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 ~  Abstract
 ~ Introduction
 ~ Case Report
 ~ Discussion
 ~ Acknowledgments
 ~  References
 ~  Article Tables

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  Table of Contents  
Year : 2012  |  Volume : 30  |  Issue : 2  |  Page : 232-236

The first case of Staphylococcus aureus ST398 causing bacteremia in an immunocompromised patient in Greece

1 Department of Microbiology, School of Medicine, National Reference Laboratory for Staphylococcal Infections, University of Patras, Greece
2 Division of Infectious Diseases, Department of Internal Medicine, University of Patras, Greece
3 Department of Microbiology, University of Patras, Greece
4 Division of Oncology, Department of Internal Medicine, School of Medicine, University of Patras, Greece

Date of Submission23-Dec-2011
Date of Acceptance01-Mar-2012
Date of Web Publication28-May-2012

Correspondence Address:
I Spiliopoulou
Department of Microbiology, School of Medicine, National Reference Laboratory for Staphylococcal Infections, University of Patras
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0255-0857.96706

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 ~ Abstract 

We describe a case of catheter-related bloodstream infection, in a patient with colon cancer, caused by a methicillin-sensitive Staphylococcus aureus strain, nontypeable by pulsed field gel electrophoresis of SmaI macrorestriction fragment analysis, belonging to ST398. The patient recovered after daptomycin therapy. This is the first report that documents the emergence of ST398 in Greece.

Keywords: Clones, ST398, Staphylococcus aureus

How to cite this article:
Drougka E, Foka A, Marangos M N, Liakopoulos A, Makatsoris T, Anastassiou E D, Petinaki E, Spiliopoulou I. The first case of Staphylococcus aureus ST398 causing bacteremia in an immunocompromised patient in Greece. Indian J Med Microbiol 2012;30:232-6

How to cite this URL:
Drougka E, Foka A, Marangos M N, Liakopoulos A, Makatsoris T, Anastassiou E D, Petinaki E, Spiliopoulou I. The first case of Staphylococcus aureus ST398 causing bacteremia in an immunocompromised patient in Greece. Indian J Med Microbiol [serial online] 2012 [cited 2020 Jul 16];30:232-6. Available from:

 ~ Introduction Top

It has recently become apparent that livestock constitutes a new methicillin-resistant Staphylococcus aureus Scientific Name Search  (MRSA) reservoir and can be a source of a novel and rapidly emerging type of MRSA. These livestock-associated clones are nontypeable by pulsed- field electrophoresis with SmaI and belong to sequence type (ST) 398. [1] MRSA ST398 account for 20% of all MRSA in the Netherlands and it has been described worldwide. [1],[2] Although ST398 transmission has been reported primarily between animals, persons with occupational exposure to livestock are at higher risk for S. aureus carriage than the general population, with an interest of whether MRSA may be transmitted between animals and humans. [1],[2] ST398 usually cause colonization; however, several cases of infections with variable clinical relevance have been described over the past few years. [1],[2] We report a case of catheter-related bloodstream infection (CRBSI) in a 68-year-old patient with cancer under treatment, in Greece, caused by S. aureus of clonal lineage ST398.

 ~ Case Report Top

The patient had been diagnosed 3 years ago with colon cancer with metastatic disease in the liver. He was treated initially with chemotherapy (oxaliplatin, 5-fluorouracil, leucovorin), followed by surgical resection of the primary tumor, but the liver metastases were unresectable. Postsurgery, he received 6 months of chemotherapy (irinotecan, 5-fluorouracil, leucovorin) in combination with bevacizumab (a monoclonal antibody targeting vascular endothelial growth factor) administered intravenously every 14 days through a surgically implanted central venous catheter (port-a cath). Subsequently, bevacizumab was continued as maintenance therapy.

Patient was treated for upper respiratory tract infection with amoxicillin/clavulanic acid a month before admission. Therapy was discontinued 3 days later because of side effects from the gastrointestinal system.

Patient felt well till 5 days before admission. He experienced headache, nausea and anorexia, without other symptoms, and begun to have fever as high as 39°C. There was no history of exposure to animals, residence in a rural area, recent travel or risk factors for human immunodeficiency virus infection. He did not use tobacco or alcohol.

