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Heterogeneous vancomycin-intermediate susceptibility in a community-associated methicillin-resistant Staphylococcus aureus epidemic clone, in a case of Infective Endocarditis in Argentina.

Sola C, Lamberghini RO, Ciarlantini M, Egea AL, Gonzalez P, Diaz EG, Huerta V, Gonzalez J, Corso A, Vilaro M, Petiti JP, Torres A, Vindel A, Bocco JL - Ann. Clin. Microbiol. Antimicrob. (2011)

Bottom Line: Infective endocarditis (IE) due to CA-MRSA with heterogeneous vancomycin-intermediate susceptibility-(h-VISA) has been recently reported, associated to an epidemic USA 300 CA-MRSA clone.Moreover, Sab2 was classified as h-VISA by three different screening methods [MHA5T-screening agar, Macromethod-E-test-(MET) and by GRD E-test] and confirmed by population analysis profile-(PAP).In addition, a significant increase in cell-wall thickness was revealed for SaB2 by electron microscopy.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina. csola@fcq.unc.edu.ar

ABSTRACT

Background: Community-Associated Methicillin Resistant Staphylococcus aureus (CA-MRSA) has traditionally been related to skin and soft tissue infections in healthy young patients. However, it has now emerged as responsible for severe infections worldwide, for which vancomycin is one of the mainstays of treatment. Infective endocarditis (IE) due to CA-MRSA with heterogeneous vancomycin-intermediate susceptibility-(h-VISA) has been recently reported, associated to an epidemic USA 300 CA-MRSA clone.

Case presentation: We describe the occurrence of h-VISA phenotype in a case of IE caused by a strain belonging to an epidemic CA-MRSA clone, distinct from USA300, for the first time in Argentina. The isolate h-VISA (SaB2) was recovered from a patient with persistent bacteraemia after a 7-day therapy with vancomycin, which evolved to fatal case of IE complicated with brain abscesses. The initial isolate-(SaB1) was fully vancomycin susceptible (VSSA). Although MRSA SaB2 was vancomycin susceptible (≤ 2 μg/ml) by MIC (agar and broth dilution, E-test and VITEK 2), a slight increase of MIC values between SaB1 and SaB2 isolates was detected by the four MIC methods, particularly for teicoplanin. Moreover, Sab2 was classified as h-VISA by three different screening methods [MHA5T-screening agar, Macromethod-E-test-(MET) and by GRD E-test] and confirmed by population analysis profile-(PAP). In addition, a significant increase in cell-wall thickness was revealed for SaB2 by electron microscopy. Molecular typing showed that both strains, SaB1 and SaB2, belonged to ST5 lineage, carried SCCmecIV, lacked Panton-Valentine leukocidin-(PVL) genes and had indistinguishable PFGE patterns (subtype I2), thereby confirming their isogenic nature. In addition, they were clonally related to the epidemic CA-MRSA clone (pulsotype I) detected in our country.

Conclusions: This report demonstrates the ability of this epidemic CA-MRSA clone, disseminated in some regions of Argentina, to produce severe and rapidly fatal infections such as IE, in addition to its ability to acquire low-level vancomycin resistance; for these reasons, it constitutes a new challenge for the Healthcare System of this country.

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Transesophageal echocardiography of a patient with infective endocarditis caused by CA-MRSA with phenotype h-VISA, Argentina. Left: On April 12, the highly mobile vegetation on the aortic valve (AV) of 20 × 41 mm (white arrow). Right: On April 24, slight decrease in the aortic valve (AV) vegetation (white arrow) and a new vegetation on the mitral valve (MV) (10 × 4.6 mm) of low motility (white arrow).
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Figure 1: Transesophageal echocardiography of a patient with infective endocarditis caused by CA-MRSA with phenotype h-VISA, Argentina. Left: On April 12, the highly mobile vegetation on the aortic valve (AV) of 20 × 41 mm (white arrow). Right: On April 24, slight decrease in the aortic valve (AV) vegetation (white arrow) and a new vegetation on the mitral valve (MV) (10 × 4.6 mm) of low motility (white arrow).

