the treatment of MRSA bacteremia because clinical, microbiological, and survival outcomes are not inferior
to those of vancomycin and adverse drug-drug or drug-food interactions.4) The analyses of adverse
events, clinical laboratory assays and other safety data suggest that linezolid was well tolerated compare with vancomycin.5) This is only the ﬁrst report in the literature on the treatment of pediatric
MRSA endocarditis with linezolid. We had better to select for pediatric patient with the emergenceof resistance to vancomycin in MRSA infections.
In conclusion, we have encountered a clinical impression of pediatric MRSA endocarditis resistant to vancomycin. We suggest linezolid could be an effective drug for the treatment of severe infections due to MRSA even in infant case.

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Staphylococcus aureus infections. Clin. Infect. Dis. 34: 1481⬃1490, 2002
2) RUBINSTEN, E.; S. K. CAMMARATA, T. H. OLIPHANT, et al. and the Linezolid Nosocomial Pneumonia
Study Group: Linezolid (PNU-100766) versus vancomycin in the treatment of hospital patients withnosocomial pneumonia: a randomized, double-blind, multicenter study. Clin. Infect. Dis. 32:402⬃412, 2001
3) BASSETTI, M.; A. D. BIAGIO, V. D. BONO, et al.: Successful treatment of methicillin-resistant Staphylococcus aureus endocarditis with linezolid. Int. J. Antimicrob. Agents 24: 83⬃84, 2004
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bacteremia: pooled analysis of randomized studies. J. Antimicrob. Chemother. 56: 923⬃929, 2005
5) TSIODRAS, S.; H. S. GOLD, G. SAKOULAS, et al.: Linezolid resistance in a clinical isolate of Staphylococcus aureus. Lancet 358: 207⬃208, 2001