On admission, his physical examination was unrevealing. The blood pressure was 110/70 mmHg, the pulse was 90 and respirations 16. No rash, petechiae, septic cutaneous lesions or lymphadenopathy was found. Inspiratory crackles were heard at both lung bases. The heart rhythm was regular without any murmur. The abdomen was soft and nontender. There was no peripheral edema or cyanosis and a neurological examination disclosed no focal abnormalities

The hematocrit was 37.3% and the white blood cell count 19,280/mm [3] with 90.5% neutrophils. The platelet count was 402,000/mm 3 (Sysmex XT-1800i, Roche Diagnostics, Basel, Switzerland). Prothrombin time was 15.8 seconds with a control of 13 seconds; partial thromboplastin time was 43.5 sec (STA Compact, Stago, Parsippany, NJ, USA). Sodium was 130.6 mmol/L, potassium 4.5 mmol/L, calcium 8.8 mg/dL, protein 6.1 gr/dL (albumin 2.8 gr/dL), (ACHITECT C8000, Abbott Laboratories, Abbott Park, IL, USA) and C-reactive protein 16.2 mg/dL (BECKMAN Coulter IMMAGE 800, Immunochemistry System, Beckman Coulter International SA, 1260 Nyon, Switzerland).

Specimens of blood and urine were obtained for culture and empirical treatment with teicoplanin and piperacillin/tazobactam intravenously was initiated. Blood cultures were performed routinely by the BacT/Alert 3D System (bioMerieux S.A. 69280, Marcy l'Etoile, France) at the Department of Microbiology, University Hospital of Patras (UHP), in Greece.

The central catheter was removed and the catheter tip was sent to the Microbiology Laboratory for culture. S. aureus was isolated from two different sets of blood samples as well as the catheter tip. Isolates were identified by Gram stain (Gram stain kit, bioMerieux), catalase and coagulase production (slidex Staph plus test, bioMerieux) and verified by molecular methods (PCR for 16S rDNA, nuc and mecA genes) [Table 1]. [3] Antibiotic susceptibility testing was performed by the disk diffusion method against antistaphylococcal agents: Cefoxitin, tetracycline, rifampicin, gentamicin, kanamycin, erythromycin, clindamycin, fusidic acid, ciprofloxacin and trimethoprim-sulphamethoxazole (SXT) (SirScan, i2a, Parc de la Mediterranée 34470, Pérols, France). [4] The MICs of oxacillin, vancomycin, teicoplanin, linezolid and daptomycin were determined by the Etest (bioMerieux). [4] Isolates were forwarded to the National Reference Laboratory for Staphylococcal infections for typing by means of SmaI (Roche Diagnostics GmbH, Mannheim, Germany) macrorestriction pattern and pulsed-field gel electrophoresis (PFGE), as previously described. [5] The mechanism of tetracycline resistance was investigated by PCR [Table 2]. [6] The genes encoding Panton-Valentine leukocidin (PVL) (lukF/lukS-PV), toxic shock syndrome toxin-1 (tst), exfoliative toxins A and B (eta, etb), egc operon (sem, seg genes), and agr groups were investigated by PCRs [Table 1]. [7],[8] Multi-locus Sequencing Typing (MLST) was performed as described (genes encoding: Carbamate kinase arcC, shikimate dehydrogenase aroE, glycerol kinase glpF, guanylate kinase gmk, phosphate acetyltransferase pta, triosephosphate isomerase tpi, acetyl coenzyme A acetyltransferase yqiL) [Table 1]. [9] All S. aureus isolates were of the same phenotype and genotype. The strain was susceptible to vancomycin (MIC: 1.5 mg/L), teicoplanin (0.5 mg/L), linezolid (1 mg/L), daptomycin (0.25 mg/L), and intermediate resistant to oxacillin (3 mg/L). It showed resistance to tetracycline and SXT. It was negative for the presence of mecA (MSSA) and the toxin genes tested, while it carried tet(M). PCR for the agr-specific types indicated that the isolate belonged to agr group 1. By PFGE of SmaI macrorestriction fragments it was nontypeable, while by MLST belonged to ST398.
Table 1: Primers used for S. aureus typing

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Table 2: Primers used for S. aureus tetracycline resistance investigation

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Antibiotic therapy was switched to daptomycin, 6 mg/kg/day intravenously, for 14 days combined with gentamicin, 80 mg every 8 hours daily, for 5 days. The patient became afebrile 48 hours later, while, additional blood cultures demonstrated no bacterial growth.

After treatment, patient and household contacts were tested and found to be negative for MRSA/S. aureus nasal and pharyngeal carriage by conventional and molecular methods (MRSA/S.aureus nasal, Gene Xpert, Cepheid, Bromma, Sweden).

 ~ Discussion Top

A peculiarity of S. aureus of clonal lineage ST398 is the indigestibility of whole cellular DNA by restriction enzyme SmaI, because of protection by a novel DNA methylation enzyme. [1] Therefore, SmaI macrorestriction patterns generate only one large fragment, as it happened with our isolates.