Mentions: MRSA grew in three blood cultures (SaB1-strain) and one urine culture (SaU-strain) taken upon admission in the ICU on April 7. A transthoracic echocardiography (TE) showed a filamentous mobile image attached to the ventricular side of the aortic valve, which resembled vegetations, suggesting a MRSA infection that met Duke's criteria for IE [14]. These isolates were susceptible to ciprofloxacin, gentamicin, rifampicin, tetracycline, trimethoprim-sulfamethoxazole-(TMP-SMX) and linezolid by disk diffusion and broth microdilution methods (see Additional file 1, Table S1) [15] and resistant to erythromycin and clindamycin (inducible resistance, D-test positive) [15]. In addition, vancomycin MIC was 1 μg/ml by broth dilution method [15]. Vancomycin treatment (15 mg/kg every 12 h) was initiated on April 7 and the patient was transferred to "Hospital-Militar-Regional-Córdoba-(HMRC)" for further evaluation on April 8. Antibiotic levels in blood were not available, so the same dose of vancomycin was continued; which is recommended to maintain the level of vancomycin in the valley of 10-15 μg/ml. The patient had fever of 39.2°C accompanied by Janeway's lesions on the hands. On April 9, valve replacement was postponed because of a worsening of the neurological symptoms and hypotension. Roth's spots were detected. The brain CT revealed no changes. On April 12, the patient presented hemodynamic and neurological improvement; a transoesophageal echocardiography (TEE) showed a highly mobile vegetation on the aortic valve (Figure 1). On April 14, the patient had altered mental status and persistent fever. Brain magnetic resonance-image-MRI with gadolinium showed multiple abscesses (Additional file 2, Figure S1). On April 15, since the patient worsened, valve replacement was postponed again; treatment failure was suspected and trimethoprim/sulfamethoxazole (15 mg/kg/day) was added to vancomycin. On April 17, the patient remained febrile, three new samples for blood culture taken on April 14 revealed MRSA (strain SaB2) with the same susceptibility to antibiotics, except for vancomycin, which reached a MIC of 2 μg/ml (broth dilution [15]. On April 20, the patient was afebrile. Three additional sets of blood cultures were drawn providing negative results. On April 24, a control TEE (Figure 1) showed a slight decrease of the size of the aortic valve vegetation and a new vegetation on the mitral valve. The patient had evident deterioration of mental and physical status and died on April 25 before surgical intervention.


Heterogeneous vancomycin-intermediate susceptibility in a community-associated methicillin-resistant Staphylococcus aureus epidemic clone, in a case of Infective Endocarditis in Argentina.

Sola C, Lamberghini RO, Ciarlantini M, Egea AL, Gonzalez P, Diaz EG, Huerta V, Gonzalez J, Corso A, Vilaro M, Petiti JP, Torres A, Vindel A, Bocco JL - Ann. Clin. Microbiol. Antimicrob. (2011)

Transesophageal echocardiography of a patient with infective endocarditis caused by CA-MRSA with phenotype h-VISA, Argentina. Left: On April 12, the highly mobile vegetation on the aortic valve (AV) of 20 × 41 mm (white arrow). Right: On April 24, slight decrease in the aortic valve (AV) vegetation (white arrow) and a new vegetation on the mitral valve (MV) (10 × 4.6 mm) of low motility (white arrow).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3111347&req=5

