Prof. Marta Mollerach Investigadora Principal CONICET Facultad de - - PowerPoint PPT Presentation

• Prof. Marta Mollerach

Investigadora Principal CONICET Facultad de Farmacia y Bioquímica Universidad de Buenos Aires

Current trends in Community acquired- Methicillin Resistant Staphylococcus aureus (CA-MRSA) in Argentina

2015

STRATEGIC OBJECTIVES

 Awareness and education  Surveillance of antimicrobial resistance  Infection prevention and control  Optimal use of antimicrobial medicines in human and animal health  R&D and investment

Global priority list of pathogens to guide research, discovery, and development of new antibiotics

Meticillin resistant Staphylococcus aureus (MRSA) HIGH PRIORITY

Staphylococcus aureus, MRSA and CA-MRSA

25% to 30% of people are colonized most common cause of skin and soft tissue infections endocarditis, osteomyelitis, pneumonia, toxic shock syndrome Methicillin Resistant S. aureus (MRSA)

Worldwide pandemia

• f MRSA in hospitals

Since 1960 ….MRSA = Nosocomial infection By the end of 20th century, another type

• f MRSA emerged among healthy

people in the community (CA-MRSA)

• SCCmec I, II o III
• Multiresistant
• SCCmec IV, V
• More susceptible to other families
• f antibiotics
• Particularly virulent.

CA-MRSA HA-MRSA

Comparison of typical CA-MRSA and HA-MRSA

1998 2002 2005 2009 Presence of Cordobés clone (ST5-MRSA-I) and > community clones in hospitals (ST5- MRSA-IV, ST30-MRSA-IV)

Egea et al., 2014

66 Hospitals

2012-2016

1 Hospital

(CABA)

Presence of community (ST5-MRSA-IV, ST30- MRSA-IV) > hospital (ST5-MRSA-I) clones in hospitals

Di Gregorio S, Mollerach M, 2015

13 Hospitals

(CABA, Pcia Bs As, Tucumán)

62,2% Brazilian clone ST239-MRSA-III

Corso et al., 1998

Emergence of “Cordobés” clone ST5-MRSA-I Similar prevalence than ST239-MRSA-III

Sola et al., 2002

6 Hospitals

Córdoba

Prevalence of Cordobés clone ST5-MRSA-I

Gardella, Mollerach M., 2005

2 Hospitals

Buenos Aires

Evolution of MRSA in Argentina (HA-MRSA clones)

Global distribution of CA-MRSA clones

DeLeo et al, 2010

Molecular epidemiology of CA-MRSA in

• Argentina. First reports

Eur J Clin Microbiol, 2006

PFGE A - ST5 - SCCmec IV

PFGE C – ST30 - SCCmecIV

Guidelines for the treatment of skin and soft tissue infections. Argentina-2009

Forunculosis, carbunclo and piomiositis, celulitis & impétigo

Vancomycin, linezolid, Daptomycin

Patients with sistemic manifestations

Empiric treatment based on β-lactam antibiotics but….

Is ST5 – SCCmec IV clone still dominant in Argentina? Prevalence of SSTIs caused by CA-MRSA in Argentina? Must we change guidelines for empirical treatment of these infections?

…questions in the CA-MRSA era

UBA & SADI (Argentinean Society for Infectious Diseases) Two prospective multicenter studies 1) Skin and soft tissue infections caused by MRSA 2) MRSA Invasive infection

Skin and Skin Structure Infections

19 Institutions

• 11 Bs.As. city
• 7 Bs.As. Province
• 1 Santa Fe

Province

311 patients were enrolled 271 (87%) positive cultures

218 (70%) MRSA

265 (85%) Monomicrobial 248 (80%) S. aureus CA-MRSA has become the most frequent cause of SSSIs (70%) in our population

Skin and skin structure infections (SSSIs) Invasive infections

ST 30-IV predominant clone causing SSSIs (65 % ) and invasive infections (82%) The association between ST30 and invasive infection is significant

% Isolates

*

10 20 30 40 50 60 70 80 90 100

IPER INVASIVAS

64,4 % 82% 24 % 7%

ST30-IVc-t019/rel ST5-IVa-t311

p=0,029, Fisher’s exact test

SSSIs Invasive Infections

Is the new predominant clone more virulent?

Higher virulence in two animal models

• f infection

ST30 – SCCmecIV is a High Risk Clone (HRC)

ST5 ST 30 1100 3 1100 4 1100 5 1100 6 1100 7 1100 8 1100 9

**

Bacterial load (CFU/lesion)

Acute oteomyelitis model

Skin infection model

ST 5 ST 30 1000 10000 100000 1000000

UFC/tibia

* (ST30 vs. ST5)

Different virulence genes profile

New questions to be answered concerning ST30-IV… Work in progress using WGS

• Is there any genomic change in ST30-MRSA-IV from 2005 to

2010-2011 that cause the expansion of this clone?

• Did it acquire additional resistance/virulence determinants?
• Genomic surveillance of MRSA
• Microevolution of MRSA in the lungs of CF patients

LEAD OVERSEAS RESEARCHER

• Prof. Dr. Marta Mollerach

Facultad de Farmacia y Bioquímica-UBA CONICET – Independent Researcher UK CO-APPLICANT

• Prof. Dr. David Aanensen

The Centre for Genomic Pathogen Surveillance - Wellcome Sanger Institute

David Aanensen / Silvia Argimón Centre for Genomic Pathogen Surveillance, United Kingdom Agnes Marie S. Figueiredo, Federal University of Rio de Janeiro, Brasil Nilton Lincopan. Institute of Biomedical Sciences, Universidade de São Paulo, Brazil. Alessandro Silveira. Universidad Regional de Blumenau, Santa Catarina, Brasil. Teresa Camou, Departamento de Laboratorios, Ministerio de Salud Pública, Uruguay Gustavo Varela, Facultad de Medicina, Universidad de la República, Uruguay Rosa Guillen Fretes, Departamento de Biología Molecular y Biotecnología, Universidad Nacional de Asunción, Paraguay Mario Fabián Martínez Mora, Laboratorio Central de Salud Pública, Paraguay Norah Balderrama Yarhui, , Hospital del Niño “Manuel Ascencio Villarroel”, Bolivia Lorena M. Soleto Ortiz, Centro Nacional de Enfermedades Tropicales, Bolivia Josefina Campos, Plataforma genómica y bioinformática, INEI-ANLIS Dr Carlos

• G. Malbrán, Argentina

Our specific aims are:

• 1. To establish a genomic surveillance network of S. aureus that allows:

A- study the population structure of S. aureus strains in SA, B- identify the circulating clones in the region and compare them within a global context, C- determine the presence of virulence factors and antibiotic resistance genes.

• 2. To develop regional capabilities for the sequencing and bioinformatic analysis of whole

genomes of S. aureus.

Facultad de Farmacia y Bioquímica Universidad de Buenos Aires (UBA) Dra Sabrina Di Gregorio Sol Haim (PhD student) Lucia Gulone (PhD student) Dra Arabela Cuirolo Dra Noella Gardella Dra Martha von Specht Dra Silvina Fernandez Dra Melina Herrera Dra Angela Famiglietti ( Hospital de Clinicas. UBA) MRSA Working Group - Argentinean Society for Infectology Children`s Hospital R- Gutierrez (Cystic Fibrosis Group) Facultad de Medicina Universidad de Buenos Aires. S. aureus Group IMPaM- Conicet

• Dr. Daniel Sordelli / Dra. Marisa Gómez

Thank you for your attention!!