The patient had no underlying cardiac predisposing conditions or clinical signs of endocarditis and a transthoracic echocardiography did not detect any vegetations. Identification of rare ST398 human outbreaks [2] supports the hypothesis that the scarce number of infections reported so far may be due to the still-limited spread of ST398 among critically ill patients, while emergence among pigs is thought to be recent.

In Greece, ST80 is the predominant clone among MRSA infections and is spread in the community and the hospitals. [10] Among bloodstream infections caused by MRSA, the most frequent characterized clone is ST80, followed by the hospital-associated clone ST239 and sporadic cases of ST30 and ST97 clones (personal data). MRSA of clonal lineage ST398 was not characterized in Greece till now. [2] In the present case, even though the isolates from all clinical specimens were methicillin-sensitive, as proved by molecular methods, they were further analyzed because of the severity of patients' disease. This is the first case of S. aureus ST398 emergence in Greece. Patient and household contacts had no animal contact and were found negative for S. aureus carriage. Therefore, we were unable to locate the source of patient's infection. Three MSSA belonging to ST398 already characterized from humans and animals in other countries are deposited in MLST data base (

In conclusion, epidemiological investigation and attention should be given to systematic and deep-seated S. aureus infections, despite methicillin resistance. Even though ST398 strains are associated with intensive animal farming, continuous surveillance in staphylococcal severe human infections should monitor the extent of disease from ST398 strains.

 ~ Acknowledgments Top

Part of this study was supported by the funds of the National Reference Laboratory for Staphylococcal Infections (C934). Some of the results were generated during routine diagnostic activities. No commercial relationship or potential conflict of interest exists. The authors are responsible for the contents of this publication.

 ~ References Top

1.Huijsdens XW, van Dijke BJ, Spalburg E, van Santen-Verheuvel MG, Heck ME, Pluister GN, et al. Community-acquired MRSA and pig farming. Ann Clin Microbiol Antimicrob 2006;5:26.  Back to cited text no. 1
2.van Cleef BA, Monnet DL, Voss A, Krziwanek K, Allerberger F, Struelens M, et al. Livestock-associated methicillin-resistant Staphylococcus aureus in humans, Europe. Emerg Infect Dis 2011;17:502-5.  Back to cited text no. 2
3.Zhang K, Sparling J, Chow BL, Elsayed S, Hussain Z, Church DL, et al. New quadriplex PCR assay for detection of methicillin and mupirocin resistance and simultaneous discrimination of Staphylococcus aureus from coagulase-negative staphylococci. J Clin Microbiol 2004;42:4947-55.  Back to cited text no. 3
4.Clinical and Laboratory Standards Institute (2009). Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. 10 th ed. Approved standard M7-A7. Wayne, PA: CLSI.  Back to cited text no. 4
5.Tenover FC, Arbeit RD, Goering RV, Mickelsen PA, Murray BE, Persing DH, et al. Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: Criteria for bacterial strain typing. J Clin Microbiol 1995;33 : 2233-9.  Back to cited text no. 5
6.Ng LK, Martin I, Alfa M, Mulvey M. Multiplex PCR for the detection of tetracycline resistant genes. Mol Cell Probes. 2001; 15: 209-15.  Back to cited text no. 6
7.Jarraud S, Mougel C, Thioulouse J, Lina G, Meugnier H, Forey F, et al. Relationships between Staphylococcus aureus genetic background, virulence factors, agr groups (alleles) and human disease. Infect Immun 2002;70:631-41.  Back to cited text no. 7
8.Lina G, Boutite F, Tristan A, Bes M, Etienne J, Vandenesch F. Bacterial competition for human nasal cavity colonization: Role of staphylococcal agr alleles. Appl Environ Microbiol 2003;69:18-23.  Back to cited text no. 8
9.Enright MC, Day NP, Davies CE, Peacock SJ, Spratt BG. Multilocus sequence typing for characterization of methicillin-resistant and methicillin-susceptible clones of Staphylococcus aureus. J Clin Microbiol 2000;38:1008-15.  Back to cited text no. 9
10.Chini V, Petinaki E, Foka A, Paratiras S, Dimitracopoulos G, Spiliopoulou I. Spread of Staphylococcus aureus clinical isolates carrying Panton-Valentin leukocidin genes during a 3-year period in Greece. Clin Microbiol Infect 2006;12:29-34.  Back to cited text no. 10


  [Table 1], [Table 2]

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