Figure 1: Transesophageal echocardiography of a patient with infective endocarditis caused by CA-MRSA with phenotype h-VISA, Argentina. Left: On April 12, the highly mobile vegetation on the aortic valve (AV) of 20 × 41 mm (white arrow). Right: On April 24, slight decrease in the aortic valve (AV) vegetation (white arrow) and a new vegetation on the mitral valve (MV) (10 × 4.6 mm) of low motility (white arrow).
Mentions: MRSA grew in three blood cultures (SaB1-strain) and one urine culture (SaU-strain) taken upon admission in the ICU on April 7. A transthoracic echocardiography (TE) showed a filamentous mobile image attached to the ventricular side of the aortic valve, which resembled vegetations, suggesting a MRSA infection that met Duke's criteria for IE [14]. These isolates were susceptible to ciprofloxacin, gentamicin, rifampicin, tetracycline, trimethoprim-sulfamethoxazole-(TMP-SMX) and linezolid by disk diffusion and broth microdilution methods (see Additional file 1, Table S1) [15] and resistant to erythromycin and clindamycin (inducible resistance, D-test positive) [15]. In addition, vancomycin MIC was 1 μg/ml by broth dilution method [15]. Vancomycin treatment (15 mg/kg every 12 h) was initiated on April 7 and the patient was transferred to "Hospital-Militar-Regional-Córdoba-(HMRC)" for further evaluation on April 8. Antibiotic levels in blood were not available, so the same dose of vancomycin was continued; which is recommended to maintain the level of vancomycin in the valley of 10-15 μg/ml. The patient had fever of 39.2°C accompanied by Janeway's lesions on the hands. On April 9, valve replacement was postponed because of a worsening of the neurological symptoms and hypotension. Roth's spots were detected. The brain CT revealed no changes. On April 12, the patient presented hemodynamic and neurological improvement; a transoesophageal echocardiography (TEE) showed a highly mobile vegetation on the aortic valve (Figure 1). On April 14, the patient had altered mental status and persistent fever. Brain magnetic resonance-image-MRI with gadolinium showed multiple abscesses (Additional file 2, Figure S1). On April 15, since the patient worsened, valve replacement was postponed again; treatment failure was suspected and trimethoprim/sulfamethoxazole (15 mg/kg/day) was added to vancomycin. On April 17, the patient remained febrile, three new samples for blood culture taken on April 14 revealed MRSA (strain SaB2) with the same susceptibility to antibiotics, except for vancomycin, which reached a MIC of 2 μg/ml (broth dilution [15]. On April 20, the patient was afebrile. Three additional sets of blood cultures were drawn providing negative results. On April 24, a control TEE (Figure 1) showed a slight decrease of the size of the aortic valve vegetation and a new vegetation on the mitral valve. The patient had evident deterioration of mental and physical status and died on April 25 before surgical intervention.

Bottom Line: Infective endocarditis (IE) due to CA-MRSA with heterogeneous vancomycin-intermediate susceptibility-(h-VISA) has been recently reported, associated to an epidemic USA 300 CA-MRSA clone.Moreover, Sab2 was classified as h-VISA by three different screening methods [MHA5T-screening agar, Macromethod-E-test-(MET) and by GRD E-test] and confirmed by population analysis profile-(PAP).In addition, a significant increase in cell-wall thickness was revealed for SaB2 by electron microscopy.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina. csola@fcq.unc.edu.ar

ABSTRACT

Background: Community-Associated Methicillin Resistant Staphylococcus aureus (CA-MRSA) has traditionally been related to skin and soft tissue infections in healthy young patients. However, it has now emerged as responsible for severe infections worldwide, for which vancomycin is one of the mainstays of treatment. Infective endocarditis (IE) due to CA-MRSA with heterogeneous vancomycin-intermediate susceptibility-(h-VISA) has been recently reported, associated to an epidemic USA 300 CA-MRSA clone.

Case presentation: We describe the occurrence of h-VISA phenotype in a case of IE caused by a strain belonging to an epidemic CA-MRSA clone, distinct from USA300, for the first time in Argentina. The isolate h-VISA (SaB2) was recovered from a patient with persistent bacteraemia after a 7-day therapy with vancomycin, which evolved to fatal case of IE complicated with brain abscesses. The initial isolate-(SaB1) was fully vancomycin susceptible (VSSA). Although MRSA SaB2 was vancomycin susceptible (≤ 2 μg/ml) by MIC (agar and broth dilution, E-test and VITEK 2), a slight increase of MIC values between SaB1 and SaB2 isolates was detected by the four MIC methods, particularly for teicoplanin. Moreover, Sab2 was classified as h-VISA by three different screening methods [MHA5T-screening agar, Macromethod-E-test-(MET) and by GRD E-test] and confirmed by population analysis profile-(PAP). In addition, a significant increase in cell-wall thickness was revealed for SaB2 by electron microscopy. Molecular typing showed that both strains, SaB1 and SaB2, belonged to ST5 lineage, carried SCCmecIV, lacked Panton-Valentine leukocidin-(PVL) genes and had indistinguishable PFGE patterns (subtype I2), thereby confirming their isogenic nature. In addition, they were clonally related to the epidemic CA-MRSA clone (pulsotype I) detected in our country.

Conclusions: This report demonstrates the ability of this epidemic CA-MRSA clone, disseminated in some regions of Argentina, to produce severe and rapidly fatal infections such as IE, in addition to its ability to acquire low-level vancomycin resistance; for these reasons, it constitutes a new challenge for the Healthcare System of this country.

Show MeSH
Related in: MedlinePlus